Multitarget Pharmacological Mechanisms and Safety Profiles of Six Ethnobotanically Prioritized Indonesian Medicinal Plants for Cardiometabolic Disorders: A Systematic Review.

This systematic review, conducted per PRISMA guidelines, examined the pharmacological activities and safety of six ethnobotanically prioritized medicinal plants for cardiometabolic disease: Gynura procumbens, Mimosa pudica, Tithonia diversifolia, Leucaena leucocephala, Smallanthus sonchifolius, and Syzygium cumini. Searches of PubMed and Scopus yielded 81 records, of which 66 studies met eligibility criteria, comprising in silico (n = 15), in vitro (n = 43), in vivo/clinical (n = 40), and safety/toxicity (n = 54) evidence. Mechanistic findings were categorized across glucose regulation, insulin signaling, lipid metabolism, vascular/endothelial function, inflammation, oxidative stress, and renal/cardiovascular complications. Gynura procumbens showed the broadest pharmacological activity, spanning glucose-lowering, lipid-modulating, vasorelaxant, and anti-inflammatory effects, alongside the most favorable short-term safety profile. Tithonia diversifolia, Leucaena leucocephala, and Smallanthus sonchifolius demonstrated robust multitarget antidiabetic activity in vitro but with accompanying hepatic, renal, or reproductive toxicity signals that may limit translation. At the same time, evidence for Mimosa pudica and Syzygium cumini remained largely preclinical, in silico, or polyherbal formulation-based. Safety data varied considerably across species and preparations, and long-term data on chronic toxicity, reproductive toxicity, and genotoxicity remain limited overall. These findings should be interpreted in light of the substantial heterogeneity in extraction methods and plant preparations, the general lack of standardized extracts, and the absence of a meta-analysis across the included studies. Overall, this review underscores the therapeutic potential of ethnobotanically selected medicinal plants for cardiometabolic disorders while highlighting the need for standardized, mechanistically validated, and clinically oriented research before therapeutic translation.