Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypogl...Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum （level） Hutch （Celastraceae） is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect （CPE） assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity （CC50 = 46.6μg/mL） and potent CPE inhibition activity, the 50% inhibitory concentration （ICs0） was 6.5 μg/mL, noticeably lower than that of Acyclovir （15.4μg /mL）. Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75% which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% （UL30）, 70.9% （UL39） and 62.6% （US6） respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.展开更多
The aneuploldy inducing activity of a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH) were investigated by means of thhree cytogenetic end points, namely C-mitotic (CM) effects, micronucleus (MN) ...The aneuploldy inducing activity of a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH) were investigated by means of thhree cytogenetic end points, namely C-mitotic (CM) effects, micronucleus (MN) and parallel chromosome structural aberration (CA) analyses in vivo. The experiments were performed on mouse bone marrow cells. THH showed similar gentoxic effects to colchicine (COL) in CM, MN and CA analyses; positive CM effects were observed accompanied with increases of mitotic index and frequencies of C-mltotic cells as well as decreased frequencies of anaphase in all of the THH-treated groups. The compound showed a positive MN response in bone marrow polychromatic erythrocytes but was negative in CA analyses. The preliminary results suggested that THH is an aneuploldy inducer in mouse bone marrow cells under present experiment conditions.展开更多
Traditionally,Tripterygium hypoglaucum(Levl.)Hutch(THH)are widely used in Chinese folk to treat rheumatoid arthritis(RA).This study aimed to investigate whether the anti-RA effect of THH is related with the gut microb...Traditionally,Tripterygium hypoglaucum(Levl.)Hutch(THH)are widely used in Chinese folk to treat rheumatoid arthritis(RA).This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota.The main components of prepared THH extract were identified by HPLC-MS.C57BL/6 mice with adjuvant-induced arthritis(AIA)were treated with THH extract by gavage for one month.THH extract significantly alleviated swollen ankle,joint cavity exudation,and articular cartilage destruction in AIA mice.The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways.THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice,featuring the increases of Bifidobacterium,Akkermansia,and Lactobacillus and the decreases of Butyricimonas,Parabacteroides,and Anaeroplasma.Furthermore,the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota.In addition,antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora.Strikingly,THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice,which validates the indispensable role of the intestinal flora.For the first time,we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway.Therefore,THH extract may serve as a microbial modulator to recover RA in clincial practice.verRAinclincial practice.展开更多
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 ...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.展开更多
AIM： To investigate the effect of Tripterygium hyp-oglaucum Hutch （THH） on the assembly and disassembly process of tubulin and its possible mode of action.METHODS： In vitro porcine brain tubulin assembly assay was...AIM： To investigate the effect of Tripterygium hyp-oglaucum Hutch （THH） on the assembly and disassembly process of tubulin and its possible mode of action.METHODS： In vitro porcine brain tubulin assembly assay was employed to analyze the inhibitory effects of THH at different concentrations （0.05 μg/L, 0.07 μg/L, 0.09μg/L）. Colchicine （0.0025 mmol/L, 0.0050 mmol/L, 0.0075 mmol/L） was used as a positive control.RESULTS： THH could significantly inhibit the assembly of isolated porcine brain tubulin at all tested concentrations.CONCLUSION： THH is capable of inducing aneuploidy in mammals via tubulin polymerization inhibition pathway and may pose a genetic risk to human beings.展开更多
Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized ...Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.展开更多
Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredien...Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.展开更多
Tripterygium hypoglaucum(Levl.)Hutch.(THH),which belongs to Tripterygium genus of Celastraceae family,is widely used as the common Chinese herbal medicine.It has been reported that the chemical constituents of T.hypog...Tripterygium hypoglaucum(Levl.)Hutch.(THH),which belongs to Tripterygium genus of Celastraceae family,is widely used as the common Chinese herbal medicine.It has been reported that the chemical constituents of T.hypoglaucum include monoterpenoids,sesquiterpenoids,diterpenoids,triterpenoids,sesquiterpene alkaloids,flavonoids,anthraquinone derivatives,et al.These compounds showed a wide range of bioactivities,such as anti-inflammatory,anti-cancer,immunosuppressive,anti-HIV,anti-fertility and insecticidal activities.In this paper,we summarized the chemical constituents and pharmacological activities of T.hypoglaucum to provide a reference for its further research and developement.展开更多
Objective To find antitumor constituents from Tripterygium hypoglaucum.Methods The chloroform extract of T.hypoglaucum was separated by silica gel column chromatography and preparative HPLC.The structures of compounds...Objective To find antitumor constituents from Tripterygium hypoglaucum.Methods The chloroform extract of T.hypoglaucum was separated by silica gel column chromatography and preparative HPLC.The structures of compounds isolated were identified by spectral analysis and chemical evidence.Results Seven compounds were isolated and identified as rhein ethyl ester(1),chrysophenol(2),physcion(3),emodin(4),wilfordine(5),wilforgine(6),and wilforine(7).The cytotoxic activities of the compounds against cancer cell lines were assayed.Conclusion Compound 1 is a new natural compound with strong activities against human cancer cell lines(A2780 and OVCAR-3) .Compounds 2-4 are isolated from this genus plants for the first time.The possible structure-activity relationship among compounds 1-4 shows that the methoxy group or oxyethyl moiety might be responsible for the cytotoxity.展开更多
The natural killer cell activity of peripheral blood mononuclear cells from 28 patients withsystemic lupus erythematosus was measured using enzyme-release assay. The patients exhibited obvi-ously decreased natural kil...The natural killer cell activity of peripheral blood mononuclear cells from 28 patients withsystemic lupus erythematosus was measured using enzyme-release assay. The patients exhibited obvi-ously decreased natural killer cell activity compared with the healthy subjects in the control group. Thenatural killer cell dysfonction was related to steroidal therapy, but not to three auto-antibodies. The re-lease of a soluble natural killer cytotoxic factor by the peripheral blood mononuclear cells was tested bycytotoxicity assay induced in K256 cells. This release was significantly lower in the test group than in thecontrol group. Pre-incubation of peripheral blood mononuclear cells with Astragalus membranaceus andTripterygium hypoglaucum considerably enhanced natural killer cytotoxicity by stimulating the release ofsoluble cytotoxic factors.展开更多
基金The Joint Funds of National Science Foundation of China (U0632010)The State Key Laboratory of Phytochemistry and Plant Resources in West China+1 种基金Chinese Academy of Sciences (O807B11211, O807E21211)"211 grant of MOE"
文摘Herpes simplex virus type 1 （HSV-1） is a commonly occurring human pathogen worldwide. There is an urgent need to discover and develop new alternative agents for the management of HSV-1 infection. Tripterygium hypoglaucum （level） Hutch （Celastraceae） is a traditional Chinese medicine plant with many pharmacological activities such as anti-inflammation, anti-tumor and antifertility. The usual medicinal part is the roots which contain about a 1% yield of alkaloids. A crude total alkaloids extract was prepared from the roots of T. hypoglaucum amd its antiviral activity against HSV-1 in Vero cells was evaluated by cytopathic effect （CPE） assay, plaque reduction assay and by RT-PCR analysis. The alkaloids extract presented low cytotoxicity （CC50 = 46.6μg/mL） and potent CPE inhibition activity, the 50% inhibitory concentration （ICs0） was 6.5 μg/mL, noticeably lower than that of Acyclovir （15.4μg /mL）. Plaque formation was significantly reduced by the alkaloids extract at concentrations of 6.25 μg/mL to 12.5 μg/mL, the plaque reduction ratio reached 55% to 75% which was 35% higher than that of Acyclovir at the same concentration. RT-PCR analysis showed that, the transcription of two important delayed early genes UL30 and UL39, and a late gene US6 of HSV-1 genome all were suppressed by the alkaloids extract, the expression inhibiting efficacy compared to the control was 74.6% （UL30）, 70.9% （UL39） and 62.6% （US6） respectively at the working concentration of 12.5μg/mL. The above results suggest a potent anti-HSV-1 activity of the alkaloids extract in vitro.
文摘The aneuploldy inducing activity of a Chinese medicinal herb, Tripterygium hypoglaucum (level) Hutch (THH) were investigated by means of thhree cytogenetic end points, namely C-mitotic (CM) effects, micronucleus (MN) and parallel chromosome structural aberration (CA) analyses in vivo. The experiments were performed on mouse bone marrow cells. THH showed similar gentoxic effects to colchicine (COL) in CM, MN and CA analyses; positive CM effects were observed accompanied with increases of mitotic index and frequencies of C-mltotic cells as well as decreased frequencies of anaphase in all of the THH-treated groups. The compound showed a positive MN response in bone marrow polychromatic erythrocytes but was negative in CA analyses. The preliminary results suggested that THH is an aneuploldy inducer in mouse bone marrow cells under present experiment conditions.
基金supported by the Health Commission of Hubei Province of China(No.ZY2021Z005)the Major Science and Technology Project in Yunnan Province(No.202102AE090042)。
文摘Traditionally,Tripterygium hypoglaucum(Levl.)Hutch(THH)are widely used in Chinese folk to treat rheumatoid arthritis(RA).This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota.The main components of prepared THH extract were identified by HPLC-MS.C57BL/6 mice with adjuvant-induced arthritis(AIA)were treated with THH extract by gavage for one month.THH extract significantly alleviated swollen ankle,joint cavity exudation,and articular cartilage destruction in AIA mice.The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways.THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice,featuring the increases of Bifidobacterium,Akkermansia,and Lactobacillus and the decreases of Butyricimonas,Parabacteroides,and Anaeroplasma.Furthermore,the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota.In addition,antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora.Strikingly,THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice,which validates the indispensable role of the intestinal flora.For the first time,we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway.Therefore,THH extract may serve as a microbial modulator to recover RA in clincial practice.verRAinclincial practice.
基金supported by the National Key R&D Program of China(No.2020YFA0908000)the National Natural Science Foundation of China(Nos.81773830 and 81973418)the Key Project at Central Government Level:the ability establishment of sustainable use for valuable Chinese medicine resources(No.2060302-1806-03),and the National Program for Special Support of Eminent Professionals.
文摘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.
基金Supported by the National Natural Science Foundation of China,No,30560061 the International Scientific Cooperation Project of Yunnan Province.
文摘AIM： To investigate the effect of Tripterygium hyp-oglaucum Hutch （THH） on the assembly and disassembly process of tubulin and its possible mode of action.METHODS： In vitro porcine brain tubulin assembly assay was employed to analyze the inhibitory effects of THH at different concentrations （0.05 μg/L, 0.07 μg/L, 0.09μg/L）. Colchicine （0.0025 mmol/L, 0.0050 mmol/L, 0.0075 mmol/L） was used as a positive control.RESULTS： THH could significantly inhibit the assembly of isolated porcine brain tubulin at all tested concentrations.CONCLUSION： THH is capable of inducing aneuploidy in mammals via tubulin polymerization inhibition pathway and may pose a genetic risk to human beings.
文摘Objective: To compare the therapeutic effects of Radix Tripterygium hypoglaucum tablet (THT) and Tripterygium glycosides tablet (TGT) in treating erosive oral lichen planus(EOLP).Methods: The patients were randomized into two groups, and they were treated with THT (n=47) or TGT (n=47), respectively. The therapeutic effects were evaluated after 3 months treatment.Results: For the patients of grade 1, the total efficacy in TGT group was 85.71%, compared with 52.38% in THT group, the efficacy was statistically greater in the group receiving TGT (P=0.043). However, for the patients of grade 2, the difference was not statistically significant (P=0.173).Conclusion: TGT is more effective in treating EOLP than THT for grade 1 patients. However, TGT is not suitable for patients of child bearing age.
基金National Natural Science Foundation of China(82360190)Hainan Natural Science Foundation(No.822RC828)Hainan Provincial Department of Education Research Project(No.Hnky2018ZD-7)。
文摘Objective:To explore the potential targets and molecular mechanisms of tripterygium hypoglaucum for oral lichen planus(OLP)by applying network pharmacology and molecular docking technology.Methods:The active ingredients and targets of tripterygium hypoglaucum were screened.OLP-related targets were predicted.The Protein-Protein Interaction(PPI)network was constructed for the intersection targets of tripterygium hypoglaucum and OLP.The“OLP-target-molecule-Tripterygium hypoglaucum”network was constructed and visualized.The intersection genes were screened for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking analysis and visualization were performed.Results:15 active ingredients and 78 targets of tripterygium hypoglaucum were obtained.9109 OLP-related targets were screened,and 54 intersection genes of tripterygium hypoglaucum with OLP were obtained.The top 10 key targets were screened from the constructed PPI network.The top 10 active ingredients of tripterygium hypoglaucum were screened from the constructed“OLP-targets of actionactive ingredients-tripterygium hypoglaucum”network.The GO and KEGG analyses of the 54 intersection targets indicated that tripterygium hypoglaucum may play a therapeutic role by regulating one carbon pool by folate,pathways in cancer,et al.Molecular docking analysis showed that dihydrofolate reductase(DHFR),phosphoribosylglycinamide formyltransferase(GART),estrogen receptor 1(ESR1),et al are the key targets for the treatment of OLP in tripterygium hypoglaucum.Conclusion:The potential key targets and molecular mechanisms of tripterygium hypoglaucum in treating OLP provide a theoretical basis for new drug development and clinical applications.
文摘Tripterygium hypoglaucum(Levl.)Hutch.(THH),which belongs to Tripterygium genus of Celastraceae family,is widely used as the common Chinese herbal medicine.It has been reported that the chemical constituents of T.hypoglaucum include monoterpenoids,sesquiterpenoids,diterpenoids,triterpenoids,sesquiterpene alkaloids,flavonoids,anthraquinone derivatives,et al.These compounds showed a wide range of bioactivities,such as anti-inflammatory,anti-cancer,immunosuppressive,anti-HIV,anti-fertility and insecticidal activities.In this paper,we summarized the chemical constituents and pharmacological activities of T.hypoglaucum to provide a reference for its further research and developement.
基金E&T modern center for Natural Products of Liaoning Province of China (2008402021)
文摘Objective To find antitumor constituents from Tripterygium hypoglaucum.Methods The chloroform extract of T.hypoglaucum was separated by silica gel column chromatography and preparative HPLC.The structures of compounds isolated were identified by spectral analysis and chemical evidence.Results Seven compounds were isolated and identified as rhein ethyl ester(1),chrysophenol(2),physcion(3),emodin(4),wilfordine(5),wilforgine(6),and wilforine(7).The cytotoxic activities of the compounds against cancer cell lines were assayed.Conclusion Compound 1 is a new natural compound with strong activities against human cancer cell lines(A2780 and OVCAR-3) .Compounds 2-4 are isolated from this genus plants for the first time.The possible structure-activity relationship among compounds 1-4 shows that the methoxy group or oxyethyl moiety might be responsible for the cytotoxity.
文摘The natural killer cell activity of peripheral blood mononuclear cells from 28 patients withsystemic lupus erythematosus was measured using enzyme-release assay. The patients exhibited obvi-ously decreased natural killer cell activity compared with the healthy subjects in the control group. Thenatural killer cell dysfonction was related to steroidal therapy, but not to three auto-antibodies. The re-lease of a soluble natural killer cytotoxic factor by the peripheral blood mononuclear cells was tested bycytotoxicity assay induced in K256 cells. This release was significantly lower in the test group than in thecontrol group. Pre-incubation of peripheral blood mononuclear cells with Astragalus membranaceus andTripterygium hypoglaucum considerably enhanced natural killer cytotoxicity by stimulating the release ofsoluble cytotoxic factors.
