Promising Anti‐Cancer Effects and Mechanisms of Baicalin and Baicalein in the Treatment of Oral Cancer: A Comprehensive Review

AIM: This review provides a comprehensive summary of the mechanisms of action and pharmacological activities of baicalin and baicalein in the therapy of oral squamous cell carcinoma (OSCC). METHODS: A comprehensive literature search was conducted using multiple electronic databases to find relevant publications. RESULTS: Baicalin and its aglycone form, baicalein, are two bioflavonoids from Scutellaria baicalensis, which exhibit selective cytotoxicity in OSCC cells by inducing apoptosis through Bax/Bcl-2 ratio modulation and caspase-3 activation with negligible toxicity to normal cells. They also suppress metastatic activities by inducing the expression of E-cadherin and reducing the expression of vimentin, MMP2, MMP9, and EMT. Antiproliferative effects are mediated by cyclin D1 and p53 inhibition, resulting in cell cycle arrest. Baicalin induces ferroptosis through ferritin heavy chain 1 and glutathione peroxidase 4 inhibition, inducing chemosensitivity. Despite their therapeutic promise, challenges such as poor solubility and low bioavailability hinder clinical translation. Innovative drug delivery systems, including nanoencapsulation, offer promising answers to these challenges. Preclinical investigations confirm their good safety profile, with few adverse effects at therapeutic doses. CONCLUSIONS: These findings underscore the potential of baicalin and baicalein as anti-cancer agents for OSCC. However, further research and clinical trials are necessary to elucidate their mechanisms.