Yan Xiang1, Tiantian Zhang2, Chunpin Yin2, Jiewen Zhou2, Rong Huang3, Shasha Gao2, Lamei Zheng2, Xiaogang Wang2, Anne Manyande4, Xuebi Tian5, Jiachun Chen2, Jinbo Fang6. 1. Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 2. School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. 3. Department of Ophthalmology, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan 430061, Hubei, China. 4. School of Psychology, Social Work and Human Sciences, University of West London, London, UK. 5. Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. 6. School of Pharmacy, Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: fangjb@hust.edu.cn.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra glaucescens Diels (SGD) is used in a subclass of traditional Chinese medicine known as "Tujia drugs". It has been long used for the treatment of rheumatoid arthritis (RA), cough with dyspnea, spontaneous sweating, night sweating, chronic diarrhea, and neurasthenia. As a woody liana growing in mountain jungles at the altitudes of 750-1800m, it is mainly distributed in Sichuan and Hubei Provinces of China. AIM OF THE STUDY: To evaluate the antiarthritic activity of acetate (EA) and n-butanol (Bu) fractions of SGD extract on a collagen-induced arthritis mice model. MATERIALS AND METHODS: Acute toxicity of EA and Bu fractions of SGD extract was evaluated by gavage on normal mice. Pharmacological investigations were conducted on arthritis male Balb/c mice. The animal model was induced by immunization with type II bovine collagen (CII) on the 1st and the 14th day of the experimental schedule. EA fraction (104, 312, 936mg/kg), Bu fraction (156, 469, 1407mg/kg) of SGD extract was orally administered every two days since the 15th day for 3 weeks. Progression of edema in the paws was measured using a vernier caliper every 3 days since the 10th day. At the end of the experiment, the spleen index and histological changes of the hind knee joints were investigated. Additionally, to explore the possible antirheumatic mechanisms of the EA and Bu fractions, ELISA was carried out to analyze TNF-α, IL-10, IL-6 and IL-1β in the serum. RESULTS: The half lethal doses of both EA and Bu fractions were much higher than the dose administered in the pharmacological investigations. Oral administration of EA fraction and Bu fraction of SGD extract significantly and does-dependently inhibited type ІІ collagen induced arthritis (CIA) in mice, as indicated by the effects on paws swelling and spleen index. Histopathological examinations demonstrated that SGD effectively protected the bones and cartilages of knee joints from erosion, lesion and deformation. Besides, the serum concentrations of cytokines TNF-α, IL-1β and IL-6 were significantly lower than the ones from the vehicle control group. Respectively, while cytokine IL-10 was remarkably higher compare with the vehicle control group. CONCLUSIONS: SGD might be a safe and effective candidate for the treatment of RA, and deserves further investigation on the chemical components in both EA and Bu fractions of SGD extract.
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra glaucescens Diels (SGD) is used in a subclass of traditional Chinese medicine known as "Tujia drugs". It has been long used for the treatment of rheumatoid arthritis (RA), cough with dyspnea, spontaneous sweating, night sweating, chronic diarrhea, and neurasthenia. As a woody liana growing in mountain jungles at the altitudes of 750-1800m, it is mainly distributed in Sichuan and Hubei Provinces of China. AIM OF THE STUDY: To evaluate the antiarthritic activity of acetate (EA) and n-butanol (Bu) fractions of SGD extract on a collagen-induced arthritismice model. MATERIALS AND METHODS: Acute toxicity of EA and Bu fractions of SGD extract was evaluated by gavage on normal mice. Pharmacological investigations were conducted on arthritis male Balb/c mice. The animal model was induced by immunization with type II bovine collagen (CII) on the 1st and the 14th day of the experimental schedule. EA fraction (104, 312, 936mg/kg), Bu fraction (156, 469, 1407mg/kg) of SGD extract was orally administered every two days since the 15th day for 3 weeks. Progression of edema in the paws was measured using a vernier caliper every 3 days since the 10th day. At the end of the experiment, the spleen index and histological changes of the hind knee joints were investigated. Additionally, to explore the possible antirheumatic mechanisms of the EA and Bu fractions, ELISA was carried out to analyze TNF-α, IL-10, IL-6 and IL-1β in the serum. RESULTS: The half lethal doses of both EA and Bu fractions were much higher than the dose administered in the pharmacological investigations. Oral administration of EA fraction and Bu fraction of SGD extract significantly and does-dependently inhibited type ІІ collagen induced arthritis (CIA) in mice, as indicated by the effects on paws swelling and spleen index. Histopathological examinations demonstrated that SGD effectively protected the bones and cartilages of knee joints from erosion, lesion and deformation. Besides, the serum concentrations of cytokines TNF-α, IL-1β and IL-6 were significantly lower than the ones from the vehicle control group. Respectively, while cytokine IL-10 was remarkably higher compare with the vehicle control group. CONCLUSIONS:SGD might be a safe and effective candidate for the treatment of RA, and deserves further investigation on the chemical components in both EA and Bu fractions of SGD extract.