Spatial Distribution of Antioxidant Activity in Baguette and Its Modulation of Proinflammatory Cytokines in RAW264.7 Macrophages

Spatial Distribution of Antioxidant Activity in Baguette and Its Modulation of Proinflammatory Cytokines in RAW264.7 Macrophages | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Spatial Distribution of Antioxidant Activity in Baguette and Its Modulation of Proinflammatory Cytokines in RAW264.7 Macrophages Huaiyu Gu, Jianqiao Zou, Zhaoshuo Yu, Lijing Ke, Fangzhou He, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3862746/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 11 Sep, 2024 Read the published version in npj Science of Food → Version 1 posted 9 You are reading this latest preprint version Abstract Baguette, a globally acclaimed bakery staple, undergoes a complex Maillard reaction during the baking process, imparting a dual composition of crispy crust and soft crumb. Maillard reaction contributes to the unique flavor and texture of baguettes. However, its specific impact on the nutritional and health attributes, particularly in terms of cellular and biological functions, are yet to be clearly elucidated. This study investigates the chemical profiles of Maillard reaction products (MRPs) in baguette crust and crumb, and spatial distribution variations in the antioxidant activity. The impacts of baguette crust and crumb on cellular reactive oxygen species, mitochondrial activity, and inflammatory factors in RAW264.7 macrophages are also determined, aiming to elucidate the influence of the Maillard reaction on baguette nutritional efficacy. From the inside out, both the browning intensity and advanced glycation end products (AGEs) gradually increased, accompanied by a significant elevation in the antioxidant capacity of the crust (tested using ORAC/ABTS/FRAP). This suggests that the Maillard reaction enhances antioxidative properties. Additionally, both the crust and crumb exhibited a strong cytocompatibility for immune cells with capable of reversing cellular oxidative stress, regulating intracellular free radical levels. The crust mitigated the peroxyl radical induced cell membrane hyperpolarization by 91% and the suppression on the oxygen respiration in mitochondria by up to 100%, showing higher activities than the crumb. Conversely, the crumb more effectively inhibited the lipopolysaccharide (LPS)-induced proinflammatory cytokines expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in macrophages. It could provide the fundamental data and cell-based approach for investigating the biological impacts of bread on mucosal immune responses, contributing to the refinement and supplementation of nutritional recommendations. Biological sciences/Biochemistry/Biophysical chemistry Biological sciences/Chemical biology/Biophysical chemistry Antioxidant Activity Baguette Cellular oxidative stress Cytokines Maillard Reaction Products RAW264.7 Macrophages Spatial Distribution Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 1. Introduction The baguette stands out as a globally renowned bread variety, distinguished by its distinctive features, including a crisp crust measuring 3–4 mm in thickness, an open and heterogeneous crumb cell structure with a rich, full-bodied flavor 1,2 . These defining characteristics are intricately linked to the Maillard reaction, a complex set of chemical processes occurring during the baking of the dough 3,4 . While existing literature extensively underscores the influence of the Maillard reaction on shaping the sensory attributes of bread 5 , particularly in terms of color and texture quality 6,7 , a notable gap persists regarding a comprehensive understanding of how the Maillard reaction specifically impacts the biological effects of baked bread. This raises the intriguing question: Is there a biological mechanism behind our love for delectable food? During food baking process, a complex cascade of nonenzymatic reactions, the so-called Maillard reaction, is taking place between carbonyl groups of reducing sugars and amino acids, peptides and amino groups of proteins 8,9 . The Maillard reaction produces a variety of bioactive compounds such as melanoidins 10 . Melanoidins, characterized as high molecular weight, brown, and nitrogenous compounds, are formed in the final stages of the Maillard reaction, with a variety of biological activities such as antioxidant 11 . The melanoidins identified in the bread crust demonstrate an individual-dependent influence on distinct microbial flora, suggesting a potential anti-inflammatory effect through the inhibition of enterobacteria 12,13 . Pronyl-lysine was a novel protein modification in bread melanoidins showed in vitro antioxidative and phased I/II enzyme modulating activity in intestinal Caco-2 cells 14 . The Maillard reaction, while also introducing certain adverse effects on food such as the formation of AGEs and acrylamide 9,15 , can be effectively managed through the precise regulation of baking conditions 3 . A healthful dietary regimen invariably exerts significant influences on immune responses, consequently playing a role in the regulation of appetite 16 . It can be posited that a health-conscious diet, through its modulation of immune reactions, augments the consumers' preference and dependence on such dietary patterns. In the context of immunometabolic dysregulation, immune cells undergo oxidative stress in the presence of inflammatory cytokines, thereby impacting appetite 17 . Prior investigations have elucidated the commendable standing of traditional and prevalent health-promoting diets, exemplified by the esteemed reputation of porcine bone soup 18,19 . Notably, the nanoparticles derived from these diets exhibit efficacious modulation of immune cell activity within the gastrointestinal mucosa, consequently ameliorating cellular oxidative stress 20–22 . Analogous observations are discerned in nanoparticles rich in polyphenols, exemplified by those found in aged vinegar 23 . Given the substantial population of immune cells, particularly macrophages, within the human intestinal mucosa, bearing pivotal roles in inflammation and metabolic disorders 24 , it is imperative to establish a comprehensive model elucidating the intricate interplay between baguette consumption and immune cells. By elucidating variances in spatial antioxidant properties, this study aims to elucidate the significant role played by the Maillard reaction in augmenting the antioxidation activity and immunocompetence of baguette. Furthermore, this study is anticipated to make a meaningful contribution to the improvement and supplementation of nutritional guidelines for baked foods and healthy diets, providing insights into the intricate relationships among the Maillard reaction, sensory preferences and desires, and underlying biological mechanisms. Such exploration is essential for a more comprehensive understanding of the overall impact of dietary choices. 2. Materials and Methods 2.1 Materials High gluten flour (Weifang Fengzheng Flour Co., Ltd., China). Instant dry yeast and bread improver (Angel, China). 96-well plate with clear/black well, T-75 and T-25 cell culture flask were from Corning Incorporated (New York, USA). Phosphate buffer saline (PBS), Hanks' balanced salt solution (HBSS), fetal bovine serum (FBS), Dulbecco’s modified Eagle medium (DMEM), penicillin-streptomycin, 0.25% Trypsin-EDTA were purchased from GIBCO (Grand Island, NY, USA). Triglyceride (TC) kit, Lactate dehydrogenase (LDH) assay kit and LDH were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). LDH cytotoxicity assay kit and human IFN-α/IFN-β/IFN-γ ELISA kit were purchased from Beyotime Biotechnology (Shanghai, China). Bicinchoninic acid (BAC) kit, MTT, 2′,7′-dichlorofluorescein diacetate (DCFH-DA, ≥ 97% purity), 2,2′-azobis (2-amidinopropane) dihydrochloride (AAPH), dimethyl sulfoxide (DMSO), Trolox (≥ 98% purity by HPLC), quercetin dihydrate (≥ 98% purity by HPLC), Nile Red, DiBAC4( 3 ), Mito-SOX Red were purchased from the Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). The deionized water was prepared with a purifier and was used for sample preparation. All other chemicals were of analytical reagent grade and obtained in China. 2.2 Samples preparation 2.2.1 Baguette making The dough formula was 450 g flour, 4 g dry yeast, 2.25 g bread improver, 4.5 g salt and 342g water. The ingredients were mixed in a mixer for 10 min at medium speed. After fermentation, gentle sheeting of the dough to final form which was put into an oven heated up to a temperature of 230 ºC and the baking time was 30 min. After baking, the baguette was left to stand for 24 h at room temperature, and then was kept frozen (at -20°C) until analysis 1,25 . 2.2.2 Preparation of baguette crust and crumb aqueous extracts The baguette crust and crumb were separated (Fig. 2 a). After ventilation and drying (at 25°C), the baguette crust and crumb were dried and then ground in a mill and screened through a 0.15 mm sieve to obtain powdered bread, stored at -20°C 26 . The optimal conditions of preparation of baguette crust and crumb aqueous extracts were determined by optimizing the material/water ratio and vortex oscillation time 27 . Mixing 3 g powdered baguette crust or crumb with 30 mL deionized water, vortexed for 30 min and placed for 30 min at room temperature. The supernatant infusion was collected by centrifuging for 15 min (4000 rpm, 25°C), and baguette crust extracts (BCstE) and baguette crumb extracts (BCmbE) were stored at -4°C. The BCstE and BCmbE were moved into a weighed glass dish with a 9 cm diameter to be dried at 105 ◦C for 3 h to determine the dry weight. 2.3 Physicochemical characterization Protein content was determined by using a BAC kit with bovine serum albumin (BSA) as a standard sample 28 . The content of total polysaccharide was determined by the Anthrone-Sulfuric acid assay, using glucose as the standard. TC content was determined by TC with GPO-PAP assay. Total phenolic contents (TPC) was determined by using the Folin-Ciocalteau reagent 29 . The turbidity of extraction was determined with an UV/VIS spectrophotometer (UV-5100, HITACHI, Japan) at 600 nm 30 . 2.4 Evaluation of browning intensity (Measurement of colour) The color of different samples was determined using a Chroma Meter (CR-400, Konica Minolta, Japan) according to the CIELab scale. Colour was expressed in L * , a * , b * Hunter scale parameters: L * or Luminance (0 to 100), a * or colouring from green to red (-120 to 120), -b * or colouring from blue to yellow (-120 to 120). The browning intensity was indicated by the yellowing index (YI = 142.86 b * / L * ) 31 . 2.5 Measurement of fluorescent AGEs Measurement of fluorescent AGEs using fluorescence assays 32,33 . Mixing 3 g powdered baguette crust or crumb with 30 mL Tris-HCl buffer (pH = 7.5) containing 36 mg streptomycin proteinase E, 150 mg sodium dodecyl sulfate and 44.1 mg CaCl 2 , and then were digested by shaking in a shaker at 30℃ for 36 h. The solutions were centrifuged at 4500 g for 10 min at 4°C and the supernatant was diluted with ultrapure water to be analyzed. The solution was measured by fluorescence spectrophotometry at excitation/emission wavelengths of 370/440 nm (glycosylated collagen), 330/420 nm (pyrrole and imidazole derivatives) and 335/385 nm (pentosidine). The parameters of the fluorescence spectrophotometer were set as: the voltage of the photomultiplier tube was 700 V, the response time was 0.5 s, the slit width was 5.0 nm on the excitation side and 5.0 nm on the emission side, and the scanning mode was time scanning for 20 s. 2.6 Determination of antioxidant activities Antioxidant activities of BCstE and BCmbE were assessed with by the following methods: (i) ABTS, (ii) Ferric reducing antioxidant power assay (FRAP assay) and (iii) oxygen radical absorbance capacity (ORAC) 20,34 . 2.7 Determination of antioxidant activity and fluorescent AGEs distributions in cross-sections of baguette As shown in Fig. 2 b, the middle and two end parts of baguette were carefully separated by a knife. The sampling schematic diagram of the transverse and longitudinal isometric sections of baguette as shown in Figs. 2 c and 2 d. The middle cross-section was divided into 5 transverse isometric parts and 3 longitudinal isometric parts, and different sampling sites were named by different numbers ( 1 – 15 ). The two end cross-sections were divided into 4 transverse isometric parts and 3 longitudinal isometric parts, and different sampling sites were named by different letters (A-L). Baguette aqueous extracts were prepared by method 2.2.2. The distributions of fluorescent AGEs in cross-sections of baguette were determined by method 2.5. The distributions of antioxidant activity in cross-sections of baguette were determined by method 2.6(iii). 2.8 Cell culture RAW 264.7 macrophages (purchased from Shanghai Institute of Life Sciences, Chinese Academy of Science) were grown at standard cell culture conditions (5% CO 2 , 37 ℃) in a T-75 cell culture flask with DMEM, supplemented with 10% FBS and 1% penicillin/streptomycin. Cells between passages 10 and 20 were used in this study. 2.9 Determination of cytotoxicity 2.9.1 MTT Assay For cellular proliferation measurement using the MTT assay 35 . RAW 264.7 macrophages were seeded in 96-well plates. After incubation for 24 h, the cell culture medium was removed and washed once with HBSS. Samples were diluted to appropriate gradient concentrations with complete DMEM. Adding 200 µL of the diluted samples to 96-well cell culture plates and setting control wells and zeroing wells. After another 24 h incubation period, the cell morphology was observed under an inverted microscope. 20 µL of solution (5 mg/mL) was added to the wells, followed by a further 3 h incubation in the dark. The cell culture medium with MTT was removed and washed twice with HBSS. 200 µL of DMSO was added to the wells, and the plate was shaken on an oscillator for 10 min. Absorbance at 570 nm was recorded by using a FlexStation 3 Plate Reader (Molecular Devices, Sunnyvale, CA, USA). The absorbance was used as a measurement of cell viability, normalized to cells incubated in a control group, which was considered 100% viable. 2.9.2 LDH Assay RAW 264.7 macrophages were seeded in 96-well plates. After incubation for 24 h, the cell culture supernatant was taken and detected by LDH cytotoxicity detection kit, and the method was strictly according to the instructions. 2.10 CAA assay The CAA assay was carried out following the method of reference 36 . RAW 264.7 macrophages were plated (6.0×10 4 cell/well) in 200 µL cell culture media/well in 96-well black. After incubation for 24 h, the cell culture medium was removed and washed twice with HBSS. Samples and standard substance (Quercetin) were diluted to appropriate gradient concentrations with complete DMEM. The diluted samples or standard substance (100 µL) and DCFH-DA (50 µM, 100 µL) were added to each well in triplicate wells, and control wells and blank wells were set up. After an-hour’s incubation at 37°C, RAW 264.7 macrophages were washed once by HBSS. Then 100 µL of AAPH (600 µM) was added to the wells and the plate was immediately placed in a FlexStation 3 Plate Reader. Real-time fluorescence was read initially and every five minutes after for 1 h with an excitation wavelength of 485 nm and an emission wavelength of 538 nm. Control wells were treated with DCFH-DA and AAPH without antioxidants, while blank wells were treated with DCFH-DA without AAPH and antioxidants. area under the fluorescence curve (AUC) was calculated with GraphPad Prism 5.0. Antioxidant activity was expressed as µmol/g quercetin equivalents using the linear regression value obtained from the quercetin calibration curve (y = 0.055x + 0.3326, R 2 = 0.9907). The result was calculated as follows: \({CAA}_{unit}=(1-\frac{{AUC}_{sample}}{{AUC}_{control}}\) ) ×100 2.11 Cell membrane potential and mitochondrial superoxide determination RAW 264.7 macrophages were seeded in 96-well black plates at 2×10 4 cells/well. After incubation for 24 h, the wells were washed twice with HBSS, and then Mito-SOX Red (200 µL, 3 µM in HBSS) was added to each well which was kept at 37°C for 10 min. 100 µL of 5 µM DiBAC4 ( 3 ) was added to each well which was incubated for 15 min. Samples (50 µL/well) are added at three ratios with HBSS as the negative control. AAPH was added into each well as the positive control group to reach a final concentration of 6.4 mM. Put the 96-well plate into FlexStation 3 Plate Reader and read the data every 10 min for 120 min at 37°C. The excitation and emission wavelength for Mito-SOX Red were set at Ex = 510 nm/ Em = 580 nm and DiBAC4( 3 ) was set at Ex = 493 nm/ Em = 516 nm. The fluorescent micrographs are taken right after the fluorometric measurement (Leica, DMI3000 B Inverted Microscope, Ex = 515–560 nm and Em = 590 nm for Mito-SOX Red, Ex = 450–490 nm and Em = 516 nm for DiBAC4( 3 ) 21 . The whole process was repeated twice to check the reproducibility. 2.12 Inflammatory cytokines determination RAW 264.7 macrophages were seeded in 12-well plates. After incubation for 24 h, the cell culture supernatant was removed. Adding 1 mL of BCstE diluted with DMEM (BCstE/DMEM = 1:5, BCstE/DMEM = 1:40) and setting a control group. After co-culture for 24 hours, the cell supernatant was collected and the levels of TNF-α, IL-1β and IL-6 were detected by ELISA kits. To determine the effect of the samples on the inflammatory factors released by cells stimulated by LPS, the cells were seeded in 12-well plates and cultured for 24 h. After removing the cell culture supernatant, 500 µL of 40 µg/mL LPS diluted with DMEM was added, and the cells were cultured for 1 h in the incubator. adding 500 µL of BCstE diluted 5-fold and 40-fold with DMEM and setting a positive control group (500 µl each DMEM and LPS, the specific operation steps were consistent with the sample group). After co-culture for 24 hours, the supernatant of cells was collected and the levels of IL-1β and IL-6 were detected by ELISA kits. 3. Results and Discussion 3.1 Physicochemical characterization As shown in Table 1 , The contents of protein and total phenol in BCstE were higher than those of BCmbE with a significant difference. The contents of dry matter, total sugar and triglyceride in BCstE and turbidity of BCstE were lower than those of BCmbE with a significant difference. Table 1 The results of physicochemical indexes of the bread crust and crumb extracts Sample Dry Matter(mg/mL) Protein(mg/mL) Total polysaccharides(mg/mL) Triglyceride(mmol/L) Total phenol(µg/mL) Turbidity(mAbs) BCstE 7.46 ± 0.07 b 0.77 ± 0.03 a 5.36 ± 0.12 b 3.67 ± 0.15 b 38.47 ± 0.79 a 74.00 ± 1.00 b BCmbE 8.57 ± 0.05 a 0.43 ± 0.02 b 5.95 ± 0.06 a 4.00 ± 0.02 a 25.29 ± 0.40 b 143.67 ± 2.08 a Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). 3.2 The degree of browning As shown in Table 2 , there were differences in chromatic values (L * , a * , b * )between bread crust and bread crumb after baking. The red-green degree (a * ) and yellow-blue degree (b * ) of bread crust were higher than those of bread crumb, but the lightness value (L * ) of bread crust was lower than that of bread crumb. Furthermore, the yellowing index of bread crust was higher than that of bread crumb with a significant difference. As shown in Table 3 and Fig. 3 , there was no significant difference in lightness value (L * ) between BCstE and BCmbE, but the yellow-blue value (b * ) of BCstE was higher than that of BCmbE and the red-green degree (a * ) of BCstE was lower than that of BCmbE. The colour of BCstE was more green and yellow than that of BCmbE. Furthermore, the yellowing index of BCstE was higher than that of BCmbE with a significant difference. The above results indicate that the browning degree of bread crust is significantly higher than that of bread crumb, which also reflects that the main part of bread browning occurred in the process of hot processing is the crust. Table 2 Chromatic value of the bread crust and crumb Sample CIELab colour Yellowing index (YI) L * a * b * BCst 57.50 ± 0.80 b 10.47 ± 1.00 a 34.86 ± 0.58 a 86.61 ± 0.24 a BCmb 66.43 ± 2.13 a -1.74 ± 0.08 b 15.69 ± 0.23 b 33.75 ± 0.59 b Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). Table 3 Chromatic value and YI of the bread crust and crumb extracts Sample CIELab colour Yellowing index (YI) L* a* b* BCstE 65.89 ± 0.98 a -1.37 ± 0.07 b 8.21 ± 0.02 a 17.81 ± 0.32 a BCmbE 65.08 ± 0.18 a -0.50 ± 0.01 a 4.83 ± 0.03 b 10.61 ± 0.10 b Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). Colour changes in baked goods occur mostly in the later stages of the Maillard reaction. the research shows that the final stage of the Maillard reaction products was darker in colour than the early low molecular weight Maillard reaction products 37 . Because a series of reactions occurred in the process of hot processing, such as cyclization, dehydration, rearrangement, isomerization and polymerization, and the final formation of nitrogenous brown copolymer or polymer (melanoid) 37,38 . And Based on the above comparison of the colour and browning degree of bread crust and crumb, the results showed that the Maillard reaction occurred faster in bread crust than in bread crumb. 3.3 The content of fluorescent AGEs As shown in Table 4 , the three kinds of fluorescent AGEs between bread crust and bread crumb had the same trend, that was the three kinds of fluorescent AGEs in the crust were higher than those in the crumb, showing a significant difference. The trend of results in Table 5 was the same as that in Table 4 exactly, that was the three fluorescent AGEs in BCstE were higher than those in BCmbE, showing a significant difference. AGEs were a complex group of compounds that were formed through Maillard reaction, a nonenzymatic reaction between reducing sugars and free amino groups 39 . Within a certain range, the amount of AGEs accumulated was proportional to the degree of Maillard reaction. So the occurrence of the Maillard reaction at the faster rate in bread crust compared to bread crumb is proved again. Table 4 The content of fluorescent AGEs in the bread crusts and crumbs Sample Fluorescent AGEs(AU) Glycosylated collagen Pentosidine Pyrrole and imidazole derivatives BCst 63770.00 ± 585.06 a 54670.00 ± 272.21 a 76880.00 ± 437.15 a BCmb 9911.00 ± 79.97 b 13380.00 ± 68.74 b 17170.00 ± 99.97 b Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). Table 5 The content of fluorescent AGEs in the bread crust and crumb extracts Sample Fluorescent AGEs(AU) Glycosylated collagen Pentosidine Pyrrole and imidazole derivatives BCstE 10374.00 ± 112.09 a 14524.00 ± 108.88 a 19212.00 ± 129.94 a BCmbE 1788.20 ± 6.69 b 2802.00 ± 19.28 b 4231.60 ± 33.35 b Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). The extraction yield of AGEs in the BCstE and BCmbE were low, among which the extraction yield of glycosylated collagen was 16–19%, pentosidine was 20–27%, pyrrole and imidazole derivatives were 24–25%, and the total fluorescent AGEs in bread crust and crumb were about 4–5 times of those in bread crust and crumb extracts (Table 6 ). It examined fluorescent Maillard reaction products in western breakfast cereal foods and found that the total content of fluorescent Maillard reaction products was about 10 times that of free fluorescent Maillard reaction products by Delgadoandrade 40 . It added bread crust powder to streptomycin proteinase E solution for digestion and found that the total fluorescent AGEs in the bread crust was only about 1.4 times that in BCE by Jia benpan 41 . The reason for the large difference between the extraction yield of fluorescent AGEs in this experiment and those in other kinds of literature is that the extraction method used in the experiment is different. Table 6 The extraction yield of fluorescent AGEs in the bread crust and crumb extracts Sample extraction yield(%) Glycosylated collagen Pentosidine Pyrrole and imidazole derivatives BCstE 16.27 ± 0.04 b 26.57 ± 0.07 a 24.99 ± 0.05 a BCmbE 18.04 ± 0.08 a 20.94 ± 0.06 b 24.65 ± 0.07 b Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). Furthermore, AGEs were a general term for a variety of substances with different molecular structures, which have the properties of cross-linking and fluorescence generation 42 . However, AGEs such as carboxymethyl-lysine, carboxyethyl-lysine, and pyrrolidine have no fluorescence, so the fluorescence can only reflect part of the content of AGEs 43 . How to better extract and more accurately determine the content of AGEs in food needs to be further explored. 3.4 Antioxidant activity The antioxidant activity of the BCstE was greater than the BCmbE with a significant difference, which was measured by ORAC, ABTS and FRAP assays (Fig. 4 ). The difference in antioxidant activity between bread crust and crumb is mainly due to the difference in antioxidant capacity of the products at different stages of the Maillard reaction. Early Maillard reaction products seem to be not connected to antioxidant activity 44 . The substances that contribute antioxidant capacity in bread are mainly products produced in the advanced and final stages of the Maillard reaction, such as melanoid, reducing ketones and volatile heterocyclic compounds. Melanoid was produced in the final stage of Maillard reaction, which has long been considered the major MRPs with high antioxidant properties 45,46 . This has been confirmed earlier in this paper that the Maillard reaction occurred faster in bread crust than in bread crumb, so the accumulation of Maillard reaction products with strong antioxidant power in the crust is higher than in the crumb. The previous studies have shown that pronyl-lysine is a novel protein modification in bread crust melanoidins showing in vitro antioxidative and high amounts in the bread crust and low amounts in the crumb 14 . 3.5 Correlation analysis As shown in Table 7 , there were a significant positive correlation between the results of the antioxidant activity of bread crust and crumb measured by ORAC, ABTS and FRAP assays, and a consistent trend was observed between the antioxidant activity values of bread crust and crumb, so they were all suitable for the determination of antioxidant activity of bread aqueous extracts. At the same time, there were a significant positive correlation among antioxidant activity, browning intensity (yellowing index), the content of fluorescent AGEs and the content of total phenolic. Table 7 The Correlation analyses of indicators in the bread crust and crumb extracts 3.6 The distribution of Antioxidant capacity and fluorescent AGEs content in the cross-section of bread As shown in Fig. 5 , the antioxidant capacity and fluorescent AGEs content gradually increased from the inside (crumb) to the outside (crust) of baguettes. It was confirmed that there was a positive correlation between antioxidant activity and fluorescent AGEs content again. The reason for the uneven distribution of antioxidant activity and fluorescent AGEs content in the bread cross-section may be that the temperature in the oven is maintained using water vapor, which easily causes uneven temperature distribution. It was found that the antioxidant activity and fluorescent AGEs content of parts of J and K in two end cross-sections were significantly lower than those of parts 12, 13 and 14 in the middle cross-section. It is possible that the temperature is highest at the bottom of the oven and the middle part of the dough will always stick to the baking pan during baking, while both end parts of the bread will deform and slightly tilt upward as the heat rises. 3.7 Cytotoxicity of bread crust and crumb extracts The survival rate of macrophages in the presence of bread crust and crumb extracts at the tested concentrations was more than 80% and less than 110% (Fig. 6 a), indicating that the samples had no acute toxic effect and proliferation effect on macrophages. Therefore, the samples were suitable for the determination of subsequent experiments. As shown in Fig. 6 b, bread crust and crumb extracts had no toxic effect on macrophages at the tested concentrations, which was consistent with the results determined by the MTT method. Surprisingly, the level of LDH in the cell supernatant was decreased in a concentration-dependent manner with. Therefore, the LDH activity in the cell supernatant was further determined. The LDH activity in the supernatant was lower than that in the normal cell group and the LDH activity in the supernatant decreased with the increase of sample concentration after 24 h of co-incubation of bread crust and crumb extracts with cells (Fig. 6 c). It guessed that bread crust and crumb extracts could regulate natural cell damage under normal metabolism through specific pathways, showing a protective effect on RAW264.7 macrophages, thereby changing the permeability of cell membrane and leading to a decrease in lactate dehydrogenase activity in the cell supernatant. The occurrence of this experimental phenomenon may be related to antioxidant activity. 3.8 Cellular antioxidant activity of bread crust and crumb extracts As shown in Fig. 7 a, The intracellular antioxidant activity of both samples was concentration-dependent and the intracellular antioxidant activity of bread crust extracts in RAW264.7 macrophages was higher than that of bread crumb extracts (p < 0.05), which was consistent with the results measured by the three chemical antioxidant assays (ORAC/ABTS/FRAP). The antioxidant capacity of bread crust and crumb extracts is converted to an equivalent concentration of quercetin based on its CAA values, and the equivalent concentrations of quercetin were 8.83 ± 0.52 µmol/g and 2.21 ± 0.94 µmol/g respectively. 3.9 Influences on cell membrane potential ( V mem ) and mitochondrial superoxide of RAW264.7 macrophages Macrophages are immune cells and their cell membrane potential and mitochondrial superoxide levels are sensitive attributes indicating their viability and physiological functions. It is shown in Figs. 7 b-f, incubation of RAW264.7 macrophages with either BCstE or BCmbE did not affect the green fluorescence emitted by DiBAC4( 3 ) on RAW264.7 macrophages, indicating the BCstE and BCmbE do not affect the V mem of RAW264.7 macrophages, even at a high concentration (BCstE and BCmbE diluted 5 times respectively). In the presence of AAPH, DiBAC4( 3 ) fluorescence in RAW264.7 macrophages was eliminated (Fig. 7 b), indicating the rising V mem and hyperpolarization of cytosolic membrane caused by AAPH-induced peroxyl radicals. Membrane hyperpolarization is known to be paralleled with the activation of macrophage functions, i.e., NO production 47 . In contrast, both BCstE and BCmbE completely or partially restored the V mem in AAPH insulted cells in a dose-dependent manner (Figs. 7 c-f), counteracted the membrane hyperpolarization caused by the extracellular peroxyl radicals. The BCstE mitigated the peroxyl radical-induced cell membrane hyperpolarization by 91% at a high concentration (sample diluted 5 times), showing higher activities than the BCmbE. Therefore, BCstE and BCmbE did not affect cytosolic membrane of normal macrophages, but could protect cytosolic membrane from AAPH-induced oxidative damage. Regardless of the effect on the intracellular or extracellular stimulation of macrophages, the ROS level in mitochondria serves as a sensitive indicator. The peroxyl radical-induced oxidative stresses suppressed the mitochondrial oxygen respiration and caused a drop in mitochondrial ROS 21 . It is shown in Figs. 7 b and 7 g, incubation of RAW264.7 macrophages with either BCstE or BCmbE did not affect the fluorescence of ROS-sensitive dye Mito-SOX Red (also named Mito-HE) in RAW264.7 macrophages. But in the presence of AAPH, Mito-HE fluorescence was reduced obviously, indicating a dropping level of ROS in mitochondria resulting from the malfunction of oxygen respiration in the organelle induced by AAPH radicals. Incubation of RAW264.7 macrophages together with AAPH and BCstE or BCmbE completely or partially counteracted this suppression on mitochondrial oxygen respiration, in a dose-dependent manner. The BCstE mitigated the suppression on the oxygen respiration in mitochondria by up to 100% at a high concentration (BCstE diluted 5 times), but the BCmbE mitigated the suppression on the oxygen respiration in mitochondria by up to 79% at a high concentration (BCmbE diluted 5 times). Therefore, the BCstE showed higher activities than the BCmbE. 3.10 Influences of BCstE and BCmbE on the content of inflammatory factors in supernatant of RAW264.7 macrophages As shown in Table 8 , within a certain concentration range, neither the BCstE nor the BCmbE could induce the production of IL-1β and IL-6, and the BCmbE did not induce the production of TNF-α. But the BCstE could induce the production of TNF-α from RAW264.7 macrophages at diluted 5/40 times, indicating that the BCstE affected inducing inflammatory response of RAW264.7 macrophages. Table 8 The content of inflammatory factors in the supernatant of RAW264.7 macrophages after incubating with BCstE or BCmbE Sample TNF-α/(pg/mL) IL-1β/(pg/mL) IL-6/(pg/mL) Control ND ND ND BCstE(1:5) 3.02 ± 1.56 ND ND BCstE(1:40) 3.20 ± 2.07 ND ND BCmbE(1:5) ND ND ND BCmbE(1:40) ND ND ND ‘ND’ indicates that not detected. There are two guesses for this experimental result as follows: the first guess is that a large number of AGEs in the BCstE can destroy the balance of oxidative stress in cells by RAGE, increasing the secretion level of inflammatory cytokine TNF-α 48 . However, the content of AGEs in BCmbE is significantly lower than that in BCstE, which has no obvious effect on the release of TNF-α in macrophages. Although the previous experiment confirmed that BCstE has intracellular antioxidant activity, it observed the antioxidant activity in a short period time. It may cause the accumulation effect of AGEs in the BCstE in the subsequent incubation, but the antioxidant substances are not enough to eliminate the oxidative stress caused by this effect on RAW264.7 macrophages. The second guess is that the presence of gluten protein in the BCstE causes the production of TNF-α. Industrial bread made from wheat flour causes systemic inflammation, which ultimately leads to increased levels of inflammation-related factors in the blood of mice. The possible reason is gluten protein triggers adaptive immune responses mediated by CD4 + Th1 cells and innate immune responses mediated by intraepithelial lymphocytes, which damage intestinal epithelial inflammatory cells 49 . Whether gluten protein in bread is concentrated in the crust needs further verification. And the above two guesses may also synergistically lead to this result, which needs to be further explored too. 3.11 Influences of BCstE and BCmbE on the content of inflammatory factors in supernatant of RAW264.7 macrophages that stimulated by LPS According to the above experimental results, it founds that the proinflammatory effect of bread water extract on macrophages was manifested as promoting the production of TNF-α, but it had no effect on the production and inhibition of IL-1β and IL-6 under normal conditions. In order to explore whether bread water extract can inhibit the production of IL-1β and IL-6 in macrophages, an experiment was designed to observe the effect of samples on the inflammatory factors released by cells stimulated by LPS. As shown in Table 9 , RAW264.7 macrophages had an inflammatory response and the cells were induced to release 26.11 pg/mL IL-1β and 39.53 pg/mL IL-6 because of the stimulation of LPS. The reason is that LPS can stimulate RAW264.7 macrophages to produce free radicals, causing oxidative damage to cells, and thus increasing the expression and release of inflammatory factors. Both BCstE and BCmbE showed different degrees of inhibitory effects on the production of IL-1β and IL-6 by RAW264.7 macrophages. The reason is that BCstE and BCmbE expressed intracellular antioxidant activity, which can eliminate the inflammatory response caused by ROS, thereby reducing the release of IL-1β and IL-6. Table 9 The content of inflammatory factors in the cell supernatant after incubating of RAW264.7 macrophages together with LPS and BCstE or BCmbE Sample IL-1β/(pg/mL) IL-6/(pg/mL) LPS 26.11 ± 13.84 a 39.53 ± 3.55 a BCstE(1:5)+ LPS 18.05 ± 2.42 b 16.18 ± 2.29 b BCstE(1:40)+ LPS 7.80 ± 5.72 c 4.53 ± 7.86 c BCmbE(1:5)+ LPS 2.97 ± 4.01 c ND BCmbE(1:40)+ LPS 1.75 ± 3.47 c ND ‘ND’ indicates that not detected. Reported values are the mean ± SD (n = 3). Values bearing different superscripts in the same column are significantly different (P < 0.05). However, the inhibitory effects on the production of IL-1β and IL-6 by BCstE and BCmbE increased with the decrease of concentration and the inhibitory effect of BCstE was less than that of BCmbE, which needs to be considered from the accumulation effect of AGEs, gluten protein, antioxidant activity and other perspectives, but the specific reasons need to be further researched. 4. Conclusion This study indicates a significant positive correlation among the antioxidative activities (ORAC/ABTS/FRAP activities), browning intensity (measured by the yellowing index), fluorescent advanced glycation end products (AGEs) content, and total phenolic content in baguette. Notably, these indicators in the crust are consistently higher than those in the crumb, underscoring the effective enhancement of antioxidant activity through the Maillard reaction in baked food. This correlation also introduces novel perspectives and indicators to elucidate the impact of moderate processing in baked foods. However, it is essential to acknowledge that the sole measurement of fluorescent AGEs content may not comprehensively reflect the total AGEs in baguette, necessitating further determination, including specific AGEs such as carboxymethyl-lysine, carboxyethyl-lysine, and pyrrolidine. Furthermore, our study leveraged RAW264.7 Macrophages to establish an experimental model, evaluating the influence of baked foods on the oxidative-reductive state and inflammatory response of immune cells in the digestive tract. Baguette crust and crumb extracts exhibited concentration-dependent intracellular antioxidative activity, mitigating peroxyl radical-induced cell membrane hyperpolarization and suppressing oxygen respiration in mitochondria. Remarkably, the crust extracts displayed superior activity compared to the crumb extracts. Additionally, baguette crust and crumb demonstrated distinct modulation of proinflammatory cytokines in RAW264.7 Macrophages, indicating the immunomodulatory potential of baguette. While these research findings offer valuable insights for the development of nutritious bread and hold significance for disease prevention through staple foods, certain challenges remain. Issues such as the accurate measurement of antioxidative substances and the optimization of extraction methods require further investigation. These efforts will provide a more scientifically robust foundation, offering nuanced insights into the overall impact of bread crust and crumb on human health. This study lays the groundwork for future research and contributes to a deeper understanding of the intricate relationship between dietary components and physiological responses. Abbreviations AAPH, 2,2′-azobis (2-amidinopropane) dihydrochloride; ABTS, 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid; AGEs, advanced glycation end products; AUC, mem extracts; BCstE, baguette crust extracts; BSA, bovine serum albumin; CAA, cellular antioxidant activity; LDH, lactate dehydrogenase; DCFH-DA, 2′,7′-dichlorofluorescein diacetate; DMEM, Dulbecco’s modified Eagle medium; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; HBSS, Hanks' balanced salt solution; FRAP, ferric reducing antioxidant power; IL-1β, interleukin-1β; IL-6, interleukin-6; LPS, lipopolysaccharide; MRPs, Maillard reaction products; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ORAC, oxygen radical absorbance capacity; PBS, phosphate buffer saline; ROS, reactive oxygen species; TC, triglyceride; TEAC, Trolox equivalent antioxidant capacity; TPC, total phenolic contents; V mem , cell membrane potential; YI, yellowing index. Declarations Acknowledgements This work was supported by the Science Innovation 2030 - Brain Science and Brain-Inspired Intelligence Technology Major Project #2021ZD0201100 Task 1 #2021ZD0201101 and the China Scholarship Council Program (No. 202208330081). Author Contributions Jianqiao Zou: Investigation, Data curation, Methodology, Writing original draft. Zhaoshuo Yu: Funding acquisition, Methodology, Validation, Writing - review & editing. Lijing Ke: Conceptualization, Supervision, Writing - review & editing . Huaiyu Gu : Funding acquisition, Supervision, Writing - review . Fangzhou He: Data collection and analysis. Patrick Wall: Conceptualization, Supervision, Writing - review & editing. Notes The authors declare no competing financial interest. References Rashidi, A., HadiNezhad, M., Rajabzadeh, N., Yarmand, M.-S. & Nemati, S. Frozen baguette bread dough I. Rheological behavior during storage. Journal of Cereal Science 72 , 24-29, doi:10.1016/j.jcs.2016.08.014 (2016). 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Additional Declarations (Not answered) Cite Share Download PDF Status: Published Journal Publication published 11 Sep, 2024 Read the published version in npj Science of Food → Version 1 posted Editorial decision: revise 20 Feb, 2024 Review # 2 received at journal 11 Feb, 2024 Review # 1 received at journal 08 Feb, 2024 Reviewer # 2 agreed at journal 01 Feb, 2024 Reviewer # 1 agreed at journal 01 Feb, 2024 Reviewers invited by journal 26 Jan, 2024 Submission checks completed at journal 14 Jan, 2024 First submitted to journal 14 Jan, 2024 Editor assigned by journal 14 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3862746","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":269431840,"identity":"827915f1-fc5a-4487-90f2-25350401ee7a","order_by":0,"name":"Huaiyu Gu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/UlEQVRIiWNgGAWjYFACHiA2YGDgZ+ZBEySoRbKZNC0gXQeI1SIfkXtM4kfB4cTNx3mPbvzBcCdxbfsBxgdv2xjkzXFoMbyRlybZY3A4cdthvrTbPAzPEredSWA2nNvGYLizAYeWGTlmEjxgLTxmtxkYgIwbDGzSvG0MCQYHcGuR/APUsrmZx+zmD4gW9t/4tMhL5JhJg2zZwMxjdoMHagszPi0GPG+MrWUM0o1ngP1i8Mx425nEZsk55yQMN+CypT3H8OabP9ay/f1nj938UXFHdtvxwwc/vCmzkcdpC0S8GZnL2AAkJLCrB9nSAKbqYHwcJo+CUTAKRsGIBgDZh16uKX/zUQAAAABJRU5ErkJggg==","orcid":"","institution":"Zhongshan School of Medicine, Sun Yat-sen University","correspondingAuthor":true,"prefix":"","firstName":"Huaiyu","middleName":"","lastName":"Gu","suffix":""},{"id":269431841,"identity":"ccf646cb-598c-4656-ab55-fd84d4fa2bf2","order_by":1,"name":"Jianqiao Zou","email":"","orcid":"","institution":"SIBS-Zhejiang Gongshang University Joint Centre for Food and Nutrition Sciences, Zhejiang Gongshang University, Hangzhou, 310012, China","correspondingAuthor":false,"prefix":"","firstName":"Jianqiao","middleName":"","lastName":"Zou","suffix":""},{"id":269431842,"identity":"c79db558-74a7-49fa-b622-f83c143382e3","order_by":2,"name":"Zhaoshuo Yu","email":"","orcid":"","institution":"National Nutrition Surveillance Centre, University College Dublin, Dublin, Ireland","correspondingAuthor":false,"prefix":"","firstName":"Zhaoshuo","middleName":"","lastName":"Yu","suffix":""},{"id":269431843,"identity":"9f181373-f1be-44d4-b7f9-b8fafb95f180","order_by":3,"name":"Lijing Ke","email":"","orcid":"https://orcid.org/0000-0002-4358-2210","institution":"University of Leeds","correspondingAuthor":false,"prefix":"","firstName":"Lijing","middleName":"","lastName":"Ke","suffix":""},{"id":269431844,"identity":"e08cb646-42ad-4e87-b418-9fc1ce62d48e","order_by":4,"name":"Fangzhou He","email":"","orcid":"https://orcid.org/0009-0007-3154-4376","institution":"Zhejiang Gongshang University","correspondingAuthor":false,"prefix":"","firstName":"Fangzhou","middleName":"","lastName":"He","suffix":""},{"id":269431845,"identity":"00a4bb52-2d23-48ef-aa79-ae8385f1b872","order_by":5,"name":"Patrick Wall","email":"","orcid":"https://orcid.org/0000-0001-5233-8714","institution":"University College Dublin","correspondingAuthor":false,"prefix":"","firstName":"Patrick","middleName":"","lastName":"Wall","suffix":""}],"badges":[],"createdAt":"2024-01-14 08:55:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3862746/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3862746/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41538-024-00302-w","type":"published","date":"2024-09-11T04:00:00+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50343277,"identity":"b6c31fb7-3fb4-4e9d-ba03-c5816bc4b635","added_by":"auto","created_at":"2024-01-30 05:35:27","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":897266,"visible":true,"origin":"","legend":"\u003cp\u003eGraphical abstract.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/4dbea44f6e50c834d1c3e4a4.png"},{"id":50343571,"identity":"b8f52c1f-560c-4e80-a6b5-ee9fdaa2af3f","added_by":"auto","created_at":"2024-01-30 05:43:27","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1353226,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram of the sampling sites. (a) The sampling sites of crust and crumb sample of baguette cross-section; (b) The sampling sites of the middle and two end parts of baguette; (c) The sampling sites of the middle cross-section of baguette (different numbers represent different sampling sites); (d) The sampling sites of two end cross-sections of baguette (different letters represent different sampling sites).\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/29d404c52b8f37c97d7c2952.png"},{"id":50342809,"identity":"56a5cab4-6b6a-41fd-bfeb-f274d8f7ff50","added_by":"auto","created_at":"2024-01-30 05:27:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":244476,"visible":true,"origin":"","legend":"\u003cp\u003eThe photo of the bread crust and crumb extracts.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/a5fa7bfb7ad613cd11b113d6.png"},{"id":50342811,"identity":"edf6da1e-0558-413a-99a2-bf9fee1a1fa0","added_by":"auto","created_at":"2024-01-30 05:27:27","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":145510,"visible":true,"origin":"","legend":"\u003cp\u003eAntioxidant activity of BCstE and BCmbE measured by ORAC(a), ABTS(b) and FRAP(c) assays. The results were presented as mean ± SD based on triple measurements. Values followed by different letters indicate significant differences (p ≤ 0.05) between different antioxidant capacity using one-way ANOVA followed by Tukey’s test for post-hoc analysis.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/a3cdb8371fa585cd8861b63f.png"},{"id":50342813,"identity":"333162a0-1af6-4eb9-81e7-5050a8642501","added_by":"auto","created_at":"2024-01-30 05:27:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":1100600,"visible":true,"origin":"","legend":"\u003cp\u003eAntioxidant activity and fluorescent AGEs heat map of the cross-section of baguette. (a) Antioxidant activity heat map of the middle part’s cross-section (ORAC assay); (b) Fluorescent AGEs heat map of the middle part’s cross-section; (c) Antioxidant activity heat map of cross-section at both ends (ORAC assay); (d) Fluorescent AGEs heat map of cross-section at both ends.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/d696b9abf9d3b0da9fc6ffa6.png"},{"id":50342815,"identity":"fbc64161-e5d0-4b1a-a768-244f5630c2c3","added_by":"auto","created_at":"2024-01-30 05:27:27","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":503415,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Toxic effection of bread crust and crumb extracts in RAW264.7 macrophages (The solid line in the figure indicates that the cell survival rate is 100%, and the dotted line indicates that the cell survival rate is 80%); (b) LDH toxic effects of bread crust and crumb extracts in RAW264.7 macrophages; (c) The activity of LDH in the cell supernatant after the sample was co-cultured with RAW264.7 macrophages for 24 hours. The results were presented as mean ± SD based on triple measurements. Different letters indicate significant differences (p ≤ 0.05) using one-way ANOVA followed by Tukey’s test for post-hoc analysis, *: p \u0026lt; 0.05.\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/d99571c6859105a01500fd14.png"},{"id":50342814,"identity":"f05bd716-27f2-4ff2-b9a9-f920c9eadc84","added_by":"auto","created_at":"2024-01-30 05:27:27","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":1229316,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Cellular antioxidant activity of bread crust and crumb extracts in RAW264.7 macrophages; (b) Effects of bread crust and crumb extracts on the membrane potential of cells plasma (indicated with green fluorescence of DiBAC4(3)) and mitochondrial superoxide (indicated with red fluorescence of MitoSOX) of RAW264.7 macrophages; (c-f) Effects of bread crust and crumb extracts on the membrane potential of RAW264.7 macrophages; (g) Effects of bread crust and crumb extracts on the mitochondrial superoxide level of RAW264.7 macrophages. The results were presented as mean ± SD based on triple measurements. Different letters indicate significant differences (p ≤ 0.05) using one-way ANOVA followed by Tukey’s test for post-hoc analysis, *: P \u0026lt; 0.05 vs Control, #: P \u0026lt; 0.05 vs AAPH.\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/898889230015f3b08f539030.png"},{"id":64362807,"identity":"3d6bac3b-7571-463a-a9c7-6f6fd99e2be2","added_by":"auto","created_at":"2024-09-12 07:28:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":8257717,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3862746/v1/482d9d92-1480-4089-8e13-8a10e20b1ac0.pdf"}],"financialInterests":"(Not answered)","formattedTitle":"Spatial Distribution of Antioxidant Activity in Baguette and Its Modulation of Proinflammatory Cytokines in RAW264.7 Macrophages","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe baguette stands out as a globally renowned bread variety, distinguished by its distinctive features, including a crisp crust measuring 3\u0026ndash;4 mm in thickness, an open and heterogeneous crumb cell structure with a rich, full-bodied flavor\u003csup\u003e1,2\u003c/sup\u003e. These defining characteristics are intricately linked to the Maillard reaction, a complex set of chemical processes occurring during the baking of the dough\u003csup\u003e3,4\u003c/sup\u003e. While existing literature extensively underscores the influence of the Maillard reaction on shaping the sensory attributes of bread\u003csup\u003e5\u003c/sup\u003e, particularly in terms of color and texture quality\u003csup\u003e6,7\u003c/sup\u003e, a notable gap persists regarding a comprehensive understanding of how the Maillard reaction specifically impacts the biological effects of baked bread. This raises the intriguing question: Is there a biological mechanism behind our love for delectable food?\u003c/p\u003e \u003cp\u003eDuring food baking process, a complex cascade of nonenzymatic reactions, the so-called Maillard reaction, is taking place between carbonyl groups of reducing sugars and amino acids, peptides and amino groups of proteins\u003csup\u003e8,9\u003c/sup\u003e. The Maillard reaction produces a variety of bioactive compounds such as melanoidins\u003csup\u003e10\u003c/sup\u003e. Melanoidins, characterized as high molecular weight, brown, and nitrogenous compounds, are formed in the final stages of the Maillard reaction, with a variety of biological activities such as antioxidant\u003csup\u003e11\u003c/sup\u003e. The melanoidins identified in the bread crust demonstrate an individual-dependent influence on distinct microbial flora, suggesting a potential anti-inflammatory effect through the inhibition of enterobacteria\u003csup\u003e12,13\u003c/sup\u003e. Pronyl-lysine was a novel protein modification in bread melanoidins showed \u003cem\u003ein vitro\u003c/em\u003e antioxidative and phased I/II enzyme modulating activity in intestinal Caco-2 cells\u003csup\u003e14\u003c/sup\u003e. The Maillard reaction, while also introducing certain adverse effects on food such as the formation of AGEs and acrylamide\u003csup\u003e9,15\u003c/sup\u003e, can be effectively managed through the precise regulation of baking conditions\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA healthful dietary regimen invariably exerts significant influences on immune responses, consequently playing a role in the regulation of appetite\u003csup\u003e16\u003c/sup\u003e. It can be posited that a health-conscious diet, through its modulation of immune reactions, augments the consumers' preference and dependence on such dietary patterns. In the context of immunometabolic dysregulation, immune cells undergo oxidative stress in the presence of inflammatory cytokines, thereby impacting appetite\u003csup\u003e17\u003c/sup\u003e. Prior investigations have elucidated the commendable standing of traditional and prevalent health-promoting diets, exemplified by the esteemed reputation of porcine bone soup\u003csup\u003e18,19\u003c/sup\u003e. Notably, the nanoparticles derived from these diets exhibit efficacious modulation of immune cell activity within the gastrointestinal mucosa, consequently ameliorating cellular oxidative stress\u003csup\u003e20\u0026ndash;22\u003c/sup\u003e. Analogous observations are discerned in nanoparticles rich in polyphenols, exemplified by those found in aged vinegar\u003csup\u003e23\u003c/sup\u003e. Given the substantial population of immune cells, particularly macrophages, within the human intestinal mucosa, bearing pivotal roles in inflammation and metabolic disorders\u003csup\u003e24\u003c/sup\u003e, it is imperative to establish a comprehensive model elucidating the intricate interplay between baguette consumption and immune cells.\u003c/p\u003e \u003cp\u003eBy elucidating variances in spatial antioxidant properties, this study aims to elucidate the significant role played by the Maillard reaction in augmenting the antioxidation activity and immunocompetence of baguette. Furthermore, this study is anticipated to make a meaningful contribution to the improvement and supplementation of nutritional guidelines for baked foods and healthy diets, providing insights into the intricate relationships among the Maillard reaction, sensory preferences and desires, and underlying biological mechanisms. Such exploration is essential for a more comprehensive understanding of the overall impact of dietary choices.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Materials\u003c/h2\u003e \u003cp\u003eHigh gluten flour (Weifang Fengzheng Flour Co., Ltd., China). Instant dry yeast and bread improver (Angel, China). 96-well plate with clear/black well, T-75 and T-25 cell culture flask were from Corning Incorporated (New York, USA). Phosphate buffer saline (PBS), Hanks' balanced salt solution (HBSS), fetal bovine serum (FBS), Dulbecco\u0026rsquo;s modified Eagle medium (DMEM), penicillin-streptomycin, 0.25% Trypsin-EDTA were purchased from GIBCO (Grand Island, NY, USA). Triglyceride (TC) kit, Lactate dehydrogenase (LDH) assay kit and LDH were purchased from Nanjing Jiancheng Bioengineering Institute (Nanjing, China). LDH cytotoxicity assay kit and human IFN-α/IFN-β/IFN-γ ELISA kit were purchased from Beyotime Biotechnology (Shanghai, China). Bicinchoninic acid (BAC) kit, MTT, 2\u0026prime;,7\u0026prime;-dichlorofluorescein diacetate (DCFH-DA, \u0026ge;\u0026thinsp;97% purity), 2,2\u0026prime;-azobis (2-amidinopropane) dihydrochloride (AAPH), dimethyl sulfoxide (DMSO), Trolox (\u0026ge;\u0026thinsp;98% purity by HPLC), quercetin dihydrate (\u0026ge;\u0026thinsp;98% purity by HPLC), Nile Red, DiBAC4(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), Mito-SOX Red were purchased from the Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). The deionized water was prepared with a purifier and was used for sample preparation. All other chemicals were of analytical reagent grade and obtained in China.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Samples preparation\u003c/h2\u003e \u003cdiv id=\"Sec5\" class=\"Section3\"\u003e \u003ch2\u003e2.2.1 Baguette making\u003c/h2\u003e \u003cp\u003eThe dough formula was 450 g flour, 4 g dry yeast, 2.25 g bread improver, 4.5 g salt and 342g water. The ingredients were mixed in a mixer for 10 min at medium speed. After fermentation, gentle sheeting of the dough to final form which was put into an oven heated up to a temperature of 230 \u0026ordm;C and the baking time was 30 min. After baking, the baguette was left to stand for 24 h at room temperature, and then was kept frozen (at -20\u0026deg;C) until analysis\u003csup\u003e1,25\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section3\"\u003e \u003ch2\u003e2.2.2 Preparation of baguette crust and crumb aqueous extracts\u003c/h2\u003e \u003cp\u003eThe baguette crust and crumb were separated (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). After ventilation and drying (at 25\u0026deg;C), the baguette crust and crumb were dried and then ground in a mill and screened through a 0.15 mm sieve to obtain powdered bread, stored at -20\u0026deg;C\u003csup\u003e26\u003c/sup\u003e. The optimal conditions of preparation of baguette crust and crumb aqueous extracts were determined by optimizing the material/water ratio and vortex oscillation time\u003csup\u003e27\u003c/sup\u003e. Mixing 3 g powdered baguette crust or crumb with 30 mL deionized water, vortexed for 30 min and placed for 30 min at room temperature. The supernatant infusion was collected by centrifuging for 15 min (4000 rpm, 25\u0026deg;C), and baguette crust extracts (BCstE) and baguette crumb extracts (BCmbE) were stored at -4\u0026deg;C. The BCstE and BCmbE were moved into a weighed glass dish with a 9 cm diameter to be dried at 105 ◦C for 3 h to determine the dry weight.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Physicochemical characterization\u003c/h2\u003e \u003cp\u003eProtein content was determined by using a BAC kit with bovine serum albumin (BSA) as a standard sample\u003csup\u003e28\u003c/sup\u003e. The content of total polysaccharide was determined by the Anthrone-Sulfuric acid assay, using glucose as the standard. TC content was determined by TC with GPO-PAP assay. Total phenolic contents (TPC) was determined by using the Folin-Ciocalteau reagent\u003csup\u003e29\u003c/sup\u003e. The turbidity of extraction was determined with an UV/VIS spectrophotometer (UV-5100, HITACHI, Japan) at 600 nm\u003csup\u003e30\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Evaluation of browning intensity (Measurement of colour)\u003c/h2\u003e \u003cp\u003eThe color of different samples was determined using a Chroma Meter (CR-400, Konica Minolta, Japan) according to the CIELab scale. Colour was expressed in L\u003csup\u003e*\u003c/sup\u003e, a\u003csup\u003e*\u003c/sup\u003e, b\u003csup\u003e*\u003c/sup\u003e Hunter scale parameters: L\u003csup\u003e*\u003c/sup\u003e or Luminance (0 to 100), a\u003csup\u003e*\u003c/sup\u003e or colouring from green to red (-120 to 120), -b\u003csup\u003e*\u003c/sup\u003e or colouring from blue to yellow (-120 to 120). The browning intensity was indicated by the yellowing index (YI\u0026thinsp;=\u0026thinsp;142.86 b\u003csup\u003e*\u003c/sup\u003e/ L\u003csup\u003e*\u003c/sup\u003e)\u003csup\u003e31\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Measurement of fluorescent AGEs\u003c/h2\u003e \u003cp\u003eMeasurement of fluorescent AGEs using fluorescence assays\u003csup\u003e32,33\u003c/sup\u003e. Mixing 3 g powdered baguette crust or crumb with 30 mL Tris-HCl buffer (pH\u0026thinsp;=\u0026thinsp;7.5) containing 36 mg streptomycin proteinase E, 150 mg sodium dodecyl sulfate and 44.1 mg CaCl\u003csub\u003e2\u003c/sub\u003e, and then were digested by shaking in a shaker at 30℃ for 36 h. The solutions were centrifuged at 4500 g for 10 min at 4\u0026deg;C and the supernatant was diluted with ultrapure water to be analyzed. The solution was measured by fluorescence spectrophotometry at excitation/emission wavelengths of 370/440 nm (glycosylated collagen), 330/420 nm (pyrrole and imidazole derivatives) and 335/385 nm (pentosidine). The parameters of the fluorescence spectrophotometer were set as: the voltage of the photomultiplier tube was 700 V, the response time was 0.5 s, the slit width was 5.0 nm on the excitation side and 5.0 nm on the emission side, and the scanning mode was time scanning for 20 s.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Determination of antioxidant activities\u003c/h2\u003e \u003cp\u003eAntioxidant activities of BCstE and BCmbE were assessed with by the following methods: (i) ABTS, (ii) Ferric reducing antioxidant power assay (FRAP assay) and (iii) oxygen radical absorbance capacity (ORAC)\u003csup\u003e20,34\u003c/sup\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Determination of antioxidant activity and fluorescent AGEs distributions in cross-sections of baguette\u003c/h2\u003e \u003cp\u003eAs shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb, the middle and two end parts of baguette were carefully separated by a knife. The sampling schematic diagram of the transverse and longitudinal isometric sections of baguette as shown in Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ec and \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ed. The middle cross-section was divided into 5 transverse isometric parts and 3 longitudinal isometric parts, and different sampling sites were named by different numbers (\u003cspan additionalcitationids=\"CR2 CR3 CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11 CR12 CR13 CR14\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The two end cross-sections were divided into 4 transverse isometric parts and 3 longitudinal isometric parts, and different sampling sites were named by different letters (A-L). Baguette aqueous extracts were prepared by method 2.2.2. The distributions of fluorescent AGEs in cross-sections of baguette were determined by method 2.5. The distributions of antioxidant activity in cross-sections of baguette were determined by method 2.6(iii).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Cell culture\u003c/h2\u003e \u003cp\u003eRAW 264.7 macrophages (purchased from Shanghai Institute of Life Sciences, Chinese Academy of Science) were grown at standard cell culture conditions (5% CO\u003csub\u003e2\u003c/sub\u003e, 37 ℃) in a T-75 cell culture flask with DMEM, supplemented with 10% FBS and 1% penicillin/streptomycin. Cells between passages 10 and 20 were used in this study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e2.9 Determination of cytotoxicity\u003c/h2\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e2.9.1 MTT Assay\u003c/h2\u003e \u003cp\u003eFor cellular proliferation measurement using the MTT assay\u003csup\u003e35\u003c/sup\u003e. RAW 264.7 macrophages were seeded in 96-well plates. After incubation for 24 h, the cell culture medium was removed and washed once with HBSS. Samples were diluted to appropriate gradient concentrations with complete DMEM. Adding 200 \u0026micro;L of the diluted samples to 96-well cell culture plates and setting control wells and zeroing wells. After another 24 h incubation period, the cell morphology was observed under an inverted microscope. 20 \u0026micro;L of solution (5 mg/mL) was added to the wells, followed by a further 3 h incubation in the dark. The cell culture medium with MTT was removed and washed twice with HBSS. 200 \u0026micro;L of DMSO was added to the wells, and the plate was shaken on an oscillator for 10 min. Absorbance at 570 nm was recorded by using a FlexStation 3 Plate Reader (Molecular Devices, Sunnyvale, CA, USA). The absorbance was used as a measurement of cell viability, normalized to cells incubated in a control group, which was considered 100% viable.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e2.9.2 LDH Assay\u003c/h2\u003e \u003cp\u003eRAW 264.7 macrophages were seeded in 96-well plates. After incubation for 24 h, the cell culture supernatant was taken and detected by LDH cytotoxicity detection kit, and the method was strictly according to the instructions.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e2.10 CAA assay\u003c/h2\u003e \u003cp\u003eThe CAA assay was carried out following the method of reference\u003csup\u003e36\u003c/sup\u003e. RAW 264.7 macrophages were plated (6.0\u0026times;10\u003csup\u003e4\u003c/sup\u003e cell/well) in 200 \u0026micro;L cell culture media/well in 96-well black. After incubation for 24 h, the cell culture medium was removed and washed twice with HBSS. Samples and standard substance (Quercetin) were diluted to appropriate gradient concentrations with complete DMEM. The diluted samples or standard substance (100 \u0026micro;L) and DCFH-DA (50 \u0026micro;M, 100 \u0026micro;L) were added to each well in triplicate wells, and control wells and blank wells were set up. After an-hour\u0026rsquo;s incubation at 37\u0026deg;C, RAW 264.7 macrophages were washed once by HBSS. Then 100 \u0026micro;L of AAPH (600 \u0026micro;M) was added to the wells and the plate was immediately placed in a FlexStation 3 Plate Reader. Real-time fluorescence was read initially and every five minutes after for 1 h with an excitation wavelength of 485 nm and an emission wavelength of 538 nm. Control wells were treated with DCFH-DA and AAPH without antioxidants, while blank wells were treated with DCFH-DA without AAPH and antioxidants. area under the fluorescence curve (AUC) was calculated with GraphPad Prism 5.0. Antioxidant activity was expressed as \u0026micro;mol/g quercetin equivalents using the linear regression value obtained from the quercetin calibration curve (y\u0026thinsp;=\u0026thinsp;0.055x\u0026thinsp;+\u0026thinsp;0.3326, R\u003csup\u003e2\u003c/sup\u003e\u0026thinsp;=\u0026thinsp;0.9907). The result was calculated as follows:\u003c/p\u003e \u003cp\u003e \u003cspan class=\"InlineEquation\"\u003e \u003cspan class=\"mathinline\"\u003e\\({CAA}_{unit}=(1-\\frac{{AUC}_{sample}}{{AUC}_{control}}\\)\u003c/span\u003e \u003c/span\u003e) \u0026times;100\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e2.11 Cell membrane potential and mitochondrial superoxide determination\u003c/h2\u003e \u003cp\u003eRAW 264.7 macrophages were seeded in 96-well black plates at 2\u0026times;10\u003csup\u003e4\u003c/sup\u003e cells/well. After incubation for 24 h, the wells were washed twice with HBSS, and then Mito-SOX Red (200 \u0026micro;L, 3 \u0026micro;M in HBSS) was added to each well which was kept at 37\u0026deg;C for 10 min. 100 \u0026micro;L of 5 \u0026micro;M DiBAC4 (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) was added to each well which was incubated for 15 min. Samples (50 \u0026micro;L/well) are added at three ratios with HBSS as the negative control. AAPH was added into each well as the positive control group to reach a final concentration of 6.4 mM. Put the 96-well plate into FlexStation 3 Plate Reader and read the data every 10 min for 120 min at 37\u0026deg;C. The excitation and emission wavelength for Mito-SOX Red were set at Ex\u0026thinsp;=\u0026thinsp;510 nm/ Em\u0026thinsp;=\u0026thinsp;580 nm and DiBAC4(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) was set at Ex\u0026thinsp;=\u0026thinsp;493 nm/ Em\u0026thinsp;=\u0026thinsp;516 nm. The fluorescent micrographs are taken right after the fluorometric measurement (Leica, DMI3000 B Inverted Microscope, Ex\u0026thinsp;=\u0026thinsp;515\u0026ndash;560 nm and Em\u0026thinsp;=\u0026thinsp;590 nm for Mito-SOX Red, Ex\u0026thinsp;=\u0026thinsp;450\u0026ndash;490 nm and Em\u0026thinsp;=\u0026thinsp;516 nm for DiBAC4(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003csup\u003e21\u003c/sup\u003e. The whole process was repeated twice to check the reproducibility.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e2.12 Inflammatory cytokines determination\u003c/h2\u003e \u003cp\u003eRAW 264.7 macrophages were seeded in 12-well plates. After incubation for 24 h, the cell culture supernatant was removed. Adding 1 mL of BCstE diluted with DMEM (BCstE/DMEM\u0026thinsp;=\u0026thinsp;1:5, BCstE/DMEM\u0026thinsp;=\u0026thinsp;1:40) and setting a control group. After co-culture for 24 hours, the cell supernatant was collected and the levels of TNF-α, IL-1β and IL-6 were detected by ELISA kits. To determine the effect of the samples on the inflammatory factors released by cells stimulated by LPS, the cells were seeded in 12-well plates and cultured for 24 h. After removing the cell culture supernatant, 500 \u0026micro;L of 40 \u0026micro;g/mL LPS diluted with DMEM was added, and the cells were cultured for 1 h in the incubator. adding 500 \u0026micro;L of BCstE diluted 5-fold and 40-fold with DMEM and setting a positive control group (500 \u0026micro;l each DMEM and LPS, the specific operation steps were consistent with the sample group). After co-culture for 24 hours, the supernatant of cells was collected and the levels of IL-1β and IL-6 were detected by ELISA kits.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and Discussion","content":"\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\n \u003ch2\u003e3.1 Physicochemical characterization\u003c/h2\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e, The contents of protein and total phenol in BCstE were higher than those of BCmbE with a significant difference. The contents of dry matter, total sugar and triglyceride in BCstE and turbidity of BCstE were lower than those of BCmbE with a significant difference.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe results of physicochemical indexes of the bread crust and crumb extracts\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDry Matter(mg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eProtein(mg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal polysaccharides(mg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTriglyceride(mmol/L)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal phenol(\u0026micro;g/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTurbidity(mAbs)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e7.46\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e74.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e8.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.95\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.40\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e143.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2 The degree of browning\u003c/h2\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, there were differences in chromatic values (L\u003csup\u003e*\u003c/sup\u003e, a\u003csup\u003e*\u003c/sup\u003e, b\u003csup\u003e*\u003c/sup\u003e)between bread crust and bread crumb after baking. The red-green degree (a\u003csup\u003e*\u003c/sup\u003e) and yellow-blue degree (b\u003csup\u003e*\u003c/sup\u003e) of bread crust were higher than those of bread crumb, but the lightness value (L\u003csup\u003e*\u003c/sup\u003e) of bread crust was lower than that of bread crumb. Furthermore, the yellowing index of bread crust was higher than that of bread crumb with a significant difference. As shown in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e, there was no significant difference in lightness value (L\u003csup\u003e*\u003c/sup\u003e) between BCstE and BCmbE, but the yellow-blue value (b\u003csup\u003e*\u003c/sup\u003e) of BCstE was higher than that of BCmbE and the red-green degree (a\u003csup\u003e*\u003c/sup\u003e) of BCstE was lower than that of BCmbE. The colour of BCstE was more green and yellow than that of BCmbE. Furthermore, the yellowing index of BCstE was higher than that of BCmbE with a significant difference. The above results indicate that the browning degree of bread crust is significantly higher than that of bread crumb, which also reflects that the main part of bread browning occurred in the process of hot processing is the crust.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eChromatic value of the bread crust and crumb\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCIELab colour\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eYellowing index (YI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eL\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e57.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.47\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.58\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e66.43\u0026thinsp;\u0026plusmn;\u0026thinsp;2.13\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e33.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.59\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eChromatic value and YI of the bread crust and crumb extracts\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eCIELab colour\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eYellowing index (YI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eL*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ea*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eb*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.37\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e65.08\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.01\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.10\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eColour changes in baked goods occur mostly in the later stages of the Maillard reaction. the research shows that the final stage of the Maillard reaction products was darker in colour than the early low molecular weight Maillard reaction products \u003csup\u003e37\u003c/sup\u003e. Because a series of reactions occurred in the process of hot processing, such as cyclization, dehydration, rearrangement, isomerization and polymerization, and the final formation of nitrogenous brown copolymer or polymer (melanoid) \u003csup\u003e37,38\u003c/sup\u003e. And Based on the above comparison of the colour and browning degree of bread crust and crumb, the results showed that the Maillard reaction occurred faster in bread crust than in bread crumb.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3 The content of fluorescent AGEs\u003c/h2\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, the three kinds of fluorescent AGEs between bread crust and bread crumb had the same trend, that was the three kinds of fluorescent AGEs in the crust were higher than those in the crumb, showing a significant difference. The trend of results in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e was the same as that in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e exactly, that was the three fluorescent AGEs in BCstE were higher than those in BCmbE, showing a significant difference. AGEs were a complex group of compounds that were formed through Maillard reaction, a nonenzymatic reaction between reducing sugars and free amino groups\u003csup\u003e39\u003c/sup\u003e. Within a certain range, the amount of AGEs accumulated was proportional to the degree of Maillard reaction. So the occurrence of the Maillard reaction at the faster rate in bread crust compared to bread crumb is proved again.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe content of fluorescent AGEs in the bread crusts and crumbs\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eFluorescent AGEs(AU)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGlycosylated collagen\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePentosidine\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePyrrole and imidazole derivatives\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e63770.00\u0026thinsp;\u0026plusmn;\u0026thinsp;585.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54670.00\u0026thinsp;\u0026plusmn;\u0026thinsp;272.21\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e76880.00\u0026thinsp;\u0026plusmn;\u0026thinsp;437.15\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmb\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9911.00\u0026thinsp;\u0026plusmn;\u0026thinsp;79.97\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13380.00\u0026thinsp;\u0026plusmn;\u0026thinsp;68.74\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17170.00\u0026thinsp;\u0026plusmn;\u0026thinsp;99.97\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe content of fluorescent AGEs in the bread crust and crumb extracts\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eFluorescent AGEs(AU)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGlycosylated collagen\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePentosidine\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePyrrole and imidazole derivatives\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10374.00\u0026thinsp;\u0026plusmn;\u0026thinsp;112.09\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14524.00\u0026thinsp;\u0026plusmn;\u0026thinsp;108.88\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19212.00\u0026thinsp;\u0026plusmn;\u0026thinsp;129.94\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1788.20\u0026thinsp;\u0026plusmn;\u0026thinsp;6.69\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2802.00\u0026thinsp;\u0026plusmn;\u0026thinsp;19.28\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4231.60\u0026thinsp;\u0026plusmn;\u0026thinsp;33.35\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eThe extraction yield of AGEs in the BCstE and BCmbE were low, among which the extraction yield of glycosylated collagen was 16\u0026ndash;19%, pentosidine was 20\u0026ndash;27%, pyrrole and imidazole derivatives were 24\u0026ndash;25%, and the total fluorescent AGEs in bread crust and crumb were about 4\u0026ndash;5 times of those in bread crust and crumb extracts (Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). It examined fluorescent Maillard reaction products in western breakfast cereal foods and found that the total content of fluorescent Maillard reaction products was about 10 times that of free fluorescent Maillard reaction products by Delgadoandrade\u003csup\u003e40\u003c/sup\u003e. It added bread crust powder to streptomycin proteinase E solution for digestion and found that the total fluorescent AGEs in the bread crust was only about 1.4 times that in BCE by Jia benpan\u003csup\u003e41\u003c/sup\u003e. The reason for the large difference between the extraction yield of fluorescent AGEs in this experiment and those in other kinds of literature is that the extraction method used in the experiment is different.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe extraction yield of fluorescent AGEs in the bread crust and crumb extracts\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"3\"\u003e\n \u003cp\u003eextraction yield(%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGlycosylated collagen\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePentosidine\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePyrrole and imidazole derivatives\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.27\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.05\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.04\u0026thinsp;\u0026plusmn;\u0026thinsp;0.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e24.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.07\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003eReported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eFurthermore, AGEs were a general term for a variety of substances with different molecular structures, which have the properties of cross-linking and fluorescence generation\u003csup\u003e42\u003c/sup\u003e. However, AGEs such as carboxymethyl-lysine, carboxyethyl-lysine, and pyrrolidine have no fluorescence, so the fluorescence can only reflect part of the content of AGEs\u003csup\u003e43\u003c/sup\u003e. How to better extract and more accurately determine the content of AGEs in food needs to be further explored.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec23\" class=\"Section2\"\u003e\n \u003ch2\u003e3.4 Antioxidant activity\u003c/h2\u003e\n \u003cp\u003eThe antioxidant activity of the BCstE was greater than the BCmbE with a significant difference, which was measured by ORAC, ABTS and FRAP assays (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e). The difference in antioxidant activity between bread crust and crumb is mainly due to the difference in antioxidant capacity of the products at different stages of the Maillard reaction. Early Maillard reaction products seem to be not connected to antioxidant activity\u003csup\u003e44\u003c/sup\u003e. The substances that contribute antioxidant capacity in bread are mainly products produced in the advanced and final stages of the Maillard reaction, such as melanoid, reducing ketones and volatile heterocyclic compounds. Melanoid was produced in the final stage of Maillard reaction, which has long been considered the major MRPs with high antioxidant properties\u003csup\u003e45,46\u003c/sup\u003e. This has been confirmed earlier in this paper that the Maillard reaction occurred faster in bread crust than in bread crumb, so the accumulation of Maillard reaction products with strong antioxidant power in the crust is higher than in the crumb. The previous studies have shown that pronyl-lysine is a novel protein modification in bread crust melanoidins showing in vitro antioxidative and high amounts in the bread crust and low amounts in the crumb\u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5 Correlation analysis\u003c/h2\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e, there were a significant positive correlation between the results of the antioxidant activity of bread crust and crumb measured by ORAC, ABTS and FRAP assays, and a consistent trend was observed between the antioxidant activity values of bread crust and crumb, so they were all suitable for the determination of antioxidant activity of bread aqueous extracts. At the same time, there were a significant positive correlation among antioxidant activity, browning intensity (yellowing index), the content of fluorescent AGEs and the content of total phenolic.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u003cstrong\u003eTable 7 The Correlation analyses of indicators in the bread crust and crumb extracts\u003c/strong\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\u003c/table\u003e\u003cimg 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\" style=\"width: 1087px; height: 500.117px;\" width=\"1087\" height=\"500.117\"\u003e\u003cbr\u003e\n \u003cp\u003e\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec25\" class=\"Section2\"\u003e\n \u003ch2\u003e3.6 The distribution of Antioxidant capacity and fluorescent AGEs content in the cross-section of bread\u003c/h2\u003e\n \u003cp\u003eAs shown in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, the antioxidant capacity and fluorescent AGEs content gradually increased from the inside (crumb) to the outside (crust) of baguettes. It was confirmed that there was a positive correlation between antioxidant activity and fluorescent AGEs content again. The reason for the uneven distribution of antioxidant activity and fluorescent AGEs content in the bread cross-section may be that the temperature in the oven is maintained using water vapor, which easily causes uneven temperature distribution. It was found that the antioxidant activity and fluorescent AGEs content of parts of J and K in two end cross-sections were significantly lower than those of parts 12, 13 and 14 in the middle cross-section. It is possible that the temperature is highest at the bottom of the oven and the middle part of the dough will always stick to the baking pan during baking, while both end parts of the bread will deform and slightly tilt upward as the heat rises.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec26\" class=\"Section2\"\u003e\n \u003ch2\u003e3.7 Cytotoxicity of bread crust and crumb extracts\u003c/h2\u003e\n \u003cp\u003eThe survival rate of macrophages in the presence of bread crust and crumb extracts at the tested concentrations was more than 80% and less than 110% (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003ea), indicating that the samples had no acute toxic effect and proliferation effect on macrophages. Therefore, the samples were suitable for the determination of subsequent experiments.\u003c/p\u003e\n \u003cp\u003eAs shown in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eb, bread crust and crumb extracts had no toxic effect on macrophages at the tested concentrations, which was consistent with the results determined by the MTT method. Surprisingly, the level of LDH in the cell supernatant was decreased in a concentration-dependent manner with. Therefore, the LDH activity in the cell supernatant was further determined. The LDH activity in the supernatant was lower than that in the normal cell group and the LDH activity in the supernatant decreased with the increase of sample concentration after 24 h of co-incubation of bread crust and crumb extracts with cells (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003ec). It guessed that bread crust and crumb extracts could regulate natural cell damage under normal metabolism through specific pathways, showing a protective effect on RAW264.7 macrophages, thereby changing the permeability of cell membrane and leading to a decrease in lactate dehydrogenase activity in the cell supernatant. The occurrence of this experimental phenomenon may be related to antioxidant activity.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec27\" class=\"Section2\"\u003e\n \u003ch2\u003e3.8 Cellular antioxidant activity of bread crust and crumb extracts\u003c/h2\u003e\n \u003cp\u003eAs shown in Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003ea, The intracellular antioxidant activity of both samples was concentration-dependent and the intracellular antioxidant activity of bread crust extracts in RAW264.7 macrophages was higher than that of bread crumb extracts (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), which was consistent with the results measured by the three chemical antioxidant assays (ORAC/ABTS/FRAP). The antioxidant capacity of bread crust and crumb extracts is converted to an equivalent concentration of quercetin based on its CAA values, and the equivalent concentrations of quercetin were 8.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.52 \u0026micro;mol/g and 2.21\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94 \u0026micro;mol/g respectively.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec28\" class=\"Section2\"\u003e\n \u003ch2\u003e3.9 Influences on cell membrane potential (\u003cem\u003eV\u003c/em\u003e\u003csub\u003emem\u003c/sub\u003e) and mitochondrial superoxide of RAW264.7 macrophages\u003c/h2\u003e\n \u003cp\u003eMacrophages are immune cells and their cell membrane potential and mitochondrial superoxide levels are sensitive attributes indicating their viability and physiological functions.\u003c/p\u003e\n \u003cp\u003eIt is shown in Figs. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eb-f, incubation of RAW264.7 macrophages with either BCstE or BCmbE did not affect the green fluorescence emitted by DiBAC4(\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) on RAW264.7 macrophages, indicating the BCstE and BCmbE do not affect the \u003cem\u003eV\u003c/em\u003e\u003csub\u003emem\u003c/sub\u003e of RAW264.7 macrophages, even at a high concentration (BCstE and BCmbE diluted 5 times respectively). In the presence of AAPH, DiBAC4(\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e) fluorescence in RAW264.7 macrophages was eliminated (Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eb), indicating the rising \u003cem\u003eV\u003c/em\u003e\u003csub\u003emem\u003c/sub\u003e and hyperpolarization of cytosolic membrane caused by AAPH-induced peroxyl radicals. Membrane hyperpolarization is known to be paralleled with the activation of macrophage functions, i.e., NO production\u003csup\u003e47\u003c/sup\u003e. In contrast, both BCstE and BCmbE completely or partially restored the \u003cem\u003eV\u003c/em\u003e\u003csub\u003emem\u003c/sub\u003e in AAPH insulted cells in a dose-dependent manner (Figs. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003ec-f), counteracted the membrane hyperpolarization caused by the extracellular peroxyl radicals. The BCstE mitigated the peroxyl radical-induced cell membrane hyperpolarization by 91% at a high concentration (sample diluted 5 times), showing higher activities than the BCmbE. Therefore, BCstE and BCmbE did not affect cytosolic membrane of normal macrophages, but could protect cytosolic membrane from AAPH-induced oxidative damage.\u003c/p\u003e\n \u003cp\u003eRegardless of the effect on the intracellular or extracellular stimulation of macrophages, the ROS level in mitochondria serves as a sensitive indicator. The peroxyl radical-induced oxidative stresses suppressed the mitochondrial oxygen respiration and caused a drop in mitochondrial ROS\u003csup\u003e21\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003eIt is shown in Figs. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eb and \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eg, incubation of RAW264.7 macrophages with either BCstE or BCmbE did not affect the fluorescence of ROS-sensitive dye Mito-SOX Red (also named Mito-HE) in RAW264.7 macrophages. But in the presence of AAPH, Mito-HE fluorescence was reduced obviously, indicating a dropping level of ROS in mitochondria resulting from the malfunction of oxygen respiration in the organelle induced by AAPH radicals. Incubation of RAW264.7 macrophages together with AAPH and BCstE or BCmbE completely or partially counteracted this suppression on mitochondrial oxygen respiration, in a dose-dependent manner. The BCstE mitigated the suppression on the oxygen respiration in mitochondria by up to 100% at a high concentration (BCstE diluted 5 times), but the BCmbE mitigated the suppression on the oxygen respiration in mitochondria by up to 79% at a high concentration (BCmbE diluted 5 times). Therefore, the BCstE showed higher activities than the BCmbE.\u003c/p\u003e\n \u003cp\u003e3.10 Influences of BCstE and BCmbE on the content of inflammatory factors in supernatant of RAW264.7 macrophages\u003c/p\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e, within a certain concentration range, neither the BCstE nor the BCmbE could induce the production of IL-1\u0026beta; and IL-6, and the BCmbE did not induce the production of TNF-\u0026alpha;. But the BCstE could induce the production of TNF-\u0026alpha; from RAW264.7 macrophages at diluted 5/40 times, indicating that the BCstE affected inducing inflammatory response of RAW264.7 macrophages.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab8\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe content of inflammatory factors in the supernatant of RAW264.7 macrophages after incubating with BCstE or BCmbE\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTNF-\u0026alpha;/(pg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-1\u0026beta;/(pg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-6/(pg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eControl\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE(1:5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.02\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE(1:40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE(1:5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE(1:40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\"\u003e\u0026lsquo;ND\u0026rsquo; indicates that not detected.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eThere are two guesses for this experimental result as follows: the first guess is that a large number of AGEs in the BCstE can destroy the balance of oxidative stress in cells by RAGE, increasing the secretion level of inflammatory cytokine TNF-\u0026alpha; \u003csup\u003e48\u003c/sup\u003e. However, the content of AGEs in BCmbE is significantly lower than that in BCstE, which has no obvious effect on the release of TNF-\u0026alpha; in macrophages. Although the previous experiment confirmed that BCstE has intracellular antioxidant activity, it observed the antioxidant activity in a short period time. It may cause the accumulation effect of AGEs in the BCstE in the subsequent incubation, but the antioxidant substances are not enough to eliminate the oxidative stress caused by this effect on RAW264.7 macrophages. The second guess is that the presence of gluten protein in the BCstE causes the production of TNF-\u0026alpha;. Industrial bread made from wheat flour causes systemic inflammation, which ultimately leads to increased levels of inflammation-related factors in the blood of mice. The possible reason is gluten protein triggers adaptive immune responses mediated by CD4\u003csup\u003e+\u003c/sup\u003eTh1 cells and innate immune responses mediated by intraepithelial lymphocytes, which damage intestinal epithelial inflammatory cells\u003csup\u003e49\u003c/sup\u003e. Whether gluten protein in bread is concentrated in the crust needs further verification. And the above two guesses may also synergistically lead to this result, which needs to be further explored too.\u003c/p\u003e\n \u003cp\u003e3.11 Influences of BCstE and BCmbE on the content of inflammatory factors in supernatant of RAW264.7 macrophages that stimulated by LPS\u003c/p\u003e\n \u003cp\u003eAccording to the above experimental results, it founds that the proinflammatory effect of bread water extract on macrophages was manifested as promoting the production of TNF-\u0026alpha;, but it had no effect on the production and inhibition of IL-1\u0026beta; and IL-6 under normal conditions. In order to explore whether bread water extract can inhibit the production of IL-1\u0026beta; and IL-6 in macrophages, an experiment was designed to observe the effect of samples on the inflammatory factors released by cells stimulated by LPS.\u003c/p\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003e, RAW264.7 macrophages had an inflammatory response and the cells were induced to release 26.11 pg/mL IL-1\u0026beta; and 39.53 pg/mL IL-6 because of the stimulation of LPS. The reason is that LPS can stimulate RAW264.7 macrophages to produce free radicals, causing oxidative damage to cells, and thus increasing the expression and release of inflammatory factors. Both BCstE and BCmbE showed different degrees of inhibitory effects on the production of IL-1\u0026beta; and IL-6 by RAW264.7 macrophages. The reason is that BCstE and BCmbE expressed intracellular antioxidant activity, which can eliminate the inflammatory response caused by ROS, thereby reducing the release of IL-1\u0026beta; and IL-6.\u003c/p\u003e\n \u003cp\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab9\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 9\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe content of inflammatory factors in the cell supernatant after incubating of RAW264.7 macrophages together with LPS and BCstE or BCmbE\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-1\u0026beta;/(pg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eIL-6/(pg/mL)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.11\u0026thinsp;\u0026plusmn;\u0026thinsp;13.84\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39.53\u0026thinsp;\u0026plusmn;\u0026thinsp;3.55\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE(1:5)+ LPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.05\u0026thinsp;\u0026plusmn;\u0026thinsp;2.42\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.18\u0026thinsp;\u0026plusmn;\u0026thinsp;2.29\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCstE(1:40)+ LPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.80\u0026thinsp;\u0026plusmn;\u0026thinsp;5.72\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.53\u0026thinsp;\u0026plusmn;\u0026thinsp;7.86\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE(1:5)+ LPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.97\u0026thinsp;\u0026plusmn;\u0026thinsp;4.01\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBCmbE(1:40)+ LPS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.75\u0026thinsp;\u0026plusmn;\u0026thinsp;3.47\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eND\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"3\"\u003e\u0026lsquo;ND\u0026rsquo; indicates that not detected. Reported values are the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (n\u0026thinsp;=\u0026thinsp;3). Values bearing different superscripts in the same column are significantly different (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eHowever, the inhibitory effects on the production of IL-1\u0026beta; and IL-6 by BCstE and BCmbE increased with the decrease of concentration and the inhibitory effect of BCstE was less than that of BCmbE, which needs to be considered from the accumulation effect of AGEs, gluten protein, antioxidant activity and other perspectives, but the specific reasons need to be further researched.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eThis study indicates a significant positive correlation among the antioxidative activities (ORAC/ABTS/FRAP activities), browning intensity (measured by the yellowing index), fluorescent advanced glycation end products (AGEs) content, and total phenolic content in baguette. Notably, these indicators in the crust are consistently higher than those in the crumb, underscoring the effective enhancement of antioxidant activity through the Maillard reaction in baked food. This correlation also introduces novel perspectives and indicators to elucidate the impact of moderate processing in baked foods. However, it is essential to acknowledge that the sole measurement of fluorescent AGEs content may not comprehensively reflect the total AGEs in baguette, necessitating further determination, including specific AGEs such as carboxymethyl-lysine, carboxyethyl-lysine, and pyrrolidine.\u003c/p\u003e \u003cp\u003eFurthermore, our study leveraged RAW264.7 Macrophages to establish an experimental model, evaluating the influence of baked foods on the oxidative-reductive state and inflammatory response of immune cells in the digestive tract. Baguette crust and crumb extracts exhibited concentration-dependent intracellular antioxidative activity, mitigating peroxyl radical-induced cell membrane hyperpolarization and suppressing oxygen respiration in mitochondria. Remarkably, the crust extracts displayed superior activity compared to the crumb extracts. Additionally, baguette crust and crumb demonstrated distinct modulation of proinflammatory cytokines in RAW264.7 Macrophages, indicating the immunomodulatory potential of baguette.\u003c/p\u003e \u003cp\u003eWhile these research findings offer valuable insights for the development of nutritious bread and hold significance for disease prevention through staple foods, certain challenges remain. Issues such as the accurate measurement of antioxidative substances and the optimization of extraction methods require further investigation. These efforts will provide a more scientifically robust foundation, offering nuanced insights into the overall impact of bread crust and crumb on human health. This study lays the groundwork for future research and contributes to a deeper understanding of the intricate relationship between dietary components and physiological responses.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAAPH, 2,2\u0026prime;-azobis (2-amidinopropane) dihydrochloride; ABTS, 2,2\u0026prime;-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid; AGEs, advanced glycation end products; AUC, \u003csub\u003emem\u003c/sub\u003eextracts; BCstE, baguette crust extracts; BSA, bovine serum albumin; CAA, cellular antioxidant activity; LDH, lactate dehydrogenase; DCFH-DA, 2\u0026prime;,7\u0026prime;-dichlorofluorescein diacetate; DMEM, Dulbecco\u0026rsquo;s modified Eagle medium; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; HBSS, Hanks\u0026apos; balanced salt solution; FRAP, ferric reducing antioxidant power; IL-1\u0026beta;, interleukin-1\u0026beta;; IL-6, interleukin-6; LPS, lipopolysaccharide; MRPs, Maillard reaction products; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; ORAC, oxygen radical absorbance capacity; PBS, phosphate buffer saline; ROS, reactive oxygen species; TC, triglyceride; TEAC, Trolox equivalent antioxidant capacity; TPC, total phenolic contents; \u003cem\u003eV\u003c/em\u003e\u003csub\u003emem\u003c/sub\u003e, cell membrane potential; YI, yellowing index.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Science Innovation 2030 - Brain Science and Brain-Inspired Intelligence Technology Major Project #2021ZD0201100 Task 1 #2021ZD0201101 and the China Scholarship Council Program (No. 202208330081).\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eJianqiao Zou:\u003c/strong\u003e Investigation, Data curation, Methodology, Writing original draft.\u003cstrong\u003e\u0026nbsp;Zhaoshuo Yu:\u0026nbsp;\u003c/strong\u003eFunding acquisition, Methodology, Validation, Writing - review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;Lijing Ke:\u0026nbsp;\u003c/strong\u003eConceptualization, Supervision, Writing - review \u0026amp; editing\u003cstrong\u003e.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eHuaiyu Gu\u003c/strong\u003e\u003cstrong\u003e:\u0026nbsp;\u003c/strong\u003eFunding acquisition, Supervision, Writing - review\u003cstrong\u003e. Fangzhou He:\u0026nbsp;\u003c/strong\u003eData collection and analysis.\u003cstrong\u003e\u0026nbsp;Patrick Wall:\u0026nbsp;\u003c/strong\u003eConceptualization, Supervision, Writing - review \u0026amp; editing.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing financial interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRashidi, A., HadiNezhad, M., Rajabzadeh, N., Yarmand, M.-S. \u0026amp; Nemati, S. Frozen baguette bread dough I. Rheological behavior during storage. \u003cem\u003eJournal of Cereal Science\u003c/em\u003e \u003cstrong\u003e72\u003c/strong\u003e, 24-29, doi:10.1016/j.jcs.2016.08.014 (2016).\u003c/li\u003e\n\u003cli\u003eMohammadi, M., Zoghi, A. \u0026amp; Azizi, M. H. 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Chemistry of gluten proteins. \u003cem\u003eFood Microbiol\u003c/em\u003e \u003cstrong\u003e24\u003c/strong\u003e, 115-119, doi:10.1016/j.fm.2006.07.004 (2007).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"npj-science-of-food","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjscifood","sideBox":"Learn more about [npj Science of Food](http://www.nature.com/npjscifood/)","snPcode":"41538","submissionUrl":"https://submission.springernature.com/new-submission/41538/3","title":"npj Science of Food","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Antioxidant Activity, Baguette, Cellular oxidative stress, Cytokines, Maillard Reaction Products, RAW264.7 Macrophages, Spatial Distribution","lastPublishedDoi":"10.21203/rs.3.rs-3862746/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3862746/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBaguette, a globally acclaimed bakery staple, undergoes a complex Maillard reaction during the baking process, imparting a dual composition of crispy crust and soft crumb. Maillard reaction contributes to the unique flavor and texture of baguettes. However, its specific impact on the nutritional and health attributes, particularly in terms of cellular and biological functions, are yet to be clearly elucidated. This study investigates the chemical profiles of Maillard reaction products (MRPs) in baguette crust and crumb, and spatial distribution variations in the antioxidant activity. The impacts of baguette crust and crumb on cellular reactive oxygen species, mitochondrial activity, and inflammatory factors in RAW264.7 macrophages are also determined, aiming to elucidate the influence of the Maillard reaction on baguette nutritional efficacy.\u003c/p\u003e\n\u003cp\u003eFrom the inside out, both the browning intensity and advanced glycation end products (AGEs) gradually increased, accompanied by a significant elevation in the antioxidant capacity of the crust (tested using ORAC/ABTS/FRAP). This suggests that the Maillard reaction enhances antioxidative properties. Additionally, both the crust and crumb exhibited a strong cytocompatibility for immune cells with capable of reversing cellular oxidative stress, regulating intracellular free radical levels. The crust mitigated the peroxyl radical induced cell membrane hyperpolarization by 91% and the suppression on the oxygen respiration in mitochondria by up to 100%, showing higher activities than the crumb. Conversely, the crumb more effectively inhibited the lipopolysaccharide (LPS)-induced proinflammatory cytokines expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6) in macrophages. It could provide the fundamental data and cell-based approach for investigating the biological impacts of bread on mucosal immune responses, contributing to the refinement and supplementation of nutritional recommendations.\u003c/p\u003e","manuscriptTitle":"Spatial Distribution of Antioxidant Activity in Baguette and Its Modulation of Proinflammatory Cytokines in RAW264.7 Macrophages","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-30 05:27:22","doi":"10.21203/rs.3.rs-3862746/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2024-02-20T09:38:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-11T11:01:14+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2024-02-08T06:31:06+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-02-01T19:43:35+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2024-02-01T06:24:15+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2024-01-26T12:59:26+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-14T20:41:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"npj Science of Food","date":"2024-01-14T08:52:09+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-14T08:52:09+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"npj-science-of-food","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"npjscifood","sideBox":"Learn more about [npj Science of Food](http://www.nature.com/npjscifood/)","snPcode":"41538","submissionUrl":"https://submission.springernature.com/new-submission/41538/3","title":"npj Science of Food","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"NPJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3b4c8a92-6347-4ee5-8c5c-fe47c63f1888","owner":[],"postedDate":"January 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":28392482,"name":"Biological sciences/Biochemistry/Biophysical chemistry"},{"id":28392483,"name":"Biological sciences/Chemical biology/Biophysical chemistry"}],"tags":[],"updatedAt":"2024-09-12T07:28:49+00:00","versionOfRecord":{"articleIdentity":"rs-3862746","link":"https://doi.org/10.1038/s41538-024-00302-w","journal":{"identity":"npj-science-of-food","isVorOnly":false,"title":"npj Science of Food"},"publishedOn":"2024-09-11 04:00:00","publishedOnDateReadable":"September 11th, 2024"},"versionCreatedAt":"2024-01-30 05:27:22","video":"","vorDoi":"10.1038/s41538-024-00302-w","vorDoiUrl":"https://doi.org/10.1038/s41538-024-00302-w","workflowStages":[]},"version":"v1","identity":"rs-3862746","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3862746","identity":"rs-3862746","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}