Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus

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'Sweet stick' leaves in Rattus...", "datePublished": "2025-08-19T08:51:28", "dateModified": "2025-10-10T16:09:26", "author": [ { "@type": "Person", "name": "Jorge Guillermo Morales Ramos" }, { "@type": "Person", "name": "Berta Loja Herrera" }, { "@type": "Person", "name": "Néstor Manuel Rodríguez Alayo" }, { "@type": "Person", "name": "Doyle Isabel Benel Fernández" }, { "@type": "Person", "name": "Luis Felipe Pérez Medina" }, { "@type": "Person", "name": "Carolina Susana Loayza Estrada" }, { "@type": "Person", "name": "María Ema Soledad Mocarro Willis" }, { "@type": "Person", "name": "César Sánchez Marín" } ], "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": " Introduction Diabetes mellitus (DM) is a chronic metabolic disease representing a global public health concern and is associated with severe complications such as cardiovascular and renal diseases. Although several species of the genus Acalypha have demonstrated biological activity, no prior studies have evaluated the hypoglycemic effect of Acalypha argomuelleri Briq., making this study relevant. Method The hypoglycemic effect of the aqueous leaf extract of A. argomuelleri Briq. (AAAE) was evaluated in an experimental model using Rattus rattus var. albinus. A randomized, prospective design was employed, consisting of a control group and three treatment groups receiving doses of 100, 150, and 300 mg/kg of the extract, respectively. Hyperglycemia was induced via oral glucose administration. Results The qualitative phytochemical analysis of AAAE revealed the presence of flavonoids, phenols, cardiotonic glycosides, and diterpenes, with no reducing sugars. The 300 mg/kg dose produced a significant and sustained reduction in blood glucose levels, reaching near-normal values at 90 minutes, demonstrating a dose- and time-dependent hypoglycemic effect. Discussion The study confirmed that AAAE has a dose-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg. This dose showed a faster and more sustained reduction in glucose levels compared to 100 and 150 mg/kg, suggesting higher efficacy at elevated concentrations. The identified flavonoids and phenols, associated with glucose metabolism modulation and pancreatic β-cell protection, likely explain the observed effect. The absence of reducing sugars indicates the hypoglycemic effect is linked to secondary metabolites. Conclusions The AAAE exhibited a significant dose- and time-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg after 90 minutes. These findings support the potential of A. argomuelleri Briq. as a natural alternative for blood glucose control, though further studies are needed to assess its safety and efficacy in clinical models. 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F1000Research 2025, 14 :800 ( https://doi.org/10.12688/f1000research.164673.1 ) 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 Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] Jorge Guillermo Morales Ramos https://orcid.org/0000-0003-0012-1817 1 , Berta Loja Herrera 2 , Néstor Manuel Rodríguez Alayo 3 , [...] Doyle Isabel Benel Fernández 1 , Luis Felipe Pérez Medina 4 , Carolina Susana Loayza Estrada https://orcid.org/0000-0001-7699-8514 1 , María Ema Soledad Mocarro Willis 5 , César Sánchez Marín 5 Jorge Guillermo Morales Ramos https://orcid.org/0000-0003-0012-1817 1 , Berta Loja Herrera 2 , [...] Néstor Manuel Rodríguez Alayo 3 , Doyle Isabel Benel Fernández 1 , Luis Felipe Pérez Medina 4 , Carolina Susana Loayza Estrada https://orcid.org/0000-0001-7699-8514 1 , María Ema Soledad Mocarro Willis 5 , César Sánchez Marín 5 PUBLISHED 19 Aug 2025 Author details Author details 1 Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 2 Faculty of Human Medicine, Universidad Mayor de San Marcos, Lima, Peru 3 Faculty of Human Medicine, Universidad Nacional Pedro Ruiz Gallo, Lambayeque, Lambayeque, Peru 4 Program of Human Medicine, Universidad Señor de Sipán, Lambayeque, Peru 5 Research Directorate, Hospital Regional Lambayeque, Lambayeque, Peru Jorge Guillermo Morales Ramos Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Berta Loja Herrera Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing Néstor Manuel Rodríguez Alayo Roles: Formal Analysis, Investigation, Methodology, Resources, Validation, Visualization, Writing – Original Draft Preparation Doyle Isabel Benel Fernández Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Visualization Luis Felipe Pérez Medina Roles: Data Curation, Formal Analysis, Investigation, Software, Validation, Visualization, Writing – Original Draft Preparation Carolina Susana Loayza Estrada Roles: Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Writing – Review & Editing María Ema Soledad Mocarro Willis Roles: Data Curation, Formal Analysis, Methodology, Resources, Validation, Visualization César Sánchez Marín Roles: Data Curation, Formal Analysis, Software, Validation, Visualization, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Plant Science gateway. Abstract Introduction Diabetes mellitus (DM) is a chronic metabolic disease representing a global public health concern and is associated with severe complications such as cardiovascular and renal diseases. Although several species of the genus Acalypha have demonstrated biological activity, no prior studies have evaluated the hypoglycemic effect of Acalypha argomuelleri Briq., making this study relevant. Method The hypoglycemic effect of the aqueous leaf extract of A. argomuelleri Briq. (AAAE) was evaluated in an experimental model using Rattus r attus var. albinus. A randomized, prospective design was employed, consisting of a control group and three treatment groups receiving doses of 100, 150, and 300 mg/kg of the extract, respectively. Hyperglycemia was induced via oral glucose administration. Results The qualitative phytochemical analysis of AAAE revealed the presence of flavonoids, phenols, cardiotonic glycosides, and diterpenes, with no reducing sugars. The 300 mg/kg dose produced a significant and sustained reduction in blood glucose levels, reaching near-normal values at 90 minutes, demonstrating a dose- and time-dependent hypoglycemic effect. Discussion The study confirmed that AAAE has a dose-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg. This dose showed a faster and more sustained reduction in glucose levels compared to 100 and 150 mg/kg, suggesting higher efficacy at elevated concentrations. The identified flavonoids and phenols, associated with glucose metabolism modulation and pancreatic β-cell protection, likely explain the observed effect. The absence of reducing sugars indicates the hypoglycemic effect is linked to secondary metabolites. Conclusions The AAAE exhibited a significant dose- and time-dependent hypoglycemic effect, with optimal efficacy at 300 mg/kg after 90 minutes. These findings support the potential of A. argomuelleri Briq. as a natural alternative for blood glucose control, though further studies are needed to assess its safety and efficacy in clinical models. READ ALL READ LESS Keywords Diabetes mellitus, Hypoglycemic effect, aqueous extract, Acalypha argomuelleri Briq Corresponding Author(s) Jorge Guillermo Morales Ramos ( [email protected] ) Close Corresponding author: Jorge Guillermo Morales Ramos Competing interests: No competing interests were disclosed. Grant information: This research received institutional funding from the University of San Martín de Porres with project code: E21102023008. Copyright: © 2025 Morales Ramos JG 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: Morales Ramos JG, Loja Herrera B, Rodríguez Alayo NM et al. Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.12688/f1000research.164673.1 ) First published: 19 Aug 2025, 14 :800 ( https://doi.org/10.12688/f1000research.164673.1 ) Latest published: 10 Oct 2025, 14 :800 ( https://doi.org/10.12688/f1000research.164673.3 )  There is a newer version of this article available. Suppress this message for one day. 1. Introduction The World Health Organization (WHO) defines Diabetes mellitus (DM) as a chronic metabolic disease characterized by elevated blood glucose levels. DM causes complications such as vascular diseases, heart conditions, blindness, renal failure, and neurological disorders. Type 1 diabetes (T1D), also known as insulin-dependent diabetes, is a chronic condition where the pancreas produces little or no insulin, which cannot be prevented. In contrast, Type 2 diabetes (T2D) typically occurs in adults, is the most common form, and is frequently associated with obesity. T2D can be prevented by avoiding complications and premature death. 1 In 2022, an estimated 828 million adults worldwide had DM, with prevalence increasing in 155 countries for men and 132 for women. Between 1990 and 2022, age-standardized prevalence rose from 7% to 14%, justifying the need to explore alternative treatments. 2 In the Americas, 112 million adults over the age of 18 are living with DM. According to data released in a report by the Pan American Health Organization (PAHO), under the heading ‘country profiles - diabetes disease burden, 2023’, revealed that DM (excluding diabetic kidney disease) increased and that the total number of deaths in 2019 was 141 812 distributed in middle-to-high income groups. 3 A projection for 2045 in Latin America and the Caribbean (LAC) estimated that the number of people with DM would reach 49 million, with a prevalence of 11.9%. Globally, it is projected that by 2035, DM2 cases would rise to 643 million, a 50% increase from current figures. 4 A review study concluded that individuals with T2DM in Latin American developing countries face a higher risk of cardiovascular or all-cause mortality compared to those in developed countries. 5 Conventional therapies for DM1 include insulin administration, while DM2 relies on oral hypoglycemic agents such as metformin. The American Diabetes Association (ADA) 2024 guidelines recommend GLP-1 analogs and SGLT2 inhibitors as first-line treatments for MN2 patients with cardiovascular disease (CV), heart failure, or chronic kidney disease. 6 Hypoglycemia has been exposed as one of the most serious adverse side effects of anti-diabetic treatments. Numerous epidemiological studies have highlighted the importance of a diet rich in plant foods including vegetables, fruits, spices and condiments in the prevention and treatment of DM. Various plants are used for their anti-diabetic and hypoglycemiant c effects, such as Morus alba L. (‘mulberry’), Juglans regia L. (‘walnut’), which are widely used throughout the world. In Peru, there is a wide diversity of plant species with hypoglycemiant effects, some of which belong to traditional medicine and are being studied for their use and toxicity, as in the case of Geranium ayavacense L. (‘pasuchaca’). 7 Various parts of the plant have been used to obtain extracts and identify their metabolites. Among the widely studied antidiabetic plants, M. alba “mulberry” stands out, whose metabolites present in the leaves include flavonoids such as rutin and quercetin-3-triglyceride, which were shown to have hypoglycemic and pharmacological effects on DM2 in animal models and humans, as synthesized in our systematic review. 8 – 11 Another plant to consider is A. wilkesiana Müll. Arg. whose aqueous extract prepared from its leaves revealed the presence of bioactive principles such as: coumarins, polyphenols, flavins, terpenes, tannins and saponosides, which have a potentiating effect on diabetic nephropathy. 12 In Iran, the hydrosol of J. regia is traditionally used to regulate blood sugar in patients with DM. Various bioactive metabolites have been identified in it, including flavonoids, phenolic compounds, limonene, myrcenes, linalool, beta-pharmesene, borneol monoterpenes, caffeic acid and coumaric acids, sinapic acid, ferulic acid, juglone, 1,4-naphthoquinone, 3-3′-bisjuglone, cyclo-tri-juglone, regiolone, tripertenes, betulin and botulinic acid. 13 – 16 In Peru, several medicinal plants, such as Geranium ayavacense Linnaeus. and Geranium ruizii Hieron (‘pasuchaca’), are recognized in traditional medicine for their medicinal properties. These plants have demonstrated hypoglycemic effects in experimental models using hyperglycemic rats ( Rattus rattus var. albinus ), with leaves are used in infusions and flowers in hydroethanolic extracts. Other species with similar therapeutic properties include Psoralea glandulosa Linnaeus. (‘cullen’), Physalis angulata Linnaeus (‘mullaca’), and Smallanthus sonchifolius (Poepp.) H. Rob (‘yacón’). 17 – 20 Numerous studies on the genus Acalypha have demonstrated its pharmacological properties, including antimicrobial effects ( A. integrifolia and A. wilkesiana ), anti-inflammatory effects ( A. fruticosa Forsskal.), and anticancer effects ( A. monostachya ). 21 – 24 Acalypha argomuelleri Briq., commonly known as ‘Sweet stick’, is a species distributed from Ecuador to Peru. It is a shrub that primarily grows in the humid tropical biome. Taxonomically, it belongs to the class Equisetopsida, subclass Magnoliidae, order Malpighiales, family Euphorbiaceae, and the genus Acalypha. Euphorbiaceae is one of the largest plant families, comprising numerous genera and approximately 6,300 species; Acalypha is the third largest genus within this family, including around 500 species. 25 , 26 This study aimed to assess the hypoglycemic effect of the aqueous extract of Acalypha argomuelleri Briq. (EAAA) using an experimental model, as no scientific evidence is currently available regarding its medicinal properties. Despite its traditional use in folk medicine, the therapeutic potential of this species remains unexplored in the scientific literature. Therefore, this research seeks not only to address this gap but also to investigate the potential of Acalypha. argomuelleri as a natural alternative for glycemic control—an approach that could prove beneficial for communities that rely heavily on traditional medicine. 2. Methods The study was carried out between January and December 2024. During this period, the following stages were completed: collection and botanical identification of the plant material, conditioning and acclimatisation of the experimental animals, as well as the preparation and administration of the alcoholic extract, followed by that of the aqueous extract of Acalypha argomuelleri Briq. The experimental phase was then carried out in the experimental physiology laboratory of the Universidad Nacional Pedro Ruiz Gallo between June and December. Blood glucose measurements were taken at specific times according to the experimental design, and the data obtained were statistically analysed to evaluate the hypoglycaemic effect of the extract. The research followed a quantitative, true experimental approach, appropriate for the study as it allows the establishment of causal relationships between the administration of the extract and changes in glucose levels. The study was prospective with a longitudinal design. A completely randomized design with control and treatment groups was used to evaluate the hypoglycemic effect of the aqueous extract of A. argomuelleri (AEAA) in hyperglycemic Rattus rattus var. albinus. a. The rats were housed in metal cages containing sterile wood shavings. The temperature was controlled at 20–24 °C, the humidity at 50–60%, and the lighting was on a 12-hour cycle. They were fed a standard diet and had access to water at all times. No environmental enrichment was applied. a. The protocol avoided painful procedures. Nontoxic doses were used, and animals were monitored regularly. b. There were no adverse events. c. Humane endpoints were not established for the study as no serious harm was expected. Animals were monitored twice daily. The corresponding permits were obtained from the National Forest and Wildlife Service (SERFOR) (Resolutions No. D000120-2023-MIDAGRI-SERFOR-ATFFS-CAJAMARCA and No. D000167-2024) for the collection of Acalypha argomuelleri Briq., as well as authorization from the Research Department of the Lambayeque Regional Hospital (HRL), including approval from the Institutional Research Ethics Committee for the use of animals (No. 026-2025). The collection of A. argomuelleri Briq. leaves at the flowering stage were carried out in the district of Querocoto, Chota province, Peru. In situ plant samples were taken and transported to the National University of Trujillo, where they were deposited in the Herbarium Truxillensis (Trujillo–La Libertad) for proper identification and registration. No previous protocol was registered en a public database. The experimental design was reviewed and approved by the Hospital ethics Committee. Preparation of the aqueous extract from Acalypha argomuelleri Briq. leaves For the preparation of the aqueous extract of A. argomuelleri (AEAA), the method described by García-Granados 27 was used, which involved the following steps: 1. Drying: The leaves were cleaned and dried at room temperature until a constant weight was achieved. 2. Grinding: The dried leaves were ground until they reached an approximate size of 2 mm. 3. Extraction: 200 g of plant material were placed in 300 mL of water at 100°C for 45 minutes. Subsequently, the mixture was filtered, pressed, and reduced to a final volume of 162 mL. 4. Concentration: The liquid was dried in an oven at 42°C for 48 hours, followed by cooling in a desiccator. By weight difference, a dry residue of 16.5 g was obtained. 5. Preparation of Solutions: Based on the dry extract, 25 mL solutions were prepared at concentrations of 100, 150, and 300 mg/mL, respectively. Phytochemical analysis A qualitative phytochemical analysis of the aqueous extract of Acalypha argomuelleri Briq. was carried out using the drop assay, following the method described by Dueñas-Deyá. 28 The presence of metabolites was determined based on specific colorimetric reactions for each group of compounds. The intensity of the color reaction qualitatively indicated the presence or absence of bioactive components using the following scale: - Absent (–) - Present in small amount (+) - Present in moderate amount (++) - Present in abundance (+++) To indicate the presence of sugars, the Benedict’s test was used following the methodology described by García-Granados. 27 Experimental design The study was conducted with 33 adult rats ( Rattus rattus var. albinus ), aged between 4 and 6 months, weighing between 190 and 230 gr., and divided into four experimental groups. The control group initially consisted of 9 rats, while each of the three treatment groups included 8 rats. To ensure sample size homogeneity and to meet the assumptions of Analysis of Variance (ANOVA), the statistical analysis was performed considering 8 rats per group over a period of six months. A hyperglycemic state was induced in the rats through oral administration of glucose (5 mL). Subsequently, the aqueous extract of Acalypha argomuelleri Briq. was administered orally in three different doses (100 mg/kg, 150 mg/kg, and 300 mg/kg). Blood glucose levels were recorded under preprandial conditions, first determining the basal level and then the hyperglycemic level, with measurements taken at 30, 60, and 90 minutes after extract administration. Blood glucose was measured using an ACCU-CHEK glucometer and test strips, selected for their accuracy and reliability, as supported by previous studies. No additional environmental enrichment was applied, which is a recognized but common limitation in preclinical pharmacological studies. Statistical analysis Data analysis was performed using SPSS software version 22.0, applying single and double-entry statistical tests. To compare the groups, an Analysis of Variance (ANOVA) based on the “F” distribution was used for multiple comparisons, followed by Duncan’s post hoc test. Results with a p-value < 0.05 were considered statistically significant. There was no blinding at any stage of the experiment. 3. Results 3.1 Phytochemical profile of the aqueous extract of Acalypha argomuelleri Briq. The qualitative phytochemical analysis revealed the presence of several bioactive compounds. The results are summarized in the following table: Constituent Test performed Presence in the leaf Diterpenes Cooper acetate test ++ Cardiotonic glycosides Keller-Kilani test + Phenols Ferric chloride test (12.5%) +++ Flavonoids Shinoda test ++ The qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides. Reducing sugars were not detected. These findings suggest that the flavonoids and phenols present in the extract may be linked to the observed hypoglycemic effect, given their potential to modulate enzymatic activity and protect pancreatic β-cells. 3.2 Blood glucose in the control group The blood glucose data from the control group rats (0 mL/kg), which did not receive treatment with AEAA, served as the reference baseline to compare the effects observed in the treated experimental groups. Basal glucose levels and the progressive reduction in blood glucose levels over time (30, 60, and 90 minutes) were monitored. These measurements showed variation among individuals, reflecting natural fluctuations in glucose levels. The data observed in Table 2 showed the glucose response in rats treated with AEAA at a dose of 100 mg/kg. Basal glucose measurements ranged from 99 mg/dL to 124 mg/dL, with an average of 111 mg/dL, which were found to be within the normal range. The highest recorded hyperglycemia peak was 342 mg/dL. At 30 minutes, most rats exhibited a significant increase in blood glucose levels. By 60 minutes, a variable decrease was observed, with some rats maintaining elevated levels, and at 90 minutes, a progressive reduction occurred, though some rats retained high levels. Table 1. Glucose response in rats treated with AEAA (Control). Rat Weight (g) Extract dose (mL/kg) Basal glucose (mg/dL) Glucose 30 min (mg/dL) Glucose 60 min (mg/dL) Glucose 90 min (mg/dL) 1 200 0 132 200 194 186 2 216 0 104 196 141 229 3 200 0 101 200 213 198 5 172 0 96 186 185 63 6 215 0 89 181 190 105 7 200 0 112 183 213 198 8 220 0 140 200 170 181 9 170 0 100 211 197 190 Table 2. Glucose response in rats treated with AEAA (100 mg/kg). Acalypha argomuelleri (100 mg/kg) Rat Weight (g) Extract dose (mL/kg) Basal glucose (mg/dL) Hyperglycemia Glucose 30 min (mg/dL) Glucose 60 min (mg/dL) Glucose 90 min (mg/dL) 1 329 0.140 121 342 156 179 180 2 268 0.110 116 155 286 256 219 3 295 0.120 124 289 131 129 130 4 286 0.120 99 256 300 152 127 5 298 0.130 115 279 201 121 99 6 266 0.110 115 160 281 250 160 7 326 0.140 120 332 178 166 120 8 286 0.120 101 256 300 152 110 At this dose, AEAA appears to induce a significant hyperglycemia peak at 30 minutes in some rats, suggesting a variable response. However, glucose levels did not decrease uniformly among all rats, as some maintained elevated levels up to 90 minutes. Although the response to the 100 mg/kg dose was not entirely uniform it appears to indicate that AEAA may have a glucose-regulating effect, which acted which acted following an initial hyperglycemic peak, with some rats showing a gradual reduction in their glucose levels over time. The results shown correspond to rats treated with AEAA at a dose of 150 mg/kg. The average basal glucose was found to be 101 mg/dL, and the hyperglycemia peak reached a maximum of 220 mg/dL. Regarding glucose progression, a less pronounced increase was observed at 30 minutes compared to the 100 mg/kg dose. By 60 minutes, a more uniform decrease was seen in most rats, and at 90 minutes, greater stability in values with a tendency toward normalization was noted. This suggests that, given the more consistent glucose reduction at 60 and 90 minutes and fewer individual fluctuations, the extract at this dose may better regulate glucose absorption, potentially making it more effective at stabilizing glucose levels ( Table 3 ). Table 3. Glucose response in rats treated with AEAA (150 mg/kg). Acalypha argomuelleri (150 mg/kg) Rat Weight (g) Extract dose (mL/kg) Basal glucose (mg/dL) Hyperglycemia Glucose 30 min (mg/dL) Glucose 60 min (mg/dL) Glucose 90 min (mg/dL) 1 385 0.288 95 206 188 165 166 2 306 0.229 102 184 158 142 148 3 287 0.215 108 162 145 134 126 4 328 0.246 96 220 158 140 118 5 288 0.216 110 188 166 145 136 6 384 0.288 106 192 169 145 133 7 285 0.215 105 194 168 133 112 8 304 0.220 100 180 147 130 105 In summary, the data from the third treatment with AEAA at a dose of 300 mg/kg indicated an average basal glucose of 78 mg/dL, while hyperglycemia peak reached a maximum of 391 mg/dL. Regarding glucose progression, extreme variability was obserbed at 30 minutes, with some rats showing high values. By 60 minutes, a more controlled decrease was observed. At 90 minutes, glucose levels were lower compared to the other doses. The interpretation, given de lower glucose levels observed, suggested that 300 mg/kg of AEAA might be the most effective dose for sustained glucose reduction and could have a long-term regulatory effect ( Table 4 ). Table 4. Glucose response in rats treated with AEAA (300 mg/kg). Acalypha argomuelleri (300 mg/kg) Rat Weight (g) Extract dose (mL/kg) Basal glucose (mg/dL) Hyperglycemia Glucose 30 min (mg/dL) Glucose 60 min (mg/dL) Glucose 90 min (mg/dL) 1 200 0.240 70 143 93 93 94 2 180 0.216 82 391 170 158 151 3 190 0.228 72 146 149 146 138 4 200 0.240 86 148 133 139 114 5 180 0.216 80 284 363 123 97 6 210 0.252 55 135 140 101 92 7 170 0.204 92 161 117 110 113 8 187 0.224 76 163 151 155 123 Table 5 , analyzed the results using the arithmetic mean ( x ¯ ), standard deviation (σ), and coefficient of variation (CV), with the following interpretations: Table 5. General Interpretation of the Mean ( x ¯ ), Standard Deviation (σ), and Coefficient of Variation (CV%) in glucose response in rats treated with AEAA. Etapa Weight (gr) Basal (mg/dL) Hyperglycemia (mg/dL) 2.5 ml glucose 30 min 60 min 90 min N Control (Without Extract) x ¯ =196.09 σ=20.07 CV=10.24 x ¯ =104.89 σ=21.23 CV=20.24 x ¯ =196.78 σ=13.97 CV=7.10 x ¯ =214.33 σ=77.70 CV=36.25 x ¯ =186.89 σ=73.56 CV=39.36 x ¯ =156.56 σ=43.66 CV=27.89 9 Treatment 1 AEAA 100 mg/kg x ¯ =294.25 σ=23.46 CV=7.97 x ¯ =113.88 σ=9.14 CV=8.03 x ¯ =258.63 σ=69.85 CV=27.01 x ¯ =229.13 σ=70.05 CV=30.57 x ¯ =175.63 σ=51.23 CV=29.17 x ¯ =143.13 σ=40.38 CV=28.91 8 Treatment 2 AEAA 150 mg/kg x ¯ =320.88 σ=41.69 CV=12.99 x ¯ =102.75 σ=5.47 CV=5.32 x ¯ =190.75 σ=17.30 CV=9.07 x ¯ =162.38 σ=13.74 CV=8.46 x ¯ =141.75 σ=10.95 CV=7.73 x ¯ =130.50 σ=19.90 CV=15.25 8 Treatment 3 AEAA 300 mg/kg x ¯ =189.63 σ=13.14 CV=6.93 x ¯ =76.63 σ=11.33 CV=14.78 x ¯ =196.38 σ=92.13 CV=46.92 x ¯ =164.50 σ=83.51 CV=50.77 x ¯ =128.13 σ=25.01 CV=19.52 x ¯ =115.25 σ=21.34 CV=18.52 8 Low CV (30%): High dispersion, unstable response. For glucose variation without AEAA application (Day 0), a normal response curve was observed following glucose administration, showing an initial high peak (214.33 mg/dL) and a progressive reduction as metabolism progressed. The high CV in subsequent minutes suggested individual differences in glucose metabolism. Regarding the glucose variation across the three treatments, the results are presented as follows: Treatment 1 with 100 mg/kg The variability analysis revealed a high CV in the glucose response, indicating that the 100 mg/kg dose of the extract did not regulate glucose homogeneously, as hyperglycemia remained elevated and variable. Treatment 2 with 150 mg/kg EAAA at 150 mg/kg stabilized glucose more effectively compared to the 100 mg/kg dose, reducing hyperglycemia in a more homogeneous and controlled manner. This was attributed to a more consistent decrease in glucose levels, with low variability observed in post-administration values. Treatment 3 with 300 mg/kg At this dose, basal glucose levels were the lowest, suggesting that the extract may have a long-term hypoglycemic effect. An extremely high CV% was observed in the first 30 minutes, indicating inconsistent initial effects of the 300 mg/kg dose across individuals. However, glucose levels progressively decreased by 90 minutes, leveling off and showing a sustained reduction. These values were the lowest among all groups, suggesting that this dose was the most effective for long-term glucose regulation. Regarding the statistical tests to assess the presence of significant differences in glucose levels at 30, 60, and 90 minutes among the experimental groups (Control, 100 mg/kg, 150 mg/kg, and 300 mg/kg of AEAA), an analysis of variance (ANOVA) and the Waller-Duncan multiple range test were performed. The ANOVA in Table 6 showed significant differences among the treatments (p = 0.000), indicating that at least one group exhibited a distinct response in glucose reduction. Table 6. ANOVA de la respuesta de glucosa en ratas tratadas con EAAA. Source of variation Sum of squares df Mean square F Sig. (p-value) Mg/dL Entre grupos 37823.083 2 18911.542 8.524 0.000 Dentro de grupos 206326.156 93 2218.561 244149.240 95 The Duncan test (Alpha = 0.05) ( Table 7 ) was used to identify differences between groups. The results revealed that the 300 mg/kg dose showed a significant difference compared to the control group, indicating that this treatment at 90 minutes produced a significant reduction in blood glucose levels compared to untreated rats. At 60 minutes, the same treatment exhibited an intermediate effect but remained significantly different from the 30 minutes time point, which the least effective. Table 7. Results of the duncan test for blood glucose levels at 30, 60 and 90 minutes. Waller-Duncan Glucose Sample size (N) Subset for α = 0.05 1 2 90 min 32 139.41 60 min 32 158.34 158.34 30 min 32 187.66 In contrast, the 100 mg/kg and 150 mg/kg doses showed no significant differences compared to the control group, suggesting they may not be sufficiently effective to impact blood glucose reduction. A practical interpretation de AEAA’s efficacy highlights the importance of higher doses (e.g., 300 mg/kg), which may be necessary to achieve a more consistent and effective effect. A realistic interpretation of EAAA’s efficacy would suggest the importance of higher concentrations, which may be necessary to achieve a more consistent and effective therapeutic effect. 4. Discussion Phytochemical analysis of A. argomuelleri leaves revealed the presence of flavonoids in moderate proportions, high levels of phenolic compounds, and the absence of sugars. This bioactives compounds, commonly found in other Acalypha species, may have been responsible for the observed effects on glucose regulation due to their highly significant hypoglycemic medicinal properties. Previous studies have documented that the hypoglycemic effects of plants associated with the presence of flavonoids and phenols, are often attributed to their ability to enhance the function of pancreatic tissue, specifically the β-cells. This effect may be achieved either by stimulating insulins secretion or by reducing intestinal glucose absorption. 12 , 29 These results ( Table 1 ) suggest that, in the absence of AEAA, the glycemic homeostasis of the rats remained relatively stable over time, although individual fluctuations were observed. Such variations could be influenced by physiological factors such as basal metabolism, prior diet, or compensatory responses to fasting before treatment administration. 30 The results obtained with AEAA at a dose of 100 mg/kg showed a variable response in blood glucose levels in rats, indicating a partially regulatory effect with individual differences in response and, consequently, a lack of uniformity in outcomes. This variability could be related to the action of the extract´s bioactive compounds—mainly flavonoids and phenols—which are known to modulate glucose metabolism. Additionally, these variations might be attributed to genetic factors, differences in extract absorption, or the complexity of interactions involving flavonoids and phenols. 31 At a dose of 150 mg/kg, a progressive decrease in blood glucose levels was observed in most rats, reaching near-normal values at 60 and 90 minutes. The lower individual variability and grater stability in glucose levels at 90 minutes suggest that this dose of AEAA may be more effectively modulating glucose absorption and metabolism than the 100 mg/kg dose. This effect could be attributed to the action of bioactive compounds, primarily flavonoids and phenols, which according to various studies, can influence glycemic homeostasis through mechanisms such as the inhibition of digestive enzymes (α-glucosidase y la α-amylase) and stimulation of insulin secretion. 32 Furthermore, the observed response in this treatment indicates that, although the effect is significant, individual differences persist, which may be linked to genetic factors or variations in the absorption and bioavailability of the extract. 33 In contrast, the results obtained with AEAA at a dose of 300 mg/kg showed a faster, sustained, and more uniform reduction in blood glucose levels. The average basal glucose recorded before hyperglycemia induction was 78 mg/dL reaching a peak of 391 mg/dL, which is characteristic of the experimental model. However, by 90 minutes glucose values were significantly lower compared to other treatments, suggesting that this dose has a more pronounced and long-lasting hypoglycemic effect. This more consistent response could be linked to a higher concentration of bioactive compounds that optimize glucose utilization in peripheral tissues, promoting more effective regulation of glycemic homeostasis. 34 Additionally, it has been proposed that flavonoids and phenols present in Acalypha species not only stimulate insulin secretion but also protect pancreatic β-cells by reducing oxidative stress and modulating the expression of pro- and anti-apoptotic genes. 35 , 36 The 300 mg/kg dose demonstrated the highest hypoglycemic efficacy, with a sustained reduction in blood glucose levels to near-normoglycemia values at 90 minutes. This finding combined with the absence of reducing sugars in the extract, suggests that the optimal concentration of flavonoids (++) and phenols (+++) may act effectively through a multifactorial mechanism targeting multiple metabolic pathways: (1) inhibition of α-glucosidase, (2) modulation of intestinal glucose absorption, and (3) protection of pancreatic β-cells against oxidative stress — key mechanisms associated with antidiabetic effects in plants such as M. alba and other Acalypha species. 8 However, the variability observed (CV > 50% at 30 minutes) highlights the influence of individual factors such as basal metabolism, bioavailability of active compounds, and hormonal fluctuations, 37 which could affect treatment response and therapeutical efficacy. Future studies—including a comprehensive phytochemical analysis and chronic diabetes models—will clarify whether A. argomuelleri Briq. Possesses additional antidiabetic effects (e.g., improvement insulin resistance or reduction of systemic oxidative stress). Current evidence indicates that the hypoglycemic effect of AEAA is dose-dependent, suggesting that the highest dose is the most effective long-term. This finding aligns with other studies in experimental models, where doses ranging from 200 to 500 mg/kg showed significant glucose reduction by 120 minutes. 38 – 40 Eight rats per group were used, which is an adequate and commonly accepted number in preclinical pharmacological evaluation studies. This sample size allowed statistically significant differences to be observed between groups, although it is recognized that further studies with larger samples could strengthen the evidence and facilitate the exploration of additional mechanisms. While the results obtained provide evidence of the hypoglycemic effect of A. argomuelleri Briq., it is important to note that this study was conducted in an experimental model using healthy albino rats. Future studies could evaluate the extract´s impact on induced diabetes models to determine its effectiveness under pathological conditions. Additionally, more detailed phytochemical analyses would be relevant to identify the compounds responsible for the hypoglycemic effect and elucidate their mechanism of action. Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans. It is suggested that the findings could be a basis for studies in other animal models or in humans, although a direct clinical application is not yet proposed. 5. Conclusions This study represents a pioneering contribution to the evaluation of the hypoglycemic effect of the aqueous extract of Acalypha argomuelleri Briq. (AEAA) in albino rats, as o prior documented research exists on the species in relation to blood glucose regulation. The key findings are as follows: • The aqueous extract of Acalypha argomuelleri Briq. At a dose of 300 mg/kg, significantly reduced blood glucose levels in Rattus rattus var. albinus compared to the control group, demonstrating a dose-dependent hypoglycemic effect. • The efficacy of the aqueous extract of Acalypha argomuelleri Briq. Increased with treatment duration, showing a progressive reduction in glucose levels due to its cumulative and sustained effect. • The 90 minute treatment exhibited the greatest reduction in glucose levels, representing the optimal timepoint to maximize the hypoglycemic effect without inducing adverse effects. Ethical considerations The corresponding permits were obtained from the National Forest and Wildlife Service (SERFOR) (Resolutions No. D000120-2023-MIDAGRI-SERFOR-ATFFS-CAJAMARCA and No. D000167-2024) for the collection of Acalypha argomuelleri Briq., as well as authorization from the Research Department of the Lambayeque Regional Hospital (HRL), including approval from the Institutional Research Ethics Committee for the use of animals (No. 026-2025). Data availability statement Underlying data Zenodo. Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. ‘Sweet stick’ leaves in Rattus rattus var. albinus, https://doi.org/10.5281/zenodo.16732470 . 41 This project contains the following underlying data: • TOLERANCE TEST DATABASE (Excel file).xlsx (Individual blood glucose data in rats by experimental group and day of evaluation). • ANOVA DATA SPSS.spv - (Results of the ANOVA analysis applying SPSS to the experimental data). • Duncan_Acalypha_test (1).txt - (Results of the Duncan/Tukey post hoc test with detailed statistical significance by pairs). • BASE DOF DATES TEST OF TOLERANCE.xlsx • MEDIA, DS Y CV ACALYPHA.docx • RESAULTS JANUARY 31.pdf The data is available under the terms of the Creative Commons Attribution 4.0 International licence (CC BY 4.0). Reporting guidelines Zenodo. Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. ‘Sweet stick’ leaves in Rattus rattus var. albinus, https://doi.org/10.5281/zenodo.16732470 . 41 This project contains the following underlying data: Author Checklist - Full 19_07_25.pdf The data is available under the terms of the Creative Commons Attribution 4.0 International licence (CC BY 4.0). References 1. Organización Mundial de la Salud (OMS): Diabetes: Datos y cifras. OMS; Accessed: Mar. 23, 2025. Reference Source 2. Zhou B, et al. : Worldwide trends in diabetes prevalence and treatment from 1990 to 2022: a pooled analysis of 1108 population-representative studies with 141 million participants. Lancet. Nov. 2024; 404 (10467): 2077–2093. PubMed Abstract | Publisher Full Text | Free Full Text 3. Organización Panamericana de la Salud (OPS): Diabetes - OPS/OMS|Organización Panamericana de la Salud. OPS/OMS; Accessed: Mar. 23, 2025. Reference Source 4. 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Publisher Full Text Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 19 Aug 2025 ADD YOUR COMMENT Comment Author details Author details 1 Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 2 Faculty of Human Medicine, Universidad Mayor de San Marcos, Lima, Peru 3 Faculty of Human Medicine, Universidad Nacional Pedro Ruiz Gallo, Lambayeque, Lambayeque, Peru 4 Program of Human Medicine, Universidad Señor de Sipán, Lambayeque, Peru 5 Research Directorate, Hospital Regional Lambayeque, Lambayeque, Peru Jorge Guillermo Morales Ramos Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing Berta Loja Herrera Roles: Conceptualization, Data Curation, Formal Analysis, Investigation, Methodology, Supervision, Validation, Visualization, Writing – Review & Editing Néstor Manuel Rodríguez Alayo Roles: Formal Analysis, Investigation, Methodology, Resources, Validation, Visualization, Writing – Original Draft Preparation Doyle Isabel Benel Fernández Roles: Conceptualization, Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Visualization Luis Felipe Pérez Medina Roles: Data Curation, Formal Analysis, Investigation, Software, Validation, Visualization, Writing – Original Draft Preparation Carolina Susana Loayza Estrada Roles: Data Curation, Formal Analysis, Investigation, Methodology, Software, Validation, Writing – Review & Editing María Ema Soledad Mocarro Willis Roles: Data Curation, Formal Analysis, Methodology, Resources, Validation, Visualization César Sánchez Marín Roles: Data Curation, Formal Analysis, Software, Validation, Visualization, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This research received institutional funding from the University of San Martín de Porres with project code: E21102023008. Article Versions (3) version 3 Revised Published: 10 Oct 2025, 14:800 https://doi.org/10.12688/f1000research.164673.3 version 2 Revised Published: 15 Sep 2025, 14:800 https://doi.org/10.12688/f1000research.164673.2 version 1 Published: 19 Aug 2025, 14:800 https://doi.org/10.12688/f1000research.164673.1 Copyright © 2025 Morales Ramos JG 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 Morales Ramos JG, Loja Herrera B, Rodríguez Alayo NM et al. Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.12688/f1000research.164673.1 ) 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 19 Aug 2025 Views 0 Cite How to cite this report: Motto AE. Reviewer Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r407373 ) The direct URL for this report is: https://f1000research.com/articles/14-800/v1#referee-response-407373 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 08 Sep 2025 Aku Enam Motto , University of Lomé, Lomé, Togo Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.181218.r407373 RESEARCH ARTICLE Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus Abstract Introduction Reformulate it Material and methods The authors should follow the ... Continue reading READ ALL RESEARCH ARTICLE Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus Abstract Introduction Reformulate it Material and methods The authors should follow the structure for more clarification and understanding Animals Plant collection and identification Preparation of the aqueous extract Phytochemical screening This is a qualitative test, so there is no need to write +++ or --- Absence - and Presence + Experimental design The authors should mention the dose of glucose administered to the rats The authors did not mention whether the manipulation occurred in fasted rats or not Precision of the sex of the animals is also needed. The measurement of the glycemia must be extended in 2 hours ( 30 min, 60 min, 60 min; 120 and 180 min) For this kind of evaluation of the hypoglycemic activity, there are a lot of adequate protocols nowadays (refer to 1&2) For a better understanding, the authors must complete the test. Statistical analysis 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? Yes Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? Partly References 1. Agalatossi H, Motto A, Lawson-Evi P, Eklu-Gadegbeku K: Antihyperglycemic and Antioxidant Properties of Sida linifolia Juss. ex Cav. (Malvaceae) Hydroalcoholic Extract in ICR Mice. Asian Science Bulletin . 2025; 3 (1): 8-19 Publisher Full Text 2. Dackey Y, Hanvi D, Motto A, Atchou K, et al.: Potential Anti-hyperglycemic Activity of the Polyherbal Combination of Carica papaya L., Persea americana Mill., and Theobroma cacao L. Leaves Extract: In vitro, Ex vivo, In vivo Studies. Journal of Advances in Medical and Pharmaceutical Sciences . 2025; 27 (2): 54-66 Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Physiology, Pharmacology, toxicology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Motto AE. Reviewer Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r407373 ) The direct URL for this report is: https://f1000research.com/articles/14-800/v1#referee-response-407373 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 Author Response 22 Sep 2025 Jorge Guillermo Morales Ramos , Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 22 Sep 2025 Author Response Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. ... Continue reading Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. Materials and methods Authors should follow the structure for greater clarity and understanding. Animals The reviewer's suggestion was accepted, incorporating the sex of the study animals and indicating that they were male. Plant collection and identification The methods of Cerrate and Romagosa et al. were used for the collection of botanical material. Cerrate E. Manera de preparar plantas para un herbario. Lima: Editorial UNMSM; 1969. Romagosa J, Rosales S, Rupérez RF, Crespo R. Enciclopedia de medicina naturalista y alternativa; 2000. Preparation of the aqueous extract Phytochemical screening The methodology mentioned the method followed by García Granados (paragraph 7, p.3, ref. 27), which describes the stages of the process. This is a qualitative test, so it is not necessary to write +++ or ---. Absence - and Presence + Version 2 of the article states that the test was qualitative with semi-quantitative estimation (p. 3, paragraph 1, Phytochemical analysis, ref. 28). Experimental design The authors should mention the dose of glucose administered to the rats. Paragraph 2 of the experimental design section indicates that the dose of glucose administered was 5 ml. The authors did not mention whether the manipulation was performed on fasted rats or not. The experimental design section mentions the conditions referred to by the reviewer (p. 7, paragraph 2). It is also necessary to specify the sex of the animals. We appreciate the reviewer's suggestion to include the sex of the rats, which were males paragraph 2(a). Blood glucose measurement should be extended to 2 hours (30 min, 60 min, 60 min; 120 and 180 min). We appreciate the reviewer's suggestion regarding the inclusion of additional times (120 and 180 minutes). In our study, 30, 60, and 90 minutes were selected because these intervals are widely used in glucose tolerance tests in preclinical models with plant extracts, as they allow both the post-load peak and the early phase of blood glucose return to be captured (Tripathi et al., 2014; Narmadha, et al., 2017). With this design, it was possible to identify the maximum hypoglycaemic effect of the extract in the critical window where changes are most evident. While we recognise that extended measurements up to 120 or 180 minutes may provide additional information, the main objective of this exploratory study was to evaluate the early hypoglycaemic response, which is adequately reflected in the 90 minutes. Undoubtedly, future studies —especially in diabetic models and chronic evaluations— will include longer times. Tripathi AK, Kohli S. Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats. J Complement Integr Med. 2014 Jun;11(2):71-81. doi: 10.1515/jcim-2014-0011. PMID: 24760764. Narmadha R, Devaki K. Toxicological evaluation and oral glucose tolerance test of ethanolic leaf extract of Barleria cristata L. in wistar albino rats. Int J Basic Clin Pharmacol [Internet]. 2017 Feb. 2 [cited 2025 Sep. 12];2(6):742-6. Available from: https://www.ijbcp.com/index.php/ijbcp/article/view/1359 Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. Materials and methods Authors should follow the structure for greater clarity and understanding. Animals The reviewer's suggestion was accepted, incorporating the sex of the study animals and indicating that they were male. Plant collection and identification The methods of Cerrate and Romagosa et al. were used for the collection of botanical material. Cerrate E. Manera de preparar plantas para un herbario. Lima: Editorial UNMSM; 1969. Romagosa J, Rosales S, Rupérez RF, Crespo R. Enciclopedia de medicina naturalista y alternativa; 2000. Preparation of the aqueous extract Phytochemical screening The methodology mentioned the method followed by García Granados (paragraph 7, p.3, ref. 27), which describes the stages of the process. This is a qualitative test, so it is not necessary to write +++ or ---. Absence - and Presence + Version 2 of the article states that the test was qualitative with semi-quantitative estimation (p. 3, paragraph 1, Phytochemical analysis, ref. 28). Experimental design The authors should mention the dose of glucose administered to the rats. Paragraph 2 of the experimental design section indicates that the dose of glucose administered was 5 ml. The authors did not mention whether the manipulation was performed on fasted rats or not. The experimental design section mentions the conditions referred to by the reviewer (p. 7, paragraph 2). It is also necessary to specify the sex of the animals. We appreciate the reviewer's suggestion to include the sex of the rats, which were males paragraph 2(a). Blood glucose measurement should be extended to 2 hours (30 min, 60 min, 60 min; 120 and 180 min). We appreciate the reviewer's suggestion regarding the inclusion of additional times (120 and 180 minutes). In our study, 30, 60, and 90 minutes were selected because these intervals are widely used in glucose tolerance tests in preclinical models with plant extracts, as they allow both the post-load peak and the early phase of blood glucose return to be captured (Tripathi et al., 2014; Narmadha, et al., 2017). With this design, it was possible to identify the maximum hypoglycaemic effect of the extract in the critical window where changes are most evident. While we recognise that extended measurements up to 120 or 180 minutes may provide additional information, the main objective of this exploratory study was to evaluate the early hypoglycaemic response, which is adequately reflected in the 90 minutes. Undoubtedly, future studies —especially in diabetic models and chronic evaluations— will include longer times. Tripathi AK, Kohli S. Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats. J Complement Integr Med. 2014 Jun;11(2):71-81. doi: 10.1515/jcim-2014-0011. PMID: 24760764. Narmadha R, Devaki K. Toxicological evaluation and oral glucose tolerance test of ethanolic leaf extract of Barleria cristata L. in wistar albino rats. Int J Basic Clin Pharmacol [Internet]. 2017 Feb. 2 [cited 2025 Sep. 12];2(6):742-6. Available from: https://www.ijbcp.com/index.php/ijbcp/article/view/1359 Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 22 Sep 2025 Jorge Guillermo Morales Ramos , Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 22 Sep 2025 Author Response Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. ... Continue reading Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. Materials and methods Authors should follow the structure for greater clarity and understanding. Animals The reviewer's suggestion was accepted, incorporating the sex of the study animals and indicating that they were male. Plant collection and identification The methods of Cerrate and Romagosa et al. were used for the collection of botanical material. Cerrate E. Manera de preparar plantas para un herbario. Lima: Editorial UNMSM; 1969. Romagosa J, Rosales S, Rupérez RF, Crespo R. Enciclopedia de medicina naturalista y alternativa; 2000. Preparation of the aqueous extract Phytochemical screening The methodology mentioned the method followed by García Granados (paragraph 7, p.3, ref. 27), which describes the stages of the process. This is a qualitative test, so it is not necessary to write +++ or ---. Absence - and Presence + Version 2 of the article states that the test was qualitative with semi-quantitative estimation (p. 3, paragraph 1, Phytochemical analysis, ref. 28). Experimental design The authors should mention the dose of glucose administered to the rats. Paragraph 2 of the experimental design section indicates that the dose of glucose administered was 5 ml. The authors did not mention whether the manipulation was performed on fasted rats or not. The experimental design section mentions the conditions referred to by the reviewer (p. 7, paragraph 2). It is also necessary to specify the sex of the animals. We appreciate the reviewer's suggestion to include the sex of the rats, which were males paragraph 2(a). Blood glucose measurement should be extended to 2 hours (30 min, 60 min, 60 min; 120 and 180 min). We appreciate the reviewer's suggestion regarding the inclusion of additional times (120 and 180 minutes). In our study, 30, 60, and 90 minutes were selected because these intervals are widely used in glucose tolerance tests in preclinical models with plant extracts, as they allow both the post-load peak and the early phase of blood glucose return to be captured (Tripathi et al., 2014; Narmadha, et al., 2017). With this design, it was possible to identify the maximum hypoglycaemic effect of the extract in the critical window where changes are most evident. While we recognise that extended measurements up to 120 or 180 minutes may provide additional information, the main objective of this exploratory study was to evaluate the early hypoglycaemic response, which is adequately reflected in the 90 minutes. Undoubtedly, future studies —especially in diabetic models and chronic evaluations— will include longer times. Tripathi AK, Kohli S. Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats. J Complement Integr Med. 2014 Jun;11(2):71-81. doi: 10.1515/jcim-2014-0011. PMID: 24760764. Narmadha R, Devaki K. Toxicological evaluation and oral glucose tolerance test of ethanolic leaf extract of Barleria cristata L. in wistar albino rats. Int J Basic Clin Pharmacol [Internet]. 2017 Feb. 2 [cited 2025 Sep. 12];2(6):742-6. Available from: https://www.ijbcp.com/index.php/ijbcp/article/view/1359 Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. Materials and methods Authors should follow the structure for greater clarity and understanding. Animals The reviewer's suggestion was accepted, incorporating the sex of the study animals and indicating that they were male. Plant collection and identification The methods of Cerrate and Romagosa et al. were used for the collection of botanical material. Cerrate E. Manera de preparar plantas para un herbario. Lima: Editorial UNMSM; 1969. Romagosa J, Rosales S, Rupérez RF, Crespo R. Enciclopedia de medicina naturalista y alternativa; 2000. Preparation of the aqueous extract Phytochemical screening The methodology mentioned the method followed by García Granados (paragraph 7, p.3, ref. 27), which describes the stages of the process. This is a qualitative test, so it is not necessary to write +++ or ---. Absence - and Presence + Version 2 of the article states that the test was qualitative with semi-quantitative estimation (p. 3, paragraph 1, Phytochemical analysis, ref. 28). Experimental design The authors should mention the dose of glucose administered to the rats. Paragraph 2 of the experimental design section indicates that the dose of glucose administered was 5 ml. The authors did not mention whether the manipulation was performed on fasted rats or not. The experimental design section mentions the conditions referred to by the reviewer (p. 7, paragraph 2). It is also necessary to specify the sex of the animals. We appreciate the reviewer's suggestion to include the sex of the rats, which were males paragraph 2(a). Blood glucose measurement should be extended to 2 hours (30 min, 60 min, 60 min; 120 and 180 min). We appreciate the reviewer's suggestion regarding the inclusion of additional times (120 and 180 minutes). In our study, 30, 60, and 90 minutes were selected because these intervals are widely used in glucose tolerance tests in preclinical models with plant extracts, as they allow both the post-load peak and the early phase of blood glucose return to be captured (Tripathi et al., 2014; Narmadha, et al., 2017). With this design, it was possible to identify the maximum hypoglycaemic effect of the extract in the critical window where changes are most evident. While we recognise that extended measurements up to 120 or 180 minutes may provide additional information, the main objective of this exploratory study was to evaluate the early hypoglycaemic response, which is adequately reflected in the 90 minutes. Undoubtedly, future studies —especially in diabetic models and chronic evaluations— will include longer times. Tripathi AK, Kohli S. Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats. J Complement Integr Med. 2014 Jun;11(2):71-81. doi: 10.1515/jcim-2014-0011. PMID: 24760764. Narmadha R, Devaki K. Toxicological evaluation and oral glucose tolerance test of ethanolic leaf extract of Barleria cristata L. in wistar albino rats. Int J Basic Clin Pharmacol [Internet]. 2017 Feb. 2 [cited 2025 Sep. 12];2(6):742-6. Available from: https://www.ijbcp.com/index.php/ijbcp/article/view/1359 Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Galán de Mera A. Reviewer Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r410405 ) The direct URL for this report is: https://f1000research.com/articles/14-800/v1#referee-response-410405 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 03 Sep 2025 Antonio Galán de Mera , Universidad San Pablo-CEU, Madrid, Spain Approved VIEWS 0 https://doi.org/10.5256/f1000research.181218.r410405 I think this is a very interesting type of manuscript that scientifically demonstrates the traditional use of certain plants in Peru that could be adopted by occidental medicine. Perhaps it would be useful to indicate whether the extracts could ... Continue reading READ ALL I think this is a very interesting type of manuscript that scientifically demonstrates the traditional use of certain plants in Peru that could be adopted by occidental medicine. Perhaps it would be useful to indicate whether the extracts could have secondary effects (although this is not the aim of this work) and what the subsequent steps would be in order to develop a pharmaceutical preparation. Although it is a pharmacological manuscript, the botanical aspects of the plant should be dealt with in more detail. For example, the way in which its ecology is dealt with is very superficial, when it is precisely a natural resource that could lead to the establishment of a nature reserve. Other points: In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). The caption for Table 6 should be in English. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Discussion: Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. 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? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Plant systematics, Biogeography, Pharmacognosy. 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Galán de Mera A. Reviewer Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r410405 ) The direct URL for this report is: https://f1000research.com/articles/14-800/v1#referee-response-410405 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 Author Response 15 Sep 2025 Jorge Guillermo Morales Ramos , Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 15 Sep 2025 Author Response 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for ... Continue reading 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for Table 6 was translated. 3. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. Answer:The suggested paragraphs were merged, mentioning some plants of Peruvian origin that were already mentioned in the article. 4. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Answer: The reviewer's suggestion has been added to the text. 5. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. Answer: The additions suggested by the reviewer were made, indicating the ecology of the plant, its use and traditional preparation. 6. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Answer: The reviewer's suggestion was accepted and the reference was added. 7. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Answer: The relevant corrections were made, adding the use and preparation of the plant, as well as an explanation of how the leaves were used in the experiment. Coordinates and the date of collection were also added, according to the herbarium voucher. Discussion: 8. Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Answer: The suggestion to replace qualitative phytochemical analysis with semi-quantitative phytochemical analysis is accepted. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. Answer: We thank the reviewer for the clarification and suggestion regarding the structure of the paragraph, and the relevant changes have been made in the paragraphs 1 y 10. 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for Table 6 was translated. 3. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. Answer:The suggested paragraphs were merged, mentioning some plants of Peruvian origin that were already mentioned in the article. 4. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Answer: The reviewer's suggestion has been added to the text. 5. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. Answer: The additions suggested by the reviewer were made, indicating the ecology of the plant, its use and traditional preparation. 6. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Answer: The reviewer's suggestion was accepted and the reference was added. 7. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Answer: The relevant corrections were made, adding the use and preparation of the plant, as well as an explanation of how the leaves were used in the experiment. Coordinates and the date of collection were also added, according to the herbarium voucher. Discussion: 8. Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Answer: The suggestion to replace qualitative phytochemical analysis with semi-quantitative phytochemical analysis is accepted. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. Answer: We thank the reviewer for the clarification and suggestion regarding the structure of the paragraph, and the relevant changes have been made in the paragraphs 1 y 10. Competing Interests: None Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 15 Sep 2025 Jorge Guillermo Morales Ramos , Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 15 Sep 2025 Author Response 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for ... Continue reading 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for Table 6 was translated. 3. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. Answer:The suggested paragraphs were merged, mentioning some plants of Peruvian origin that were already mentioned in the article. 4. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Answer: The reviewer's suggestion has been added to the text. 5. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. Answer: The additions suggested by the reviewer were made, indicating the ecology of the plant, its use and traditional preparation. 6. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Answer: The reviewer's suggestion was accepted and the reference was added. 7. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Answer: The relevant corrections were made, adding the use and preparation of the plant, as well as an explanation of how the leaves were used in the experiment. Coordinates and the date of collection were also added, according to the herbarium voucher. Discussion: 8. Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Answer: The suggestion to replace qualitative phytochemical analysis with semi-quantitative phytochemical analysis is accepted. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. Answer: We thank the reviewer for the clarification and suggestion regarding the structure of the paragraph, and the relevant changes have been made in the paragraphs 1 y 10. 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for Table 6 was translated. 3. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. Answer:The suggested paragraphs were merged, mentioning some plants of Peruvian origin that were already mentioned in the article. 4. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Answer: The reviewer's suggestion has been added to the text. 5. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. Answer: The additions suggested by the reviewer were made, indicating the ecology of the plant, its use and traditional preparation. 6. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Answer: The reviewer's suggestion was accepted and the reference was added. 7. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Answer: The relevant corrections were made, adding the use and preparation of the plant, as well as an explanation of how the leaves were used in the experiment. Coordinates and the date of collection were also added, according to the herbarium voucher. Discussion: 8. Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Answer: The suggestion to replace qualitative phytochemical analysis with semi-quantitative phytochemical analysis is accepted. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. Answer: We thank the reviewer for the clarification and suggestion regarding the structure of the paragraph, and the relevant changes have been made in the paragraphs 1 y 10. Competing Interests: None Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 3 VERSION 3 PUBLISHED 19 Aug 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 3 (revision) 10 Oct 25 read Version 2 (revision) 15 Sep 25 read read Version 1 19 Aug 25 read read Antonio Galán de Mera , Universidad San Pablo-CEU, Madrid, Spain Aku Enam Motto , University of Lomé, Lomé, Togo MARIO ANTONIO BOLARTE ARTEAGA , UNIVERSIDAD CONTINENTAL, Lima, Peru Bolarte Artega Mario Antonio , Universidad Continental - Los Olivos Lima, Lima Region, Peru 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 Galán de Mera 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. 14 Oct 2025 | for Version 3 Antonio Galán de Mera , Universidad San Pablo-CEU, Madrid, Spain 0 Views copyright © 2025 Galán de Mera 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 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 As I indicated last time, my decision is ACCEPTED. Competing Interests No competing interests were disclosed. Reviewer Expertise Plant systematics, Biogeography, Pharmacognosy. 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. reply Respond to this report Responses (0) Galán de Mera A. Peer Review Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.188409.r422492) 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/14-800/v3#referee-response-422492 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 BOLARTE ARTEAGA M et al. 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. 24 Sep 2025 | for Version 2 MARIO ANTONIO BOLARTE ARTEAGA , UNIVERSIDAD CONTINENTAL, Lima, Peru Bolarte Artega Mario Antonio , Universidad Continental - Los Olivos Lima, Lima Region, Lima District, Peru 0 Views copyright © 2025 BOLARTE ARTEAGA M et al. 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 (1) Approved 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 I NTRODUCTION The introduction to the manuscript presents a clear and well-structured overview of the scientific and ethnobotanical context of Acalypha argomuelleri as a species of medicinal interest, citing other native Peruvian and foreign species. The authors successfully articulate the importance of preclinical studies in animal models with the need to scientifically validate the traditional uses reported in local communities. Likewise, an adequate literature review is included that places the work within the framework of current research on hypoglycaemic plants, allowing the reader to understand both the relevance from a biological point of view and the value from another point of view, which is the cultural value of the natural resource studied. The writing is fluid, coherent, and sufficient to justify the objective of the study, so I believe that this section does not require additional modifications. The manuscript addresses a relevant topic in the field of pharmacognosy and complementary medicine, evaluating the hypoglycaemic effect of Acalypha argomuelleri, a little-studied species with potential therapeutic application. METHODOLOGY The methodology presented in the manuscript is clear and consistent with the objectives set out. The glucose tolerance test procedure, the administration of the extract in different doses, and the recording of the glycaemic response are described accurately, ensuring reproducibility in future studies. Likewise, the use of statistical analysis using ANOVA followed by Duncan's test is relevant and correctly applied, lending strength to the results. I believe that the methodology section does not require further modification, as it meets the standards of rigour and transparency expected in this type of research. RESULTS The results section is organised in a clear and coherent manner, adequately presenting both the experimental data and its statistical analysis. The tables accurately indicate the variations in glucose levels following the administration of the extract in different doses, which facilitates understanding of the findings. In addition, Duncan's test is correctly described, allowing significant differences between groups to be identified. The writing is objective and avoids premature interpretations, limiting itself to presenting the findings as they were obtained. I consider the results to be sufficient, well presented, and requiring no further modification. DISCUSSION The discussion is solid and adequately fulfils the purpose of interpreting the results in light of existing scientific evidence. The authors make relevant comparisons with other plants known for their hypoglycaemic activity, which places their findings in a broader context and gives the study international relevance. Furthermore, there is a balance between the interpretation of the data and the recognition of limitations, as well as the mention of future lines of research, demonstrating a forward-looking and responsible approach. The writing is clear, coherent and well structured, allowing the reader to understand both the scope and potential of the extract of the plant studied. I consider that this section does not require any modifications. 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? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Pharmacogenomics, Medicina plants and Pharmacology We confirm that we have read this submission and believe that we have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (1) Author Response 26 Sep 2025 Jorge Guillermo Morales Ramos, Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru We thank the reviewer for approving the article without comments. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern BOLARTE ARTEAGA MA and Mario Antonio BA. Peer Review Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.187885.r410404) 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/14-800/v2#referee-response-410404 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Galán de Mera 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. 16 Sep 2025 | for Version 2 Antonio Galán de Mera , Universidad San Pablo-CEU, Madrid, Spain 0 Views copyright © 2025 Galán de Mera 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 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 I agree with this new amended version and recommend acceptance Thank you very much. Kind regards Competing Interests No competing interests were disclosed. Reviewer Expertise Plant systematics, Biogeography, Pharmacognosy. 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. reply Respond to this report Responses (0) Galán de Mera A. Peer Review Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.187885.r414413) 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/14-800/v2#referee-response-414413 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Motto 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. 08 Sep 2025 | for Version 1 Aku Enam Motto , University of Lomé, Lomé, Togo 0 Views copyright © 2025 Motto 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 (1) Not Approved 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 RESEARCH ARTICLE Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus Abstract Introduction Reformulate it Material and methods The authors should follow the structure for more clarification and understanding Animals Plant collection and identification Preparation of the aqueous extract Phytochemical screening This is a qualitative test, so there is no need to write +++ or --- Absence - and Presence + Experimental design The authors should mention the dose of glucose administered to the rats The authors did not mention whether the manipulation occurred in fasted rats or not Precision of the sex of the animals is also needed. The measurement of the glycemia must be extended in 2 hours ( 30 min, 60 min, 60 min; 120 and 180 min) For this kind of evaluation of the hypoglycemic activity, there are a lot of adequate protocols nowadays (refer to 1&2) For a better understanding, the authors must complete the test. Statistical analysis 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? Yes Are all the source data underlying the results available to ensure full reproducibility? No source data required Are the conclusions drawn adequately supported by the results? Partly References 1. Agalatossi H, Motto A, Lawson-Evi P, Eklu-Gadegbeku K: Antihyperglycemic and Antioxidant Properties of Sida linifolia Juss. ex Cav. (Malvaceae) Hydroalcoholic Extract in ICR Mice. Asian Science Bulletin . 2025; 3 (1): 8-19 Publisher Full Text 2. Dackey Y, Hanvi D, Motto A, Atchou K, et al.: Potential Anti-hyperglycemic Activity of the Polyherbal Combination of Carica papaya L., Persea americana Mill., and Theobroma cacao L. Leaves Extract: In vitro, Ex vivo, In vivo Studies. Journal of Advances in Medical and Pharmaceutical Sciences . 2025; 27 (2): 54-66 Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Physiology, Pharmacology, toxicology I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 22 Sep 2025 Jorge Guillermo Morales Ramos, Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru Abstract The sex of the rats was added to the summary. Introduction Reformulate It has been reformulated by adding Peruvian plants with hypoglycaemic effects (page 3, paragraph 10), article v2. Materials and methods Authors should follow the structure for greater clarity and understanding. Animals The reviewer's suggestion was accepted, incorporating the sex of the study animals and indicating that they were male. Plant collection and identification The methods of Cerrate and Romagosa et al. were used for the collection of botanical material. Cerrate E. Manera de preparar plantas para un herbario. Lima: Editorial UNMSM; 1969. Romagosa J, Rosales S, Rupérez RF, Crespo R. Enciclopedia de medicina naturalista y alternativa; 2000. Preparation of the aqueous extract Phytochemical screening The methodology mentioned the method followed by García Granados (paragraph 7, p.3, ref. 27), which describes the stages of the process. This is a qualitative test, so it is not necessary to write +++ or ---. Absence - and Presence + Version 2 of the article states that the test was qualitative with semi-quantitative estimation (p. 3, paragraph 1, Phytochemical analysis, ref. 28). Experimental design The authors should mention the dose of glucose administered to the rats. Paragraph 2 of the experimental design section indicates that the dose of glucose administered was 5 ml. The authors did not mention whether the manipulation was performed on fasted rats or not. The experimental design section mentions the conditions referred to by the reviewer (p. 7, paragraph 2). It is also necessary to specify the sex of the animals. We appreciate the reviewer's suggestion to include the sex of the rats, which were males paragraph 2(a). Blood glucose measurement should be extended to 2 hours (30 min, 60 min, 60 min; 120 and 180 min). We appreciate the reviewer's suggestion regarding the inclusion of additional times (120 and 180 minutes). In our study, 30, 60, and 90 minutes were selected because these intervals are widely used in glucose tolerance tests in preclinical models with plant extracts, as they allow both the post-load peak and the early phase of blood glucose return to be captured (Tripathi et al., 2014; Narmadha, et al., 2017). With this design, it was possible to identify the maximum hypoglycaemic effect of the extract in the critical window where changes are most evident. While we recognise that extended measurements up to 120 or 180 minutes may provide additional information, the main objective of this exploratory study was to evaluate the early hypoglycaemic response, which is adequately reflected in the 90 minutes. Undoubtedly, future studies —especially in diabetic models and chronic evaluations— will include longer times. Tripathi AK, Kohli S. Pharmacognostical standardization and antidiabetic activity of Syzygium cumini (Linn.) barks (Myrtaceae) on streptozotocin-induced diabetic rats. J Complement Integr Med. 2014 Jun;11(2):71-81. doi: 10.1515/jcim-2014-0011. PMID: 24760764. Narmadha R, Devaki K. Toxicological evaluation and oral glucose tolerance test of ethanolic leaf extract of Barleria cristata L. in wistar albino rats. Int J Basic Clin Pharmacol [Internet]. 2017 Feb. 2 [cited 2025 Sep. 12];2(6):742-6. Available from: https://www.ijbcp.com/index.php/ijbcp/article/view/1359 View more View less Competing Interests None reply Respond Report a concern Motto AE. Peer Review Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r407373) 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/14-800/v1#referee-response-407373 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Galán de Mera 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. 03 Sep 2025 | for Version 1 Antonio Galán de Mera , Universidad San Pablo-CEU, Madrid, Spain 0 Views copyright © 2025 Galán de Mera 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 (1) Approved 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 I think this is a very interesting type of manuscript that scientifically demonstrates the traditional use of certain plants in Peru that could be adopted by occidental medicine. Perhaps it would be useful to indicate whether the extracts could have secondary effects (although this is not the aim of this work) and what the subsequent steps would be in order to develop a pharmaceutical preparation. Although it is a pharmacological manuscript, the botanical aspects of the plant should be dealt with in more detail. For example, the way in which its ecology is dealt with is very superficial, when it is precisely a natural resource that could lead to the establishment of a nature reserve. Other points: In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). The caption for Table 6 should be in English. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Discussion: Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. 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? Yes Are all the source data underlying the results available to ensure full reproducibility? Yes Are the conclusions drawn adequately supported by the results? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Plant systematics, Biogeography, Pharmacognosy. 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. reply Respond to this report Responses (1) Author Response 15 Sep 2025 Jorge Guillermo Morales Ramos, Faculty of Human Medicine, Universidad De San Martín de Porres, Lambayeque, Peru 1. In the title, add the family after Acalypha argomuelleri Briq. (Euphorbiaceae). Answer: The addition suggested by the reviewer was made. 2. The caption for Table 6 should be in English. Answer: The legend for Table 6 was translated. 3. In paragraph 6 of the introduction, I believe that if the new plant that causes hypoglycaemia is Peruvian, more plants from Peru that cause this effect should be added, and not just Geranium ayavacense. Furthermore, three paragraphs below, a very similar paragraph is repeated, and what is detailed in it should be included here. Join two paragraphs. Answer:The suggested paragraphs were merged, mentioning some plants of Peruvian origin that were already mentioned in the article. 4. In paragraph 7, line 4: THESE ARE NOT SYSTEMATIC REVIEWS OF PLANTS (BOTANICAL EXPRESSION), THEY ARE PHYTOCHEMICAL AND PHARMACOLOGICAL REVIEWS: It should be stated: as synthesised in our ongoing phytochemical and pharmacological reviews. Answer: The reviewer's suggestion has been added to the text. 5. Paragraph 12 and 13 of the introduction: 'the humid tropical biome': This is taken from IPNI, but IPNI is not accurate for ecological data. What is its distribution in Peru? Add some bibliographical references about its distribution. There is no humid tropical biome. It should be indicated whether it is a humid tropical forest, humid tropical shrubs, a savannah-type forest, etc., and also the bibliographical reference from which this information is taken. IF WE ARE DISCUSSING ABOUT A NATURAL RESOURCE, IT IS VERY IMPORTANT TO CORRECTLY INDICATE THE ECOLOGICAL CONDITIONS OF THE LOCATION. A PHARMACOLOGICAL STUDY CAN LEAD TO A WHOLE CONSERVATION STRATEGY. Answer: The additions suggested by the reviewer were made, indicating the ecology of the plant, its use and traditional preparation. 6. 'traditional use in folk medicine': What is it used for in traditional medicine? Please specify it, and add a bibliographical reference. Answer: The reviewer's suggestion was accepted and the reference was added. 7. Methods, paragraph 5: WHY HAVE ONLY THE LEAVES BEEN USED? AND WHY HAVE THEY BEEN COLLECTED WHEN THE PLANT IS IN BLOOM? PERHAPS BECAUSE THAT IS HOW IT IS DONE IN TRADITIONAL MEDICINE? THE REASON SHOULD BE STATED. In that paragraph, after Peru: Cajamarca Department, Peru. Also add coordinates and date of collection. National University of Trujillo: Is the registered name IN ENGLISH? OR IS IT UNIVERSIDAD NACIONAL DE TRUJILLO? After registration, the voucher number must be added to the HUT herbarium, which is the acronym for the herbarium. Answer: The relevant corrections were made, adding the use and preparation of the plant, as well as an explanation of how the leaves were used in the experiment. Coordinates and the date of collection were also added, according to the herbarium voucher. Discussion: 8. Phytochemical analysis: The intensity of the color reaction qualitatively indicated...but also quantitative? I believe you are showing colour intensity according to quantity, so wouldn't that also be quantitative analysis? Furthermore, in paragraph 2 of the results , the authors wrote the sentence ‘Qualitative phytochemical analysis revealed an abundant presence of phenols, a moderate amount of flavonoids and diterpenes, and a small quantity of cardiotonic glycosides’. Answer: The suggestion to replace qualitative phytochemical analysis with semi-quantitative phytochemical analysis is accepted. Discussion, paragraph 1: The authors wrote: 'Previous studies have documented that the hypoglycemic effects of plants associated' Which plants? Paragraph 10 of the discussion states: ' Taken together, these findings suggest that AEAA could represent a natural alternative in complementary medicine for blood glucose control, with potential therapeutic applications in the management of type 2 diabetes mellitus (T2DM). However further studies are required to validate its efficacy in humans.' What success rate could extracts from this plant have in humans, considering that it is used in traditional medicine? Could a medicine be manufactured that could be dispensed in pharmacies? These would be interesting points to add to the discussion. Answer: We thank the reviewer for the clarification and suggestion regarding the structure of the paragraph, and the relevant changes have been made in the paragraphs 1 y 10. View more View less Competing Interests None reply Respond Report a concern Galán de Mera A. Peer Review Report For: Hypoglycemic effect of the aqueous extract from Acalypha argomuelleri Briq. 'Sweet stick' leaves in Rattus rattus var. albinus [version 1; peer review: 1 approved, 1 not approved] . F1000Research 2025, 14 :800 ( https://doi.org/10.5256/f1000research.181218.r410405) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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