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1.
Pharm Biol ; 61(1): 213-227, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36688426

RESUMO

CONTEXT: Guilu-Erxian-Glue (GLEXG) is a traditional Chinese formula used to improve male reproductive dysfunction. OBJECTIVE: To investigate the ferroptosis resistance of GLEXG in the improvement of semen quality in the oligoasthenospermia (OAS) rat model. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats were administered Tripterygium wilfordii polyglycoside, a compound extracted from Tripterygium wilfordii Hook F. (Celastraceae), at a dose of 40 mg/kg/day, to establish an OAS model. Fifty-four SD rats were randomly divided into six groups: sham, model, low-dose GLEXG (GLEXGL, 0.25 g/kg/day), moderate-dose GLEXG (GLEXGM, 0.50 g/kg/day), high-dose GLEXG (GLEXGH, 1.00 g/kg/day) and vitamin E (0.01 g/kg/day) group. The semen quality, structure and function of sperm mitochondria, histopathology, levels of oxidative stress and iron, and mRNA levels and protein expression in the Keap1/Nrf2/GPX4 pathway, were analyzed. RESULTS: Compared with the model group, GLEXGH significantly improved sperm concentration (35.73 ± 15.42 vs. 17.40 ± 4.12, p < 0.05) and motility (58.59 ± 11.06 vs. 28.59 ± 9.42, p < 0.001), and mitigated testicular histopathology. Moreover, GLEXGH markedly reduced the ROS level (5684.28 ± 1345.47 vs. 15500.44 ± 2307.39, p < 0.001) and increased the GPX4 level (48.53 ± 10.78 vs. 23.14 ± 11.04, p < 0.01), decreased the ferrous iron level (36.31 ± 3.66 vs. 48.64 ± 7.74, p < 0.05), and rescued sperm mitochondrial morphology and potential via activating the Keap1/Nrf2/GPX4 pathway. DISCUSSION AND CONCLUSIONS: Ferroptosis resistance from GLEXG might be driven by activation of the Keap1/Nrf2/GPX4 pathway. Targeting ferroptosis is a novel approach for OAS therapy.


Assuntos
Ferroptose , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Tripterygium , Fator 2 Relacionado a NF-E2/metabolismo , Análise do Sêmen , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Sementes , Ferro/metabolismo , Transdução de Sinais
2.
Pharm Biol ; 61(1): 324-336, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36694954

RESUMO

CONTEXT: Tripterygium glycosides (TG), a traditional Chinese medicine, has been used to treat chronic urticaria (CU) in China, and the evidence of TG for CU needs to be updated thoroughly. OBJECTIVE: To systematically evaluate the efficacy and safety of TG combined with H1-antihistamine (H1-AH) in adults with CU. METHODS: Eligible randomized controlled trials were searched in eight databases until May 31, 2022, including CNKI, WanFang, VIP, SinoMed, PubMed, Cochrane Library, Embase, and Web of Science. The search terms included urticaria, Tripterygium, Lei Gong Teng, and Leigongteng. Rev Man 5.3 and Stata 12.0 were used for statistical analysis. RESULTS: A total of 27 studies with 2788 patients were included. The pooled results showed that TG plus H1-AH was superior to H1-AH alone in cure rate (RR = 1.37, 95% CI = 1.15 to 1.63, p = 0.0003), total efficacy rate (RR = 1.40, 95% CI = 1.30 to 1.50, p < 0.00001), pruritus (MD = -0.32, 95% CI = -0.54 to -0.11, p = 0.003), wheal number (MD = -0.31, 95% CI = -0.55 to -0.07, p = 0.01), wheal size (MD = -0.32, 95% CI = -0.46 to -0.19, p < 0.00001), and the serum level of immunoglobulin E (SMD = -1.39, 95% CI = -2.42 to -0.36, p = 0.008). Moreover, adverse events between two groups were mild, and their incidences were not significantly different. CONCLUSIONS: The combination of TG and H1-AH is a promising and safe treatment for adults with refractory CU. Further high-quality studies are needed to confirm the evidence.


Assuntos
Urticária Crônica , Medicamentos de Ervas Chinesas , Humanos , Adulto , Tripterygium , Glicosídeos/efeitos adversos , Cobre , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/efeitos adversos
3.
BMC Complement Med Ther ; 23(1): 9, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627617

RESUMO

BACKGROUND: Tripterygium wilfordii Hook. F. (TwHF), a traditional Chinese medicine, is widely used in the treatment of rheumatoid arthritis. Due to multiorgan toxicity, particularly hepatotoxicity, the application of TwHF is restricted. To clarify the hepatotoxic substances, zebrafish, hepatocytes and macrophages were used for screening based on hepatotoxic injury patterns. This study provides a basis for further elucidation of the hepatotoxic mechanism of TwHF. METHODS: First, 12 compounds were selected according to the chemical categories of TwHF. The fluorescence area and fluorescence intensity of zebrafish livers were observed and calculated. The viability of two hepatocyte lines was detected by CCK8 assay. TNF-α and IL-1ß mRNA expression in bone marrow-derived macrophages was used to evaluate macrophage activation, a factor of potential indirect hepatotoxicity. Finally, the hepatotoxic characteristics of 4 representative components were verified in mice in vivo. RESULTS: Parthenolide, triptolide, triptonide, triptobenzene H, celastrol, demethylzeylasteral, wilforlide A, triptotriterpenic acid A and regelidine significantly reduced the fluorescence area and fluorescence intensity of zebrafish livers. The viability of L-02 or AML-12 cells was significantly inhibited by parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, and triptotriterpenic acid A. Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral and triptobenzene H significantly increased TNF-α and IL-1ß mRNA levels in macrophages, while triptophenolide, hypodiolide and wilforine significantly reduced TNF-α and IL-1ß mRNA levels. Triptotriterpenic acid A, celastrol and triptobenzene H at a dose of 10 mg/kg significantly increased the levels of mouse serum alanine aminotransferase and aspartate aminotransferase and aggravated liver inflammation. CONCLUSIONS: Parthenolide, triptolide, triptonide, celastrol, demethylzeylasteral, triptotriterpenic acid A and triptobenzene H might be the main hepatotoxic components of TwFH. Among them, only triptotriterpenic acid A presents direct hepatotoxicity. Triptobenzene H exerts indirect liver damage by activating macrophages. Parthenolide, triptolide, triptonide, celastrol, and demethylzeylasteral can directly and indirectly cause liver injury.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Camundongos , Animais , Tripterygium/química , Peixe-Zebra , Fator de Necrose Tumoral alfa , RNA Mensageiro
4.
Pharm Biol ; 61(1): 80-88, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36541729

RESUMO

CONTEXT: Qingluotongbi formula (QLT) is a Chinese medicine compound consisting of Tripterygium wilfordii Hook. f. (Celastraceae, TW), Panax notoginseng (Burkill) F.H.Chen (Araliaceae, PN), Rehmannia glutinosa (Gaertn.) DC. (Orobanchaceae, RG), Sinomenium acutum (Thunb.) Rehder & E.H. Wilson (Menispermaceae, SA), and Bombyx mori L. (Bombycidae, BM). OBJECTIVE: This study investigated the protective effect and possible mechanism of QLT against TW-induced liver injury in mice. MATERIALS AND METHODS: To establish the model of TW-induced liver injury in mice, C57BL/6J mice were randomly divided into 4 groups: control group, low-dose TW group, middle-dose TW group, and high-dose TW group. To observe the effects of QLT and its individual ingredients against TW-induced liver injury, C57BL/6J mice were randomly divided into 7 groups: control group, TW group, QLT group, PN group, RG group, SA group, BM group.After administration for 7 days, C57BL/6J mice were tested for biochemical indicators and liver pathological changes. Then, we evaluated the mitochondrial function and analysed the gene and protein expression related to the peroxisome proliferator-activated receptor alpha (PPARα)/peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) pathway by quantitative real-time PCR (qRT-PCR) and Western blotting. RESULTS: Compared with the control group (0.30 ± 0.35), TW significantly increased mice liver histological score (L, 0.95 ± 1.14; M, 1.25 ± 1.16; H, 4.00 ± 1.13). QLT and its ingredients significantly improved the pathology scores (CON, 0.63 ± 0.74; TW, 4.19 ± 1.53; QLT, 1.56 ± 0.62; PN, 1.94 ± 0.68; RG, 2.75 ± 1.39; SA, 4.13 ± 0.99; BM, 4.13 ± 0.99). Western blot and qRT-PCR analysis revealed that QLT and its ingredients reversed TW-induced suppression of PPARα/PGC1-α pathway.Discussion and conclusions: These findings provide valuable information for compound compatibility studies and TW clinical applications.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Tripterygium , Camundongos , Animais , Tripterygium/química , PPAR alfa/genética , PPAR alfa/metabolismo , PPAR alfa/farmacologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos C57BL , Fígado , Ácidos Graxos/farmacologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
5.
Eur Rev Med Pharmacol Sci ; 26(23): 8756-8770, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36524494

RESUMO

OBJECTIVE: To evaluate the effects and safety of Tripterygium wilfordii polyglycoside (TWP) in the treatment of immunoglobulin A (IgA) nephropathy. SUBJECTS AND METHODS: A computer-assisted study search of Chinese Biomedical Database (CBM), Chinese Journal Full-text Database (CNKI), Wanfang Database, Chinese Scientific Journal Database (VIP), PubMed, Medline, EMBASE and Cochrane Library was performed, with the time range of retrieval set between the establishment of the database to December 31, 2019. Articles of randomized controlled trials on the treatment of IgA nephropathy by Tripterygium wilfordii polyglycoside were collected, and then screened according to the inclusion and exclusion criteria. Next, the quality of the papers was assessed, effective data were extracted, and a meta-analysis of the included studies was conducted using the Review Manager 5.3 software provided by the Cochrane Collaboration. RESULTS: Thirty randomized controlled trials (RCT) were included ultimately, and the meta-analysis showed that 1) Single (Sgl) TWP group was superior to angiotensin-converting enzyme inhibitor/angiotension receptor blocker (ACEI/ARB) group in terms of complete remission [odds ratio (OR) = 4.74, p-value < 0.00001], total remission (OR = 3.90, p-value < 0.0001), 24-hour proteinuria [mean difference (MD) = 1.18, p-value < 0.00001], and serum albumin (MD = - 8.23, p-value < 0.00001), and no significant difference in serum creatinine (MD = 2.09, p-value = 0.08) was found between Sgl TWP and control groups; TWP + ACEI/ARB group was superior in complete remission (OR = 2.57, p-value < 0.00001), total remission (OR = 4.36, p-value < 0.00001), serum albumin [standardized mean difference (SMD) = -0.68, p-value = 0.0005], 24-hour proteinuria (SMD = 1.24, p-value < 0.00001) and serum creatinine (SMD = 0.48, p-value = 0.006); 2) TWP group was superior to glucocorticoid group in complete remission (OR = 1.93, p-value < 0.0010), total remission (OR = 3.71, p-value < 0.00001), serum albumin (MD = -3.50, p-value = 0.002), 24-hour proteinuria (SMD = 0.93, p-value < 0.0001) and serum creatinine (SMD = 0.88, p-value = 0.006); 3) TWP group was better than mycophenolate mofetil (MMF) group in complete remission (OR = 2.05, p = 0.005), total remission (OR = 3.30, p-value = 0.002), 24-hour proteinuria (MD = 2.61, p-value < 0.0001), and serum albumin (MD = -6.43, p-value < 0.00001), but the differences in serum creatinine (MD = 1.28, p-value = 0.89) between TWP and control groups were not significant. Besides, TWP + ACEI/ARB group had a higher adverse reaction rate than the control group (OR = 2.21, p-value = 0.04), but there was no significant difference in the adverse reaction rate between other control and experimental groups (p-value > 0.05). CONCLUSIONS: The present evidence shows that Tripterygium wilfordii polyglycoside can effectively improve the remission rate, reduce proteinuria, and protect kidney function of IgA nephropathy patients, and also has good safety. However, limited by the quality of the included studies, the effects and safety of Tripterygium wilfordii polyglycoside in the treatment of IgA nephropathy need to be verified by more high-quality, large-scale, multi-center RCTs.


Assuntos
Glomerulonefrite por IGA , Tripterygium , Humanos , Tripterygium/efeitos adversos , Glomerulonefrite por IGA/tratamento farmacológico , Creatinina , Antagonistas de Receptores de Angiotensina , Proteinúria , Albumina Sérica
6.
Molecules ; 27(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364101

RESUMO

Tripterygium wilfordii Hook. f. is a well-known traditional Chinese medicine used to treat autoimmune diseases. Sesquiterpene pyridine alkaloids (SPAs) are a major class of components found in this herb that have piqued the interest of researchers due to their complex and diverse structures as well as significant biological activities. In this study, ten new SPAs, wilfordatine A-J (1-10), were isolated from the roots of T. wilfordii, along with ten known analogues (11-20). Their structures were primarily elucidated by extensive 1D and 2D NMR spectroscopic analysis. To search for more immunosuppressive ingredients related to the clinical efficacy of T. wilfordii, the total alkaloids (TA) and compounds 4, 5, and 9-16 were tested for their inhibitory effects on nuclear factor-kappa B (NF-κB) pathway in Lipopolysaccharide (LPS) induced HEK293/NF-κB-Luc cells. Among them, TA, compounds 5, 11, and 16 showed potent immunosuppressive activity, with IC50 values of 7.25 µg/mL, 8.75 µM, 0.74 µM, and 15.66 µM, respectively, and no influence on the cell viability at a concentration of 100 µg/mL (TA) or 100 µM (5, 11, and 16). Accordingly, TA, 5, 11, and 16, especially 11, were identified as promising candidates for further investigation into their potential use as immunosuppressive agents.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Humanos , Tripterygium/química , NF-kappa B , Células HEK293 , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Alcaloides/farmacologia , Alcaloides/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Piridinas/farmacologia , Piridinas/química , Imunossupressores/farmacologia
7.
Syst Rev ; 11(1): 226, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36271453

RESUMO

BACKGROUND: Recently, several systematic reviews (SRs) and meta-analyses (MAs) of Tripterygium wilfordii polyglycoside (TWP) have reported significant benefits on diabetic kidney disease (DKD). However, the adoption of TWP for DKD remains uncommon. This study aimed to evaluate and summarize the current evidence on TWP for DKD. METHODS: We searched PubMed, Web of Science, SINOMED, Embase, Cochrane Library, CNKI database, Wan Fang database, and VIP database, up to June 4, 2022. SRs of TWP on DKD were included. Two authors independently assessed eligibility, extracted data, and graded the quality of evidence. We appraised the reporting and methodological quality of the included studies based on the PRISMA statement and AMSTAR 2. RESULTS: We included 19 SRs and MAs. Seventeen MAs of proteinuria were identified; all suggested TWP exhibited anti-proteinuria function on DKD. Of these, only 2 were graded as moderate quality of evidence. Eighteen MAs estimated the reno-protective effect of TWP; nine of them showed that TWP improved renal function, including 2 MAs rated as moderate quality of evidence. Eleven SRs showed the serum albumin level was elevated in the TWP group. Of those, four were rated as moderate quality of evidence. Fourteen MAs of the incidence of adverse events were included. Twelve MAs indicated TWP increased the risk of adverse events, of which 4 were graded with moderate quality of evidence. Twenty of the 27 items in the PRISMA checklist were adequately reported with more than 75% compliance among the included SRs, while five of the 12 items in the PRISMA checklist for abstract were found to have less than 50% compliance. The overall reporting quality of SRs published in English was higher than that in Chinese. The methodological quality of the included SRs appraised by AMSTAR-2 ranged from critically low to moderate. CONCLUSION: TWP appears effective for DKD on improving proteinuria and increasing the level of serum albumin, accompanied by a higher risk of adverse events. The evidence would be more credible and valuable to guide decision if the quality of the SRs and primary studies is improved. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021249560.


Assuntos
Nefropatias Diabéticas , Tripterygium , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Tripterygium/efeitos adversos , Revisões Sistemáticas como Assunto , Metanálise como Assunto
8.
Arch Razi Inst ; 77(2): 753-760, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-36284975

RESUMO

Tripterygium wilfordii is a medicinal plant that plays a crucial role in health care programs, especially in developing countries, and had anti-tumor, anti-inflammatory, anti-fertility, anti-bacterial, and other therapeutic effects. This study was designed to determine the anti-proliferative effects of methanolic extract of T. wilfordii on the WRL-68 cell line and the function of polycystin-1 (PC-1). The half-maximal inhibitory concentration (IC50) values were recorded in WRL-68 and AsPC-1 cell lines as 193 µg/ml and 149.2 µg/ml, respectively, at 2-2.55 and 2-2.2 µg/ml methanolic plant concentrations. The maximum cytotoxic activities of the extract on the growth inhibition of WRL-68 and AsPC-1 were generally observed at 97.64% and 95.94% at extract concentrations of 50 µg/ml and 25 µg/ml, respectively. The pharmacognostic profile of T. wilfordii extract was found to be alkaloids, tannins, terpenoides, flavonoids, glycosides, and phenols. The extracts of T. wilfordii were tested through gas chromatography-mass spectrometry showing four peaks representing mostly of 3-Oxobutanol; ethyl acetate; acetic acid ethyl ester; chlorbromuron; 1-(methylthio)-, (E)-; n-Hexadecanoic acid; tetradecanoic acid; and 9-Octadecenoic acid. Therefore, the results of this study revealed that the methanolic extract of T. wilfordii was more potential in inducing anti-proliferative activity of WRL-68 and AsPC-1 human cell lines than the control. In addition, the current study was the first study that reported the anti-proliferative potential of T. wilfordii in the treatment of human embryonic liver WRL-68 cancer cells.


Assuntos
Alcaloides , Tripterygium , Humanos , Animais , Tripterygium/química , Metanol , Canais de Cátion TRPP , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ácido Oleico , Ácido Palmítico , Ácido Mirístico , Flavonoides , Taninos , Fenóis , Anti-Inflamatórios , Acetatos , Linhagem Celular , Glicosídeos , Ésteres
9.
Fitoterapia ; 163: 105333, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36244595

RESUMO

Pentacyclic triterpenoids are important natural products widely presenting in nature with rich bioactivities. Tripterygium wilfordii Hook. f., a precious Chinese medicinal material, is used to cure rheumatoid arthritis, nephrotic syndrome, systemic lupus erythematosus. Triterpenoids are one of the important active components of Tripterygium wilfordii Hook. f. Demethylzeylasteral extracted from Tripterygium wilfordii Hook. f. had numerous pharmacological effects, including anticancer, anti-inflammatory, immune suppression, anti-fertility, antivirus, antimicrobial. In this paper, we summarized comprehensively pharmacological activities of demethylzeylasteral for potential application as a therapeutic agent.


Assuntos
Medicamentos de Ervas Chinesas , Triterpenos , Tripterygium , Estrutura Molecular , Triterpenos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia
10.
Anal Cell Pathol (Amst) ; 2022: 4807028, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061150

RESUMO

Objective: Valsartan has been studied to exert effects on kidney disease. However, the concrete function of valsartan in combination with tripterygium glycosides in chronic nephritis remained largely unknown. The study was designed to unravel the impacts of valsartan and tripterygium glycosides in chronic nephritis through the Toll-like Receptor 4 (TLR4) pathway. Methods: The renal function indicators such as serum creatinine (Scr), blood urea nitrogen (BUN) and ß2 microglobulin (ß2-MG), 24 h urine protein (Upro) levels, and blood lipid indicators such as total cholesterol (TC), low-density lipoprotein (LDL-C), triacylglycerol (TG) and high-density lipoprotein (HDL-C), inflammatory factors (e.g., IL-1ß and IL-8), and the proportion of T lymphocyte subpopulations (CD4+ and CD8+) were detected in chronic nephritis patients before and after treatment with valsartan alone or valsartan combined with tripterygium glycosides. Symptoms of adverse reactions were recorded. TLR4 expression in the patients' serum was examined. Results: Compared to patients before treatment, after treatment with valsartan alone or valsartan combined with tripterygium glycosides, the renal function indicators Scr, BUN, and 24 h levels were reduced, and TC, TG, and LDL-C levels were reduced, while HDL-C levels were elevated; inflammatory responses (IL-1ß and IL-8) were mitigated; CD4+ ratio and CD4+/CD8+ ratio increased yet CD8+ ratio decreased; TLR4 expression was silenced after treatment. All of the changes were more obvious in patients after being treated with valsartan combined with tripterygium glycosides. Conclusion: Valsartan in combination with tripterygium glycosides protects against chronic nephritis via suppressing the Toll-like Receptor 4 pathway.


Assuntos
Glicosídeos , Nefrite , Tripterygium , Valsartana , LDL-Colesterol , Glicosídeos/uso terapêutico , Humanos , Interleucina-1beta , Interleucina-8 , Nefrite/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Tripterygium/química , Valsartana/uso terapêutico
11.
Chin J Nat Med ; 20(9): 691-700, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36162954

RESUMO

Tripterygium hypoglaucum (Levl.) Hutch, a traditional Chinese medicinal herb with a long history of use, is widely distributed in China. One of its main active components, celastrol, has great potential to be developed into anti-cancer and anti-obesity drugs. Although it exhibits strong pharmacological activities, there is a lack of sustainable sources of celastrol and its derivatives, making it crucial to develop novel sources of these drugs through synthetic biology. The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases. Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases (CYP450s). Here, we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum (Levl.) Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast. Through substrate supplementation and in vitro enzyme analysis, ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid, which is considered a vital step in the biosynthesis of celastrol, and will lay a foundation for further analysis of its biosynthetic pathway.


Assuntos
Fármacos Antiobesidade , Triterpenos , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Triterpenos Pentacíclicos , Esqualeno/análogos & derivados , Tripterygium/metabolismo , Triterpenos/metabolismo
12.
J Pharm Biomed Anal ; 221: 115028, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36108463

RESUMO

Tripterygium glycoside tablet (TGT) has been used clinically to alleviate diabetic nephropathy (DN) for decades. However, the mechanism of its anti-DN has not been fully clarified. The aim of this study was to elucidate molecular mechanism of TGT in repairing renal function injury. The results of biochemical parameters and renal histopathology implied that TGT intervention could attenuate creatinine, albumin excretion rate and histological injury of kidney in DN mouse model. Moreover, UHPLC-QTOF-MS/MS-based untargeted metabolomic analysis indicated that 11 metabolites in kidney of mice with DN were restored after TGT treatment, and the most prominent metabolic alteration was triglyceride (TG) metabolism. Mechanistically, TGT effectively improved the function of impaired kidney by promoting TG catabolism via modulation of adipose triglyceride lipase in DN mice. Our findings identified the link between circulating metabolites and DN, suggesting that it might be a possibility to intervene in DN by targeting metabolism.


Assuntos
Glicosídeos Cardíacos , Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Renal , Albuminas , Animais , Creatinina/metabolismo , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Rim/metabolismo , Lipase , Camundongos , Insuficiência Renal/patologia , Comprimidos/metabolismo , Espectrometria de Massas em Tandem , Triglicerídeos , Tripterygium/química
13.
J Tradit Chin Med ; 42(5): 671-680, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36083472

RESUMO

OBJECTIVE: To investigate the effectiveness and safety of tripterygium glycosides (TG) tablet for the treatment of Lupus nephritis (LN). METHODS: Several databases were systematically searched including PubMed, Embase, Cochrane, Wiley, China National Knowledge Infrastructure Database, SinoMed and Wanfang Library till June 20, 2020. Revman5.3 was utilized to analyze the data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. RESULTS: In total, 8 randomized controlled trials involving 583 participants were identified. Meta-analyses showed that, compared with glucocorticoids (GC) alone, the combination with TG tablet provided a statistically significant improvement in total remission (TR) ( = 1.27, 95% : 1.08-1.50, = 0.004), complete remission (CR) ( = 1.61, 95% : 1.05-2.47, = 0.03) and C3 levels ( = 0.27, 95% : 0.14-0.39, < 0.000 1), C4 levels ( = 0.12, 95% : 0.07-0.17, < 0.000 01). No significant differences were seen in TR, CR, proteinuria, serum creatinine, C3 and C4 (TR: = 1.00, 95% : 0.87-1.16, = 0.95; CR: = 1.10, 95% : 0.78-1.56, = 0.58; proteinuria levels: = -0.06, 95% : -0.13 to 0.01, = 0.10; serum creatinine levels: = -0.01, 95%: -7.36 to 7.35, = 1.00; C3 levels: = 0.01, 95%: -0.06 to 0.07, = 0.84; C4 levels: = -0.01, 95%: -0.03 to 0.01, = 0.49) between azathioprine (AZA) / leflomit (LEF) + GC and TG tablet + GC. Adverse events (hepatic dysfunction, nausea, vomitting) showed no statistical differences between the TG tablet + GC group and the GC group. There were more new onset of irregular menstruation in the TG tablet + GC group than those in the AZA + GC ( = 3.57, 95% : 1.40-9.11, = 0.008) /LEF+ GC ( = 6.69, 95% : 2.42-18.46, = 0.000 2) group, but leucopenia lower than those in AZA + GC group ( = 0.38, 95% : 0.17-0.85, = 0.02) and alopecia ( = 0.14, 95% : 0.03-0.77, = 0.02) and rash ( = 0.09, 95% : 0.01-0.69, = 0.02) lower than those in LEF + GC group. CONCLUSIONS: This review indicates that TG tablet maybe effective in LN treatment. Nevertheless, adverse events cannot be ignored. Large sample, multi-center, high-quality clinical studies are needed to verify the exact effects and safety of TG tablet in treatment of LN.


Assuntos
Nefrite Lúpica , Tripterygium , Creatinina , Feminino , Glicosídeos/uso terapêutico , Humanos , Nefrite Lúpica/tratamento farmacológico , Proteinúria/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Comprimidos/uso terapêutico , Tripterygium/química
14.
Zhongguo Zhong Yao Za Zhi ; 47(16): 4292-4304, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046855

RESUMO

Sesquiterpene pyridine alkaloids are important components in Tripterygium plants, possessing a wide range of pharmacological activities, such as anti-inflammation immunosuppression, anti-tumor, anti-virus, and deinsectization, and are of great research value. They are composed of highly oxidized dihydro-ß-furansquiterpene and pyridine dicarboxylic acid through ester bonds. According to the structural characteristics of pyridine dicarboxylic acid fragments, they can be divided into various structural subtypes. Up to now, more than 110 sesquiterpene pyridine alkaloids have been isolated and identified from Tripterygium plants. This study reviewed the structural features and spectral(i.e., UV, IR, MS, and NMR) characteristics of sesquiterpene pyridine alkaloids and summarized the structural elucidation process in detail to provide references for their further research and development.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Sesquiterpenos , Alcaloides/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Estrutura Molecular , Piridinas/química , Piridinas/farmacologia , Tripterygium/química
15.
Comput Math Methods Med ; 2022: 7523673, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35959351

RESUMO

Purpose: This research mainly clarifies the impacts of low-dose- (LD-) total glycosides of Tripterygium wilfordii (GTW) plus methotrexate (MTX) on immunological function and inflammation level in patients with rheumatoid arthritis (RA). Methods: We enrolled 106 RA patients treated in Yanbian University Hospital between July 2019 and July 2021, including 56 cases (research group) intervened by LD-total GTW plus MTX and 50 cases (control group) treated with MTX, in addition to conventional treatment given to both groups. The improvement in immunological function (immunoglobulin (Ig) A, IgG, and IgM), inflammatory cytokines (ICs; C-reaction protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)), incidence of adverse reactions (ARs), joint function, and patient satisfaction were observed and compared. Results: Statistical better improvements of immunological function, ICs, and joint function were observed in the research group compared with the control group. Besides, patient satisfaction was higher and the incidence of ARs was lower in the research group. Conclusions: LD-total GTW plus MTX is highly effective and safe in enhancing the immunity, lowering the inflammation level, and improving the joint function of RA patients.


Assuntos
Artrite Reumatoide , Tripterygium , Artrite Reumatoide/tratamento farmacológico , Glicosídeos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Metotrexato/efeitos adversos , Resultado do Tratamento
16.
Nat Commun ; 13(1): 5011, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008399

RESUMO

The diterpenoid triepoxides triptolide and triptonide from Tripterygium wilfordii (thunder god wine) exhibit unique bioactivities with potential uses in disease treatment and as a non-hormonal male contraceptives. Here, we show that cytochrome P450s (CYPs) from the CYP71BE subfamily catalyze an unprecedented 18(4→3) methyl shift required for biosynthesis of the abeo-abietane core structure present in diterpenoid triepoxides and in several other plant diterpenoids. In combination with two CYPs of the CYP82D subfamily, four CYPs from T. wilfordii are shown to constitute the minimal set of biosynthetic genes that enables triptonide biosynthesis using Nicotiana benthamiana and Saccharomyces cerevisiae as heterologous hosts. In addition, co-expression of a specific T. wilfordii cytochrome b5 (Twcytb5-A) increases triptonide output more than 9-fold in S. cerevisiae and affords isolation and structure elucidation by NMR spectroscopic analyses of 18 diterpenoids, providing insights into the biosynthesis of diterpenoid triepoxides. Our findings pave the way for diterpenoid triepoxide production via fermentation.


Assuntos
Diterpenos , Tripterygium , Sistema Enzimático do Citocromo P-450/genética , Diterpenos/química , Saccharomyces cerevisiae/genética , Tripterygium/genética , Triterpenos
17.
Molecules ; 27(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014337

RESUMO

Tripterygium glycosides tablets (TGTs) are widely used in clinical practice to treat rheumatoid arthritis and other autoimmune diseases, with significant beneficial effects but also high toxicity, necessitating rigorous quality evaluation and control. In current study, a rapid resolution liquid chromatography tandem electrospray ionization triple quadrupole mass spectrometry (RRLC-ESI-MS/MS) method was developed and validated for the quantitative analysis of 14 components of ten batches of TGTs produced by different manufacturers, including four diterpenoids, three triterpenoids, and seven sesquiterpene alkaloids. Meanwhile, the NO inhibition effects of these TGTs were evaluated in LPS-induced RAW264.7 cells for their downstream anti-inflammatory activities, as well as their cytotoxicity. The results indicate that the TGTs from different manufacturers showed poor quality consistency, as evidenced by large variations in chemical profiles and biological effects, which may increase the risks associated with clinical use. To improve the quality status of TGTs, it is crucial to identify indicator components whose characterization can accurately reflect the efficacy and toxicity of TGTs from which they were derived. Our study reveals that triptolide, triptoquinone B, celastrol, and demethylzelaysteral considerably contributed to the anti-inflammatory activity and/or cytotoxicity of TGTs, implying that they should be further investigated as candidate indicator components for TGT quality control.


Assuntos
Medicamentos de Ervas Chinesas , Tripterygium , Bioensaio , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Glicosídeos/química , Comprimidos/química , Espectrometria de Massas em Tandem/métodos , Tripterygium/química
18.
Pharmacol Res ; 184: 106405, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36028187

RESUMO

OBJECTIVES: To explore efficacy and safety, as well as efficacy mechanisms, main efficacy characteristics, and efficacy influencing factors of TG, in combination with one conventional DMARD, to provide guidance for the clinical application of TG in treating RA. METHODS: We searched the databases of PubMed, Embase, Web of Science, Cochrane Library, Ovid, Scopus, Clinicaltrials.gov, CNKI, Wanfang, SinoMed, VIP, Chinese Clinical Trial Registry, KTKP, and J-STAGE to August 12, 2022. All included studies were analyzed with Stata 16.0 software and Review Manager 5.4 software according to the PRISMA Statement. RESULTS: Thirty-eight randomized controlled trials (RCTs) were included. Combined TG was superior in 28-joint count Disease Activity Score (DAS28) and American College of Rheumatology 50 response (ACR50) and did not increase adverse events (AEs). Combined TG significantly suppressed interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). And combined TG showed significant advantages in improving tender joint count (TJC), swollen joint count (SJC), pain score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and physician's and patient's global assessments of disease activity. However, the average age of the intervention population, treatment course, the combined DMARDs category, and the risk of bias were important factors influencing the above effects. CONCLUSIONS: The combination of TG is superior to conventional DMARD monotherapy in improving RA conditions with a good safety profile. This effect is closely related to the mechanism of TG reducing IL-1, IL-6 and TNF-α. And the combination of TG shows better effect in all aspects such as improving joint signs, symptoms, inflammatory indicators, and overall health. But for those under 45 years of age, with short-term intermittent dosing, in combination with MTX may be more beneficial for TG to show better efficacy.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Proteína C-Reativa , Glicosídeos/uso terapêutico , Humanos , Interleucina-1 , Interleucina-6 , Metotrexato/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Tripterygium , Fator de Necrose Tumoral alfa
19.
Fitoterapia ; 161: 105250, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35798062

RESUMO

Three undescribed acylated sucroses (1-3), one undescribed butenolide analog (4) along with three known compounds (5-7) were isolated from the aqueous EtOH extract of the dried leaves of Tripterygium wilfordii. Their structures were elucidated on the basis of spectroscopic analyses, electron circular dichroism (ECD) techniques, and saccharide hydrolysis. All the isolated compounds were tested for their anti-tyrosinase effects. Among them, 6 exhibited similar inhibitory effects on tyrosinase with IC50 values of 0.073 mM comparing to arbutin. Additionally, the possible mechanism of the interaction between 6 and the active site of tyrosinase was explored by molecular docking.


Assuntos
Monofenol Mono-Oxigenase , Tripterygium , 4-Butirolactona/análogos & derivados , Simulação de Acoplamento Molecular , Estrutura Molecular , Tripterygium/química
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(6): 949-954, 2022 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-35790448

RESUMO

OBJECTIVE: To conduct qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets, a compound preparation of traditional Chinese herbal medicine. METHODS: Thin-layer chromatography (TLC) was used for qualitative analysis of Tripterygium hypoglaucum in Yining Tablets and the analytical protocols were optimized. High-performance liquid chromatography (HPLC) was used to quantitatively analyze the content of triptolide (the main active ingredient of Tripterygium hypoglaucum) in Yinning Tablets. RESULTS: The results of TLC analysis showed that the test sample of Yinning Tablets and the positive control samples both produced clear, well separated spots without obvious interference in the blank samples. Assessment of the influences of the thin-layer plates from different manufacturers, temperature and humidity on the test results demonstrated good durability of the test. HPLC analysis of triptolide showed a good linear relationship within the concentration range of 1-100 µg/mL (regression equation: A=22.219C-19.165, r=0.9999); the contents of triptolide in 3 batches of Yinning tablets were 0.34, 0.34, and 0.28 µg per tablet, all within the range of 0.28-0.34 µg per tablet. It was finally determined that each Yinning tablet should not contain more than 0.6 µg of triptolide. CONCLUSION: TLC and HPLC are simple, accurate, durable and specific for qualitative and quantitative analyses of Tripterygium hypoglaucum in Yinning Tablets.


Assuntos
Preparações de Plantas , Tripterygium , China , Cromatografia Líquida de Alta Pressão/métodos , Comprimidos , Tripterygium/química
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