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Jun-Xiang Wang,1,* Jia-Hui Zhang,1,* Mu Guo,1,* Wei-Rui Huang,1 Han-Lu Zheng,1 Yi-Qi Liao,1 Ying-Xue Yan,1 Zhao-Long Lin,1 Neng-Fu Qiu,1 Cui-Ting Dai,2 Xiang-Bin Yu,1 Yue Yu1 1School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Pathology, The People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fuzhou, 350004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue Yu; Xiang-Bin Yu, Email yyu@fjmu.edu.cn; yxb4666@fjmu.edu.cnIntroduction: Given the limitations and adverse effects of current rheumatoid arthritis (RA) treatments, there is an urgent need for safer and more effective therapeutic options. Levamisole (LVM) is a non-specific immunomodulator with potential for treating skin diseases, tumors, and autoimmune disorders. Recognizing LVM’s potential despite its controversial reputation, this study aimed to investigate its safety profile and therapeutic efficacy towards RA.Methods: To evaluate the potential toxicity of LVM, a 28-day oral administration was conducted in SD rats, assessing general toxicity and neurotoxicity using serum biochemical indicators, the Morris water maze test, transmission electron microscopy, and H&E staining. Subsequently, the therapeutic effects of LVM on RA were evaluated.Results: The results showed that 30 mg/kg LVM has promising therapeutic effects in the treatment of RA with negligible toxicity from 45 mg/kg to 180 mg/kg.Discussions: This study provides valuable preclinical data on the safety and efficacy of LVM, laying the groundwork for future clinical applications and potentially offering a safer and more effective treatment option for RA patients.Keywords: levamisole, general toxicity, neurotoxicity, rheumatoid arthritis

Wei-Rui Huang,1,* Quan-Hui Fang,1,* Xiang-Bin Yu,1 Wei-Hong Ge,2,3 Yue Yu1 1School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China; 2Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 3School of Pharmacy, Macau University of Science and Technology, Macau SAR, 999078, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yue Yu, School of Pharmacy & Fujian Center for New Drug Safety Evaluation, Fujian Medical University, Fuzhou, 350122, People’s Republic of China, Email yyu@fjmu.edu.cn Wei-Hong Ge, Department of Pharmacy, Nanjing Drum Tower Hospital, Nanjing, 210008, People’s Republic of China, Email 413811252@163.comAbstract: Aloe barbadensis Mill. has a long history of medicinal use in the annals of traditional Chinese medicine, wherein it has garnered considerable renown. Its multifaceted therapeutic properties, characterized by its anti-inflammatory and antibacterial attributes, alongside its established efficacy as a laxative agent, have been extensively documented. This review commences with an exploration of the nomenclature, fundamental characteristics, and principal constituents of Aloe barbadensis Mill. responsible for its laxative effects. Subsequently, we delve into an extensive examination of the molecular mechanisms underlying Aloe barbadensis Mill.’s laxative properties, types of constipation treatments, commercially available preparations, considerations pertaining to toxicity, and its clinical applications. This review aims to serve as a comprehensive reference point for healthcare professionals and researchers, fostering an enhanced understanding of the optimal utilization of Aloe barbadensis Mill. in the treatment of constipation. Keywords: Aloe barbadensis Mill, constipation, laxative