GREEN SYNTHESIS STRATEGIES, MECHANISTIC UNDERSTANDING AND CLINICAL TRANSLATION PROSPECTS OF "PLANT-DERIVED NANOMEDICINES FOR THE DUAL MANAGEMENT OF DIABETES MELLITUS AND HYPERTENSION

Abstract

The burden of diabetes mellitus and hypertension, two often coexisting parts of metabolic syndrome, is still rising world-wide and there is a need for safer and more effective therapeutic alternatives. The plant-derived nanomedicines are an amalgamation of ethnopharmacological knowledge and cutting-edge nanotechnology that deliver higher bioavailability, targeted delivery, and multi-pathway modulation. This review extensively discusses the green synthesis of nanoparticles from medicinal plants that have proven antidiabetic and antihypertensive effects, and explores the phytochemical basis for bioreduction, the mechanistic pathways involved in dual therapeutic effects, and the structural properties that influence their biological activity. We critically review the recent progress of development of monometallic, bimetallic and polymeric nanoformulations from different plant sources like Calotropis procera, Curcuma longa, Elettaria cardamomum, Piper longum, Quercus infectoria and various Citrus species. Focus has been given to strategies to increase the bioaccessibility of inherently labile phytoconstituents to achieve synergistic inhibition of α-amylase, α-glucosidase and angiotensin-converting enzyme (ACE). By systematic analysis of in vitro, ex vivo and preclinical evidence, we find key structure-activity relationships and propose frameworks of mechanism of action for phytochemical corona composition and therapeutic outcome. Moreover, we discuss some of the major translational hurdles such as scalability, reproducibility, assessment of toxicity and regulatory issues. In this review, present knowledge is summarized and future research directions are identified to be crucial for the successful translation of plant-derived nano-medicines to the clinical arena, for the co-management of diabetes and hypertension.