WenJun Zhang School of Life Sciences, Sun Yat-sen University, Guangzhou, China Network Biology ISSN 2220-8879 http://www.iaees.org/publications/journals/nb/online-version.asp 2027 17 1 1 19 International Academy of Ecology and Environmental Sciences Hong Kong 24 February 2026 27 March 2026 1 March 2027 baicalein Scutellaria baicalensis Oroxylum indicum flavonoids pharmacokinetics bioavailability anti-cancer neuroprotection clinical trials Baicalein (5,6,7-trihydroxyflavone), a major bioactive flavonoid aglycone derived primarily from the roots of Scutellaria baicalensis Georgi and Oroxylum indicum (L.) Kurz, has garnered significant scientific interest over the past decades due to its diverse and potent pharmacological activities. This comprehensive review systematically examines the multifaceted aspects of baicalein, encompassing its discovery, natural sources, chemical properties, extraction and purification methods, and challenging pharmacokinetic profile. The review delves deeply into the extensive spectrum of its pharmacological effects and underlying molecular mechanisms, including its potent anti-cancer, anti-inflammatory, antioxidant, anti-aging, neuroprotective, cardioprotective, hepatoprotective, renoprotective, anti-diabetic, and anti-microbial activities. Furthermore, it provides an up-to-date synthesis of available clinical trial data, safety evaluations, and quality control standards. Despite its remarkable therapeutic potential, the clinical translation of baicalein is significantly hampered by intrinsic challenges, primarily its poor water solubility, low oral bioavailability, and extensive first-pass metabolism. This review critically discusses these obstacles, explores current nanoformulation strategies designed to overcome them, and outlines future research directions necessary to harness the full therapeutic power of this promising natural compound. http://www.iaees.org/publications/journals/nb/articles/2027-17(1)/Baicalein.pdf