摘要：
Sceletorines A and B, two unique alkaloids, were isolated for the first time from the aerial parts of Mesembryanthemum tortuosum. Their structures were determined by the extensive spectroscopic methods and their absolute configuration was established with ECD calculations. Plausible biosynthetic pathways for 1 and 2 are proposed and a relationship to the previously assumed artifact, channaine is also addressed.
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.
作者机构：
[Raman, Vijayasankar; Fantoukh, Omer; Ali, Zulfiqar; Khan, Ikhlas A.; Huang, Ying; Parveen, Abidah; Alhusban, Manal; Wang, Yan-Hong] Univ Mississippi, Natl Ctr Nat Prod Res, Sch Pharm, University, MS 38677 USA.;[Fantoukh, Omer; Parveen, Abidah; Alhusban, Manal; Khan, Ikhlas A.] Univ Mississippi, Dept Biomol Sci, Div Pharmacognosy, Sch Pharm, University, MS 38677 USA.;[Parveen, Abidah] Univ Sci & Technol, Havelian, Pakistan.;[Wang, Wei; Huang, Ying] Hunan Univ Chinese Med, Sch Pharm, TCM & Ethnomed Innovat & Dev Lab, Changsha, Hunan, Peoples R China.;[Fantoukh, Omer] King Saud Univ, Coll Pharm, Dept Pharmacognosy, Riyadh, Saudi Arabia.
通讯机构：
[Ali, Z; Khan, IA; Khan, Ikhlas A.] U;Univ Mississippi, Natl Ctr Nat Prod Res, Sch Pharm, University, MS 38677 USA.;Univ Mississippi, Dept Biomol Sci, Div Pharmacognosy, Sch Pharm, University, MS 38677 USA.
关键词：
Tinospora crispa;isolation;NMR;tinocrispide;borapetol A
摘要：
A new rearranged clerodane diterpenoid, tinocrispide was isolated from the stems of Tinospora crispa along with thirteen known compounds including eight clerodane diterpenoids. Among the known compounds baenzigeride A, (6S, 9 R)-vomifoliol and steponine are being reported for the first time from T. crispa. Their structures were elucidated by 1 D and 2 D NMR and confirmed by HRESIMS. The 13C NMR data of borapetol A has been revised.
期刊：
Evidence-Based Complementary and Alternative Medicine,2019年2019:ARTN 3710363 ISSN：1741-427X
通讯作者：
Wang, Yuhong
作者机构：
[Liu, Zhuo; Zhao, Hongqing; Luo, Weixu; Jia, Ling; Wang, Yuhong] Hunan Univ Chinese Med, Training Bases, Hunan Key Lab Chinese Mat Med Powder & Innovat Dr, Changsha 410208, Hunan, Peoples R China;[Han, Yuanshan; Wang, Yuhong] Hunan Univ Chinese Med, Hosp 1, Changsha 410007, Hunan, Peoples R China
通讯机构：
[Wang, Yuhong] H;Hunan Univ Chinese Med, Training Bases, Hunan Key Lab Chinese Mat Med Powder & Innovat Dr, Changsha 410208, Hunan, Peoples R China. Hunan Univ Chinese Med, Hosp 1, Changsha 410007, Hunan, Peoples R China.
摘要：
Objectives. Diabetes mellitus is frequently accompanied by depression (diabetes-depression, DD), and DD patients are at higher risk of diabetes-related disability and mortality than diabetes patients without depression. Hippocampal degeneration is a major pathological feature of DD. Here, we investigated the contribution of the Glu-mGluR2/3-ERK signaling pathway to apoptosis of hippocampal neurons in DD model rats. Methods. The DD model was established by high-fat diet (HFD) feeding and streptozotocin (STZ) injection followed by chronic unpredictable mild stress (CUMS). Other groups were subjected to HFD + STZ only (diabetes alone) or CUMS only (depression alone). Deficits in hippocampus-dependent memory were assessed in the Morris water maze (MWM), motor activity in the open field test (OFT), and depression-like behavior in the forced swim test (FST). Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) was used to estimate the rate of hippocampal neuron apoptosis. Hippocampal glutamate (Glu) content was measured by high performance liquid chromatography. Hippocampal expression levels of mGluR2/3, ERK, and the apoptosis effector caspase-3 were estimated by immunohistochemistry and Western blotting. Results. DD model rats demonstrated more severe depression-like behavior in the FST, greater spatial learning and memory deficits in the MWM, and reduced horizontal and vertical activity in the OFT compared to control, depression alone, and diabetes alone groups. All of these abnormalities were reversed by treatment with the mGluR2/3 antagonist LY341495. The DD group also exhibited greater numbers of TUNEL-positive hippocampal neurons than all other groups, and this increased apoptosis rate was reversed by LY341495. In addition, hippocampal expression levels of caspase-3 and mGluR2/3 were significantly higher, ERK expression was lower, and Glu was elevated in the DD group. The mGluR2//3 antagonist significantly altered all these features of DD. Conclusions. Comorbid diabetes and depression are associated with enhanced hippocampal neuronal apoptosis and concomitantly greater hippocampal dysfunction. These pathogenic effects are regulated by the Glu-mGluR2/3-ERK signaling pathway.
