胡伟锋等[10]通过动物实验研究发现雷公藤内酯醇可降低类风湿关节炎模型大鼠血清中炎症细胞因子TNF-α、 IL-4 、IL-6的表达水平;进一步从网络药理学方面阐明雷公藤内酯醇的抗炎机制为通过调节丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路来抑制炎症细胞因子的产生和调节血管内皮生长因子(vascular endothelial growth factor,VEGF)信号转导通路在病变关节中抑制细胞因子的表达,来减少胶原蛋白的产生、抑制滑膜细胞增殖、减弱侵袭能力等。二者相互配合,从两个方面起到抗炎治疗作用。除了抑制炎症细胞因子的产生外,雷公藤多苷还通过抑制与炎症相关的细胞发挥抗炎作用。ZHAO等[11]研究表明雷公藤多苷可改善咪喹莫特诱导的皮肤损伤,机制是通过抑制信号传导及转录激活因子(signal transducers and activators of transcription,STAT3)的磷酸化抑制Th17细胞的作用。
2.2.1 对细胞免疫的调节 雷公藤甲素呈剂量相关性抑制T细胞的增殖、诱导T细胞的凋亡、恢复Th1/Th2细胞平衡,调节细胞免疫。牛瑞芳等[12]在研究雷公藤多苷短期治疗对桥本病甲状腺组织中T细胞亚群等免疫学指标的影响中发现:雷公藤多苷通过下调总T淋巴细胞,减轻淋巴细胞浸润程度;能够下调C
C
辅助性T细胞,降低T细胞亚群中辅助性T细胞百分比,纠正Th1/Th2失衡状态,减少自身抗体产生;提高C
C
调节性T细胞百分比,提示雷公藤多苷可提高Treg细胞的数量,上调Treg细胞的百分比,进而抑制自身反应性T细胞的活化、增殖,维持机体免疫耐受;上调C
C
细胞毒T细胞,抑制免疫亢进,改善免疫紊乱。自身免疫性疾病多因免疫功能紊乱而发生,雷公藤可恢复T淋巴细胞的比例,调节免疫功能,可能是它治疗免疫性疾病的机制之一。进一步研究[13]发现雷公藤调节细胞免疫的机制是不同程度地抑制T细胞中因刺激产生的NF-κB激酶抑制因子α(inhibitor α of nuclear factor kappa-B kinase,IKKα)和IKKβ。由此可知雷公藤调节细胞免疫的机制是通过抑制IKKα和IKKβ实现的。
雷公藤多苷对关节炎软骨具有保护作用。其骨保护作用与免疫抑制和抗炎作用有密切关系;此外其骨保护作用还与抑制滑膜细胞增生和软骨组织表达NF-κB受体活化因子(receptor activator for nuclear factor-κB,RANK)和NF-κB受体活化因子配体(receptor activator for nuclear factor-κB ligand,RANKL)有关,其机制为通过调节MAPK信号转导通路来抑制炎症细胞因子的产生和调节VEGF信号转导通路在关节抑制细胞因子的表达,减少胶原蛋白的产生、抑制滑膜细胞增殖、减弱侵袭能力等[32]。陈晓昱[33]研究发现雷公藤甲素可抑制模型大鼠膝骨关节炎滑膜中c-Jun及MMP-9表达,降低外周血前列腺素E2及IL-8水平,抑制炎症反应,对骨关节炎有治疗作用。提示雷公藤多苷治疗膝骨关节炎的机制是通过抑制炎症因子的产生,从而保护关节。
CHU KD,ZHENG HY,LIH,et al.The Shuangtengbitong tincture treatment of collagen-induced arthritis via downregulation of the expression of IL-6,IL-8,TNF-α and NF-κB[J].,2013,5(2):423-428.
Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease and may lead to joint damage, synovial membrane destruction and cartilage and bone damage. RA is closely associated with increased expression of interleukin (IL)-6, IL-8, tumor necrosis factor-α (TNF-α) and nuclear transcription factor-κB (NF-κB). Therefore, inhibition of the expression of IL-6, IL-8, TNF-α and NF-κB is a promising strategy for the development of novel anti-RA therapies. The aim of this study was to investigate the effect of shuangtengbitong tincture (STBT) on the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of rats with collagen-induced arthritis (CIA). STBT as a clinical prescription created at Fujian University of Traditional Chinese Medicines (TCM) Affiliated People’s Hospital has been shown to be clinically effective in the treatment of RA. The model of Wistar rats with CIA was created using bovine type II collagen. The two treatment groups with CIA were administered STBT (1 ml per time) or Votalin (651 cm per time) for 651 month continuously. Following treatment, STBT suppressed paw swelling significantly (P<0.05) compared with the model group. STBT also improved pathological changes, STBT-treated rats showed a significant improvement in synovial hyperplasia, inflammatory infiltration, cartilage and bone destruction and other symptoms. The protein expression levels of IL-6, IL-8, TNF-α and NF-κB were markedly suppressed in synovial tissues of STBT-treated and Votalin-treated rats. Our findings demonstrate for the first time that STBT markedly reduces paw swelling, improves pathological changes and increases the expression of IL-6, IL-8, TNF-α and NF-κB in synovial tissues of CIA rats, which may partially explain the anti-RA activity of STBT.
ZHAO JZ,DI TT,WANGY,et al.Multi-glycoside of Tripterygium wilfordii Hook F ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses[J].,2016,38(3):747-757.
Multi-glycoside ofTripterygium wilfordiiHook. f. (GTW) possesses anti-inflammatory and immunosuppressive properties, and has been used as a traditional treatment for psoriasis for many years, although the underlying immunological mechanisms remain poorly understood. The T helper (Th)17 cell response is considered to play a major role in the pathogenesis of psoriasis. Th17 cells are implicated in the mechanism of pathogenesis of imiquimod (IMQ)-induced skin inflammation. Using a mouse model, we demonstrated that GTW protected mice from developing psoriasis-like lesions induced by topical IMQ administration. This protection was associated with significantly decreased mRNA levels of Th17 cytokines such as interleukin (IL)-17A, IL-17F and IL-22 in mouse skin samples as well as fewer IL-17-secreting splenic CD4+lymphocytes in IMQ-exposed mice. There were no significant effects on the proportion of CD4+interferon (IFN)-+T cells, CD4+IL-4+T cells and CD4+CD25+Foxp3+Treg cells in the spleen cells. Taken together with the unchanged mRNA levels of Th1 cytokine IFN-, Th2 cytokine IL-4 and Treg cytokine IL-10 in IMQ-exposed mouse skin following GTW administration, our findings suggest that the immunosuppressive effect of GTW in psoriasis is exerted mainly on Th17 cells, rather than on Th1, Th2 or Treg cells. Furthermore, we showed that GTW suppressed Th17 function through the inhibition of STAT3 phosphorylation. These results have the potential to pave the way for the use of GTW as an agent for the treatment of psoriasis.
HO LJ,CHANG WL,CHENA,et al.Differential immu-nomodulatory effects by Tripterygium wilfordii Hook F derived refined extract PG27 and its purified component PG490 (triptolide) in human peripheral blood T cells:potential therapeutics for arthritis and possible mechanisms explaining in part Chinese herbal theory “Junn-Chenn-Zuou-SS”[J].,2013,11(1):294.
GUL,BAIW,LIS,et al.Celastrol prevents atherosclerosis via inhibiting LOX-1 and oxidative stress.[J].,2013,8(6):e65477.
Celastrol is a triterpenoid compound extracted from the Chinese herb Tripterygium wilfordii Hook F. Previous research has revealed its anti-oxidant, anti-inflammatory, anti-cancer and immunosuppressive properties. Here, we investigated whether celastrol inhibits oxidized low-density lipoprotein (oxLDL) induced oxidative stress in RAW 264.7 cells. In addition, the effect of celastrol on atherosclerosis in vivo was assessed in apolipoprotein E knockout (apoE(-/-)) mouse fed a high-fat/high-cholesterol diet (HFC). We found that celastrol significantly attenuated oxLDL-induced excessive expression of lectin-like oxidized low density lipoprotein receptor-1(LOX-1) and generation of reactive oxygen species (ROS) in cultured RAW264.7 macrophages. Celastrol also decreased IB phosphorylation and degradation and reduced production of inducible nitric oxide synthase (iNOS), nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)- and IL-6. Celastrol reduced atherosclerotic plaque size in apoE(-/-) mice. The expression of LOX-1 within the atherosclerotic lesions and generation of superoxide in mouse aorta were also significantly reduced by celastrol while the lipid profile was not improved. In conclusion, our results show that celastrol inhibits atherosclerotic plaque developing in apoE(-/-) mice via inhibiting LOX-1 and oxidative stress.
LI JM,ZHAANGY,TANGL,et al.Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer’s disease[J].,2016,11(9):1492-1498.
The principal pathology of Alzheimer's disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile pl aques,which in turn induce neuroinflammation in the brain.Triptolide,a natural extract from the vine-like herb Tripterygium wilfordii Hook F,has potent anti-inflammatory and immunosuppressive efficacy.Therefore,we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice(aged 4–4.5 months) for 45 days.Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells,and transformed microglial cells into the resting state.Further,triptolide(5 μg/kg/d) also reduced the total number of hippocampal astrocytes.Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimer's disease.
BAIS,HUZ,YANGY,et al.Anti-inflammatory and neuro-protective effects of triptolide via the NF-κB signaling pathway in a rat MCAO model[J].,2016,299(2):256-266.
Stroke is the leading cause of neurological disability in humans. Middle cerebral artery occlusion (MCAO) followed by reperfusion is widely accepted to mimic stroke in basic medical research. Triptolide is one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, and has been reported to have potent anti-inflammatory and immunosuppressive properties. Since its preclinical effects on stroke were still unclear, we decided to study the effects of Triptolide on focal cerebral ischemia/reperfusion injury in this study. The results showed that Triptolide treatment significantly attenuates brain infarction volume, water content, neurological deficits, and neuronal cell death rate, which were increased in the MCAO model rats. Immunohistochemistry was used to analyze the expression of glial fibrillary acidic protein (GFAP), Cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and NF-κB in the ischemic brains. The administration of Triptolide showed down-regulation of the iNOS, COX-2, GFAP, and NF-κB expression in MCAO rats. It also increased the expression of bcl-2, and suppressed levels of bax and caspase-3 compared with the MCAO group. Our findings revealed that Triptolide exerts its neuroprotective effects against inflammation with the involvement of inhibition of NF-κB activation. Anat Rec, 299:256–266, 2016. 08 2015 Wiley Periodicals, Inc.
LI WY,YANGY,HUZ,et al.Neuroprotective effects of DAHP and triptolide in focal cerebral ischemia via apoptosis inhibition and PI3K/Akt/mTOR pathway activation[J].,2015,9(48):48-60.
Triptolide (TP), one of the major active components of the traditional Chinese herb Tripterygium wilfordii Hook F, and 2, 4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of tetrahydrobiopterin (BH4) synthesis, have been reported to have potent anti-inflammatory and immunosuppressive properties. However, the protective effects of TP and DAHP on cerebral ischemia have not been reported yet. In this study, we investigated the neuroprotective effects of TP and DAHP in a middle cerebral artery occlusion (MCAO) rat model. Furthermore, we examined whether the neuroprotective effects of TP and DAHP were associated with the inhibition of apoptosis through suppressing BH4 and inducible NOS (iNOS) synthesis or the activation of the phosphoinositide-3-kinase/serine-threonine kinase Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway. Our results showed that pretreatments with TP (0.2 mg/kg) and DAHP (0.5 g/kg) significantly reduced ischemic lesion volume, water content, and neuronal cell death compared with the vehicle MCAO rats. In addition, compared with the MCAO group, TP, and DAHP pretreatment groups significantly reduced astrocyte numbers, caspase-3, cleaved caspase-3, and NF-B up-regulation, while increased Bcl-2 expression. Moreover, protein expressions of PI3K, Akt, and mTOR increased, while extracellular signal-regulated protein kinases 1 and 2 (ERK1 and ERK2) phosphorylation decreased in both the TP-treated rats and DAHP-treated rats. These results demonstrate that TP and DAHP can decrease cell apoptosis in focal cerebral ischemia rat brains and that the mechanism may be related to the activation of the PI3K/Akt/mTOR pathway and inactivation of the ERK1/2 pathway. Thus our hypothesis was reached PI3K/Akt/mTOR and ERK1/2 pathways may provide distinct cellular targets for a new generation of therapeutic agents for the treatment of stroke, and TP and DAHP may be potential neuroprotective agents for cerebral ischemia/reperfusion injury.
MA RX,XUY,JIANGW,et al.Combination of Tripterv-gium wilfordii Hook F and angiotensin receptor blocker synergistically reduces excretion of urinary podocytes in patients with type 2 diabetic kidney disease[J].Biotech Biotechnol Equip,2015,29,(1):139-146.
目的观察雷公藤甲素对膝部骨关节炎滑膜c-Jun、MMP-9及血清PGE2、IL-8水平的影响,探讨其在膝部骨关节炎中的药理学价值。方法 45只SD大鼠随机分为正常对照组、模型对照组及雷公藤甲素组,建立碘乙酸钠(Monosodium iodoacetate,MIA)膝关节炎模型,并给予雷公藤甲素干预,以Western blot及(qRT)-PCR法检测c-Jun及M M P-9在膝关节滑膜中蛋白及mRNA水平表达,以酶联免疫法检测外周血中PGE2及IL-8水平。结果 Western blot及(qRT)-PCR显示,c-Jun及MMP-9在膝关节滑膜组织中蛋白及mRNA水平上均有表达,雷公藤甲素组及正常对照组明显低于模型对照组(P〈0.01),雷公藤甲素组与正常对照组比较差异无统计学意义(P〉0.05);在血清PGE2及IL-8表达上,雷公藤甲素组及正常对照组明显低于模型对照组(P〈0.05)。结论雷公藤甲素可抑制骨关节炎滑膜中c-Jun及MMP-9表达,降低外周血PGE2及IL-8水平,抑制炎症反应,对骨关节炎有治疗作用。
ZHAOF,HUANGW,ZHANGZ,et al.Triptolide induces protective autophagy through activation of the CaMKKβ-AMPK signaling pathway in prostate cancer cells[J].,2016,7(5):5366-5382.
Abstract Triptolide, an active compound extracted from the Chinese herb thunder god vine (Tripterygium wilfordii Hook F.), has potent anti-tumor activity. Recently, triptolide was found to induce autophagy in cancer cells. However, the effects of triptolide on autophagy in human prostate cancer (PCa) cells have not yet been clearly elucidated. In this study, we demonstrated that triptolide induces autophagy in three PCa cell lines, PC-3, LNCaP and C4-2. Furthermore, we found that triptolide mediates intracellular accumulation of free calcium by stimulating the endoplasmic reticulum (ER) stress response. This activates the CaMKK-AMPK signaling pathway, which in turn inhibits mTOR and activates both ULK1 and Beclin 1, finally resulting in autophagy. Moreover, we found that treatment with autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) enhances triptolide-induced PCa cell death and growth inhibition. Using a PC-3-xenografted mouse model, we showed that blocking autophagy with CQ significantly promoted triptolide-induced tumor growth inhibition in vivo. Overall, our results show that triptolide induces protective autophagy through the CaMKK-AMPK pathway in PCa cells, implying that a combination of triptolide with autophagy inhibitors may potentially be an effective therapeutic strategy for PCa.
XIE CQ,ZHOUP,ZUOJ,et al.Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways[J].,2016,12(5):3586-3590.
Multidrug resistance (MDR) is a major obstacle in the effective chemotherapeutic treatment of cancers. Triptolide (TPL) is a diterpenoid isolated from Tripterygium02wilfordii Hook. f., a traditional Chinese medicine. It was demonstrated in our previous study that TPL exerts anti62MDR cancers on various MDR cell lines (including A549/Taxol, MCF627/ADR and Bel7402/562Fu). The present study was designed to investigate its anti62proliferative activity on A549/Taxol cells, and explore the underlying mechanism of action. The anti62proliferative activity of TPL on A549/Taxol cells was assessed by 362(4,562dimethylthiazol62262yl)622,562diphenyltetrazolium bromide (MTT) assay. Its pro62apoptosis and cell cycle arrest activities were analyzed by flow cytometry. Western blot assay was employed to investigate the levels of mitogen-activated protein kinases (MAPKs) and apoptosis62related proteins in cells. TPL efficiently suppressed the proliferation of A549/Taxol cells. Co62treatment with MAPK inhibitors in the MTT assay indicated that the extracellular signal62regulated kinase (ERK) and c62Jun N62terminal kinase (JNK) pathways were involved in the process. Upregulation of p62p38, p62ERK, p62GSK623β, Bax and cleaved caspases623 and 629, and downregulation of p62JNK, p62Akt and Bcl622 were observed upon treatment with TPL in the A549/Taxol cells. The results from flow cytometry assay revealed that TPL induced apoptosis and S62phase arrest in A549/Taxol cells. This occurred as a result of the upregulation of p62ERK and p62GSK623β, and the downregulation of p62JNK and p62Akt, and was responsible for the subsequent anti-proliferative activity.
CHAUHANL,JENKIMS GD,BHISEN,et al.Genome-wide association analysis identified splicing single nucleotide polymorphism in CFLAR predictive of triptolide chemo-sensitivity[J].,2015,16(1):483-500.
Background Triptolide is a therapeutic diterpenoid derived from the Chinese herb Tripterygium wilfordii Hook f. Triptolide has been shown to induce apoptosis by activation of pro-apoptotic proteins, inhibiting NFkB and c-KIT pathways, suppressing the Jak2 transcription, activating MAPK8/JNK signaling and modulating the heat shock responses. Results In the present study, we used lymphoblast cell lines (LCLs) derived from 55 unrelated Caucasian subjects to identify genetic markers predictive of cellular sensitivity to triptolide using genome wide association study. Our results identified SNPs on chromosome 2 associated with triptolide IC 50 (p???<???0.0001). This region included biologically interesting genes as CFLAR, PPIl3, Caspase 8/10, NFkB and STAT6. Identification of a splicing-SNP rs10190751, which regulates CFLAR alternatively spliced isoforms predictive of the triptolide cytotoxicity suggests its role in triptolides action. Our results from functional studies in Panc-1 cell lines further demonstrate potential role of CFLAR in triptolide toxicity. Analysis of gene-expression with cytotoxicity identified JAK1 expression to be a significant predictor of triptolide sensitivity. Conclusions Overall out results identified genetic factors associated with triptolide chemo-sensitivity thereby opening up opportunities to better understand its mechanism of action as well as utilize these biomarkers to predict therapeutic response in patients.
LIH,PANG,JIANGZ,et al.Triptolide inhibits human breast cancer MCF-7 cell growth via downregulation of the ER|[alpha]|-mediated signaling pathway[J].,2015,36(5):606-613.
To investigate the anticancer mechanisms of triptolide, a diterpenoid isolated from the plant Tripterygium wilfordii Hook F, against human breast cancer cells and the involvement of the estrogen receptor-α (ERα)-mediated signaling pathway in particular.Human breast cancer ERα-positive MCF-7 cells and ERα-negative MDA-MB-231 cells were tested. PrestoBlue assay was used to evaluate the cell viability. The levels of ERα mRNA and protein were detected with real-time PCR and immunoblotting, respectively. Mouse models of MCF-7 or MDA-MB-231 xenograft tumors were treated with triptolide (0.4 mg·kg(-1)·d(-1), po) or a selective estrogen receptor modulator tamoxifen (mg·kg(-1)·d(-1), po) for 3 weeks, and the tumor weight and volume were measured.Triptolide (5-200 nmol/L) dose-dependently inhibited the viability of both MCF-7 and MDA-MB-231 cells, with a more potent inhibition on MCF-7 cells. Knockdown of ERα in MCF-7 cells by siRNA significantly attenuated the cytotoxicity of triptolide, whereas overexpression of ERα in MDA-MB-231 cells markedly enhanced the cytotoxicity. Triptolide dose-dependently decreased the expression of ERα in MCF-7 cells and MCF-7 xenograft tumors. Furthermore, treatment of MCF-7 cells with triptolide inhibited the phosphorylation of ERK1/2 in dose- and time-dependent manners. In the mice xenografted with MCF-7 cells, treatment with triptolide or tamoxifen resulted in significant reduction in the tumor weight and volume. Similar effects were not obtained in the mice xenografted with MDA-MB-231 cells.The anticancer activity of triptolide against ERα-positive human breast cancer is partially mediated by downregulation of the ERα-mediated signaling pathway.
JIANGX,HUANG XC,AOL,et al.Total alkaloids of Tripterygium hypoglaucum (levl.)Hutch inhibits tumor growth both in vitro and in vivo[J].,2014,151(1):292-298.
THHta was effective in inhibiting tumor growth both in vitro and in vivo at less toxic concentrations by inducing apoptosis which suggested it could be developed as a potential anticancer agent.
LIU TE,ZHANGL,WANGS,et al.Tripterygium glycosi-des induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway[J].,2015,10(1):12-18.
Premature ovarian failure (POF) is a typical pathological disease of the reproductive system in aging females. Infection, inflammation, immune abnormalities, genetic mutation, radiotherapy and chemotherapy can cause POF. Tripterygium glycosides (TGs) are a component extracted from the Chinese herb Tripterygium02wilfordii Hook.02f., also known as Huangteng. Although TGs have been used to treat various diseases, drug resistance and toxicity can affect patients. The aim of the present study was to investigate the mechanism of TG62induced POF in rats. The rats were treated with different concentrations of TG, and pathology assays showed that the TG62induced POF was predominantly composed of interstitial cells in a fibrous matrix with a reduced number of follicles at each stage and an increased number of collapsed oocytes. Furthermore, reverse transcription62quantitative polymerase chain reaction (PCR) and immunohistochemistry assays indicated that the expression levels of serine/threonine kinase0211 (Stk11), p53 p21 and activated caspase623 were elevated significantly in the TG62treated groups. Serine0215 phosphorylation of p53 was also enhanced significantly in the TG62treated groups. In addition, a chromatin immunoprecipitation62PCR assay revealed that the TGs induced p53 activation and enhanced the transcription of p21. In conclusion, TGs induce apoptosis and necrosis in rat ovarian tissues, as well as POF, via p53 phosphorylation and activation of the Stk11-p53-p21 signaling pathway.
KONGX,ZHANGY,LIUC,et al.Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade[J].,2013,8(10):e77513.
Rheumatoid arthritis (RA) is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA) model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (1109“45 0008g/kg/day) starting on the day 1 after first immunization. The arthritis scores (P<0.05) and the arthritis incidence (P<0.05) of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 1109030445 0008g/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05). Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS09“RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS09“RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-02±, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-0205-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the angiogenic activators and inhibiting the activation of mitogen-activated protein kinase downstream signal pathway.
SHANP,LUZ,YEL,et al.Effect of Tripterygium wilfordii polyglycoside on experimental prostatitis caused by ureaplasma urealyticumin rats[J].,2016,15(22):3722-3726.
Prostatitis is a common and refractory urological disease with complicated etiology.Ureaplasma urealyticum(UU) has a close relationship with human urinary tract infection that can induce nonbacterial prostatitis.Tripterygium wilfordiipolyglycoside (TWP) is a non-steroidal immune inhibitor that causes significant immune suppression and anti-inflammatory effects. Its role in prostatitis caused by UU has not yet been established. The aim of this study was to investigate the effect of TWP on UU-infected prostatitis in a rat model. UU-infected prostatitis SD model rats were randomly divided into 2 groups: the prostatitis group (model group) and the TWP treatment group (treatment group). At 7 days after treatment, prostate weight, leucocyte count, lecithin corpuscles, UU infection rate, and UU microbe count were compared between the 2 groups. Serum inflammatory cytokines TNF-α was determined by ELISA, and ICAM-1 and NF-κB expression were detected. UU infection rate was 80% after modeling. The rat prostate weight and leucocyte count in the model group increased significantly, while lecithin corpuscles decreased. Compared with controls, inflammatory factor TNF-α, ICAM-1, and NF-κB expression were obviously higher (P<0.05). TWP markedly reduced prostate weight and leucocyte count, increased lecithin corpuscles, and decreased UU microbe count and TNF-α, ICAM-1, and NF-κB expression (P<0.05). TWP can inhibit expression of inflammatory factors and may be useful in treating UU-infected prostatitis through reducing UU infection rate.
... 胡伟锋等[10]通过动物实验研究发现雷公藤内酯醇可降低类风湿关节炎模型大鼠血清中炎症细胞因子TNF-α、 IL-4 、IL-6的表达水平;进一步从网络药理学方面阐明雷公藤内酯醇的抗炎机制为通过调节丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路来抑制炎症细胞因子的产生和调节血管内皮生长因子(vascular endothelial growth factor,VEGF)信号转导通路在病变关节中抑制细胞因子的表达,来减少胶原蛋白的产生、抑制滑膜细胞增殖、减弱侵袭能力等.二者相互配合,从两个方面起到抗炎治疗作用.除了抑制炎症细胞因子的产生外,雷公藤多苷还通过抑制与炎症相关的细胞发挥抗炎作用.ZHAO等[11]研究表明雷公藤多苷可改善咪喹莫特诱导的皮肤损伤,机制是通过抑制信号传导及转录激活因子(signal transducers and activators of transcription,STAT3)的磷酸化抑制Th17细胞的作用. ...
Multi-glycoside of Hook F ameliorates imiquimod-induced skin lesions through a STAT3-dependent mechanism involving the inhibition of Th17-mediated inflammatory responses
1
2016
... 胡伟锋等[10]通过动物实验研究发现雷公藤内酯醇可降低类风湿关节炎模型大鼠血清中炎症细胞因子TNF-α、 IL-4 、IL-6的表达水平;进一步从网络药理学方面阐明雷公藤内酯醇的抗炎机制为通过调节丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号转导通路来抑制炎症细胞因子的产生和调节血管内皮生长因子(vascular endothelial growth factor,VEGF)信号转导通路在病变关节中抑制细胞因子的表达,来减少胶原蛋白的产生、抑制滑膜细胞增殖、减弱侵袭能力等.二者相互配合,从两个方面起到抗炎治疗作用.除了抑制炎症细胞因子的产生外,雷公藤多苷还通过抑制与炎症相关的细胞发挥抗炎作用.ZHAO等[11]研究表明雷公藤多苷可改善咪喹莫特诱导的皮肤损伤,机制是通过抑制信号传导及转录激活因子(signal transducers and activators of transcription,STAT3)的磷酸化抑制Th17细胞的作用. ...
Differential immu-nomodulatory effects by Hook F derived refined extract PG27 and its purified component PG490 (triptolide) in human peripheral blood T cells:potential therapeutics for arthritis and possible mechanisms explaining in part Chinese herbal theory “Junn-Chenn-Zuou-SS”
Triptolide exerts pro-apoptotic and cell cycle arrest activity on drug-resistant human lung cancer A549/Taxol cells via modulation of MAPK and PI3K/Akt signaling pathways
Tripterygium glycosi-des induce premature ovarian failure in rats by promoting p53 phosphorylation and activating the serine/threonine kinase 11-p53-p21 signaling pathway