Exploring the therapeutic potential of Chinese herbs on comorbid type 2 diabetes mellitus and Parkinson's disease: A mechanistic study

Ethnopharmacological relevance: Type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD) are chronic conditions that affect the aging population, with increasing prevalence globally. The rising prevalence of comorbidity between these conditions, driven by demographic shifts, severely impacts the quality of life of patients, posing a significant burden on healthcare resources. Chinese herbal medicine has been used to treat T2DM and PD for millennia. Pharmacological studies have demonstrated that medicinal herbs effectively lower blood glucose levels and exert neuroprotective effects, suggesting their potential as adjunctive therapy for concurrent management of T2DM and PD. Aim of the study: To elucidate the shared mechanisms underlying T2DM and PD, particularly focusing on the potential mechanisms by which medicinal herbs (including herbal formulas, single herbs, and active compounds) may treat these diseases, to provide valuable insights for developing therapeutics targeting comorbid T2DM and PD. Materials and methods: Studies exploring the mechanisms underlying T2DM and PD, as well as the treatment of these conditions with medicinal herbs, were extracted from several electronic databases, including PubMed, Web of Science, Google Scholar, and China National Knowledge Infrastructure (CNKI). Results: Numerous studies have shown that inflammation, oxidative stress, insulin resistance, impaired autophagy, gut microbiota dysbiosis, and ferroptosis are shared mechanisms underlying T2DM and PD mediated through the NLRP3 inflammasome, NF-kappa B, MAPK, Keap1/Nrf2/ARE, PI3K/AKT, AMPK/SIRT1, and System XC- GSH-GPX4 signaling pathways. Thirty-four medicinal herbs, including 2 herbal formulas, 4 single herbs, and 28 active compounds, have been reported to potentially exert anti-T2DM and anti-PD effects by targeting these shared mechanisms. Conclusions: Traditional Chinese medicine effectively combats T2DM and PD through shared pathological mechanisms, highlighting their potential for application in treating these comorbid conditions.