作者机构：
[彭清华] Institute of Tradition Chinese Medicine Diagnostics, Changsha, 410208, China;College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China;[喻嵘; 宋厚盼; 蔡雄; Zeng M.-Y.; 陈小娟; 谢明霞; 陈新怡] Institute of Tradition Chinese Medicine Diagnostics, Changsha, 410208, China, College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, China
摘要：
Depression is a common psychiatric disorder that affects almost 10% of children and adolescents worldwide. Numerous synthetic chemical antidepressants used to treat depression have adverse side effects. Therefore, new therapeutic approaches for depression treatment are urgently needed. Leonurus cardiaca has recently been shown to be effective for the treatment of nervous system diseases such as depression, but its mechanism is not clear. In this study, we aimed to reveal the mechanism underlying leonurine’s antidepressant activity. Leonurine was used to treat corticosterone-induced PC12 cells to examine its effect on neurite outgrowth and neurotrophic factors after treatment with the inhibitor of glucocorticoid receptor (GR) and serum-inducible and glucocorticoid-inducible kinase 1 (SGK1). Methyl thiazolyl tetrazolium assays were used to evaluate the viability of cells. High content analysis was used to detect cell area, total neurite length, maximum neurite length, and expression of GR, SGK1, brain-derived neurotrophic factor (BDNF), neurotrophic factor-3 (NT-3), and B-cell lymphoma-2 (BCL-2). The results showed that leonurine increased cell viability in a concentration-dependent manner, with the maximal prosurvival effect at 60 μM. Leonurine increased cell area, total neurite length, and maximum neurite length of corticosterone-induced PC12 cells, increased the expression of GR, BDNF, NT-3, and BCL-2, and decreased the expression of SGK1. After treatment with GR inhibitor RU486, the expressions of GR, BDNF, NT-3, and BCL-2 were significantly decreased and SGK1 was increased. In contrast, treatment with GSK650394 had the opposite effect of RU486. Our data indicate that leonurine promotes neurite outgrowth and neurotrophic activity in cultured PC12 cells, and its potential mechanism may involve the GR/SGK1 signaling pathway.
作者机构：
[Yu Huanghe; Zeng Rong; Tasneem, Shumaila; Qiu Yi-xing; Li Bin; Wang Wei] Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Sch Pharm, Changsha 410208, Hunan, Peoples R China;[Yu Huanghe; Zeng Rong; Tasneem, Shumaila; Qiu Yi-xing; Li Bin; Wang Wei] Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, Changsha 410208, Hunan, Peoples R China;[Yu Huanghe; Lin Ye; Li Xin; Zhen, Yang; Wang Yu-hong; Cai Xiong] Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Changsha 410208, Hunan, Peoples R China
通讯机构：
[Wang Wei; Cai Xiong] H;Hunan Univ Chinese Med, TCM & Ethnomed Innovat & Dev Int Lab, Sch Pharm, Changsha 410208, Hunan, Peoples R China. Hunan Univ Chinese Med, Innovat Mat Med Res Inst, Sch Pharm, Changsha 410208, Hunan, Peoples R China. Hunan Univ Chinese Med, Inst Innovat & Appl Res Chinese Med, Changsha 410208, Hunan, Peoples R China.
摘要：
BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune diseased state, characterized by hyperplasia of the synovial membrane, degradation of cartilage, and bone erosion of diarthrodial joints. Kadsura heteroclita (Roxb) Craib (Schizandraceae), a traditional Tujia ethnomedicine called Xue Tong in China, has been long used for the prevention and treatment of rheumatic and arthritic diseases, especially in the southern China. This study aimed to evaluate anti-arthritic effects of the ethanol extract of Kadsura heteroclita stems (KHS) on complete Freund's adjuvant (CFA)-induced arthritis (AIA) in rats, as well as to explore the underlying mechanisms of anti-arthritis. METHODS: AIA was established in male Sprague-Dawley (SD) rats as described previously, and animals were daily treated by gavage with KHS ethanol extract (200, 400, or 800mg/kg) or vehicle (0.3% CMCNa) throughout the 30-day experiment. The incidence and severity of arthritis were evaluated using clinical parameters. At the end of experiments, tissue swelling and bone destruction of the hind paws were assessed by computed tomography (CT) and histopathological analyses. Serum levels of tumor necrosis factor (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and IL-17A and IL-17F were measured by ELISA, and protein expression of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitor of MMP-1 (TIMP-1) were detected by Western blot. RESULTS: Treatment with KHS dose-dependently inhibited paw swelling and reduced arthritis scores of AIA rats. CT images displayed that KHS remarkably protected AIA rats from tissue swelling and bone erosion of joints. Histopathological analyses revealed that KHS markedly reduced inflammatory cell infiltration, synovial proliferation, and the formation of pannus in the ankle joints of AIA rats. KHS was found to significantly suppress the production of TNF-alpha, IL-1 beta, IL-6, IL-17A and IL-17F, inhibited the protein expression of MMP-1 and MMP-3, and elevated the protein expressions of TIMP-1. CONCLUSION: KHS demonstrates potential anti-arthritic effects via inhibiting pivotal mediators of inflammation and cartilage destruction. This study strongly supports identification and isolation of active fractions of KHS which would be a potential candidate for further investigation as a new anti-arthritic botanical drug.
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Buyang huanwu decoction (BYHWD) is a classic recipe in traditional Chinese medicine (TCM) to supplement Qi and activate blood. It has been used to recover the neural function after the injury of central nervous system for hundreds of years in China. AIM OF THE STUDY: This study investigated whether Buyang huanwu decoction (BYHWD) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation had synergistic effect on neuroprotection of red nucleus neurons after spinal cord injury (SCI). MATERIALS AND METHODS: Rubrospinal tract (RST) transection model was established and BMSCs were collected. The forelimb locomotor function was recorded using inclined plate test and spontaneous vertical exploration. cAMP level in red nucleus was detected with Enzyme-linked immunosorbent assay (ELISA). Morphology and number of red nucleus neurons was observed using Nissl's staining. Expression of cAMP-response element binding protein (CREB), ras homolog gene family member A (RhoA) and nerve growth factor (NGF) in red nucleus was detected using immunohistochemistry, qRT-PCR and Western-blotting. RESULTS: The combination of BYHWD and BMSCs transplantation could improve the forelimb locomotor function significantly and give the red nucleus somas a better protection. Meanwhile, cAMP level, CREB and NGF increased, while RhoA decreased remarkably in the BYHWD+BMSCs group. CONCLUSIONS: BYHWD combined with BMSCs transplantation had synergistic effect on neuroprotection of red nucleus neurons after SCI; the mechanism may be related to up-regulating cAMP level, activating the cAMP/CREB/RhoA signaling pathway, and promoting expression of NGF.
摘要：
Neurons undergo degeneration, apoptosis and death due to ischaemic stroke. The present study investigated the effect of Sijunzi decoction (SJZD), a type of traditional Chinese medicine known as invigorating spleen therapy, on anoikis (a type of apoptosis) in rat brains following cerebral ischaemia-reperfusion. Rats were randomly divided into sham, model, nimodipine and SJZD low/medium/high dose groups. A middle cerebral artery occlusion model was established. Neurobehavioural scores were evaluated after administration for 14 days using a five-grade scale. Blood-brain barrier permeability and apoptotic rate were detected using Evans blue (EB) extravasation and TUNEL staining, respectively. Tissue inhibitor of metalloproteinase 1 (TIMP-1), matrix metalloproteinase 9 (MMP-9) and collagen IV (COL IV) were determined using immunohistochemistry. Neurobehavioural scores decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.05). Compared with the sham group, EB extravasation was higher in the model group (P<0.01). The amount of EB extravasation decreased in the SJZD high dose and nimodipine groups compared to the model group (P<0.01), and extravasation in the SJZD high dose group was lower than the SJZD low and medium dose groups (P<0.01). TIMP-1 and MMP-9 expression and apoptotic rate increased, but COL IV decreased significantly in the hippocampus of the model group compared to the sham group (P<0.01). TIMP-1 and COL IV expression increased significantly and MMP-9 and apoptotic rate decreased remarkably in all SJZD and nimodipine groups compared to the model group (P<0.01). TIMP-1 and COL IV expression decreased, but MMP-9 expression and apoptotic rate increased in the SJZD low and medium dose groups compared to the SJZD high dose group (P<0.01). SJZD rescued neurons and improved neurobehavioural function in rats following cerebral ischaemia-reperfusion, especially when used at a high dose. The mechanism may be related to protection of the extracellular matrix followed by anti-apoptotic effects.
作者机构：
[黄惠勇; 蔡雄] Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;[余清平; 潘波; 陈安; 殷坚] Key Discipline of Anatomy and Histoembryology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;School of Dentistry, University of California Los Angeles, California, CA 9005, United States;[李丰] Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China, School of Dentistry, University of California Los Angeles, California, CA 9005, United States;[李亮] Provincial Key Laboratory of TCM Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China, Key Discipline of Anatomy and Histoembryology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
通讯机构：
[Huang, H.-Y.] P;Provincial Key Laboratory of TCM Diagnostics, China
摘要：
Objective Qing Fu Juan Bi Tang (QFJBT) is an anti-arthritic Chinese medicine formula consisting of five herbs: Aconiti Lateralis Radix Praeparata (Fu Zi, 附子), Sinomenii Caulis (Qing Feng Teng, 青风藤), Astragali Radix (Huang Qi, 黄芪), Paeoniae Radix Alba (Bai Shao, 白芍) and Moutan Cortex (Mu Dan Pi, 牡丹皮), which have well-established histories of use for treatment of rheumatic and arthritic diseases. We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis (RA). Methods The combinative approaches of chemical assessment, toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT. Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents, potent anti-inflammatory and antinociceptive activities, and favorable safety profile. Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography (HPLC) demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent. General toxicological studies showed a favorable safety profile of QFJBT. The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose. In the chronic oral toxicity study, the results of laboratory investigation showed that QFJBT at doses of 3.89, 6.80 and 9.72 g/kg body weight (equivalent to 40, 70 and 100-fold clinical doses, respectively) caused no changes in all hematological parameters and blood biochemical parameters of rats. No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT. Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.
作者机构：
[蔡雄] Institute of Innovation and Applied Research in Chinese Medicine, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[陈聪; 李鑫; 彭清华; 宋厚盼] School of Basic Chinese Medical Sciences, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[王炜] School of Pharmaceutical Sciences, Hunan University of Chinese Medicine, Hunan, Changsha, 410208, China;[唐琳] School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangdong, Guangzhou, 510224, China;[刘良] State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, Macau
通讯机构：
[CAI, X.] I;Institute of Innovation and Applied Research in Chinese Medicine, Hunan, China
关键词：
青附蠲痹汤;类风湿关节炎;制备工艺;质量控制;安全性;抗炎镇痛
摘要：
Objective Qing Fu Juan Bi Tang (QFJBT) is an anti-arthritic Chinese medicine formula consisting of five herbs: Aconiti Lateralis Radix Praeparata (Fu Zi, 附子), Sinomenii Caulis (Qing Feng Teng, 青风藤), Astragali Radix (Huang Qi, 黄芪), Paeoniae Radix Alba (Bai Shao, 白芍) and Moutan Cortex (Mu Dan Pi, 牡丹皮), which have well-established histories of use for treatment of rheumatic and arthritic diseases. We intended to establish the optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT to develop it as a novel botanical drug product for treatment of rheumatoid arthritis (RA). Methods The combinative approaches of chemical assessment, toxicological and pharmacological evaluation were explored to define the pharmaceutical preparation of QFJBT. Results The optimized and standardized pharmaceutical procedures and manufacturing processes for the pilot production of QFJBT were established in terms of greatest chemical contents of bioactive constituents, potent anti-inflammatory and antinociceptive activities, and favorable safety profile. Quality analysis of the pilot product of QFJBT by high-performance liquid chromatography (HPLC) demonstrated that the chromatographic fingerprint profiles of three batches of QFJBT were basically identical and the contents of four characteristic and bioactive markers were relatively consistent. General toxicological studies showed a favorable safety profile of QFJBT. The maximum tolerated single dose of QFJBT was determined in both sexes of rats to be 33.63 g/kg body weight which is equivalent to 346 times of clinical dose. In the chronic oral toxicity study, the results of laboratory investigation showed that QFJBT at doses of 3.89, 6.80 and 9.72 g/kg body weight (equivalent to 40, 70 and 100-fold clinical doses, respectively) caused no changes in all hematological parameters and blood biochemical parameters of rats. No mortality or specific toxic responses were observed in animals after three months of repeated dosing with QFJBT. Conclusion The optimized and standardized pharmaceutical and manufacturing processes for the production of QFJBT have been successfully screened and identified through established rigorous in-process controls.
