Traditional uses, phytochemistry, pharmacology, pharmacokinetics and toxicology of the fruit of Tetradium ruticarpum: A review

The fruit of Tetradium ruticarpum (FTR) known as Tetradii fructus or Evodiae fructus (Wu-Zhu-Yu in Chinese) is a versatile herbal medicine which has been prescribed in Chinese herbal formulas and recognized in Japanese Kampo. FTR has been clinically used to treat various diseases such as headache, vomit, diarrhea, abdominal pain, dysmenorrhea and pelvic inflammation for thousands of years. The present paper aimed to provide comprehensive information on the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, drug interaction and toxicology of FTR in order to build up a foundation on the mechanism of ethnopharmacological uses as well as to explore the trends and perspectives for further studies. This review collected the literatures published prior to July 2020 on the phytochemistry, pharmacology, pharmacokinetics and toxicity of FTR. All relevant information on FTR was gathered from worldwide accepted scientific search engines and databases, including Web of Science, PubMed, Elsevier, ACS, ResearchGate, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). Information was also obtained from local books, PhD. and MSc. Dissertations as well as from Pharmacopeias. FTR has been used as an herbal medicine for centuries in East Asia. A total of 165 chemical compounds have been isolated so far and the main chemical compounds of FTR include alkaloids, terpenoids, flavonoids, phenolic acids, steroids, and phenylpropanoids. Crude extracts, processed products (medicinal slices) and pure components of FTR exhibit a wide range of pharmacological activities such as antitumor, anti-inflammatory, antibacterial, anti-obesity, antioxidant, insecticide, regulating central nervous system (CNS) homeostasis, cardiovascular protection. Furthermore, bioactive components isolated from FTR can induce drug interaction and hepatic injury. Therapeutic potential of FTR has been demonstrated with the pharmacological effects on cancer, inflammation, cardiovascular diseases, CNS, bacterial infection and obesity. Pharmacological and pharmacokinetic studies of FTR mostly focus on its main active alkaloids. Further in-depth studies on combined medication and processing approaches mechanisms, pharmacological and toxic effects not limited to the alkaloids, and toxic components of FTR should be designed.