Combination of plant metabolites hinders starch digestion and glucose absorption while facilitating insulin sensitivity to diabetes.

Autor:	Huang X; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Lin K; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Liu S; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Yang J; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Zhao H; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Zheng XH; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Tsai MJ; Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan., Chang CS; Department of Biotechnology and Food Technology, Southern Taiwan University of Science and Technology, Tainan, Taiwan., Huang L; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China., Weng CF; Functional Physiology Section, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.; Institute of Respiratory Disease, Department of Basic Medical Science, Xiamen Medical College, Xiamen, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Jun 05; Vol. 15, pp. 1362150. Date of Electronic Publication: 2024 Jun 05 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1362150
Abstrakt:	Introduction: Diabetes mellitus (DM) is a common endocrine disease resulting from interactions between genetic and environmental factors. Type II DM (T2DM) accounts for approximately 90% of all DM cases. Current medicines used in the treatment of DM have some adverse or undesirable effects on patients, necessitating the use of alternative medications. Methods: To overcome the low bioavailability of plant metabolites, all entities were first screened through pharmacokinetic, network pharmacology, and molecular docking predictions. Experiments were further conducted on a combination of antidiabetic phytoactive molecules (rosmarinic acid, RA; luteolin, Lut; resveratrol, RS), along with in vitro evaluation (α-amylase inhibition assay) and diabetic mice tests (oral glucose tolerance test, OGTT; oral starch tolerance test, OSTT) for maximal responses to validate starch digestion and glucose absorption while facilitating insulin sensitivity. Results: The results revealed that the combination of metabolites achieved all required criteria, including ADMET, drug likeness, and Lipinski rule. To determine the mechanisms underlying diabetic hyperglycemia and T2DM treatments, network pharmacology was used for regulatory network, PPI network, GO, and KEGG enrichment analyses. Furthermore, the combined metabolites showed adequate in silico predictions (α-amylase, α-glucosidase, and pancreatic lipase for improving starch digestion; SGLT-2, AMPK, glucokinase, aldose reductase, acetylcholinesterase, and acetylcholine M2 receptor for mediating glucose absorption; GLP-1R, DPP-IV, and PPAR-γ for regulating insulin sensitivity), in vitro α-amylase inhibition, and in vivo efficacy (OSTT versus acarbose; OGTT versus metformin and insulin) as nutraceuticals against T2DM. Discussion: The results demonstrate that the combination of RA, Lut, and RS could be exploited for multitarget therapy as prospective antihyperglycemic phytopharmaceuticals that hinder starch digestion and glucose absorption while facilitating insulin sensitivity. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Huang, Lin, Liu, Yang, Zhao, Zheng, Tsai, Chang, Huang and Weng.)
Databáze:	MEDLINE
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