Binglang (Areca catechu L., ARECAE SEMEN), recognized as one of the "Four Major Southern Medicinal Herbs" in China, is predominantly cultivated in India, Malaysia, and China's Hainan, Yunnan, and Taiwan (Peng et al., 2015; Sun et al., 2024). Based on application, binglang is classified into edible and medicinal types (Wei et al., 2023). Edible varieties include dried binglang (processed through boiling fixation and drying) and fresh green binglang. Medicinal use of binglang dates back over 1800 years, with its earliest documentation as "Binmen" in Li Dangzhi Yaolu during the Three Kingdoms period (Wang et al., 2024). Classical medical texts such as Mingyi Bielu describe its diuretic, digestive, and anthelmintic properties, while Compendium of Materia Medica emphasizes its efficacy against constipation and intestinal parasites (Peng et al., 2015). The Pharmacopoeia of the People's Republic of China (2020) (Xu et al., 2021) officially recognizes its therapeutic effects against tapeworm disease, ascariasis, food stagnation, constipation, and edema.

Binglang contains abundant bioactive compounds including alkaloids, polyphenols, flavonoids, and polysaccharides, demonstrating multiple pharmacological activities such as anthelmintic, antioxidant, anti-inflammatory, and neuroprotective effects (Wang et al., 2024). The aqueous extract of binglang exhibits anthelmintic activity by reducing worm number, altering their protein profile, and causing damage to Ascaridia galli in the intestine (Mubarokah et al., 2019). The binglang polyphenols inhibited the mitogen-activated protein kinase (MAPK) pathway and activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) antioxidant pathways to reduce lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) generation in RAW 264.7 cells (Yi et al., 2022). Both binglang and their water-soluble components show significant anti-inflammatory effects in carrageenan-, prostaglandin E2 (PGE2), and arachidonic acid-induced edema models, along with dose-dependent analgesic activity in formalin and acetic acid writhing tests (Khan et al., 2011). Additionally, binglang modulates the hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor signaling pathway to alleviate depressive behaviors (Yao et al., 2023), while polysaccharides promote mucosal repair and immune enhancement (Chen et al., 2024).

Recent studies have increasingly focused on the toxicological effects of long-term or excessive binglang consumption (Huang et al., 2024; Jeng et al., 2001). Studies indicate strong associations between binglang chewing and oral carcinogenesis (D'Souza and Addepalli, 2018) as well as oral submucous fibrosis (Chang et al., 2013; Jayaswal et al., 2024). Animal studies demonstrate that arecoline induces hepatotoxicity through ultrastructural damage and elevated serum liver enzyme levels (Dasgupta et al., 2006), promotes chronic kidney disease via renal tubulointerstitial fibrosis (Lin et al., 2016). Binglang extract causes significant spermatotoxicity including reduced sperm count and morphological abnormalities (Wu et al., 2010).

While current toxicological research predominantly focuses on arecoline, systematic safety evaluations of binglang extracts or formulated products remain scarce. Therefore, this study developed a standardized binglang extract powder (binglang tiqusan, BLTQS) and conducted comprehensive toxicological assessments through acute and 180-day chronic toxicity tests in Sprague-Dawley (SD) rats, aiming to establish its safety profile for potential clinical applications.