Bioactive Flavonoids from Scutellaria baicalensis in Non-Small Cell Lung Cancer: Mechanistic Insights and Emerging Translational Perspectives

Abstract: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related morbidity and mortality globally, and developing effective treatment strategies is a major challenge. In recent years, Scutellaria baicalensis Georgi has attracted increasing attention due to its multi-target pharmacological properties and relatively favorable safety profile. In this review, we systematically summarize the current literature from PubMed, Web of Science, and Embase, focusing on the pharmacokinetic characteristics, pharmacological mechanisms, and potential translational relevance of the bioactive constituents of S. baicalensis in NSCLC. The toxicity profiles of key flavonoids were also predicted using ADMETlab 2.0. Accumulating evidence, primarily derived from in vitro and in vivo preclinical studies, suggests that the flavonoid constituents of S. baicalensis exert anti-NSCLC effects across multiple stages of tumor development. These effects include early modulation of inflammation and oxidative stress, inhibition of tumor proliferation, epigenetic regulation, and suppression of metastasis and therapeutic resistance. The underlying mechanisms involve processes such as cell-cycle arrest, apoptosis, autophagy, ferroptosis, and remodeling of the tumor immune microenvironment. Overall, these compounds generally exhibit low systemic toxicity, although long-term or high-dose exposure may be associated with mild fluctuations in liver enzymes and lipid metabolism. Furthermore, nanocarrier-based delivery systems have been shown to improve bioavailability and tumor-targeting efficiency. Despite these promising findings, current evidence remains largely preclinical, and clinical validation is still limited. Therefore, further well-designed clinical studies and advanced drug-delivery strategies are required to facilitate the translation of S. baicalensis -derived compounds into clinical applications for NSCLC. Flowchart of Scutellaria baicalensis in pharmacokinetics, safety and anti-NSCLC mechanisms.It starts with Scutellaria baicalensis, showing its chemical structures. An arrow leads to Pharmacokinetics, depicting organs like the liver and kidneys and pills. From Pharmacokinetics, an arrow points to Anti-NSCLC Mechanisms, showing interactions with elements like Baicalein and pathways such as PI3K/AKT and mTOR. Another arrow connects Anti-NSCLC Mechanisms to Safety and Advanced Drug Delivery Systems, featuring lungs, a syringe and a hazard symbol. An arrow from Safety and Advanced Drug Delivery Systems loops back to Scutellaria baicalensis, completing the cycle. Keywords: baicalin, baicalein, cancer, pharmacological mechanisms, drug delivery