An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats

Bibliographic Details
Title: An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats
Authors: Archana K. Thikekar, Asha B. Thomas, Sohan S. Chitlange
Source: Phytomedicine Plus, Vol 5, Iss 2, Pp 100751- (2025)
Publisher Information: Elsevier, 2025.
Publication Year: 2025
Collection: LCC:Other systems of medicine
Subject Terms: Diabetes, Glimepiride, IME-9, PK/PD, HDI, Other systems of medicine, RZ201-999
More Details: Background: Currently, herbs are frequently employed for medicinal or dietary purposes alongside both prescribed and over-the-counter medications. Despite being perceived as natural and benign, herbs carry the potential to interact with medications, potentially leading to adverse reactions or diminished efficacy of the medications. It is worth noting that herbs comprise different amounts of active phytochemicals that can affect enzymatic systems, transporters and physiological processes. The focus of this study is to investigate the effects of the herbal formulation IME-9 on the pharmacokinetics (PK) and pharmacodynamics (PD) of Glimepiride (GP) and whether it is advantageous, detrimental or has no consequences. Purpose: In this study, the PK and PD interactions of GP (0.82 mg/kg) with IME-9 (132.24 mg/kg p.o.) was studied in diabetic rats (induced by Nicotinamide-STZ) by concomitant administration of both the drugs orally for a period of 21 days. Methods: The RP-HPLC technique was devised and validated in accordance with the guidelines set by the US Food and Drug Administration (FDA). PK and PD parameters were computed on both day 1 and 21 in vivo. In silico molecular docking investigations were conducted using Autodock Vina 1.2.3 to assess the binding affinity of the 46 primary phytoconstituents present in IME 9 with CYP2C9 enzymes. Toxicity assessments were carried out utilizing the MTT assay. Results: Concurrent administration of GP and IME-9 in diabetic rats resulted in elevated Cmax and AUC0-48hrs of GP, while no alteration in Tmax was noticed. This led to a reduction in Vd and CL together with an increase in t1/2 and mean residence time. Notably, the combination treatment (GP+IME-9) significantly decreased FBGL, TC and TG levels compared to individual therapy groups, suggesting synergistic pharmacodynamic effects. In silico molecular docking predictions revealed that the majority of phytoconstituents present in IME-9 formulation act as an inhibitor of the CYP2C9 enzyme. Conclusions: GP and IME-9 together could enhance the hypoglycemic effect and increase systemic exposure of GP.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2667-0313
Relation: http://www.sciencedirect.com/science/article/pii/S2667031325000247; https://doaj.org/toc/2667-0313
DOI: 10.1016/j.phyplu.2025.100751
Access URL: https://doaj.org/article/eaa83b33583a4a47bd349dd403da4dff
Accession Number: edsdoj.83b33583a4a47bd349dd403da4dff
Database: Directory of Open Access Journals
More Details
ISSN:26670313
DOI:10.1016/j.phyplu.2025.100751
Published in:Phytomedicine Plus
Language:English