In vivo and network pharmacological analysis of the antidiabetic and antihyperlipidemic metabolites of Litsea cubeba fruits

Diabetes mellitus is a major endocrine dysfunction that severely threatens the global population. Litsea cubeba (Lour.) Pers. (Lauraceae), commonly known as mountain pepper, has been utilized in many chronic disorders in different countries. However, the antidiabetic activity of this plant has not been explored to date. The present study aimed to explore the antidiabetic and antihyperlipidemic activities of the methanolic extract of fruits of L. cubeba (LCMF) from the Darjeeling Himalaya, India, through in vivo experimentations and network pharmacological analysis. The HFD-STZ induced diabetic model rats were treated with LCMF for 28 days and were examined for blood glucose, lipid profile, liver and kidney function parameters, hepatic antioxidant status and histopathology of liver, kidney and pancreas. The LCMF treatment effectively lowered (about 25%) high blood glucose levels and improved serum lipid profiles, liver glycogen content, and normalized antioxidant status. A significant increment in endogenous insulin (6.83 mU/L) and C-peptide levels (0.86 ng/mL), along with the regeneration of beta islets, were observed. LC-MS/MS and in silico networkpharmacological analysis showed the presence of some important metabolites, viz. thymol, scopoline, isosafrole, safrole, arecoline, etc. that interact with the target proteins (viz. IL6, ADRB1 etc.), transcription factors (viz. NFKB1, CYP1A1 etc.) and enzymes (viz. a-glucosidase, a-amylase etc.) associated with diabetes and hyperlipidemia. The study for the first time proved that the traditional edible fruits of L. cubeba have potent antidiabetic and antihyperlipidemic properties. The subsequent detailed characterization and mode of action studies would lead to discovering new antidiabetic and antihyperlipidemic drugs for human use. (c) 2022 SAAB. Published by Elsevier B.V. All rights reserved.

Automated summary

The study demonstrates the potent antidiabetic and antihyperlipidemic properties of Litsea cubeba fruits and provides insights into the underlying mechanisms through network pharmacological analysis.