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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1362150
This article is part of the Research Topic Diabetes and cardiovascular disease: new therapeutic interventions View all 7 articles

Combination of Plant Metabolites Exerts Compatibly Hindering Starch Digestion and Glucose Absorption with Facilitating Insulin Sensitivity Towards Diabetes Subtitle: Synergy of metabolites abrogates hyperglycemia

Provisionally accepted
Xin Huang Xin Huang 1Kaihuang Lin Kaihuang Lin 1Sinian Liu Sinian Liu 1Junxiong Yang Junxiong Yang 1Haowei Zhao Haowei Zhao 1Xiaohui Zheng Xiaohui Zheng 1May-Jywan Tsai May-Jywan Tsai 2Chun-Sheng Chang Chun-Sheng Chang 3Liyue Huang Liyue Huang 1Ching Feng Weng Ching Feng Weng 1*
  • 1 Xiamen Medical College, Xiamen, Fujian Province, China
  • 2 Taipei Veterans General Hospital, Taipei, Taipei County, Taiwan
  • 3 Southern Taiwan University of Science and Technology, Tainan, Taiwan

The final, formatted version of the article will be published soon.

    Introduction: Diabetes mellitus (DM), a common endocrine disease, is attributable to the interaction of genetic and environmental factors, and remarkably type 2 DM (T2DM) accounts for approximately 90% of all cases. Current DM treatments of medicines have some adverse or undesirable effects on patients, necessitating the usage of alternative medications.To overcome low bioavailability of plant metabolites, this study was screened all entities firstly through the prediction of pharmacokinetics, network pharmacology and molecular docking. And the experiment was further identified combination of anti-diabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS) accompanied with the evaluation of in vitro (α-Amylase inhibition assay) and diabetic mice test (OGTT and OSTT) for the maximal response in validating starch digestion and glucose absorption concomitant with facilitating insulin sensitivity.The results revealed that these metabolites achieved all the solicited criteria including ADMET, drug likeness, Lipinski rule. To disclose the underlying mechanism in diabetic hyperglycemia and T2DM treatment, network pharmacology was executed via regulatory network, PPI network, GO and KEGG enrichment analysis. Furthermore, combinatory metabolites had an adequate prediction in silico output (α-Amylase, α-Glucosidase, Pancreatic lipase for ameliorating starch digestion; SGLT-2, AMPK, Glucokinase, Aldose reductase, Acetylcholinesterase, Acetylcholine M2 receptor under mediating glucose absorption; and GLP-1R, DPP-IV, and PPAR-γ under regulating insulin sensitivity), in vitro α-Amylase inhibition, and in vivo efficacy tests in OSTT versus Acarbose and in OGTT versus Metformin and insulin for nutraceuticals against T2DM.Discussion: These results extraordinarily demonstrated that the combination of RA, Lut, and RS might be exploiting multi-target therapy for prospectively antihyperglycemic phyto-pharmaceuticals by hindering starch digestion, glucose absorption and facilitating insulin sensitivity.

    Keywords: Anti-hyperglycemia, Combinatory chemistry, Phytopharmaceutical, polyphenol, in silico, Multi-target

    Received: 27 Dec 2023; Accepted: 29 Apr 2024.

    Copyright: © 2024 Huang, Lin, Liu, Yang, Zhao, Zheng, Tsai, Chang, Huang and Weng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Ching Feng Weng, Xiamen Medical College, Xiamen, Fujian Province, China

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