Terpenes and terpenoids modulating TRPV channels in diabetes: role in fibrosis and inflammatory signaling.

Transient receptor potential vanilloid (TRPV) channels are non-selective cation channels that mediate thermosensation, nociception, osmotic balance, and metabolic regulation. In diabetes, altered TRPV channel expression and decreased calcium influx key pathways modulates, include NF-κB, AMPK, and TGF-β, promoting extracellular matrix accumulation and fibrotic remodelling. The limited availability of pathway specific interventions highlights TRPV channels as potential therapeutic target in diabetes. Recently, natural phytoconstituents have shown to exhibit TRPV channel modulating properties. Studies also highlights the potential of terpenes and terpenoids to inhibit NF-κB mediated inflammation, and activate AMPK-promoted metabolic homeostasis, mitigating diabetes-associated tissue damage. Preclinical studies have explored major terpenoids such as d-limonene, p-cymene and carvacrol in diabetic models. These compounds have been reported to improve glucose tolerance and alter the blood glucose levels via different molecular mechanisms. Clinically, there are limited evidences reporting terpenoids in the metabolic syndrome and TRPV modulation. Example, Astaxanthin, a tetraterpenoid has multiple human trials in type 2 diabetes, reducing diabetic biomarkers like SIRT1, HbA1c, and fasting glucose. This review summarizes current evidence on terpenes and terpenoids in diabetes with their reported and proposed interactions with TRPV1, TRPV4 with particular emphasis on their potential links to oxidative stress, NF-κB-mediated inflammation, TGF-β-associated fibrosis, and metabolic signaling. By distinguishing experimentally supported TRPV modulation with mechanistic associations and which require further validation, this review provides an integrated framework for understanding potential contribution of terpenoid-TRPV interactions to diabetes progression and its inflammatory and fibrotic complications, while highlighting key gaps for future experimental and translational investigation.