Sophoridine: A review of its pharmacology, pharmacokinetics and toxicity

Sophoridine is a bioactive alkaloid found in many Chinese herbs, such as Sophora alopecuroides l, Euchresta japonica Benth and Sophora moocrorftinan. Sophoridine hydrochloride injection has been approved as an anticancer drug in China.This review aims to provide a comprehensive summary on the pharmacological, molecular mechanism, pharmacokinetic and toxicity studies of sophoridine.PubMed, Web of Science and China National Knowledge Infrastructure were used for a systematic search with the keywords including "sophoridine", "pharmacology", "pharmacokinetics", and "toxicity".Emerging evidence suggests that sophoridine exhibits a broad spectrum of pharmacological activities including antitumor, anti-inflammatory, antiviral, myocardialprotective and hepatoprotective activities. These pharmacological properties lay foundation for using the plants containing sophoridine for the treatment of numerous diseases, such as cancer, colitis, injury of lungs, ischemia myocardial,etc. The mechanisms involved in the pharmacological actions of sophoridine are regulation of NF-κB, TLR4/IRF3, JNK/ERK, Akt/mTOR signaling pathways, down-regulating the expression of HMG3B, bcl-2, MMP-2, MMP-9, TNF-α, IL-1β IL-6 and other cytokines or kinases. However, an increasing number of published reports indicated that sophoridine has serious adverse effects. The primary toxic effects are neurotoxicity and acute toxicity, which are of wide concern in worldwide. Moreover, sophoridine is reported to distribute in kidney, liver, uterus, lung and other organs. It undergoes glucuronidation and excreted in urine.Future studies should elucidate the detailed in vivo metabolism studies on sophoridine. The effect of substituent functional groups on sophoridine on metabolism, the enzymes involved in the metabolism and the chemistry of metabolites also should be studied. Either structural modification of sophoridine or its combined with other drugs may play a pivotal role to enhance its pharmacological activities and reduce its toxicity.