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A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids

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Abstract

Diabetes mellitus (DM), a metabolic and endocrine condition, poses a serious threat to human health and longevity. The emerging role of gut microbiome associated with bioactive compounds has recently created a new hope for DM treatment. UHPLC-HRMS methods were used to identify these compounds in a poly herbal ethanolic extract (PHE). The effects of PHE on body weight (BW), fasting blood glucose (FBG) level, gut microbiota, fecal short-chain fatty acids (SCFAs) production, and the correlation between DM-related indices and gut microbes, in rats were investigated. Chebulic acid (0.368%), gallic acid (0.469%), andrographolide (1.304%), berberine (6.442%), and numerous polysaccharides were the most representative constituents in PHE. A more significant BW gain and a reduction in FBG level towards normal of PHE 600 mg/kg treated rats group were resulted at the end of 28th days of the study. Moreover, the composition of the gut microbiota corroborated the study’s hypothesis, as evidenced by an increased ratio of Bacteroidetes to Firmicutes and some beneficial microbial species, including Prevotella copri and Lactobacillus hamster. The relative abundance of Bifidobacterium pseudolongum, Ruminococcus bromii, and Blautia producta was found to decline in PHE treatment groups as compared to diabetic group. The abundance of beneficial bacteria in PHE 600 mg/kg treatment group was concurrently associated with increased SCFAs concentrations of acetate and propionate (7.26 nmol/g and 4.13 nmol/g). The findings of this study suggest a promising approach to prevent DM by demonstrating that these naturally occurring compounds decreased FBG levels by increasing SCFAs content and SCFAs producing gut microbiota.

Graphical Abstract

Flow chart summarizing research on the dual therapeutic approach to diabetes mellitus via bioactive chemicals found in a poly herbal extract and the management of gut microbiota in relation to DM. (SCFAs, short chain fatty acids; SMB53, a genus of bacterial microbiota of small intestine; LPS, lipopolysaccharide)

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Acknowledgements

The author is thankful to the Indian Institute of Technology (BHU) and MHRD, India, for fellowship. The authors thankfully acknowledge to Prof. Sushant Kumar Shrivastava formal Head of Department, Pharmaceutical Engineering and Technology, IIT (BHU) Varanasi-221 005, Uttar Pradesh, India, for guidance during the work. The author is also thankful to SATHI BHU for the High-Resolution Accurate Mass Spectrometry (HRMS) study for plant metabolomics.

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Authors and Affiliations

  1. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Amit Kumar Singh & Sunil Kumar Mishra

  2. Department of Botany, MMV, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Pradeep Kumar & Kavindra Nath Tiwari

  3. Academy of Biology and Biotechnology, Southern Federal University, Rostov On Don, Russia

    Vishnu D. Rajput & Tatiana Minkina

  4. Department of Chemistry, Mariahu PG College, VBS Purvanchal University, Jaunpur, Uttar Pradesh, 222161, India

    Anand Kumar Singh

  5. Department of Kaychikitsa, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221005, India

    Ajay Kumar Pandey

  6. Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, USA

    Prabhat Upadhyay

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Contributions

Amit Kumar Singh: conceptualization, methodology, writing-original draft preparation. Pradeep Kumar: methodology, writing—original draft preparation. Vishnu D Rajput: conceptualization, formal analysis, validation. Sunil Kumar Mishra: conceptualization, methodology, formal analysis, supervision. Kavindra Nath Tiwari: conceptualization, formal analysis, validation. Anand Kumar Singh: formal analysis, investigation, writing—review and editing. Tatiana Minkina: formal analysis, writing—review and editing, validation. Ajay Kumar Pandey: formal analysis, validation. Prabhat Upadhyay: formal analysis, validation. All authors have read and agreed to the final version of the manuscript.

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Correspondence to Sunil Kumar Mishra.

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All of the tests were carried out in compliance with Institutional animal experimentation rules. The Central Animal Ethics Committee, as per CPCSEA guidelines at IMS BHU Varanasi 221005 (Reg. No. 542/GO/Rebi//S/02/CPCSEA dated 26.5.2017), approved this study (Approval number: Dean/2021/IAEC/2560). The CPCSEA guidelines were fully followed in the experiment.

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Singh, A.K., Kumar, P., Mishra, S.K. et al. A Dual Therapeutic Approach to Diabetes Mellitus via Bioactive Phytochemicals Found in a Poly Herbal Extract by Restoration of Favorable Gut Flora and Related Short-Chain Fatty Acids. Appl Biochem Biotechnol (2024). https://doi.org/10.1007/s12010-024-04879-6

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