An eco-friendly one-pot extraction process for curcumin and its bioenhancer, piperine, from edible plants in exosome-like nanovesicles

Abstract

Curcumin has been extensively studied for its medicinal benefits, though its therapeutic use is limited by a lack of aqueous solubility and bioavailability. Piperine from black pepper is known to synergistically enhance the bioavailability of curcumin. However, both curcumin and piperine lack aqueous solubility and require extraction using non-eco-friendly solvents and further nano-encapsulation for in vivo application. Exosome-like nanovesicles (ENVs) are natural extracellular vesicles produced by plants that are isolated by green methods. ENVs purified from several edible plants contain host-plant-derived phytochemicals in a soluble form with enhanced bioavailability. However, the combined isolation of two or more bio-actives with synergistic effects from different host plants in the ENV form has never been attempted. Herein, we describe a green method for co-purifying both curcumin and piperine by combined homogenization of plant materials followed by polyethylene glycol-based precipitation of ENVs from the aqueous extract. The hybrid ENVs isolated from a mixed homogenate of turmeric and pepper (TPENV) possessed both curcumin and piperine. TPENVs showed spontaneous intracellular entry and displayed anti-inflammatory activity by downregulating LPS-induced pro-inflammatory markers in murine macrophages. Compared to ENVs isolated from turmeric alone (TENVs), TPENVs demonstrated enhanced percutaneous penetration into porcine skin and were resistant to harsh gastrointestinal conditions under simulated in vitro digestion. Intriguingly, this approach also endowed TPENVs with ∼8-fold higher curcumin content compared to TENVs. Overall, the process developed here provides a simple, environmentally-friendly and sustainable strategy for one-pot isolation of curcumin with piperine in ENVs, in a soluble and bioavailable form. Given the demonstrated anti-inflammatory activity of curcumin and piperine, TPENVs can be used as topical therapeutics for treating inflammatory skin diseases, where intradermal delivery of such bio-actives is essential to increase their efficacy.