Alisols A-C and their acetate derivatives: a review of natural occurrence, pharmacology, semisynthesis, pharmacokinetics, and metabolism.

Alisols, a distinctive group of protostane-type triterpenoids predominantly found in the rhizomes of Alisma orientale (Sam.) Juzep., have attracted due to their broad pharmacological potential. This review first provides an integrated overview of alisol A (1), alisol A 23-acetate (2), alisol A 24-acetate (3), alisol B (4), alisol B 23-acetate (5), alisol C (6), and alisol C 23-acetate (7), focusing on their natural occurence, pharmacological activities, semisynthesis, pharmacokinetic and metabolic profiles. References were collected from PubMed, Web of Science, Scopus, Google Scholar, and SciFinder using keywords alisols, protostane triterpenoids, Alisma orientale, semisynthesis, pharmacology, mechanisms, and pharmacokinetics. Original research articles from the 1970s reporting chemical characterization and pharmacology were included, while studies lacking relevance were excluded. Alisols 1-7 exhibited wide-ranging pharmacological activities, including anticancer, antidiabetes, antiallergic, antibacterial, anti-viral, anti-hyperlipidemic, anti-obesity, and vasorelaxant activities. They also protect the neurons, liver, kidneys, gastrointestinal tract, bones, and skin. These activities are associated with apoptosis, autophagy, and cytokine and oxidative inhibitions, and the modulation of various signaling pathways, such as the AMPK, PI3K, Akt, mTOR, and FXR. Semisynthesis, particularly esterification, dehydration, and epoxidation, enhanced pharmacological values and revealed structure-activity relationships. Pharmacokinetic data indicated rapid biotransformation, pH-dependent interconversion, and gut microbiota-associated metabolism.