Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry

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Hamoda" }, { "@type": "Person", "name": "Fouad Lamgharie" }, { "@type": "Person", "name": "Sameh S. M. Soliman" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": " Background The rise of multidrug-resistant pathogens and emerging new microbes due to climate change highlight the urgent need for alternative antimicrobials. Plants, as they adapt to environmental shifts, produce diverse metabolites with potent antibacterial properties, offering a sustainable source to combat antibiotic resistance and emerging microbial threats. In this context, Citrullus colocynthis fruits, known for their antimicrobial activity and adaptation to the hot Gulf region, were screened to identify accessions with strong antibacterial activity and distinct metabolic profiles. Methods The rinds and pulps of three C. colocynthis accessions were screened for their effectiveness against Staphylococcus aureus and Escherichia coli. Minimum inhibitory concentration (MIC50) tests determined activity levels, and GC-MS/MS metabolic profiling analyzed the chemical composition of rind and pulp extracts. Enrichment and network analyses were performed to identify metabolic pathways and potential bacterial targets. Results Rind extracts demonstrated stronger antibacterial activity than pulp, with accession S2 showing the highest activity against S. aureus (MIC50 = 15.74 μg/ml), outperforming other accessions. Metabolic profiling revealed distinct metabolite clusters between rind and pulp, with the rind containing unique compounds like butyric acid, α-linolenic acid, and β-sitosterol. Enrichment analysis indicated that unsaturated fatty acid biosynthesis and other fatty acid metabolism pathways were enriched in the accession S2 rind, supporting its antibacterial potency. Network analysis pinpointed bacterial fatty acid synthase enzymes (FabZ, FabI, and FabH) as potential S. aureus targets of C. colocynthis rind fatty acids. Conclusions The distinct metabolic profiles and strong antibacterial activity of C. colocynthis rind, especially in accession S2, underscore its potential as a sustainable source for plant-based nutraceuticals. Its unique adaptability and antimicrobial properties present a promising strategy for combating multidrug-resistant pathogens. 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F1000Research 2025, 14 :277 ( https://doi.org/10.12688/f1000research.160758.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Research Article Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] Shaimaa Al Nablsi 1 , Ali El Keblawy 1,2 , Rania Hamdy https://orcid.org/0000-0002-4748-8790 3 , Alshaimaa M. Hamoda 4,5 , Fouad Lamgharie 6 , Sameh S. M. Soliman https://orcid.org/0000-0002-7691-615X 4,7 Shaimaa Al Nablsi 1 , Ali El Keblawy 1,2 , [...] Rania Hamdy https://orcid.org/0000-0002-4748-8790 3 , Alshaimaa M. Hamoda 4,5 , Fouad Lamgharie 6 , Sameh S. M. Soliman https://orcid.org/0000-0002-7691-615X 4,7 PUBLISHED 10 Mar 2025 Author details Author details 1 Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, Sharjah, United Arab Emirates 2 Faculty of Pharmacy, Al Salam University, Al Salam University, Tanta, Egypt 3 Research Institute for Science and Engineering (RISE),, University of Sharjah, Sharjah, University of Sharjah, Sharjah, 27272,, United Arab Emirates 4 Research Institute for Medical and Health Sciences (RIMHS), University of Sharjah, Sharjah, University of Sharjah, 27272, United Arab Emirates 5 Faculty of Pharmacy,, Assiut University, Assiut, Assiut, Egypt 6 Fujairah Research Centre (FRC), Fujairah Research Centre, Fujairah, Fujairah, United Arab Emirates 7 Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, Sharjah, United Arab Emirates Shaimaa Al Nablsi Roles: Data Curation, Formal Analysis, Methodology, Writing – Original Draft Preparation Ali El Keblawy Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation, Writing – Review & Editing Rania Hamdy Roles: Data Curation, Formal Analysis, Software, Writing – Review & Editing Alshaimaa M. Hamoda Roles: Formal Analysis, Methodology Fouad Lamgharie Roles: Funding Acquisition, Project Administration, Resources Sameh S. M. Soliman Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Background The rise of multidrug-resistant pathogens and emerging new microbes due to climate change highlight the urgent need for alternative antimicrobials. Plants, as they adapt to environmental shifts, produce diverse metabolites with potent antibacterial properties, offering a sustainable source to combat antibiotic resistance and emerging microbial threats. In this context, Citrullus colocynthis fruits, known for their antimicrobial activity and adaptation to the hot Gulf region, were screened to identify accessions with strong antibacterial activity and distinct metabolic profiles. Methods The rinds and pulps of three C. colocynthis accessions were screened for their effectiveness against Staphylococcus aureus and Escherichia coli. Minimum inhibitory concentration (MIC 50 ) tests determined activity levels, and GC-MS/MS metabolic profiling analyzed the chemical composition of rind and pulp extracts. Enrichment and network analyses were performed to identify metabolic pathways and potential bacterial targets. Results Rind extracts demonstrated stronger antibacterial activity than pulp, with accession S2 showing the highest activity against S. aureus (MIC 50 = 15.74 μg/ml), outperforming other accessions. Metabolic profiling revealed distinct metabolite clusters between rind and pulp, with the rind containing unique compounds like butyric acid, α-linolenic acid, and β-sitosterol. Enrichment analysis indicated that unsaturated fatty acid biosynthesis and other fatty acid metabolism pathways were enriched in the accession S2 rind, supporting its antibacterial potency. Network analysis pinpointed bacterial fatty acid synthase enzymes (FabZ, FabI, and FabH) as potential S. aureus targets of C. colocynthis rind fatty acids. Conclusions The distinct metabolic profiles and strong antibacterial activity of C. colocynthis rind, especially in accession S2, underscore its potential as a sustainable source for plant-based nutraceuticals. Its unique adaptability and antimicrobial properties present a promising strategy for combating multidrug-resistant pathogens. READ ALL READ LESS Keywords Multidrug-resistant pathogens; Antibiotic resistance; Citrullus colocynthis; Antibacterial activity; Fatty acid metabolism; GC-MS/MS; Climate change adaptation. Corresponding Author(s) Ali El Keblawy ( [email protected] ) Sameh S. M. Soliman ( [email protected] ) Close Corresponding authors: Ali El Keblawy, Sameh S. M. Soliman Competing interests: No competing interests were disclosed. Grant information: This research was supported by a grant from the Fujairah Research Center (grant number 133065). Additional funding was provided by the University of Sharjah, Research Office, Project Code 963/2023. Copyright: © 2025 Al Nablsi S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Al Nablsi S, El Keblawy A, Hamdy R et al. Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.12688/f1000research.160758.1 ) First published: 10 Mar 2025, 14 :277 ( https://doi.org/10.12688/f1000research.160758.1 ) Latest published: 10 Mar 2025, 14 :277 ( https://doi.org/10.12688/f1000research.160758.1 ) 1. Introduction Antimicrobial resistance (AMR) has become a critical global health threat, necessitating urgent prioritization of research and intervention efforts. 1 The 2024 WHO Bacterial Priority Pathogens List (BPPL) ranks antibiotic-resistant pathogens into high-priority pathogens, like methicillin-resistant Staphylococcus aureus ( MRSA ) and multidrug-resistant Neisseria gonorrhoeae , present major challenges in healthcare and community settings. 1 In the Gulf Cooperation Council (GCC) region, MRSA , extended-spectrum beta-lactamase (ESBL)-resistant Enterobacteriaceae , and vancomycin-resistant Enterococcus faecium are especially concerning. 2 In Bahrain, ESBL-resistant Enterobacteriaceae ranks highest, followed by MRSA , reflecting the region's high prevalence of multidrug-resistant pathogens. 2 The United Arab Emirates (UAE) faces a significant burden from priority pathogen infections and a worrisome rise in antibiotic resistance. 3 The top five reported pathogens in the UAE include Staphylococcus aureus , Escherichia coli , Klebsiella pneumoniae , Candida spp., and Pseudomonas aeruginosa. 3 Among these, S. aureus and E. coli present major public health threats, causing infections ranging from skin conditions to severe bloodstream infections. 4 The increasing prevalence of antibiotic-resistant strains, such as MRSA, is particularly alarming due to the challenges they pose in treatment and the severe health risks they carry. 5 Moreover, the UAE's hot climate contributes to the spread of microbial diseases, with high humidity and temperatures promoting bacterial growth and transmission. 6 Recent research shows that rising local temperatures are linked to increased antibiotic resistance in pathogens, with a 10°C rise correlating with 4.2% and 3.6% increases in resistance for E. coli and S. aureus , respectively. 6 This underscores the need for novel approaches to mitigate AMR in regions like the UAE. The escalating global antimicrobial resistance (AMR) poses a dire threat to public health, diminishing the effectiveness of traditional antibiotics and leaving infections increasingly untreatable. 1 This alarming trend demands urgent innovation, particularly in exploring novel plant-based antimicrobials as sustainable and effective alternatives. 7 Given the alarming rise in AMR, Citrullus colocynthis stands out as a native Gulf plant with promising potential due to its unique secondary metabolites, which have demonstrated antimicrobial properties against resistant pathogens like S. aureus. 8 , 9 Harnessing bioactive compounds from plants reduces dependence on synthetic drugs, slowing resistance development. With lower toxicity and eco-friendly production, plant-based solutions offer a vital strategy to combat antimicrobial resistance (AMR) and protect future generations from this growing threat. 7 , 10 Climatic changes, particularly shifts in temperature, significantly impact the production of plant metabolites, including those with antimicrobial properties. 11 , 12 Plants adapt to these environmental stressors by altering their metabolic pathways, often increasing the production of secondary metabolites that serve protective functions. 13 For example, elevated temperatures and CO 2 levels have been shown to enhance the accumulation of bioactive compounds such as phenylpropanoids, alkaloids, and terpenoids, which are known for their antimicrobial properties. 14 , 15 These compounds not only help plants survive under harsh conditions but also exhibit strong antimicrobial activities, making them a potential source for novel treatments against resistant pathogens. 16 Additionally, climate-induced stress enhances the plant’s ability to produce these antimicrobial metabolites, highlighting the interconnection between environmental changes and plant resilience. 17 This adaptive response positions plants as a sustainable source of bioactive compounds, offering valuable solutions in addressing the rising issue of antimicrobial resistance. Citrullus colocynthis , a native plant of the Gulf region, produces a wide range of secondary metabolites, including phenolics, flavonoids, and essential oils, which exhibit potent antibacterial, antifungal, and antioxidant activities. 18 , 19 However, its reported antimicrobial activity varies across studies, depending on various factors such as environmental conditions and genetic variability. 20 , 21 The bioactive compounds of C. colocynthis are known to be influenced by environmental factors such as temperature, the specific fruit part, and the particular plant accession being studied. Previous studies on C. colocynthis have shown promising antimicrobial properties but have not systematically examined the interplay between genetic variability, environmental conditions, and specific fruit parts. 22 , 23 This study seeks to bridge this gap by identifying accessions with superior antimicrobial profiles. Our earlier investigations demonstrated that plants growing in the extreme desert conditions of the UAE exhibited significant variations in their total phenolic content and antioxidant activities depending on the fruit part analyzed, whether rind, pulp, or seed. Notably, the rinds and pulps of C. colocynthis fruits contained higher phenolic content than seeds, especially in fruits harvested during the summer. Furthermore, the antioxidant and phenolic content were higher in some accessions compared to others, highlighting the genetic influence on metabolite production in this species. 24 This variability underscores the necessity of further investigating the antimicrobial properties of the rinds and pulps of fruits collected in summer from different accessions. The higher phenolic content and unique metabolites found in these fruit parts, particularly under harsh environmental conditions of summer, highlight C. colocynthis as a promising source of antimicrobial agents. 18 We hypothesize that the unique metabolic adaptations of C. colocynthis accessions to the UAE's extreme climate not only enhance their antimicrobial activity but also provide a blueprint for developing plant-based solutions to AMR. By identifying the specific metabolites and their pathways, this study aims to open new avenues for sustainable pharmaceutical applications. Therefore, the present study aimed at examining the variation in antimicrobial activities and metabolic profiles of the rind and pulp from different C. colocynthis accessions grew during the summer. By focusing on S. aureus and E. coli model pathogens representing Gram-positive and Gram-negative bacteria, respectively we aim to evaluate the antimicrobial spectrum of C. colocynthis metabolites robustly. This approach is expected to identify accessions with superior antimicrobial activity, which can then be optimized for further applications. 2. Methods 2.1. Sample collection and preparation Fresh Citrullus colocynthis fruits were collected from three accessions (numbers 6, 10, and 13 reported in Al-Nablsi et al. 16 from the desert of Al Faya, Sharjah Emirate, UAE (25.051065° N 55.795627° E). Our previous study revealed significant genetic, morphological, and seed dormancy variations among these accessions. 24 Accession 13 displayed larger fruit size, heavier seeds, and lower seed dormancy, resulting in faster germination, particularly under higher temperatures. In contrast, accessions 6 and 10 exhibited smaller fruits, lighter seeds, and higher seed dormancy. 24 In this study, the same three accessions are referred to as S1, S2, and S3 for accessions 6, 10, and 13, respectively. Three distinct individuals representing each accession were collected from a single population in September 2019 ( Figure 1 ). The collected fruits were washed and separated into pulp, rind, and seeds. Each part was dried separately in the shade at room temperature for two weeks, ground into a fine powder using a laboratory blender, and stored at room temperature prior to antibacterial analysis. Figure 1. Citrullus colocynthis population and fruit morphology across different accessions from Al Faya deserts. (A) Overview of the population, and (B) Fruits from three different accessions. The fruits display distinct morphological differences, including size and rind stripe patterns. 2.2. Metabolic extraction Metabolic extraction was performed according to the previously reported method, 24 breiefly100 mg of air-dried rinds and pulps samples from three accessions of C. colocynthis fruits were extracted by soaking in 1 ml of absolute methanol overnight, followed by water bath sonication at RT for 2 h. The extracts were filtered using Whatman No.1 filter paper (Whatman International Ltd., England), dried under a vacuum, dissolved in DMSO, and stored in the fridge until used for biological screening. 2.3. Screening assay To identify the antibacterial activity of C. colocynthis fruit extracts, a spotting assay was conducted to screen the antibacterial activity of C. colocynthis fruit extracts of the pulp and rind of the three accessions S1, S2, and S3. The extract solutions at 10 mg/ml were employed. Each extract was tested on both Gram-positive S. aureus (ATCC 29213) and Gram-negative E. coli (ATCC 25922). A standard inoculum of the testing bacteria was prepared in 0.9% saline solution from a 24 h agar plate using the direct colony suspension method. The inoculum optical density was adjusted using dens check device to give a 1 × 10 8 CFU/ml concentration equivalent to 0.5 McFarland standard solution. The standard inoculum was further diluted to give a final bacterial concentration of 5 × 10 5 CFU/ml, following the Clinical and Laboratory Standards Institute (CLSI) guidelines. 25 Nearly 5 μl of each prepared extract was spotted on the streaked agar plate, in addition to positive and negative controls: Colistin (0.7 μg/ml), Vancomycin (3 μg/ml), and DMSO (100%), respectively. The plates were incubated at 37 o C, and the results were observed and recorded after 24 h. 2.4. Antibacterial activity of C. colocynthis fruits extract The broth microdilution method using a 96-well microplate was performed to measure the minimal inhibitory concentration (MIC) that inhibits visible bacterial growth. Around 100 μl of bacterial cultures in Muller-Hinton Broth (MHB) was added to each well of a 96-well plate. Then 100 μl of each prepared plant extract were added to each well at different concentrations (0, 50, 100, 200, 300 μg/ml). DMSO and Vancomycin were employed as negative and positive controls, respectively. The plate was sealed by parafilm to avoid the evaporation of the solution, and incubated overnight at 37 °C. The bacterial growth was measured using a microplate reader (Epoch TM 2 Microplate spectrophotometer, BioTek Instruments, Inc., Winooski, VT USA) at OD 570 . Excel and GraphPad prism software (La Jolla, CA, USA, version 9, https://www.graphpad.com ) was used to analyze the data obtained from the microplate reader. 2.5. GC-MS/MS analysis The dried extract was treated with 20 μL of 20 mg/ml methoxyamine in pyridine and 50 μL of hexane. The mixture was vortexed and incubated in a water bath at 37 °C for 1.5 h. 26 , 27 Following this, 90 μL of N -trimethylsilyl- N -methyl trifluoroacetamide and trimethylchlorosilane (MSTFA + 1% TMS) were added, and the samples were vortexed for 30 sec and further incubated in a water bath at 37 °C for 1 h. The resulting solution was filtered using 0.45 μm syringe filters (nylon syringe filter, Membrane Solutions, Auburn, WA, USA) and subjected to GC-MS/MS analysis using multiple reaction monitoring (MRM). 28 , 29 The samples were incubated at 330 minutes and then analysed using GC-MS, following a method previously described. 30 GC-MS analysis was conducted using a Shimadzu QP2010 GC-2010 coupled with a GC-MS QP-2010 Ultra and equipped with an auto-sampler (AOC-20i + s). A Restek Rtx-5 ms column was used, with helium as the carrier gas. The analysis temperature was initially set at 35°C for 2 min, followed by an increase of 10°C/min until reaching 250°C. Subsequently, the temperature was increased by 20°C/min until reaching 320°C and held for 23 min. The injection volume and temperature were 1 μl and 250°C, respectively, using splitless-injection mode. The mass spectrometer operated in electron compact mode with an electron energy of 70 eV. The ion source and interface temperatures were set at 240°C and 250°C, respectively. The MS mode was set to scan mode 35–450 m/z with a scan speed of 1428. Spectral data were interpreted using the NIST 14 Mass Spectral Library. 30 2.6. Metabolomic analysis The antimicrobial metabolites were imported into MetaboAnalyst (v.5.0), available a ( https://www.metaboanalyst.ca/home.xhtml ) for further analysis. Hierarchical cluster analysis (HCA), partial least squares-discriminant analysis (PLS-DA), and metabolite set enrichment analysis were conducted. 31 2.7. Network target predication The STRING (Search Tool for the Retrieval of Interacting Genes/Proteins) database (version 10.0) at http://string-db.org// was used to identify protein interaction involved in unique metabolic pathways in S. aureus. The search parameters were adjusted according to interaction types and confidence thresholds. The results comprising protein interaction networks were obtained and examined to find protein clusters associated with metabolic pathways. Additional research, including validation and functional enrichment analysis, verified the proteins involved in S. aureus metabolic activities. 2.8. Statistical analysis The data were collected and analyzed using GraphPad Prism 9.0 (GraphPad Software, La Jolla, CA, USA, https://www.graphpad.com )). Statistical significance was measured using one-way ANOVA for measuring MIC of the plant extracts. Every test was conducted at least in three independent replicas, and the values were expressed as the mean ± standard error (SE) of the mean. The significance was adjusted at P < 0.05. 3. Results 3.1. Different fruits accessions and different fruit parts showed variable antibacterial activity The antibacterial activity of different parts (rind and pulp) of C. colocynthis fruits collected in summer was assessed using spotting assay against the gram-positive S. aureus and gram-negative E. coli. Interestingly, rinds and pulp extracts showed positive effects against S. aureus ( Figure 2A ), but not against E. coli ( Figure 2B ). The best activity was mainly for the rind extract of samples 1, 3, 5, 7, 9, 11, 13, 15, and 17, while only sample 12 of the pulp from accession S2 showed inhibition against S. aureus. Selected samples that showed an inhibitory zone were selected for further microdilution assay to measure their MIC 50 values. MIC 50 value of accession S2 was 15.74 μg/ml, followed by the pulp of accession S2 with a MIC 50 value of 165.6 μg/ml. On the other hand, other accessions showed lower activity with higher MIC 50 values of 259 μg/ml for accession S3 and 462.8 μg/ml for accession 1 ( Table 1 , Figure 3 ). Figure 2. Antibacterial assay of C. colocynthis fruits parts extracts. (A) S. aureus. (B) E . coli. Vancomycin and Colistin at 3 μg/ ml and 0.7 μg/ml, respectively and DMSO were employed as controls. Where sample codes are the following, 1: (S1/rind/R1), 2: (S1/pulp/R1), 3: (S1/rind/R2), 4: (S1/pulp/R2), 5: (S1/rind/R3), 6: (S1/Pulp/R3), 7: (S2/rind/R1), 8: (S2/pulp/R1), 9: (S2/rind/R2), 10: (S2/pulp/R2), 11: (S2/rind/R3), 12: (S2/pulp/R3), 13: (S3/rind/R1), 14: (S3/pulp/R1), 15: (S3/rind/R2), 16:(S3/pulp/R2), 17: (S3/rind/R3), and 18: (S3/pulp/R3). Table 1. MIC 50 values of C. colocynthis fruits parts. C. colocynthis accession/fruit parts MIC 50 (S1/rind) 462.8 ±0.06 (S2/rind) 15.74 ± 0.34 (S2/pulp) 165.6 ± 0.76 (S3/rind) 259.0 ± 0.85 Figure 3. MIC 50 values of the selected C. colocynthis fruits parts. 3.2. Different antimicrobial metabolites responsible for variable antibacterial activities of the fruit parts Multivariate analyses, including hierarchical cluster analysis (HCA), were performed to assess the metabolic profile in different accessions and parts of C. colocynthis fruits. This analysis revealed two distinct clusters, one representing the rind and the other for the pulp ( Figure 4A ). Additionally, partial least squares discriminant analysis (PLS-DA) was conducted to investigate the natural variations in metabolic traits among different accessions of C. colocynthis fruit rind and pulp as indicated in Figure 4B . The analysis identified distinct metabolic signatures, with the rind extract containing predominantly unique antimicrobial metabolites. These metabolites include 1-monolinolein, α-linolenic acid, dodecanoic acid, mandelic acid, dodecane acid, butanoic acid, β-tocopherol, 1-heptacosanol, 9,12-octadecadienoic acid, D-mannopyranose, β-sitosterol, D-glucitol, and palmitic acid. Conversely, only three unique metabolites were found exclusively in the pulp, namely D-(-)-tagatofuranose, D-fructose, and 1,3,5-cycloheptatriene ( Table 2 ). Figure 4. Metabolic analysis of C. colocynthis fruit rind and pulp. (A) Heat map analysis was conducted on the metabolic profiles of C. colocynthis fruit rind and pulp using GC-MS/MS analysis. Three rind accessions (RS1, RS2, RS3) and three pulp accessions (PS1, PS2, PS3) were included. The color scale ranging from red to blue indicated differences in metabolite expression, with red indicating high expression and blue indicating low expression. Mean percentage area values were calculated for each group. Euclidean distance was used to measure similarity. (B) PLS-DA was used to analyze all C. colocynthis fruit rind and pulp metabolites. 1 represents rind, while 2 represents pulp. Table 2. Relative concentrations of antimicrobial summer metabolites in C. colocynthis fruit rinds and pulps. Means (% ± SD) were detected with the same letter with a metabolite do not differ significantly at P ≤ 0.05. Metabolites Pulp Rind Accession 1 Accession 2 Accession 3 Accession 1 Accession 2 Accession 3 α-Linolenic 0 (a) 0 (a) 0 (a) 6.65 ± 3.5 (b) 0 (a) 0 (a) β-Alanine 0 (a) 0.17 ± 0.09 (b) 0 (a) 0.11 ± 0.06 (ab) 0.08 ± 0 (ab) 0.47 ± 0.03 (c) β-Sitosterol 0 (a) 0 (a) 0 (a) 0 (a) 1.7 ± 0.85 (b) 0 (a) β-Tocopherol 0 (a) 0 (a) 0 (a) 0.05 ± 0.03 (a) 0.21 ± 0.07 (a) 0 (a) 1-Heptacosanol 0 (a) 0 (a) 0 (a) 0.05 ± 0.03 (a) 0.35 ± 0.03 (b) 0.71 ± 0.05 (c) 1-Monolinolein 0 (a) 0 (a) 0 (a) 0.69 ± 0.19 (b) 0 (a) 0 (a) 1,3,5-Cycloheptatriene 0 (b) 0 (b) 1.76 ± 0.22 (a) 0 (b) 0 (b) 0 (b) 11-Methyltricosane 0 (b) 0.49 ± 0.06 (d) 2.77 ± 0.22 (a) 0 (b) 0 (b) 0.94 ± 0.07 (c) 2-Butenedioic 40.76 ± 7.38 (c) 14.85 ± 8.54 (b) 9.06 ± 1.02 (ab) 0 (a) 0.08 ± 0 (a) 0 (a) 2-Butenedioic 0 (a) 11.25 ± 5.63 (b) 0 (a) 0 (a) 0 (a) 0 (a) 9,12-Octadecadienoic 0 (a) 0 (a) 0 (a) 0.11 ± 0.09 (a) 0.87 ± 0.07 (b) 0 (a) 9,12,15-Octadecatrienoic 0.7 ± 0.13 (b) 0.25 ± 0.03 (c) 0 (a) 0.05 ± 0.03 (a) 0.57 ± 0.03 (b) 0 (a) Arachidic 1.18 ± 0.25 (bcd) 1.48 ± 0.17 (bd) 3.79 ± 0.08 (a) 0.49 ± 0.29 (cdf ) 1.95 ± 0.13 (b) 5.24 ± 0.76 (e) Aucubin 0.1 ± 0.05 (b) 0 (b) 10.38 ± 0.68 (a) 0 (b) 1.68 ± 0.33 (b) 0 (b) Butanedioic 11.43 ± 3.65 (b) 0.67 ± 0.14 (a) 0 (a) 2.79 ± 1.56 (a) 3.92 ± 0.62 (a) 11.53 ± 1.23 (b) Butanoic 0 (a) 0 (a) 0 (a) 0 (a) 0.08 ± 0 (b) 0 (a) Citric 0 (a) 18.3 ± 9.16 (b) 0 (a) 0 (a) 0 (a) 20.68 ± 0.97 (b) D-(-)-Fructopyranose 1.31 ± 0.31 (b) 10.21 ± 1.3 (c) 7.32 ± 1 (a) 2.01 ± 0.43 (b) 2.2 ± 0.51 (b) 2.68 ± 1.19 (b) D-(-)-Tagatofuranose 2.03 ± 1.42 (a) 0 (a) 0 (a) 0.98 ± 0.51 (a) 0.52 ± 0.32 (a) 1.98 ± 1 (a) D-Fructose 31.09 ± 6.1 (b) 0 (a) 0 (a) 37.17 ± 9.77 (b) 0 (a) 0 (a) D-Glucitol 0 (a) 0 (a) 0 (a) 18.8 ± 6.38 (b) 11.47 ± 0.89 (bc) 0 (a) D-Gluconic 0 (b) 3.85 ± 0.38 (c) 1.52 ± 0.03 (a) 0 (b) 0 (b) 0 (b) D-Mannitol 0 (a) 1.16 ± 0.26 (ab) 0 (a) 0.7 ± 0.13 (ab) 2.34 ± 0.2 (b) 18.06 ± 1.71 (c) D-Mannopyranose 0 (a) 0 (a) 0 (a) 0 (a) 1.52 ± 0.14 (ab) 2.19 ± 1.24 (b) Dodecane 0 (a) 0 (a) 0 (a) 0 (a) 0.05 ± 0.03 (a) 0.38 ± 0.06 (b) Dodecanoic 0 (a) 0 (a) 0 (a) 0 (a) 0 (a) 0.47 ± 0.03 (b) Ethanolamine 0 (a) 5.64 ± 0.53 (d) 1.01 ± 0.26 (a) 1.38 ± 0.48 (ac) 13.34 ± 2.85 (b) 11.08 ± 0.79 (b) Glycerol 11.05 ± 6.16 (bcd) 30.69 ± 3.36 (de) 54.07 ± 0.76 (a) 6.7 ± 0.76 (bc) 32.96 ± 8.39 (e) 0 (b) Mandelic 0 (a) 0 (a) 0 (a) 0 (a) 0 (a) 15.75 ± 5.3 (b) Myristic 0 (b) 0.99 ± 0.11 (ce) 2.26 ± 0.39 (a) 0.29 ± 0.2 (be) 1.38 ± 0.06 (c) 7.83 ± 0.35 (d) Palmitic 0 (a) 0 (a) 0 (a) 20.96 ± 5.23 (b) 22.7 ± 11.43 (b) 0 (a) Phosphoric 0.35 ± 0.06 (b) 0 (c) 6.07 ± 0.12 (a) 0 (c) 0 (c) 0 (c) 3.3. The rind of accession S2 demonstrated a wider array of metabolites in comparison to the pulp in alignment with antibacterial activity The rind of C. colocynthis showed a higher metabolic spectrum compared to the pulp. The rind of accession S2 displayed the highest number of antimicrobial metabolites compared to accessions S1 and S3, with 21, 15, and 18 metabolites, respectively. For the pulp, the numbers of compounds recorded in accessions S2, S1, and S3 were 14, 11, and 10, respectively ( Figure 5 ). Figure 5. The number of metabolites in the rind and the pulp. 3.4. Unique metabolic profile in the rind of C. colocynthis accession S2 Heat map analysis indicated that the rind of accession S2 demonstrated a unique metabolic, represented by distinct metabolite clustering from the other accessions ( Figure 6 ). This unique metabolite profile can be represented by butanoic acid, β-sitosterol, and butenedioic acid. VIP metric was also used to determine the most important variables among the shared metabolites in the PLS-DA model, particularly in comparison to the other accessions. Accession S2 showed palmitic acid, ethanolamine, 9,12-octadecadienoic acid, and 9,12,15-octadecatrienoic acid as the highly expressed metabolites compared to other accessions ( Figure 7 ). These metabolites are of particular interest due to their potential antimicrobial activity. 32 Figure 6. Heat map analysis of the rinds of different C. colocynthis accessions (RS1, RS2, RS3). The color scale ranging from red to blue indicated differences in metabolite expression, with red indicating high expression and blue indicating low expression. Figure 7. The Variable Importance in Projection (VIP) metric score of the different C. colocynthis accessions (RS1, RS2, RS3). It wascalculated as the weighted sum of absolute regression coefficients. Where Sample 1; RS1, 2; RS2, 3; RS3 and the color-coded boxes on the right side indicate the relative concentrations of each metabolite in the studied groups, with red indicating high expression and blue indicating low expression. 3.5. Enriched metabolic pathways of unique metabolites in C. colocynthis fruit rind indicated that the potential antibacterial activity is owing to fatty acids contents The top enriched pathways of the identified unique metabolites are unsaturated fatty acid biosynthesis, fatty acid biosynthesis, linolenic acid metabolism and α-linolenic acid metabolism, elongation of fatty acid, and butyrate metabolism ( Figure 8 ). Fatty acid was reported to exhibit antimicrobial activity by targeting essential enzymes in bacterial survival. 33 Figure 8. Metabolite set enrichment analysis of the unique metabolic pathway in the rind of C. colocynthis. 3.6. Fatty acid synthesis (FAS) revealed by network analysis as a molecular target against S. aureus STRING, a website employed to identify molecular targets influenced by enriched pathways in different organisms, 34 was employed here to identify S. aureus targets affected by C. colocynthis enriched pathways. The network analysis involved constructing a protein-protein interaction (PPI) network to reveal both known and predicted targets, highlighting crucial interactions with S. aureus proteins. The results pinpointed three bacterial enzymes, FabZ, FabI, and FabH, as probable targets for intervention ( Figure 9 ). These three enzymes are essential to the synthesis of fatty acids, a critical step in the metabolism of bacteria. 35 Moreover, the bacterial FAS differs from mammalian FAS analogues providing a safety and selectivity profile. Figure 9. Target-pathway network analysis by STRING database. 4. Discussion The present study indicated that the antibacterial activity of C. colocynthis differed between different accessions, the fruit parts, and the tested microorganism. Several studies have shown variations in the antimicrobial activity of C. colocynthis extracts among different populations. 21 It has been shown that the ethanol extract of C. colocynthis fruit from a Pakistan population exhibited inhibitory activity against Bacillus subtilis , but not against the Gram-negative bacteria E. coli and P. aeruginosa. 19 It is reported that the ethanolic extract of C. colocynthis fruit extract from an Iranian population showed an inhibitory effect comparable to that of the antibiotic novobiocin. 36 Additionally, in a Tunisian population, the aqueous fruit extracts demonstrated strong antimicrobial activity against Candida albicans , Candida glabrata , Escherichia coli , and Pseudomonas aeruginosa. 37 This is consistent with prior research highlighting the variable antimicrobial efficacy of C. colocynthis extracts against diverse microorganisms. 29 , 30 These findings underscore the influence of genetic and environmental factors on the bioactive potential of C. colocynthis , supporting the need for studies like this one that systematically examine accessions adapted to extreme environments like the UAE. This study also showed greater antibacterial activity for the fruit rinds rather than the pulps. The rinds of the three accessions showed significant growth inhibition against S. aureus , while only the pulp of one accession, S2, showed such inhibition. Similarly, the methanolic extract of dried fruit pulp of C. colocynthis was assessed and showed no effects against thirty bacterial isolates (10 Gram-positive and 20 Gram-negative) and five fungal species. 38 On the other hand, antimicrobial activities of fruit rind, pulp, and seeds against S. aureus were reported, 39 with greater activity in the pulp. This robust antibacterial activity suggests that C. colocynthis could be a valuable source of natural antimicrobial compounds that may eventually replace synthetic derivatives. 30 The metabolic distinctions between rinds and pulps may reflect tissue-specific roles in plant defense mechanisms, offering insights into the evolutionary adaptation of C. colocynthis to its harsh environment. Future studies should explore the biochemical pathways that underlie this tissue-specific bioactivity. The fruits collected in the summer exerted effects on the Gram-positive S. aureus but not on the Gram-negative E. coli. In consistence, Arora et al., 1999, showed that the antibacterial activity of C. colocynthis fruit extracts exhibited more pronounced growth inhibition against S. aureus and minimum effect on E. coli. 40 , 41 Similarly, it has been reported that ethanolic extracts of C. colocynthis fruits were more effective against S. aureus than E. coli. 42 The same authors also observed that the inhibitory effect of ethanolic extract was higher than water extract, and the ethyl acetate extract showed greater antibacterial activity against S. aureus than E. coli. 43 This differential efficacy highlights the potential specificity of C. colocynthis metabolites toward Gram-positive bacterial cell wall structures. This specificity could serve as a focus for developing targeted antibacterial therapies. The highest antibacterial activity of the rind of accession S2 can be attributed to the existence of unique metabolites, in addition to the predominance of other metabolites reported with antimicrobial activity ( Table 2 ). These metabolites include butyric acid, α-linolenic acid and other unsaturated fatty acids such as 9,12-octadecadienoic acid and 9,12,15-octadecatrienoic acid, which could potentially serve as biomarkers for strong antibacterial activity. Butyric acid, a short-chain fatty acid, has been shown to significantly suppress the growth of S. aureus in vivo and in vitro. 44 The butyric acid derivative has also shown the ability to stimulate the production of pro-inflammatory interleukin (IL)-6 and drastically diminish S. aureus colonization. 45 This emphasizes the potential of butyrate derivatives as anti-inflammatory agents with bactericidal action against S. aureus. 45 Additionally, recent research underscores the influence of α-linolenic acid metabolite on fatty acid (FA) biosynthesis in S. aureus , indicating that it primarily targets the FA biosynthesis pathway, particularly the FabI enzyme in S. aureus. 46 These unsaturated fatty acid metabolites have been reported for their antimicrobial effects. 47 , 48 9,12-Octadecadienoic acid has demonstrated significant antimicrobial activity against multidrug-resistant S. aureus ( MRSA ) with potent anti-inflammatory properties. 47 , 49 Similarly, 9,12,15-octadecatrienoic acid is known for its antimicrobial and anti-inflammatory activity. 50 Additionally, they are linked to the enzymes involved in fatty acid synthesis (FAS) 51 and act as regulators or substrates of these enzymes; hence, they can affect the rate and composition of fatty acid synthesis within the bacterial cells. 52 Consequently, these metabolites could serve as valuable biomarkers for identifying accessions with strong antibacterial activity, offering potential for pharmaceutical applications, particularly in topical treatments and managing chronic infections caused by Gram-positive bacteria. Pathway analysis indicated the enrichment of unsaturated fatty acid biosynthesis and other fatty acid metabolism in the fruit rind. This suggests that fatty acid biosynthesis pathways may play a crucial role in the antimicrobial activity of C. colocynthis , possibly by targeting essential bacterial enzymes such as FabZ, FabI, and FabH. 53 The identification of these enzymes as potential targets against S. aureus provides a molecular basis for developing novel antimicrobials. 54 Targeting bacterial fatty acid synthesis pathways is effective in inhibiting bacterial growth. 55 Interestingly, the bacterial fatty acid biosynthesis pathway differs from its mammalian counterpart, making it a selective and safe target for therapeutic intervention. 56 , 57 This property enhances the potential clinical applicability of the metabolites identified in this study. This study revealed that some individuals of the C. colocynthis population adapted to the hot climate of the UAE and developed a promising selective antibacterial activity by expressing unique metabolite profile. Improving Citrullus plants' adaptability to hot temperatures and antibacterial capabilities could have significant consequences in the pharmaceutical industry and nutraceuticals. Comprehending the genetic and external factors that impact the production of antimicrobial secondary metabolites is essential; direct breeding and selection initiatives towards cultivating genotypes with enhanced antibacterial capabilities could be the strategy of choice. 58 Techniques like metabolic engineering and genetic engineering can also be used to manipulate key pathways involved in the synthesis of antimicrobial metabolites like fatty acids. 59 Moreover, the potential synergy between these plant metabolites and conventional antibiotics warrants exploration, as such combinations may help overcome existing drug resistance mechanisms. Investigating the role of the plant microbiome in boosting antimicrobial activity may provide new approaches to boosting Citrullus plants' antibacterial capabilities. 60 A comprehensive strategy combining genetic, environmental, and cultural strategies is required to enhance the antibacterial capabilities of Citrullus plants and accomplish their full potential, while adapting to the hot climate. Additionally, studies on the stability and bioavailability of these metabolites under various conditions could pave the way for their practical application in drug formulation. These developments may eventually result in novel plant-based therapies for combating drug-resistant pathogens. 5. Conclusion This study highlights the potential of C. colocynthis as a source of antibacterial agents, particularly the rind. The unique antibacterial activity and metabolic profile of accession S2 suggest that it can serve as a promising candidate for further investigation and optimization to develop a plant variety that can tolerate the hot environment while exerting valuable pharmaceutical potential. The findings underscore the importance of environmental and genetic factors in shaping the bioactive potential of C. colocynthis metabolites. Author contributions Conceptualization, A.E., S.S.; methodology, S.A., S. H.; software, R.H.; validation, A. E, S.S.; formal analysis, S. A., R. H, and S.H.; resources, F.L.R.; data curation, S. A, A.E., S.S., R.H.; writing original draft preparation, S.A; writing—review and editing, A.E. S.S., R.H; supervision, A.E., S.S.; project administration, A.E., S.S., and F.L.R.; funding acquisition F.L.R. Data availabitlity statement Figshare: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry, DOI: https://doi.org/10.6084/m9.figshare.25125647.v2 The project contains the following underlying data: • GC_table_antimicrobial • Number of metabolites, MIC Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0). The project includes the file GC-MS_Data.xlsx, which contains processed GC-MS, Number of metabolites, MIC analysis data, number of metabolites, including peak intensities and identified metabolites. References 1. Jesudason T: WHO publishes updated list of bacterial priority pathogens. The Lancet Microbe. 2024; 5 (9): 100940. PubMed Abstract | Publisher Full Text 2. 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Publisher Full Text Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 10 Mar 2025 ADD YOUR COMMENT Comment Author details Author details 1 Department of Applied Biology, College of Sciences, University of Sharjah, Sharjah, Sharjah, United Arab Emirates 2 Faculty of Pharmacy, Al Salam University, Al Salam University, Tanta, Egypt 3 Research Institute for Science and Engineering (RISE),, University of Sharjah, Sharjah, University of Sharjah, Sharjah, 27272,, United Arab Emirates 4 Research Institute for Medical and Health Sciences (RIMHS), University of Sharjah, Sharjah, University of Sharjah, 27272, United Arab Emirates 5 Faculty of Pharmacy,, Assiut University, Assiut, Assiut, Egypt 6 Fujairah Research Centre (FRC), Fujairah Research Centre, Fujairah, Fujairah, United Arab Emirates 7 Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah, Sharjah, United Arab Emirates Shaimaa Al Nablsi Roles: Data Curation, Formal Analysis, Methodology, Writing – Original Draft Preparation Ali El Keblawy Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation, Writing – Review & Editing Rania Hamdy Roles: Data Curation, Formal Analysis, Software, Writing – Review & Editing Alshaimaa M. Hamoda Roles: Formal Analysis, Methodology Fouad Lamgharie Roles: Funding Acquisition, Project Administration, Resources Sameh S. M. Soliman Roles: Conceptualization, Data Curation, Project Administration, Supervision, Validation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This research was supported by a grant from the Fujairah Research Center (grant number 133065). Additional funding was provided by the University of Sharjah, Research Office, Project Code 963/2023. Article Versions (1) version 1 Published: 10 Mar 2025, 14:277 https://doi.org/10.12688/f1000research.160758.1 Copyright © 2025 Al Nablsi S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Al Nablsi S, El Keblawy A, Hamdy R et al. Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.12688/f1000research.160758.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 10 Mar 2025 Views 0 Cite How to cite this report: Krongrawa W. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416946 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416946 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 14 Oct 2025 Wantanwa Krongrawa , Silpakorn University, Nakorn Pathom, Thailand Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176700.r416946 Overall comments and questions The line number should be shown, it is difficult for the reviewers to check it (if possible). Introduction Some words in the article ... Continue reading READ ALL Overall comments and questions The line number should be shown, it is difficult for the reviewers to check it (if possible). Introduction Some words in the article should be spaced. For example, in the introduction part, E. coli and model should be separated. Moreover, in the method part was also found. Please check it thoroughly. Please check the scientific name of plant, it should be italic style , please correct it at the introduction part and the others. Methods The typos of some vocabularies were detected, e.g., breiefly > briefly The authors should state the average room temperature records since the room temperature of each area might be varied across the countries. Were environmental factors (soil, temperature, collection time) recorded for each accession? Why did the authors soak the plant material with methanol for overnight and then water bath sonication for 2 hours? Is it possible to reduce the time-consuming process by using sonication instead? Please clarify it Please provide more information regarding the conditions used for sonication process. Equipment, frequency, power? And how did you record or monitor the temperature during the process since during the experiment the temperature may rise as extraction time increases? The process for drying the extract samples should be explained more, what were the conditions used for drying them? Rotary evaporator? Temperature ? and kindly describe more why the samples were dissolved by DMSO before keeping in fridge? Please explain in detail why the spotting assay was selected for screening activity? Why were the S. aureus and E. coli chosen for your antimicrobial activity? What were the criteria for consideration? Please check the concentration of the positive standards used for the typical analysis for antimicrobial test. Results Please change the scientific name of the plant in italic style in Table 1. In addition, the unit of MIC₆₀ was not clear. It is important for Table to be self-explanatory. A MIC may be incorrected, it should be an MIC, please correct it throughout the manuscript. The antimicrobial result images should be adjusted to remove the shadow visible at the top. This could be misleading to the reader. What did relative concentration mean? What was the equation for this calculation? In addition, I have found that some relative concentration (the result of beta-tocopherol for rind sample for accession 1, 0.05 ± 0.03) exhibited high standard deviation, Was it favorable result? Figure 6, Was it better to use a symbol for chemical name ? For example, ß-tocopherol instead of b-tocopherol, etc. In addition, the alphabetical letter or not should be uniform. 2-butanedioic acid >> 2-Butanedioic acid. In addition, the resolution of the Figure should be improved. The typos for the chemical name in Figure 7 were also observed. Please revise this Figure. The results obtained from GC/MS were not observed. Could you please explain to me where the results from GC/MS analyses were indicated? Discussion The use of tense should be corrected (as well as whole manuscript). In vivo and in vitro should be italic. How did the inhibition efficiency (mm or µg/mL) compare numerically to those previous reports? How could you confirm that the identified metabolites are indeed responsible for the observed antibacterial activity? Was any correlation analyzed between metabolite abundance and antibacterial activity? Conclusion The explanation of accession S2 as having "unique antibacterial activity and metabolic profile" provides ambiguous terminology rather than clarifies the actual findings. Please add some brief quantitative descriptors: What precisely makes S2 unique? Does it exhibit lower MIC values, broader spectrum activity against both Gram-positive and Gram-negative bacteria, or distinct metabolite composition? References The reference list formatting appears to be inconsistent. For example, some references list all authors, while others use ‘et al.’ Please revise the references to ensure a uniform style throughout all reference lists, in accordance with the journal’s guidelines. Language correction This manuscript contains several typographical and grammatical errors. I suggest the authors thoroughly proofread the manuscript and consider using professional language-editing services or reliable grammar-checking to improve readability. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. Reviewer Expertise: Extractions and relevant biological activities I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Krongrawa W. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416946 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416946 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Poonia A. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416948 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416948 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 06 Oct 2025 Amrita Poonia , Banaras Hindu University, Varanasi, Uttar Pradesh, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176700.r416948 Comments Abstract: Rewrite the abstract including purpose, results and impact of this article on research for societal benefits. Keywords: avoid repetition of keywords from title for more visibility of journal and article. ... Continue reading READ ALL Comments Abstract: Rewrite the abstract including purpose, results and impact of this article on research for societal benefits. Keywords: avoid repetition of keywords from title for more visibility of journal and article. Please go through the entire manuscript to fix language and tense issues. Write the scientific names in italics. Without line numbering in the manuscript, it is difficult to review it properly. Add line numbering Introduction and other parts : Needs to be rewrite and strengthen with latest literature. Latest literature/ References suggested Rao, V., Poonia, A. Citrullus colocynthis (bitter apple): bioactive compounds, nutritional profile, nutraceutical properties and potential food applications: a review. Food Prod Process and Nutr 5 , 4 (2023). https://doi.org/10.1186/s43014-022-00118-9 7. Justify the novelty of work in the last paragraph of the introduction part. 8. Metabolic extraction-explain the air drying here. How it is possible to dry pulp in air, explain? 9. Dried under a vacuum, dissolved in DMSO, and stored in the fridge until used for biological screening. This line is not clear, rewrite it. 10. Please abbreviate DMSO here and similarly throughout the manuscript 11. Why Gram-positive S. aureus (ATCC 29213) and Gram-negative E. coli (ATCC 25922) were selected? Explain the criteria of selection 12. How were MIC 50 values calculated? 13. It was calculated as the weighted sum of absolute regression coefficients: Explain and rewrite these lines 14. Citrullus colocynthis population and fruit morphology across different accessions : explain the effects of these on the metabolites as well as antimicrobial analysis. What was the basis of selection of fruit for final analysis? 15. There are multiple instances of grammatical inconsistencies, wordiness, and redundancy. 16. Some sentences are too long and could be simplified for better readability. 17. There are also a few incorrect word choices and issues with subject-verb agreement. Double-check all references for proper citation formatting. The manuscript needs a thorough checkup using professional English grammar tools. Conclusion : Rewrite with inclusion of outcomes of article and future prospects in the field. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Valorization of Food and dairy by- products I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Poonia A. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416948 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416948 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Thamer FH. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r377383 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-377383 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 28 Apr 2025 Faten Hameed Thamer , Sana'a University, Sana'a, Yemen Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176700.r377383 Your Report I have carefully read your manuscript entitled: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry. The topic of the paper ... Continue reading READ ALL Your Report I have carefully read your manuscript entitled: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry. The topic of the paper is interesting and valuable, but the form of the manuscript needs some modifications for indexing. Please see my comments: The introduction is informative but could benefit from a clearer structure. Consider breaking it down into distinct sub-sections (e.g., background, significance of AMR, potential of Citrullus colocynthis ) to improve readability and logical flow. The text mentions Citrullus colocynthis as a promising candidate due to its secondary metabolites. Expanding on previous studies that highlight its antimicrobial activity or providing comparative data with other plants could reinforce your rationale. In the methods section, more detail is needed regarding the sample collection process. For instance, what criteria were used to select accessions 6, 10, and 13? Were these based on previous findings, or are they randomly selected? Clarification is needed about the time of sample collection and the conditions under which the plants were grown, as these factors can significantly influence metabolite production. The methods section does not specify the analytical techniques employed to assess antimicrobial activity or metabolite profiles. Details on methods such as chromatography, spectrophotometry, or microbiological assays should be included to add transparency and reproducibility. It would be beneficial to explicitly state the hypotheses of the study and the expected outcomes regarding the antimicrobial efficacy of the different fruit parts of C. colocynthis . This would guide readers on the study's direction and objectives. Ensure that all cited studies in the introduction related to the antimicrobial properties of Citrullus colocynthis are current and relevant. If possible, provide a brief comparison of findings from the cited studies to give context to your own research. Depending on the guidelines of the journal, add any necessary ethical considerations related to plant collection and research. If any permits were required for collecting C. colocynthis , please specify. The mention of climate-related impacts on Citrullus colocynthis could be expanded to include specific examples or data from previous research. This may provide a stronger basis for discussing the adaptive capabilities of the plant under extreme condition The metabolic extraction method is briefly described but could benefit from more detail regarding the rationale behind using absolute methanol. Discussing why this solvent is chosen over others and its impact on compound extraction would be valuable. The text mentions using "100 mg of air-dried rinds and pulps." It would be helpful to provide information on how the samples were prepared prior to drying and if there were any specific conditions (e.g., air drying time and temperature). Consider elaborating on the sonication parameters, such as frequency and power settings, as these can significantly affect the efficiency of the extraction process. Were these parameters optimized for your specific samples? While stated that extracts were stored in the fridge, it would be beneficial to specify the temperature range and duration of storage, as these factors can influence the stability and efficacy of the extracts. The screening assay section should include more information on the rationale for using the spotting method. Additionally, details on how many replicates were performed and how results were statistically analyzed would enhance the rigor of the findings. The inclusion of positive and negative controls is great. However, consider specifying how the concentrations of vancomycin and colistin were determined as controls, and whether these are typical concentrations used in similar studies. The methodology mentions data analysis with Excel and GraphPad Prism but does not elaborate on the specific analyses performed (e.g., statistical tests used). Including this information can provide clarity on how results were interpreted. The section on GC-MS/MS analysis appears to be incomplete. Ensure to provide detailed information on the methodology, including the conditions (temperature, carrier gas flow rate, etc.) and the purpose of this analysis in the context of characterizing the extracts. To enhance reproducibility, consider including a description of the equipment used for the extractions and assays, such as model numbers, brands, and any relevant calibrations performed. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests: No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Thamer FH. Reviewer Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r377383 ) The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-377383 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (0) Version 1 VERSION 1 PUBLISHED 10 Mar 2025 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 1 10 Mar 25 read read read Faten Hameed Thamer , Sana'a University, Sana'a, Yemen Amrita Poonia , Banaras Hindu University, Varanasi, India Wantanwa Krongrawa , Silpakorn University, Nakorn Pathom, Thailand Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Krongrawa W. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 14 Oct 2025 | for Version 1 Wantanwa Krongrawa , Silpakorn University, Nakorn Pathom, Thailand 0 Views copyright © 2025 Krongrawa W. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Overall comments and questions The line number should be shown, it is difficult for the reviewers to check it (if possible). Introduction Some words in the article should be spaced. For example, in the introduction part, E. coli and model should be separated. Moreover, in the method part was also found. Please check it thoroughly. Please check the scientific name of plant, it should be italic style , please correct it at the introduction part and the others. Methods The typos of some vocabularies were detected, e.g., breiefly > briefly The authors should state the average room temperature records since the room temperature of each area might be varied across the countries. Were environmental factors (soil, temperature, collection time) recorded for each accession? Why did the authors soak the plant material with methanol for overnight and then water bath sonication for 2 hours? Is it possible to reduce the time-consuming process by using sonication instead? Please clarify it Please provide more information regarding the conditions used for sonication process. Equipment, frequency, power? And how did you record or monitor the temperature during the process since during the experiment the temperature may rise as extraction time increases? The process for drying the extract samples should be explained more, what were the conditions used for drying them? Rotary evaporator? Temperature ? and kindly describe more why the samples were dissolved by DMSO before keeping in fridge? Please explain in detail why the spotting assay was selected for screening activity? Why were the S. aureus and E. coli chosen for your antimicrobial activity? What were the criteria for consideration? Please check the concentration of the positive standards used for the typical analysis for antimicrobial test. Results Please change the scientific name of the plant in italic style in Table 1. In addition, the unit of MIC₆₀ was not clear. It is important for Table to be self-explanatory. A MIC may be incorrected, it should be an MIC, please correct it throughout the manuscript. The antimicrobial result images should be adjusted to remove the shadow visible at the top. This could be misleading to the reader. What did relative concentration mean? What was the equation for this calculation? In addition, I have found that some relative concentration (the result of beta-tocopherol for rind sample for accession 1, 0.05 ± 0.03) exhibited high standard deviation, Was it favorable result? Figure 6, Was it better to use a symbol for chemical name ? For example, ß-tocopherol instead of b-tocopherol, etc. In addition, the alphabetical letter or not should be uniform. 2-butanedioic acid >> 2-Butanedioic acid. In addition, the resolution of the Figure should be improved. The typos for the chemical name in Figure 7 were also observed. Please revise this Figure. The results obtained from GC/MS were not observed. Could you please explain to me where the results from GC/MS analyses were indicated? Discussion The use of tense should be corrected (as well as whole manuscript). In vivo and in vitro should be italic. How did the inhibition efficiency (mm or µg/mL) compare numerically to those previous reports? How could you confirm that the identified metabolites are indeed responsible for the observed antibacterial activity? Was any correlation analyzed between metabolite abundance and antibacterial activity? Conclusion The explanation of accession S2 as having "unique antibacterial activity and metabolic profile" provides ambiguous terminology rather than clarifies the actual findings. Please add some brief quantitative descriptors: What precisely makes S2 unique? Does it exhibit lower MIC values, broader spectrum activity against both Gram-positive and Gram-negative bacteria, or distinct metabolite composition? References The reference list formatting appears to be inconsistent. For example, some references list all authors, while others use ‘et al.’ Please revise the references to ensure a uniform style throughout all reference lists, in accordance with the journal’s guidelines. Language correction This manuscript contains several typographical and grammatical errors. I suggest the authors thoroughly proofread the manuscript and consider using professional language-editing services or reliable grammar-checking to improve readability. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? Partly Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. Reviewer Expertise Extractions and relevant biological activities I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Krongrawa W. Peer Review Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416946) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416946 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Poonia A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 06 Oct 2025 | for Version 1 Amrita Poonia , Banaras Hindu University, Varanasi, Uttar Pradesh, India 0 Views copyright © 2025 Poonia A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments Abstract: Rewrite the abstract including purpose, results and impact of this article on research for societal benefits. Keywords: avoid repetition of keywords from title for more visibility of journal and article. Please go through the entire manuscript to fix language and tense issues. Write the scientific names in italics. Without line numbering in the manuscript, it is difficult to review it properly. Add line numbering Introduction and other parts : Needs to be rewrite and strengthen with latest literature. Latest literature/ References suggested Rao, V., Poonia, A. Citrullus colocynthis (bitter apple): bioactive compounds, nutritional profile, nutraceutical properties and potential food applications: a review. Food Prod Process and Nutr 5 , 4 (2023). https://doi.org/10.1186/s43014-022-00118-9 7. Justify the novelty of work in the last paragraph of the introduction part. 8. Metabolic extraction-explain the air drying here. How it is possible to dry pulp in air, explain? 9. Dried under a vacuum, dissolved in DMSO, and stored in the fridge until used for biological screening. This line is not clear, rewrite it. 10. Please abbreviate DMSO here and similarly throughout the manuscript 11. Why Gram-positive S. aureus (ATCC 29213) and Gram-negative E. coli (ATCC 25922) were selected? Explain the criteria of selection 12. How were MIC 50 values calculated? 13. It was calculated as the weighted sum of absolute regression coefficients: Explain and rewrite these lines 14. Citrullus colocynthis population and fruit morphology across different accessions : explain the effects of these on the metabolites as well as antimicrobial analysis. What was the basis of selection of fruit for final analysis? 15. There are multiple instances of grammatical inconsistencies, wordiness, and redundancy. 16. Some sentences are too long and could be simplified for better readability. 17. There are also a few incorrect word choices and issues with subject-verb agreement. Double-check all references for proper citation formatting. The manuscript needs a thorough checkup using professional English grammar tools. Conclusion : Rewrite with inclusion of outcomes of article and future prospects in the field. Is the work clearly and accurately presented and does it cite the current literature? Partly Is the study design appropriate and is the work technically sound? No Are sufficient details of methods and analysis provided to allow replication by others? No If applicable, is the statistical analysis and its interpretation appropriate? Yes Are all the source data underlying the results available to ensure full reproducibility? Partly Are the conclusions drawn adequately supported by the results? No Competing Interests No competing interests were disclosed. Reviewer Expertise Valorization of Food and dairy by- products I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Poonia A. Peer Review Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r416948) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-416948 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Thamer F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 28 Apr 2025 | for Version 1 Faten Hameed Thamer , Sana'a University, Sana'a, Yemen 0 Views copyright © 2025 Thamer F. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Your Report I have carefully read your manuscript entitled: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry. The topic of the paper is interesting and valuable, but the form of the manuscript needs some modifications for indexing. Please see my comments: The introduction is informative but could benefit from a clearer structure. Consider breaking it down into distinct sub-sections (e.g., background, significance of AMR, potential of Citrullus colocynthis ) to improve readability and logical flow. The text mentions Citrullus colocynthis as a promising candidate due to its secondary metabolites. Expanding on previous studies that highlight its antimicrobial activity or providing comparative data with other plants could reinforce your rationale. In the methods section, more detail is needed regarding the sample collection process. For instance, what criteria were used to select accessions 6, 10, and 13? Were these based on previous findings, or are they randomly selected? Clarification is needed about the time of sample collection and the conditions under which the plants were grown, as these factors can significantly influence metabolite production. The methods section does not specify the analytical techniques employed to assess antimicrobial activity or metabolite profiles. Details on methods such as chromatography, spectrophotometry, or microbiological assays should be included to add transparency and reproducibility. It would be beneficial to explicitly state the hypotheses of the study and the expected outcomes regarding the antimicrobial efficacy of the different fruit parts of C. colocynthis . This would guide readers on the study's direction and objectives. Ensure that all cited studies in the introduction related to the antimicrobial properties of Citrullus colocynthis are current and relevant. If possible, provide a brief comparison of findings from the cited studies to give context to your own research. Depending on the guidelines of the journal, add any necessary ethical considerations related to plant collection and research. If any permits were required for collecting C. colocynthis , please specify. The mention of climate-related impacts on Citrullus colocynthis could be expanded to include specific examples or data from previous research. This may provide a stronger basis for discussing the adaptive capabilities of the plant under extreme condition The metabolic extraction method is briefly described but could benefit from more detail regarding the rationale behind using absolute methanol. Discussing why this solvent is chosen over others and its impact on compound extraction would be valuable. The text mentions using "100 mg of air-dried rinds and pulps." It would be helpful to provide information on how the samples were prepared prior to drying and if there were any specific conditions (e.g., air drying time and temperature). Consider elaborating on the sonication parameters, such as frequency and power settings, as these can significantly affect the efficiency of the extraction process. Were these parameters optimized for your specific samples? While stated that extracts were stored in the fridge, it would be beneficial to specify the temperature range and duration of storage, as these factors can influence the stability and efficacy of the extracts. The screening assay section should include more information on the rationale for using the spotting method. Additionally, details on how many replicates were performed and how results were statistically analyzed would enhance the rigor of the findings. The inclusion of positive and negative controls is great. However, consider specifying how the concentrations of vancomycin and colistin were determined as controls, and whether these are typical concentrations used in similar studies. The methodology mentions data analysis with Excel and GraphPad Prism but does not elaborate on the specific analyses performed (e.g., statistical tests used). Including this information can provide clarity on how results were interpreted. The section on GC-MS/MS analysis appears to be incomplete. Ensure to provide detailed information on the methodology, including the conditions (temperature, carrier gas flow rate, etc.) and the purpose of this analysis in the context of characterizing the extracts. To enhance reproducibility, consider including a description of the equipment used for the extractions and assays, such as model numbers, brands, and any relevant calibrations performed. Is the work clearly and accurately presented and does it cite the current literature? Yes Is the study design appropriate and is the work technically sound? Yes Are sufficient details of methods and analysis provided to allow replication by others? Yes If applicable, is the statistical analysis and its interpretation appropriate? Partly Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Partly Competing Interests No competing interests were disclosed. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Thamer FH. Peer Review Report For: Prioritizing Citrullus colocynthis accessions and fruit parts with promising antibacterial activity and adaption to the hot climate of the UAE for the future pharmaceutical industry [version 1; peer review: 3 approved with reservations] . F1000Research 2025, 14 :277 ( https://doi.org/10.5256/f1000research.176700.r377383) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/14-277/v1#referee-response-377383 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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