WenJun Zhang School of Life Sciences, Sun Yat-sen University, Guangzhou, China Selforganizology ISSN 2410-0080 http://www.iaees.org/publications/journals/selforganizology/online-version.asp 2028 15 1-2 1 20 International Academy of Ecology and Environmental Sciences Hong Kong 16 March 2026 13 May 2026 1 June 2028 matrine Sophora flavescens antitumor anti-inflammatory hepatoprotective pharmacokinetics medicine Matrine is a tetracyclic quinolizidine alkaloid derived primarily from the dried roots of Sophora flavescens Aiton, a traditional Chinese medicinal herb with a history spanning centuries in East Asian medicine. In recent decades, matrine has emerged as a compound of significant scientific interest due to its broad spectrum of pharmacological activities and relatively favorable safety profile. This comprehensive review systematically examines the current state of knowledge regarding matrine, covering its discovery and historical background, physicochemical properties, extraction and purification methodologies, pharmacokinetic characteristics, and the molecular mechanisms underlying its major pharmacological effects. Particular emphasis is placed on the antitumor activities of matrine, which involve the regulation of core oncogenic signaling pathways including Wnt/beta-catenin, MAPK/ERK, and PI3K/AKT/mTOR, as well as the induction of multiple programmed cell death modalities such as apoptosis, autophagy, pyroptosis, and ferroptosis. The anti-inflammatory mechanisms of matrine are explored in detail, with focus on its ability to suppress the TLR4/NF-kB/MAPK signaling axis and regulate macrophage polarization. Hepatoprotective effects are discussed in the context of matrine's bidirectional actions on the liver, mediated through Ca2+ homeostasis regulation and multiple downstream pathways including Nrf2 and NF-kB signaling. The wound healing potential of matrine is examined, highlighting its anti-inflammatory, angiogenic, and tissue-regenerative properties. Clinical applications of matrine, particularly in chronic hepatitis B and liver diseases, are reviewed alongside systematic evaluations of its efficacy and safety. Structural modification strategies aimed at improving the pharmacological profile of matrine are summarized, as are advances in nano-delivery systems designed to enhance its bioavailability. The review concludes with an assessment of current challenges and future research directions, including the need for high-quality clinical trials, the development of targeted delivery systems, and the exploration of combination therapies. http://www.iaees.org/publications/journals/selforganizology/articles/2028-15(1-2)/Matrine.pdf