Chinese Herbal Medicines for Diabetic Cardio-Cerebrovascular Diseases: Key Bioactive Metabolites and Action...

Currently, the global incidence of diabetes is increasing, particularly in populous developing regions. In China, over 290 million people are affected by diabetic cardio-cerebrovascular diseases. These diseases account for more than 40% of deaths and impose a significant economic burden on both society and families. Diabetes can result in vascular complications through multiple mechanisms, including cardiovascular and cerebrovascular diseases. Current management guidelines recommend conducting risk assessments before prescribing medications like antihypertensives, hypoglycemics, and lipid-lowering drugs, alongside lifestyle interventions, to help prevent cardio-cerebrovascular diseases. However, pharmacological approaches have several limitations, including adverse drug reactions and variability in patient responses. Chinese herbal medicine (CHM) exerts its therapeutic effects via bioactive metabolites that modulate multiple molecular targets, including enzymes, receptors, and transcriptional regulators, through complex interactions with cellular signaling networks. While modern pharmacological research validates its polypharmacological mechanisms, concerns persist regarding potential botanical drug interactions, toxicological profiles, and pharmacokinetic variability of certain botanicals. Only through a balanced scientific approach can CHM's unique therapeutic value be fully realized. This review evaluates the efficacy of CHM in mitigating metabolic disorders, focusing on its diverse pharmacological mechanisms, including antioxidant defenses, inflammation suppression, and programmed cell death regulation. It elucidates the role of pivotal signaling cascades, including the glucagon (GLC)/5'-adenosine monophosphate-activated protein kinase (AMPK)/nuclear transcription factor-κB (NF-κB) axis, the GLC/peroxisome proliferator-activated receptor α (PPARα)/PGC-1α pathway, as well as the PI3K/Akt and AMPK/mammalian target of rapamycin (mTOR) signaling pathway, alongside oxidative stress and inflammatory responses. However, future research should prioritize well-structured clinical trials and mechanistic studies to substantiate CHM's therapeutic potential.