An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats
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 dimini...
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Elsevier
2025-05-01
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| Series: | Phytomedicine Plus |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667031325000247 |
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| author | Archana K. Thikekar Asha B. Thomas Sohan S. Chitlange |
| author_facet | Archana K. Thikekar Asha B. Thomas Sohan S. Chitlange |
| author_sort | Archana K. Thikekar |
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| description | 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. |
| format | Article |
| id | doaj-art-eaa83b33583a4a47bd349dd403da4dff |
| institution | Kabale University |
| issn | 2667-0313 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Phytomedicine Plus |
| spelling | doaj-art-eaa83b33583a4a47bd349dd403da4dff2025-02-08T05:01:30ZengElsevierPhytomedicine Plus2667-03132025-05-0152100751An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic ratsArchana K. Thikekar0Asha B. Thomas1Sohan S. Chitlange2Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, IndiaCorresponding author at: Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune 411 018, India.; Department of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, IndiaDepartment of Pharmaceutical Chemistry, Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, Maharashtra, IndiaBackground: 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.http://www.sciencedirect.com/science/article/pii/S2667031325000247DiabetesGlimepirideIME-9PK/PDHDI |
| spellingShingle | Archana K. Thikekar Asha B. Thomas Sohan S. Chitlange An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats Phytomedicine Plus Diabetes Glimepiride IME-9 PK/PD HDI |
| title | An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats |
| title_full | An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats |
| title_fullStr | An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats |
| title_full_unstemmed | An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats |
| title_short | An in-vivo herb-drug interaction study of IME-9 and glimepiride in nicotinamide-STZ-induced diabetic rats |
| title_sort | in vivo herb drug interaction study of ime 9 and glimepiride in nicotinamide stz induced diabetic rats |
| topic | Diabetes Glimepiride IME-9 PK/PD HDI |
| url | http://www.sciencedirect.com/science/article/pii/S2667031325000247 |
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