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Abstract Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of Hemidesmus indicus var. pubescens root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between β-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that β-sitosterol (− 10.2 kcal/mol) and hemidesmin-2 (− 8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate − 100 µg/mL (standard) and test extract (500 and 1000 µg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that H. indicus var. pubescens root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications. Graphic Abstract

Curcumin has been shown to possess high cytotoxicity towards various cell lines. But its low aqueous solubility and bioavailability limit its use as an effective cytotoxic agent. It has been reported that metformin selectively kills cancer stem cells and blocks tumor growth. Preclinical studies show the effectiveness of both curcumin and metformin in breast cancer. Conjugation of metformin and curcumin may result in synergistic cancer therapy by improving the aqueous solubility of curcumin and hence its bioavailability. In the present study, curcumin-metformin conjugate and the free drugs curcumin and metformin were subjected to docking analysis against the breast cancer targets such as epidermal growth factor receptor, kinesin spindle protein, cyclin-dependent kinase, human placental aromatase, and human estrogen receptor. Docking studies were performed using Autodock Vina. The results signify that curcumin-metformin conjugate showed higher binding energy ranging between -7.4 to -9.7 Kcal/mol than curcumin and metformin. The stability of the conjugate-receptor complex and interactions between them was further evaluated by molecular dynamics simulation. The results showed that the conjugate can interact effectively with human placental aromatase and can be considered for further studies.