Aim To study the chemical constituents of seeds of Herpetospermum caudigerum. Methods Column chromatography was used in the isolation procedure, and the structure was elucidated by spectral data, whose pharmacologic a...Aim To study the chemical constituents of seeds of Herpetospermum caudigerum. Methods Column chromatography was used in the isolation procedure, and the structure was elucidated by spectral data, whose pharmacologic activity was assayed in vitro. Results A new compound named herpetin was isolated, whose structure was determined to be 3-benzofuran methanol-2, 3-dihydm-2-（4- hydroxy-3-methoxyphenyl ）-4-methoxy-6-[ tetrahydm-2-（ 3-hydroxy-4-methoxyphenyl ）-3-methanol ]-2- furanmethyl, showed significant inhibitory effects on HBV-DNA and the replication and expression of HBsAg and HBeAg. Conclusion Herpetin offers wide research and development prospect.展开更多
The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(H...The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.展开更多
Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflamm...Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflammation.Methods:Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice.The protein levels of interferon-γ(IFN-γ),tumor necrosis factor-a(TNF-a),and interleukin-17A(IL-17A)in mouse skin samples were examined using immunohistochemical staining.In vitro,IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1(ICAM-1)and chemokine CXC ligand 9(CXCL9)using Western blotting and reverse transcription-quantitative polymerase chain reaction.The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.Results:EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ,TNF-a,and IL-17A in psoriatic lesions.Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes.Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression.Seven primary compounds including ehletianol C,dehydrodiconiferyl alcohol,herpetrione,herpetin,herpetotriol,herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Conclusion:Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.展开更多
Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butan...Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum(chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione(HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid(BLA), blood urea nitrogen(BUN), malondialdehyde(MDA), hepatic glycogen(HG), lactic dehydrogenase(LDH), superoxide dismutase(SOD) and glutathione peroxidase(GPx) determined following the recommended procedures provided by the commercial kits. Results: Compared with the control group, the lignans extract(ethyl acetate fraction) of Herpetospermum caudigerum and HPE could significantly prolonged the exhaustive swimming time(P<0.05 or P<0.01), and also increased the HG levels(P<0.05 or P<0.01) and the activities of antioxidant enzymes(SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups(P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group(P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters. Conclusions: The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.展开更多
文摘Aim To study the chemical constituents of seeds of Herpetospermum caudigerum. Methods Column chromatography was used in the isolation procedure, and the structure was elucidated by spectral data, whose pharmacologic activity was assayed in vitro. Results A new compound named herpetin was isolated, whose structure was determined to be 3-benzofuran methanol-2, 3-dihydm-2-（4- hydroxy-3-methoxyphenyl ）-4-methoxy-6-[ tetrahydm-2-（ 3-hydroxy-4-methoxyphenyl ）-3-methanol ]-2- furanmethyl, showed significant inhibitory effects on HBV-DNA and the replication and expression of HBsAg and HBeAg. Conclusion Herpetin offers wide research and development prospect.
基金financially supported by the National Key New Drugs Innovation Foundation(No.2016X09101073)the National Natural Science Foundation of China(No.81573697)
文摘The present study was designed to improve storage stability and oral bioavailability of Ganneng dropping pills(GNDP) by transforming lignans of Herpetospermum caudigerum(HL) composed of herpetrione(HPE) and herpetin(HPN) into nanosuspension(HL-NS), the main active ingredient of GNDP, HL-NS was prepared by high pressure homogenization and lyophilized to transform into solid nanoparticles(HL nanoparticles), and then the formulated HL nanoparticles were perfused into matrix to obtain NS-GNDP by melting method. For a period of 3 months, the content uniformity, storage stability and pharmacokinetics test in vivo of NS-GNDP were evaluated and compared with regular GNDP at room temperature. The results demonstrated that uniformity of dosage units of NS-GNDP was acceptable according to the criteria of Chinese Pharmacopoeia 2015 J. Physical stability of NS-GNDP was investigated systemically using photon correlation spectroscopy(PCS), zeta potential measurement, and scanning electron microscopy(SEM). There was a slight increase in particles and PI of HL-NS re-dispersed from NS-GNDP after storage for 3 months, compared with new formulated NS-GNDP, which indicated a good redispersibility of the NS-GNDP containing HL-NS after storage. Besides, chemical stability of NS-GNDP was studied and the results revealed that HPE and HPN degradation was less when compared with that of GNDP, providing more than 99% of drug residue after storage for 3 months. In the dissolution test in vitro, NS-GNDP remarkably exhibited an increased dissolution velocity compared with GNDP and no distinct dissolution difference existed within 3 months. The pharmacokinetic study showed that HPE and HPN in NS-GNDP exhibited a significant increase in AUC0–t, Cmax and decrease in Tmax when compared with regular GNDP. These results indicated that NS-GNDP possessed superiority with improved storage stability and increased dissolution rate and oral bioavailability.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82174202,No.32270407 and No.82074428)Natural Science Foundation of Sichuan Province(Grant No.2022NSFSC0726)+2 种基金Innovative Team Projects of Shanghai Municipal Commission of Health(Grant No.2022CX001)Innovation Foundation of the Affiliated Hospital of Chengdu University(Grant No.CDFYCX202209)Major Research and Development Plan of Xizang Autonomous Region(Grant No.XZ202201ZY0031G).
文摘Objective:To explore whether the ethanol extract of Herpetospermum caudigerum Wall(EHC),a Xizang medicinal plant traditionally used for treating liver diseases,can improve imiquimod-induced psoriasis-like skin inflammation.Methods:Immunohistochemistry and immunofluorescence staining were used to determine the effects of topical EHC use in vivo on the skin pathology of imiquimod-induced psoriasis in mice.The protein levels of interferon-γ(IFN-γ),tumor necrosis factor-a(TNF-a),and interleukin-17A(IL-17A)in mouse skin samples were examined using immunohistochemical staining.In vitro,IFN-γ-induced HaCaT cells with or without EHC treatment were used to evaluate the expression of keratinocyte-derived intercellular cell adhesion molecule-1(ICAM-1)and chemokine CXC ligand 9(CXCL9)using Western blotting and reverse transcription-quantitative polymerase chain reaction.The protein synthesis inhibitor cycloheximide and proteasome inhibitor MG132 were utilized to validate the EHC-mediated mechanism underlying degradation of ICAM-1 and CXCL9.Results:EHC improved inflammation in the imiquimod-induced psoriasis mouse model and reduced the levels of IFN-γ,TNF-a,and IL-17A in psoriatic lesions.Treatment with EHC also suppressed ICAM-1 and CXCL9 in epidermal keratinocytes.Further mechanistic studies revealed that EHC suppressed keratinocyte-derived ICAM-1 and CXCL9 by promoting ubiquitin–proteasome-mediated protein degradation rather than transcriptional repression.Seven primary compounds including ehletianol C,dehydrodiconiferyl alcohol,herpetrione,herpetin,herpetotriol,herpetetrone and herpetetrol were identified from the EHC using ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry.Conclusion:Topical application of EHC ameliorates psoriasis-like skin symptoms and improves the inflammation at the lesion sites.
基金Supported by the National Key New Drugs Innovation Foundation(No.2009ZX09103-349)the Beijing Natural Science Foundation(No.7122176)
文摘Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum(chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione(HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid(BLA), blood urea nitrogen(BUN), malondialdehyde(MDA), hepatic glycogen(HG), lactic dehydrogenase(LDH), superoxide dismutase(SOD) and glutathione peroxidase(GPx) determined following the recommended procedures provided by the commercial kits. Results: Compared with the control group, the lignans extract(ethyl acetate fraction) of Herpetospermum caudigerum and HPE could significantly prolonged the exhaustive swimming time(P<0.05 or P<0.01), and also increased the HG levels(P<0.05 or P<0.01) and the activities of antioxidant enzymes(SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups(P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group(P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters. Conclusions: The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.
