Phytochemistry, biological activities, and toxicological insights into the genus Cyclea (Menispermaceae): A comprehensive review
Abstract
The genus Cyclea (Menispermaceae) comprises about 31 species distributed across southern and south-eastern Asia, several of which are long established in traditional and folk medicine, yet no genus-level synthesis of their chemistry, pharmacology, and safety exists. This review highlights the phytochemistry, biological activities, and toxicology of Cyclea spp., separates within-genus evidence from mechanistic data borrowed from related genera, and identifies research priorities. PubMed, Scopus, and Web of Science were accessed for recent literature on phytochemistry, pharmacology, and toxicity. The genus is chemically unified by bisbenzylisoquinoline alkaloids of tetrandrine, curine, and cycleanine types; tetrandrine is the marker alkaloid of C. peltata; C. barbata additionally yields azafluoranthene alkaloids, a phytoecdysone, and a gel-forming low-methoxyl pectin, and C. gracillima is rich in phenolic acids and flavonoids. Extracts and isolated constituents show anticancer, anti-inflammatory, antioxidant, antiplasmodial, antidiabetic, diuretic, hepatoprotective, and antivenom activities consistent with traditional use. Toxicological data are sparse and partly conflicting: an alkaloid extract of C. peltata gave an acute oral LD50 >2500 mg/kg in mice, whereas values for C. barbata leaf extracts span 617 to >30,000 mg/kg. Tetrandrine is a cytochrome P450-activated hepatic and pulmonary toxicant and a weak genotoxicant, and substitution by aristolochic acid-containing Aristolochia species remains unaddressed. With no clinical or pharmacokinetic study reported, safety margins cannot be calculated. Cyclea is a promising but underexplored source of bisbenzylisoquinoline alkaloids. Authenticated standardized material, bioassay-guided fractionation, rigorous in vitro and in vivo replication, and guideline-compliant toxicology and pharmacokinetics are prerequisites for clinical translation.