Eugenia jambolana extract reduces the systemic exposure of Sitagliptin and improves conditions associated with diabetes: A pharmacokinetic and a pharmacodynamic herb-drug interaction study

Abstract

Eugenia jambolana (EJ) is an Indian traditional herb widely used for the treatment of diabetes mellitus. This herb is globally marketed as single or multi herb formulations. Many diabetes patients consume EJ extract oral hypoglycemic drugs together. This calls for a need to assess risks versus benefit of this co-administration. In present investigation, pharmacodynamic and pharmacokinetic interactions of aqueous extract of EJ seeds at the dose of 400 mg/kg are studied with 10 mg/kg of oral hypoglycaemic drug sitagliptin (SITA) by co-administrating them for 28 days in streptozotocin (STZ) induced diabetic rats. The pharmacokinetic parameters of SITA were determined using HPLC-ESI-MS/MS and it was found that the combination treatment reduces the systemic exposure of SITA by showing 38.70% reduction in concentration maximum (Cmax) and 22.40% reduction in area under curve (AUC). Despite low levels of SITA, the combination demonstrated a significant reduction in blood glucose level when compared with individual drug and individual extract administered groups during pharmacodynamic study. In addition, the liver function, the kidney function and the lipid parameters were found to be significantly improved and beneficial effects were found with respect to food intake and water intake and urine output in case of combination treatment groups when compared with individual treatment groups. Histopathological examination of pancreatic tissue suggests its significant recovery of having normal acinus with better cell protection in combination treatment. In conclusion, the combination treatment demonstrated reduced systemic exposure of SITA without compromising on its antihyperglycemic activity and improvement in conditions associated with diabetes.

Herb‐drug interactions in diabetes mellitus: A review based on pre‐clinical and clinical data

“…Besides, the liver and kidney functions, lipid parameters were found to be improved. Histopathology of pancreatic tissue in combination group, observed significant recovery with normal acinus and better cell protection (Vora et al, 2018).…”

“…Besides, the liver and kidney functions, lipid parameters were found to be improved. Histopathology of pancreatic tissue in combination group, observed significant recovery with normal acinus and better cell protection (Vora et al, 2018). In view of the above mentioned reports it can be proposed that the concomitant administration of Syzygium cumini with hypoglycemic agents (substrates of CYP2C9 like Nateglinide, Glyburide, Glimepiride, Gliclazide, Glipizide, and Rosiglitazone) with the narrow therapeutic range may show alterations in the pharmacokinetic profile of the drugs, leading to significant herb‐drug interactions (HDI).…”

Effect of herbal formulation on glimepiride pharmacokinetics and pharmacodynamics in nicotinamide-streptozotocin-induced diabetic rats

“…The mechanism of action of a combination is unlikely to be as important as that of the individual medications [ 6 , 7 ]. However, the latest studies showed that there exist interactions between some commonly administered traditional medicinal herbs and widely used oral hypoglycemic agents in diabetes mellitus [ [8] , [9] , [10] , [11] , [12] , [13] , [14] , [15] ]. Thereby, efforts should be made to identify the therapeutic potential of herbs, assessment of the toxicity, efficacy and mode of action in HDIs to promote their safe and efficient use.…”

Herb-Drug Interaction: Application of a UPLC-MS/MS Method to Determine the Effect of Polygonum capitatum Extract on the Tissue Distribution and Excretion of Levofloxacin in Rats

“…A reasonable herb-drug interaction (HDI) can enhance efficacy and reduce adverse reactions [ 4 ]. For example, the combination of Eugenia jambolana extract and sitagliptin caused significant improvement in the comorbidities associated with diabetes mellitus compared to sitagliptin treatment alone [ 5 ]. Pittosporum angustifolium Lodd.…”