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BACKGROUND:Tripterygium wilfordi and its certain monomers have exact clinical effects on rheumatoid arthritis. However, there are few studies about a systematic discussion on pharmacodynamic material basis and molecular mechanism of Tripterygium wilfordi. OBJECTIVE:To explore the pharmacodynamic material basis and molecular mechanism ofTripterygium wilfordi in treating rheumatoid arthritis. METHODS: Based on the platform of Discovery Studio 4.0, the molecular set of Tripterygium wilfordiwas built and compared with the rheumatoid arthritis drug set from Therapeutic Target Database in chemical space. After that, network pharmacology was used to explore the interactions ofTripterygium wilfordi and therapeutic targets related to rheumatoid arthritis. RESULTS AND CONCLUSION:The molecular sets ofTripterygium wilfordi and drugs for treating rheumatoid arthritis had similar chemical space. The pharmacodynamic material basis ofTripterygium wilfordi had 46 compounds, such as celacinnine, epigalocatechin, euonine, triptolide. They could mediate inflammation, regulate immune response, inhibit cartilage and bone destruction, improve blood stasis-type rheumatoid arthritis by acting on 10 targets, such as tumor necrosis factor-α, JAK-1, matrix metaloproteinase-1, matrix metaloproteinase-3, matrix metaloproteinase-9. Computer simulation could intuitively trace out the multi-ingredient, multi-target and multi-pathway effects of Tripterygium wilfordi.
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BACKGROUND:Tougu Xiaotong Capsule (TGXTC) is a clinical prescription for the treatment of osteoarthritis;however, its mechanism has not been ful y elucidated. Urokinase-type plasminogen activator (uPA) system participating in the degradation of the extracel ular matrix of articular cartilage and hyperplasia of joint synovium plays an important role in the pathological process of osteoarthritis. OBJECTIVE:To investigate the effects of TGXTC medicated serum on the expression of uPA, uPA receptor (uPAR), plasminogen activator inhibitors (PAIs), matrix metal oproteinase-3 (MMP-3), interleukin-1 beta (IL-1β) and tumor necrosis factor-α(TNF-α) in osteoarthritis synovial cel s of rats and to discuss the mechanism by TGXTC medicated serum prevents and cures osteoarthritis. METHODS:Rat models with knee osteoarthritis were established by injecting 4%papain into the knee joint cavity. Primary synoviocytes and osteoarthritis synoviocytes were cultured with col agenase digestion method. The cultured synoviocytes were divided into normal group, model group and TGXTC group. The western blot method was adopted to detect uPA, uPAR, PAI, MMP-3, IL-1βand TNF-αprotein expression of synoviocytes after acting by TGXTC medicated serum for 72 hours. RESULTS AND CONCLUSION:The expression of uPA, uPAR, MMP-3, IL-1βand TNF-αwere decreased, while PAI was increased in the TGXTC group, and there were significant differences when compared with model group. In a word, TGXTC can significantly inhibit the expression of uPA, uPAR, MMP-3, IL-1β, TNF-α, and improve PAI expression in synoviocytes, which may partly explain the mechanism of the treatment of Tougu Xiaotong Capsule on osteoarthritis.
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BACKGROUND:Tougu Xiaotong capsule is the clinical prescription for the treatment of osteoarthritis, however, its mechanism has not been fuly elucidated. Urokinase type plasminogen activator system which participated in the degradation of the extracelular matrix of articular cartilage and hyperplasia of joint synovium plays an important role in the pathological process of osteoarthritis. OBJECTIVE: To determine the effect ofTougu Xiaotong capsule on urokinase-type plasminogen activator system in knee cartilage tissues of knee osteoarthritis rats. METHODS: Of 144 Sprague-Dawley rats, 120 rats were randomly made into models of knee osteoarthritisvia intra-articular injection of papain, and randomly assigned to model group,Zhuanggu Guanjie Wan group [1.2 g/(kg?d)], low-doseTougu Xiaotong capsule group [0.092 g/(kg?d)], moderate-doseTougu Xiaotong capsule group [0.184 g/(kg?d)] and high-doseTougu Xiaotong capsule group [0.368 g/(kg?d)]. Each group contained 24 rats. Every 2 weeks was considered as a course, with a 2-day interval, totaly 4 courses. The remaining 24 normal rats were included in the blank group. After every two courses, a batch of experimental animals was sacrificed. The pathological changes were observed folowing staining with hematoxylin and eosin. The positive cels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by immunohistochemistry. The protein levels of urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor and plasminogen activator inhibitor were measured by western blot assay. RESULTS AND CONCLUSION:Mankin’s score was significantly lower in theTougu Xiaotong capsule group and Zhuanggu Guanjie Wan group compared with the model group (P < 0.01), in a time-dependent manner. Immunohistochemical staining indicated that the positive cels of urokinase-type plasminogen activator and urokinase-type plasminogen activator receptor were significantly decreased, but plasminogen activator inhibitor was significantly increased in theTougu Xiaotong capsule group andZhuanggu Guanjie Wangroup in a time-dependent manner. Western blot assay results had an identical trend to immunohistochemistry. These indicated thatTougu Xiaotong capsule showed preventive and therapeutic effects on osteoarthritis by regulating urokinase-type plasminogen activator system.
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BACKGROUND:Tougu Xiaotong Capsule has pretty good clinical therapeutic effect on osteoarthritis of early and middle periods. However, the mechanism of Tougu Xiaotong Capsule is not ful y clarified. The RhoA GTPases can regulate chondrocyte apoptosis and hypertrophy. OBJECTIVE:To observe the Tougu Xiaotong Capsule on the expression of Rac1and Cdc42 in tumor necrosis factor-α-induced in vitro cultured rat articular chondrocytes, and to explore its mechanism of action for combating osteoarthritis. METHODS:Knee cartilage of the 4-week-old Sprague-Dawley rats was used to stably establish in vitro culture system of chondrocytes. Passage 3 chondrocytes were identified by toluidine blue staining. Chondrocyte apoptosis was successful y induced by 20μg/L tumor necrosis factor-αand then Tougu Xiaotong Capsule at different dosage (500, 100, 20 mg/L) was given after 24-hour incubation. MTT assay was used to detect cellsurvival, flow cytrometry to measure mitochondrial membrane potential, and western blot assay to determine the protein expression of Rac1, Cdc42, Bax and Bcl-2. RESULTS AND CONCLUSION:Tougu Xiaotong Capsule could reduce tumor necrosis factor-α-induced apoptosis of chondrocytes to improve the survival rate of the cells, and at the same time, could down-regulate the protein expression of Rac1, Cdc42 and Bax and increase the protein expression of Bcl-2 significantly (P<0.05). Tougu Xiaotong Capsule possibly plays a therapeutic efficacy on osteoarthritis by reducing promote apoptosis Rac1, Cdc42 and Bax expression and increasing apoptosis inhibiting gene Bcl-2 expression, thereby to inhibit apoptosis of chondrocytes.
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AIM:To investigate the anti-tumor effects of Chinese medicine Fuzhengyiliufufang(FZYLFF) and its mechanism.METHODS:Molecular docking was apllied to simulate the interactions between Chinese medicine small molecules and TNF-?,IL-2 receptors respectively,with the aid of ligand-fit module in the software package Cerius2 4.10 of Accelrys company,to predict the effects of FZYLFF on anti-tumor.RESULTS:According to the dockscore of original ligand and the receptor as threshold value,thirty-seven molecules were predicted to have good interactions with TNF-? and ten molecules with IL-2.CONCLUSION:FZYLFF is a promising Chinese medicine for tumor therapy.Its mechanism is possibly attributed to indirect inhibition by interfering inflammatory cell factors and enhancing immunoregulation.
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AIM: To investigate the effects of Co-SZ eye drop on galactose cataract in rats. METHODS: Based on folk remedy, SZ eye drop was made from leech, as a modified SZ eye drop, Co-SZ eye drop was enriched in Zinc and Vitamin C. In the present study, animal model of galactose cataract in SD rats was used. All animals were randomly divided into 3 groups : control group(using 0.9 % NaCl instead of SZ and Co SZ), SZ group and Co-SZ group. Lens opacities were examined dynamically in each groups via FS-3V slit-lamp microscope. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH) and soluble protein (SP) in the lenses were measured in 15 days. RESULTS: Both the Co-SZ and SZ eye drops could significantly delay and alleviate galactose cataract in rats, with better effect of Co-SZ than SZ eye drop. The antioxidant index indicated that SOD, GSH-Px, GSH in Co-SZ and SZ group were significantly higher than that in control group. Furthermore, SOD, GSH-Px in Co-SZ group were higher than that in SZ group significantly. CONCLUSION: Co-SZ eye drops could significantly delay and alleviate galactose cataract in rats, the effect is much better than SZ eye drops. The different effect between SZ and Co-SZ eye drops could be raised from the different content of Zinc, which is involved in anti-oxidation.
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AIM: To investigate the protective effect of five natural anti-oxidants (schisandrin B, Sch B; silibinin, SIB; propyl gallate, PG; sodium ferulate, SF; total flavonoids of hippophase, TFH) on experimental oxidative injuries of lens. METHODS: All fresh transparent lenses of rabbit eyes except control group were bathed in Fenton reaction system in order to produce a model of oxidative damages of lens, meanwhile Sch B, SIB, PG, SF, TFH and pirenoxine sodium (PS) were added in the reaction system in different groups respectively. Lenses were incubated for 24 hours. Then total protein (TP), soluble protein (SP), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), vitamin C (Vit C), total activities of anti-oxidation (TAO) and malondiaoldehyde (MDA) in homogenized lenses were measured to observe the effects of five anti-oxidants on above index. RESULTS: Five anti-oxidants increased the anti-oxidative index and decreased MDA in lens of oxidative damages in different levels, the effects are better than that of PS, especially in group SF and Sch B. CONCLUSION: The five natural anti-oxidants protected lens against experimental oxidative injuries very well. There are wide prospects to pursue effective anti-cataract drugs from natural anti-oxidants.