IL-37 is an anti-inflammatory cytokine that was only recently identified, and it is highly expressed in tissues from patients with inflammatory and autoimmune diseases. Inflammatory cytokines and inflammatory stimuli ...IL-37 is an anti-inflammatory cytokine that was only recently identified, and it is highly expressed in tissues from patients with inflammatory and autoimmune diseases. Inflammatory cytokines and inflammatory stimuli can induce the upregulation of IL-37. However, it has not been reported whether anti-inflammatory medications induce the expression of IL-37. In this work, we uncovered, for the first time, that two main bioactive components, triptolide and triptonide, from the herb Tripterygium wilfordii Hook f. （TwHF）, which possess anti-inflammatory activity, upregulate the expression of IL-37, and this expression was suppressed by ERKI/2 and p38 MAPK inhibitors. Overall, our research demonstrated, for the first time, that anti-inflammatory active components （triptolide and triptonide） upregulated the expression of IL-37 most likely via activation of the ERKI/2 and p38 MAPK pathways.展开更多
Background：Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F （TwHF） compared with acitretin in psoriasis.We aimed to compare the efficacy and safety of TwHF compared with a...Background：Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F （TwHF） compared with acitretin in psoriasis.We aimed to compare the efficacy and safety of TwHF compared with acitretin in the treatment of moderate to severe psoriasis vulgaris.Methods：Adults with Psoriasis Area Severity Index （PASI） score ＞ 10 and psoriasis-affected body surface area ＞ 10％ were randomized into a TwHF （20 mg,3 times a day） or acitretin group （30 mg,once a day）.The treatment course lasted for 8 weeks.Patients were assessed at baseline and at 2,4,and 8 weeks.Laboratory tests were performed at baseline,week 4,and week 8.The data were analyzed using paired samples t-test or analysis of variance （ANOVA）.Results：A total of 115 patients was enrolled （58 TwHF; 57 acitretin）.The median PASI score improved in the TwHF group by 50.4％ and in the acitretin group by 42.7％.There was no significant difference in median PASI improvement between two groups at 2,4,and 8 weeks.There was also no significant difference in PASI 25,PASI 50,PASI 75,and PASI 90 response between the two groups at 2,4,and 8 weeks.There was a significant increase in the level of aspartate transaminase and triglycerides in the TwHF group （P =0.026 and P =0.011,respectively）.In the acitretin group,there was a significant increase in the level of alanine transaminase,cholesterol,and high-density lipoprotein （P =0.030,P ＜ 0.01,and P ＜ 0.01,respectively）.Conclusions：There was no significant difference in treatment efficacy between the TwHF and acitretin groups within 8 weeks,but there were fewer treatment-related adverse events in the TwHF group.展开更多
Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythe...Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and kidney disease, especially in traditional Chinese medicine. The mechanisms underlying its effects may be diverse but they remain unclear, and its toxicity and side effects limit its wider clinical application. This review summarizes the clinical application of Tripterygium wilfordii Hook F in recent years, as well as the results of studies into its mechanisms and toxicity, to provide a reference for its future clinical application.展开更多
As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic p...As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.展开更多
With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nep...With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.展开更多
AIM： To analyze the gene expression profiles of mice livers injured by Leigongteng and explore the relationship between the differentially expressed genes and liver damage. METHODS： The experimental mice were random...AIM： To analyze the gene expression profiles of mice livers injured by Leigongteng and explore the relationship between the differentially expressed genes and liver damage. METHODS： The experimental mice were randomly divided into a control group and a liver-injured group in which the mice were administrated 33 μγ, of triptolide/ kg per day for 30 d. Liver mRNAs were extracted from animals in both groups and were reverse-transcribed to cDNA with dUTP labeled by different fluorescence （Cy3, Cy5） as hybridization probes. The mixed probes were hybridized with oligonucleotide microarray chips. The fluorescent signal results were acquired by scanner and analyzed with software. RESULTS： Among the 35852 target genes, 29 genes were found to be significantly differentially expressed, with 20 genes up-regulated and 9 genes down-regulated. The reliability of the differentially expressed genes was validated by RT-PCR experiments of 5 randomly selected differentially expressed genes. CONCLUSION： Based on the biological functions of the differentially expressed genes, it is obvious that the occurrence and development of liver damage induced by Leigongteng in mice are highly associated with immune response, metabolism, apoptosis and the cell skeleton of liver cells. This might be important for elucidating the regulatory network of gene expression associated with liver damage and it may also be important for discovering the pathogenic mechanisms of liver damage induced by Leigongteng.展开更多
Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its r...Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone（DXM） and azathioprine（AZA） on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.展开更多
Two new terpenes,triptobenzene P（1）and wilforone（2）were isolated from Tripterygium wilfordii,as well as 10 known terpenes.Their structures were elucidated by spectroscopic methods.Compounds 2-4,8,10,and 11 showed ...Two new terpenes,triptobenzene P（1）and wilforone（2）were isolated from Tripterygium wilfordii,as well as 10 known terpenes.Their structures were elucidated by spectroscopic methods.Compounds 2-4,8,10,and 11 showed significant immunosuppressive activities.展开更多
OBJECTIVE: To investigate the effectiveness a cream onjoint pain and swelling in patients with rheumatoid arthritis(RA). The cream, topically used, in was prepared with Tripterygium wilfordii Hook F(TwHF), Mangxiao(Na...OBJECTIVE: To investigate the effectiveness a cream onjoint pain and swelling in patients with rheumatoid arthritis(RA). The cream, topically used, in was prepared with Tripterygium wilfordii Hook F(TwHF), Mangxiao(Nalrii Sulfas), Chuanxiong(Rhizoma Chuanxiong), stir-frying with liquid adjuvant Ruxiang(Olibanum), and stir-frying with liquid adjuvant Moyao(Myrrh).METHODS: Patients were 1∶1 randomized to addon TwHF cream twice a day or placebo for 4 weeks.The primary endpoint was achievement rate of20% improvement in American College of Rheuma-tology criteria(ACR20) at week 4. Secondary endpoints were ACR50, 28-joint count Disease Activity Score(DAS28) improvement and safety profiles.Statistical analyses were performed using intention to treat analysis(ITT) set.RESULTS: A total of 70 active RA patients were enrolled. At week 4, the ACR20 was 34.3%(12/35) in TwHF cream group and 11.4%(4/35) in placebo group(P = 0.015). Similarly, a higher ACR50 responder proportion was seen in TwHF cream group with 17.1%(6/35) comparing to it in placebo group with 2.9%(1/35)(P = 0.046). The TwHF cream group also had more improvement than the placebo group on DAS28-ESR(1.1 vs 0.5, P = 0.001), DAS28-CRP(1.4 vs 0.7, P = 0.001), tender joint count(5.5 vs2.6, P = 0.018), swollen joint count(3.5 vs 1.6, P =0.003) and Physician's global assessment(25.8 vs13.0, P = 0.002), as well as C-reactive protein(11.2 vs 2.7, P = 0.048). Except 2 skin allergy events in TwHF cream group, no other substantive adverse events were observed.CONCLUSION: On the short term, TwHF cream is likely to be an effective and safety complimentary treatment in patients with active RA.展开更多
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 ...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-dependent- ly 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/PS 1 double transgenic mice with Alzheimer＇s disease.展开更多
In this study a reliable protocol was developed for the establishment of commercial in vitro cultures of Tripterygium wilfordii Hook f.. Juvenile shoots from one-year-old elite plants were used as the source of explan...In this study a reliable protocol was developed for the establishment of commercial in vitro cultures of Tripterygium wilfordii Hook f.. Juvenile shoots from one-year-old elite plants were used as the source of explants. New axillary shoots were obtained after 30 days of culture on a MS medium supplemented with BAP （2.0 mg.L^-1） and NAA （0.1 mg.L^-1）. The optimal multiplication medium was a modified MS medium supplemented with BAP （1.0 mg.L^-1） and NAA （0.1 mg.L^-1）. This yielded a multiplication rate of 2.4 for each subculture. Slightly more than 92% of shoots rooted when cultured on a modified MS medium containing IBA （0.2 mg.L^-1） and activated charcoal （0.5 mg.L^-1）. Activated charcoal promoted both a strong and a high rooting rate during the rooting phase. Plantlets were transferred to pots for a short acclimatization stage in a greenhouse where 95% of the plantlets survived. This highly reproducible procedure can be adopted for large-scale propagation of T. wilfordii.展开更多
The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase(HDR) is the last step key enzyme of the methylerythritol phosphate(MEP) pathway,synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphat...The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase(HDR) is the last step key enzyme of the methylerythritol phosphate(MEP) pathway,synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate,which is important for regulation of isoprenoid biosynthesis.Here the full-length cDNA of HDR,designated TwHDR(GenBank Accession No.KJ933412.1),was isolated from Tripterygium wilfordii for the first time.TwHDR has an open reading frame(ORF) of 1386 bp encoding461 amino acids.TwHDR exhibits high homology with HDRs of other plants,with an N-terminal conserved domain and three conserved cysteine residues.TwHDR cDNA was cloned into an expression vector and transformed into an Escherichia coli hdr mutant.Since loss-of-function E.coli hdr mutant is lethal,the result showed that transformation of TwHDR cDNA rescued the E.coli hdr mutant.This complementation assay suggests that the TwHDR cDNA encodes a functional HDR enzyme.The expression of TwHDR was induced by methyl-jasmonate(MJ) in T.wilfordii suspension cells.The expression of TwHDR reached the highest level after 1 h of MJ treatment.These results indicate that we have identified a functional TwHDR enzyme,which may play a pivotal role in the biosynthesis of diterpenoid triptolide in T.wilfordii.展开更多
The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside(GTW) against testosterone-induced benign prostatic hyperplasia(BPH) in rats. A total of 45 rats were randomly ...The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside(GTW) against testosterone-induced benign prostatic hyperplasia(BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group(sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg-1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg-1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone(DHT) levels in serum and prostate, and the serum prostate specific antigen(PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.展开更多
Three new sesquiterpene alkaloids,1-desacetylwilforgine（1）,1-desacetylwilforine（2）,and 9′-hydroxy-2-nicotinoylwilforine （3） were isolated from the roots of Tripterygium wilfordii Hook f.,along with six known al...Three new sesquiterpene alkaloids,1-desacetylwilforgine（1）,1-desacetylwilforine（2）,and 9′-hydroxy-2-nicotinoylwilforine （3） were isolated from the roots of Tripterygium wilfordii Hook f.,along with six known alkaloids.Their structures were established on the basis of spectral analysis.展开更多
Objective To study the protective effect of Tripterygium wilfordii polycoride（TWP） against TNBS/ethanol-induced ulcerative colitis（UC） rat model. Methods TNBS and ethanol enema were adopted to build TNBS/ethanol-i...Objective To study the protective effect of Tripterygium wilfordii polycoride（TWP） against TNBS/ethanol-induced ulcerative colitis（UC） rat model. Methods TNBS and ethanol enema were adopted to build TNBS/ethanol-induced UC rat model. Ninety male Wistar rats were divided into six groups： normal, model, low-, medium-, high-dose TWP and azathioprine（AZA） groups, each for 15 rats. All rats were administered by corresponding medicine for 14 d. After 14 d, corresponding colon tissues underwent general and microscopic evaluation. Blood samples were taken from heart and serum was separated by centrifugation. MDA, SOD, GSH, IL-1β and TNF-α levels in serum were tested by ELISA. Colonic samples underwent RT-PCR and Western blotting analysis. Results DAI, general and microscopic evaluation all showed that TWP could promote colonic mucosa healing and such effect was equal to AZA. ELISA results about lipid peroxidation indicated that TWP could decrease MDA level and increase SOD and GSH levels in a dose-dependent manner. TWP with high dose could strongly decrease the MDA level and increase the SOD and GSH levels（P 〈 0.01）. ELISA results about inflammatory cytokines indicated that TWP could inhibit the expression of IL-1β and TNF-α in a dose-dependent manner. Western blotting analysis and RT-PCR all indicated that no matter in mR NA level or protein level, TWP could inhibit the expression of NF-κB, TNF-α, IL-1β, and IFN-γ in a dose-dependent manner. The inhibitory effect of AZA towards NF-κB was slightly weaker than TWP with high dose（P 〉 0.05）, whereas slightly stronger towards terminal inflammatory cytokines（P 〉 0.05）. Conclusion TWP could significantly lower the infiltration of inflammatory cells under microscope, eventually led to mucosa healing, the mechanism of which was to inhibit lipid peroxidation, then further inhibit NF-κB activation, eventually lower the expression of inflammatory meditors locally and systemically.展开更多
Objective To investigate the possible bone changes in female patients with systemic lupus erythematosus (SLE) induced by long term administration of Tripterygium Wilfordii Hook F (TW) Methods 70 female SLE p...Objective To investigate the possible bone changes in female patients with systemic lupus erythematosus (SLE) induced by long term administration of Tripterygium Wilfordii Hook F (TW) Methods 70 female SLE patients were divided into 4 groups accordiog to their drug history: SLE disease control group, corticosteroids treatment group, TW treatment group, and both corticosteroids and TW treatment group Bone mineral density (BMD) of the lumbar spine 2-4 and biochemical markers of bone turnover were studied Results Long term administration of TW could significantly decrease BMD levels in female SLE patients ( P <0 05) The patients receiving TW for more than 5 years had significantly lower BMD levels compared with those for less than 5 years The degree of decreased BMD induced by TW was less severe compared with that of prednisone No significant differences were observed in the biochemical markers of bone turnover among four groups ( P >0 05) Conclusion Long term administration of TW could decrease BMD levels in women Osteoporosis may be an important problem for SLE patients treated with TW展开更多
Considerable efforts have been made to develop a male contraceptive and the studies have provided very useful infor-mation in this field. At least five different strategies to develop a male contraceptive have been pu...Considerable efforts have been made to develop a male contraceptive and the studies have provided very useful infor-mation in this field. At least five different strategies to develop a male contraceptive have been pursued, namely: inhi-bition of sperm production, interference with sperm function, interruption of sperm transport, prevention of sperm de-position, and prevention of sperm-egg interaction. Of all these approaches, inhibition of sperm production by using an-drogens either alone or in combination with progestins have given the most encouraging results. A nmnber of clinicaltrials substantiate that it is indeed possible to have a reversible, effective and safe hormonal method of contraception. Apostmeiotic and epididymal approach to interfere with sperm function or the secretory and metabolic processes of theepididymis is another attractive option of male contraceptive development. A number of chemical compounds have beenidentified which interfere with sperm function in the epididymis without affecting sperm production, however, the com-pounds evaluated so far were found to be toxic. Interruption of sperm transport through the vas either by vasectomy orpercutaneous intmvasal injection of liquids which form cure-in-place plugs is also an attractive option. However, re-versibility of the methods is of concern in their wide scale use. The major constraint in developing a long-acting male contraceptive seems to be the need for greater investment forproduct development. The clinical trials for evaluating the efficacy and safety of the new products and formulationsstretch over several years and require enormous financial commitment. Nevertheless, the long-term gain of having along-acting reversible contraceptive for men is far greater than the financial commitments over few years. Male attitudetowards using methods of family planning is much more favourable than originally believed. The pharmaceutical indus-try as well as the health care providers therefore have a greater responsibility. For early development 展开更多
BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s...BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s syndrome,among others.The pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune system.The prevalence and morbidity of rheumatic immune diseases are high,imposing a significant burden on patients'quality of life and socio-economic costs.Currently,the treatment of rheumatic immune diseases mainly relies on Western medicine,such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,and biologics.However,the therapeutic effects of Western medicine are not ideal,some patients poorly respond or are resistant to Western medicine,and long-term use often causes various adverse reactions.AIM To systematically evaluate the efficacy and safety of Tripterygium wilfordii gly-cosides tablets combined with Western medicine in the treatment of patients with rheumatic immune diseases.METHODS This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases.Chinese and English databases were searched for randomized controlled trials(RCTs)on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western medicine.The quality of the included studies was assessed using the Cochrane risk of bias assessment tool.Meta-analysis was performed using RevMan 5.4 software.RESULTS The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune diseases.The combined treatment significantly reduced the risk of disease recurrence(relative risk=1.07,95%confidence interval:1.01-1.15,P<0.05)and showed no significant heterogeneity(I2=0%,P=0.53),indicating that Tripterygium wilfordii glycosides tablets combined with Western medicine is an e展开更多
文摘IL-37 is an anti-inflammatory cytokine that was only recently identified, and it is highly expressed in tissues from patients with inflammatory and autoimmune diseases. Inflammatory cytokines and inflammatory stimuli can induce the upregulation of IL-37. However, it has not been reported whether anti-inflammatory medications induce the expression of IL-37. In this work, we uncovered, for the first time, that two main bioactive components, triptolide and triptonide, from the herb Tripterygium wilfordii Hook f. （TwHF）, which possess anti-inflammatory activity, upregulate the expression of IL-37, and this expression was suppressed by ERKI/2 and p38 MAPK inhibitors. Overall, our research demonstrated, for the first time, that anti-inflammatory active components （triptolide and triptonide） upregulated the expression of IL-37 most likely via activation of the ERKI/2 and p38 MAPK pathways.
文摘Background：Few clinical trials have evaluated the efficacy and safety of Tripterygium wilfordii Hook F （TwHF） compared with acitretin in psoriasis.We aimed to compare the efficacy and safety of TwHF compared with acitretin in the treatment of moderate to severe psoriasis vulgaris.Methods：Adults with Psoriasis Area Severity Index （PASI） score ＞ 10 and psoriasis-affected body surface area ＞ 10％ were randomized into a TwHF （20 mg,3 times a day） or acitretin group （30 mg,once a day）.The treatment course lasted for 8 weeks.Patients were assessed at baseline and at 2,4,and 8 weeks.Laboratory tests were performed at baseline,week 4,and week 8.The data were analyzed using paired samples t-test or analysis of variance （ANOVA）.Results：A total of 115 patients was enrolled （58 TwHF; 57 acitretin）.The median PASI score improved in the TwHF group by 50.4％ and in the acitretin group by 42.7％.There was no significant difference in median PASI improvement between two groups at 2,4,and 8 weeks.There was also no significant difference in PASI 25,PASI 50,PASI 75,and PASI 90 response between the two groups at 2,4,and 8 weeks.There was a significant increase in the level of aspartate transaminase and triglycerides in the TwHF group （P =0.026 and P =0.011,respectively）.In the acitretin group,there was a significant increase in the level of alanine transaminase,cholesterol,and high-density lipoprotein （P =0.030,P ＜ 0.01,and P ＜ 0.01,respectively）.Conclusions：There was no significant difference in treatment efficacy between the TwHF and acitretin groups within 8 weeks,but there were fewer treatment-related adverse events in the TwHF group.
基金Project supported by the Foundation of Key Discipline Construction of Zhejiang Province for Traditional Chinese Medicine(No.2017XKA36)the Medical and Health Science Foundation of Zhejiang Province(No.2019327552)+1 种基金the Foundation of Key Research Project of Zhejiang Province for Traditional Chinese Medicine(No.2019ZZ014)the Foundation of Science and Technology Department of Zhejiang Province for Beneficial Technology Research of Social Development(No.2015C33146),China。
文摘Tripterygium wilfordii Hook F has significant anti-inflammatory and immunosuppressive properties and is widely used for treating autoimmune and inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and kidney disease, especially in traditional Chinese medicine. The mechanisms underlying its effects may be diverse but they remain unclear, and its toxicity and side effects limit its wider clinical application. This review summarizes the clinical application of Tripterygium wilfordii Hook F in recent years, as well as the results of studies into its mechanisms and toxicity, to provide a reference for its future clinical application.
基金Supported by the Scientific Research Fund for the Doctoral Young Scholars,Shanxi University of Chinese Medicine(No.2015BK16)
文摘As a major active component extracted from traditional Chinese herb Tripterygium wilfordii Hook F, triptolide exhibits multiple pharmacological effects. Autophagy is an evolutionary conserved intracellular catabolic process involved in cytoplasmic materials degradation. Autophagic dysfunction contributes to the pathologies of many human diseases, which makes it a promising therapeutic target. Recent studies have shown that triptolide exerts neuroprotection, anti-tumor activities, organ toxicity, and podocyte protection by modulating autophagy. This article highlights the current information on triptolide-modulated autophagy, analyzes the possible pathways involved, and describes the crosstalk between autophagy and apoptosis modulated by triptolide, in hope of providing implications for the roles of autophagy in pharmacological effects of triptolide and expanding its novel usage as an autophagy modulator.
基金National Natural Science Foundation of China(Nos.81673684,81703626,81573690)Double First-Class University projects(No.CPU2018GY33)。
文摘With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.
基金the Prophase Special Funds for Major State Basic Research of China, No.2002ccc00300the Major Emphasized Research Project of the Technology Office of Hubei province, No. 2003AA303B02
文摘AIM： To analyze the gene expression profiles of mice livers injured by Leigongteng and explore the relationship between the differentially expressed genes and liver damage. METHODS： The experimental mice were randomly divided into a control group and a liver-injured group in which the mice were administrated 33 μγ, of triptolide/ kg per day for 30 d. Liver mRNAs were extracted from animals in both groups and were reverse-transcribed to cDNA with dUTP labeled by different fluorescence （Cy3, Cy5） as hybridization probes. The mixed probes were hybridized with oligonucleotide microarray chips. The fluorescent signal results were acquired by scanner and analyzed with software. RESULTS： Among the 35852 target genes, 29 genes were found to be significantly differentially expressed, with 20 genes up-regulated and 9 genes down-regulated. The reliability of the differentially expressed genes was validated by RT-PCR experiments of 5 randomly selected differentially expressed genes. CONCLUSION： Based on the biological functions of the differentially expressed genes, it is obvious that the occurrence and development of liver damage induced by Leigongteng in mice are highly associated with immune response, metabolism, apoptosis and the cell skeleton of liver cells. This might be important for elucidating the regulatory network of gene expression associated with liver damage and it may also be important for discovering the pathogenic mechanisms of liver damage induced by Leigongteng.
基金National Natural Science Foundation of China Granted Project(81273903)
文摘Objective To investigate the inhibitory effect of Tripterygium wilfordii polycoride（TWP） towards the pro-inflammatory factors（TNF-α and IL-1β） on the inflammatory reaction in macrophages induced by LPS and its regulatory effect and influence on the inflammation via TLR4/NF-k B. Methods The MTT method was adopted to test the effect of drugs, TWP, dexamethasone（DXM） and azathioprine（AZA） on cell growth and to select the appropriate concentration. LPS was used to induce the inflammatory reaction in RAW264.7 cell line of mice. Elisa kit was adopted to test the levels of TNF-α and IL-1β. Western blotting was adopted to test the protein expression of TNF-α and IL-1β. RT-PCR was adopted to test the expression of TLR4 and NF-κB. Results The inhibiting effect of TWP on the release of TNF-α and IL-1β in a dose dependent manner. The inhibitory effect of three different TWP dose groups is weaker than that in DXM group. However, TWP in high dose is better than AZA on TNF-α and is as strong as AZA on IL-1β. The dose dependent manner also exits in the effect on the expression of TLR4 and NF-κB, the effect is not weaker, but even stronger than that of DXM and AZA. Conclusion The research shows that down regulation of TLR4 and NF-k B p65 may be one of the mechanisms about the TWP inhibitory effect on TNF-α and IL-1β.
文摘Two new terpenes,triptobenzene P（1）and wilforone（2）were isolated from Tripterygium wilfordii,as well as 10 known terpenes.Their structures were elucidated by spectroscopic methods.Compounds 2-4,8,10,and 11 showed significant immunosuppressive activities.
基金the grants from National key research and development program(No.2018YFC1705200)the Beijing Municipal Science&Technology Commission(No.Z161100001816046)
文摘OBJECTIVE: To investigate the effectiveness a cream onjoint pain and swelling in patients with rheumatoid arthritis(RA). The cream, topically used, in was prepared with Tripterygium wilfordii Hook F(TwHF), Mangxiao(Nalrii Sulfas), Chuanxiong(Rhizoma Chuanxiong), stir-frying with liquid adjuvant Ruxiang(Olibanum), and stir-frying with liquid adjuvant Moyao(Myrrh).METHODS: Patients were 1∶1 randomized to addon TwHF cream twice a day or placebo for 4 weeks.The primary endpoint was achievement rate of20% improvement in American College of Rheuma-tology criteria(ACR20) at week 4. Secondary endpoints were ACR50, 28-joint count Disease Activity Score(DAS28) improvement and safety profiles.Statistical analyses were performed using intention to treat analysis(ITT) set.RESULTS: A total of 70 active RA patients were enrolled. At week 4, the ACR20 was 34.3%(12/35) in TwHF cream group and 11.4%(4/35) in placebo group(P = 0.015). Similarly, a higher ACR50 responder proportion was seen in TwHF cream group with 17.1%(6/35) comparing to it in placebo group with 2.9%(1/35)(P = 0.046). The TwHF cream group also had more improvement than the placebo group on DAS28-ESR(1.1 vs 0.5, P = 0.001), DAS28-CRP(1.4 vs 0.7, P = 0.001), tender joint count(5.5 vs2.6, P = 0.018), swollen joint count(3.5 vs 1.6, P =0.003) and Physician's global assessment(25.8 vs13.0, P = 0.002), as well as C-reactive protein(11.2 vs 2.7, P = 0.048). Except 2 skin allergy events in TwHF cream group, no other substantive adverse events were observed.CONCLUSION: On the short term, TwHF cream is likely to be an effective and safety complimentary treatment in patients with active RA.
基金supported by China Postdoctoral Science Foundation,No.2016M590757the Postdoctoral Science Foundation of Xiangya Hospital of Central South University of China,No.20+4 种基金the Hunan Provincial Natural Science Foundation of China,No.2015JJ6010a grant from the Basic Research Program of Science and Technology Commission Foundation of Hunan Province of China,No.2015JC3059the Project Fund of the Department of Education in Hunan Province of China,No.15A023,13C1107the Scientific Research Project Fund of Health Department of Hunan Province of China,No.B2011-071,B2016096a grant from the Construction Program of the Key Discipline in Hunan Province of China
文摘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-dependent- ly 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/PS 1 double transgenic mice with Alzheimer＇s disease.
基金supported by the Youth Talent Project of Science and Technology Department, Fujian Province (No. 2007F3017)the Research Project of the Forestry Department, Fujian Province (Minlin 2004 Kehan No. 8)
文摘In this study a reliable protocol was developed for the establishment of commercial in vitro cultures of Tripterygium wilfordii Hook f.. Juvenile shoots from one-year-old elite plants were used as the source of explants. New axillary shoots were obtained after 30 days of culture on a MS medium supplemented with BAP （2.0 mg.L^-1） and NAA （0.1 mg.L^-1）. The optimal multiplication medium was a modified MS medium supplemented with BAP （1.0 mg.L^-1） and NAA （0.1 mg.L^-1）. This yielded a multiplication rate of 2.4 for each subculture. Slightly more than 92% of shoots rooted when cultured on a modified MS medium containing IBA （0.2 mg.L^-1） and activated charcoal （0.5 mg.L^-1）. Activated charcoal promoted both a strong and a high rooting rate during the rooting phase. Plantlets were transferred to pots for a short acclimatization stage in a greenhouse where 95% of the plantlets survived. This highly reproducible procedure can be adopted for large-scale propagation of T. wilfordii.
基金supported by the National Natural Science Foundation of China(Nos.81422053 and 81373906 to Wei Gao,and No.81325023 to Luqi Huang)the National High Technology Research and Development Program of China(863 Program,No.2015AA0200908)
文摘The 4-hydroxy-3-methylbut-2-enyl diphosphate reductase(HDR) is the last step key enzyme of the methylerythritol phosphate(MEP) pathway,synthesizing isopentenyl diphosphate and its allyl isomer dimethylallyl diphosphate,which is important for regulation of isoprenoid biosynthesis.Here the full-length cDNA of HDR,designated TwHDR(GenBank Accession No.KJ933412.1),was isolated from Tripterygium wilfordii for the first time.TwHDR has an open reading frame(ORF) of 1386 bp encoding461 amino acids.TwHDR exhibits high homology with HDRs of other plants,with an N-terminal conserved domain and three conserved cysteine residues.TwHDR cDNA was cloned into an expression vector and transformed into an Escherichia coli hdr mutant.Since loss-of-function E.coli hdr mutant is lethal,the result showed that transformation of TwHDR cDNA rescued the E.coli hdr mutant.This complementation assay suggests that the TwHDR cDNA encodes a functional HDR enzyme.The expression of TwHDR was induced by methyl-jasmonate(MJ) in T.wilfordii suspension cells.The expression of TwHDR reached the highest level after 1 h of MJ treatment.These results indicate that we have identified a functional TwHDR enzyme,which may play a pivotal role in the biosynthesis of diterpenoid triptolide in T.wilfordii.
基金supported by National Natural Science Foundation of China(Nos.81173651,81320108029,and 81303301)2011 Program for Excellent Scientific,Technological Innovation Team of Jiangsu Higher Educationthe 111 Project(No.111-2-07)
文摘The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside(GTW) against testosterone-induced benign prostatic hyperplasia(BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group(sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg-1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg-1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone(DHT) levels in serum and prostate, and the serum prostate specific antigen(PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.
基金supported by the Natural Science Foundation of Fujian Province,China(No. 2009J01103).
文摘Three new sesquiterpene alkaloids,1-desacetylwilforgine（1）,1-desacetylwilforine（2）,and 9′-hydroxy-2-nicotinoylwilforine （3） were isolated from the roots of Tripterygium wilfordii Hook f.,along with six known alkaloids.Their structures were established on the basis of spectral analysis.
基金National Natural Science Foundation of China Granted Project(No.81273903 and No.81673798)
文摘Objective To study the protective effect of Tripterygium wilfordii polycoride（TWP） against TNBS/ethanol-induced ulcerative colitis（UC） rat model. Methods TNBS and ethanol enema were adopted to build TNBS/ethanol-induced UC rat model. Ninety male Wistar rats were divided into six groups： normal, model, low-, medium-, high-dose TWP and azathioprine（AZA） groups, each for 15 rats. All rats were administered by corresponding medicine for 14 d. After 14 d, corresponding colon tissues underwent general and microscopic evaluation. Blood samples were taken from heart and serum was separated by centrifugation. MDA, SOD, GSH, IL-1β and TNF-α levels in serum were tested by ELISA. Colonic samples underwent RT-PCR and Western blotting analysis. Results DAI, general and microscopic evaluation all showed that TWP could promote colonic mucosa healing and such effect was equal to AZA. ELISA results about lipid peroxidation indicated that TWP could decrease MDA level and increase SOD and GSH levels in a dose-dependent manner. TWP with high dose could strongly decrease the MDA level and increase the SOD and GSH levels（P 〈 0.01）. ELISA results about inflammatory cytokines indicated that TWP could inhibit the expression of IL-1β and TNF-α in a dose-dependent manner. Western blotting analysis and RT-PCR all indicated that no matter in mR NA level or protein level, TWP could inhibit the expression of NF-κB, TNF-α, IL-1β, and IFN-γ in a dose-dependent manner. The inhibitory effect of AZA towards NF-κB was slightly weaker than TWP with high dose（P 〉 0.05）, whereas slightly stronger towards terminal inflammatory cytokines（P 〉 0.05）. Conclusion TWP could significantly lower the infiltration of inflammatory cells under microscope, eventually led to mucosa healing, the mechanism of which was to inhibit lipid peroxidation, then further inhibit NF-κB activation, eventually lower the expression of inflammatory meditors locally and systemically.
文摘Objective To investigate the possible bone changes in female patients with systemic lupus erythematosus (SLE) induced by long term administration of Tripterygium Wilfordii Hook F (TW) Methods 70 female SLE patients were divided into 4 groups accordiog to their drug history: SLE disease control group, corticosteroids treatment group, TW treatment group, and both corticosteroids and TW treatment group Bone mineral density (BMD) of the lumbar spine 2-4 and biochemical markers of bone turnover were studied Results Long term administration of TW could significantly decrease BMD levels in female SLE patients ( P <0 05) The patients receiving TW for more than 5 years had significantly lower BMD levels compared with those for less than 5 years The degree of decreased BMD induced by TW was less severe compared with that of prednisone No significant differences were observed in the biochemical markers of bone turnover among four groups ( P >0 05) Conclusion Long term administration of TW could decrease BMD levels in women Osteoporosis may be an important problem for SLE patients treated with TW
文摘Considerable efforts have been made to develop a male contraceptive and the studies have provided very useful infor-mation in this field. At least five different strategies to develop a male contraceptive have been pursued, namely: inhi-bition of sperm production, interference with sperm function, interruption of sperm transport, prevention of sperm de-position, and prevention of sperm-egg interaction. Of all these approaches, inhibition of sperm production by using an-drogens either alone or in combination with progestins have given the most encouraging results. A nmnber of clinicaltrials substantiate that it is indeed possible to have a reversible, effective and safe hormonal method of contraception. Apostmeiotic and epididymal approach to interfere with sperm function or the secretory and metabolic processes of theepididymis is another attractive option of male contraceptive development. A number of chemical compounds have beenidentified which interfere with sperm function in the epididymis without affecting sperm production, however, the com-pounds evaluated so far were found to be toxic. Interruption of sperm transport through the vas either by vasectomy orpercutaneous intmvasal injection of liquids which form cure-in-place plugs is also an attractive option. However, re-versibility of the methods is of concern in their wide scale use. The major constraint in developing a long-acting male contraceptive seems to be the need for greater investment forproduct development. The clinical trials for evaluating the efficacy and safety of the new products and formulationsstretch over several years and require enormous financial commitment. Nevertheless, the long-term gain of having along-acting reversible contraceptive for men is far greater than the financial commitments over few years. Male attitudetowards using methods of family planning is much more favourable than originally believed. The pharmaceutical indus-try as well as the health care providers therefore have a greater responsibility. For early development
文摘BACKGROUND Rheumatic immune diseases are a group of chronic inflammatory diseases charac-terized by joint and systemic multi-organ involvement,including rheumatoid arthritis,systemic lupus erythematosus,and Sjogren’s syndrome,among others.The pathogenesis of these diseases is related to the abnormal activation and regulatory imbalance of the immune system.The prevalence and morbidity of rheumatic immune diseases are high,imposing a significant burden on patients'quality of life and socio-economic costs.Currently,the treatment of rheumatic immune diseases mainly relies on Western medicine,such as non-steroidal anti-inflammatory drugs,glucocorticoids,disease-modifying antirheumatic drugs,and biologics.However,the therapeutic effects of Western medicine are not ideal,some patients poorly respond or are resistant to Western medicine,and long-term use often causes various adverse reactions.AIM To systematically evaluate the efficacy and safety of Tripterygium wilfordii gly-cosides tablets combined with Western medicine in the treatment of patients with rheumatic immune diseases.METHODS This study conducted a meta-analysis to systematically evaluate the efficacy and safety of Tripterygium wilfordii glycosides tablets combined with Western medicine for patients with rheumatic immune diseases.Chinese and English databases were searched for randomized controlled trials(RCTs)on the treatment of rheumatic immune diseases with Tripterygium wilfordii glycosides tablets combined with Western medicine.The quality of the included studies was assessed using the Cochrane risk of bias assessment tool.Meta-analysis was performed using RevMan 5.4 software.RESULTS The meta-analysis included 11 RCTs involving 1026 patients with rheumatic immune diseases.The combined treatment significantly reduced the risk of disease recurrence(relative risk=1.07,95%confidence interval:1.01-1.15,P<0.05)and showed no significant heterogeneity(I2=0%,P=0.53),indicating that Tripterygium wilfordii glycosides tablets combined with Western medicine is an e
