A Natural Compound Methylnissolin: Physicochemical Properties, Pharmacological Activities, Pharmacokinetics and Resource Development

Ziyang Lin,1– 4 Mingjie Liang,2 Xianlong Zhang,1,2 Zhuo Cen,1,3,4 Fengxin Kang,2 Baien Liang,2 Ying Lai,2 Minyi Li,2 Tingting Duan,2 Junzheng Yang,2 Bo Liu1,3– 5 1The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Guangdong Nephrotic Drug Engineering Technology Research Center, Guangdong Consun Pharmaceutical Group, Guangzhou, People’s Republic of China; 3State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 4Guangzhou Key Laboratory of Chirality Research on Active Components of Traditional Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, People’s Republic of China; 5Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of ChinaCorrespondence: Junzheng Yang; Bo Liu, Email [email protected]; [email protected]: Methylnissolin (also known as Astrapterocarpan) is an isoflavonoid compound featuring a pterocarpan core structure. To date, leguminous plants of the genus Astragalus remain the exclusive natural source of Methylnissolin and its glycoside derivative, Methylnissolin-3-O-glucoside. Upon oral administration, Methylnissolin and its glycosides enter systemic circulation and modulate signaling pathways such as RIPK2/ASK1, PI3K/AKT, IκB/NF-κB, MAPK, and Nrf2/HO-1. Their pharmacological activities span anti-inflammatory, antioxidant, glucose-lipid metabolism regulation, and antitumor effects, underscoring their broad potential for drug development. This review comprehensively evaluates the physicochemical properties, pharmacological activities, mechanisms of action, pharmacokinetic characteristics, and toxicological profile of Methylnissolin and its glycoside derivatives. Notably, we systematically elucidate the metabolic fate of methylnissolin, identifying hydroxylation, demethylation, dimerization, hydration, and dehydrogenation as predominant biotransformation pathways. Furthermore, the influence of factors such as plant variety, geographical origin, and processing methods on Methylnissolin and its glycoside content in Astragalus membranaceus is analyzed, providing crucial insights for drug development and resource utilization.Keywords: methylnissolin, methylnissolin-3-O-glucoside, astrapterocarpan, astragalus mongholicus, pharmacokinetics, pharmacological activity