Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperre...Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.展开更多
In order to observe the therapeutic effects of Huanglian Fire-Purging Mixture (黄连清降合剂) on primary hypertension, 46 cases of primary hypertension in the treatment group were treated with Huanglian Fire-Purging Mi...In order to observe the therapeutic effects of Huanglian Fire-Purging Mixture (黄连清降合剂) on primary hypertension, 46 cases of primary hypertension in the treatment group were treated with Huanglian Fire-Purging Mixture to clear away heat from the liver, relieve mental stress, purge fire and remove toxin;and the other 26 cases of primary hypertension in the control group were treated with Niuhuang Bolus for Lowering Blood Pressure (牛黄降压丸). The effect in the treatment group was obviously superior to that in the control group (P＜0.05). The Huanglian Fire-Purging Mixture shows noticeable effects 3-6 hours after medication. The mixture can improve the clinical symptoms, the left ventricular diastolic function and myocardial ischemia, correct dyslipoproteinemia and dysglycemia, and reduce blood viscosity. And it is safe and with no obvious adverse reactions.展开更多
Objective This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula(平阳降压方,PYJYF)in treating hypertension,based on network pharmacology,and to verify the subsequent predictions through an...Objective This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula(平阳降压方,PYJYF)in treating hypertension,based on network pharmacology,and to verify the subsequent predictions through animal experiments.Methods The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),Encyclopedia of Traditional Chinese Medicine(ETCM),and Drug Bank databases and available literature.The hypertension target genes were screened based on Therapeutic Target Database(TTD),GeneCards,Online Mendelian Inheritance in Man(OMIM),UniProt,and relevant literature.The component-disease-target network intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension.To verify this prediction,we used PYJYF to intervene in spontaneously hypertensive rats(SHRs)and Wistar–Kyoto rats(WKY)as normal control,and the noninvasive tail artery manometry method was used to measure systolic blood pressure(SBP)in the rat tail before PYJYF intervention.After drug intervention,the SBP of each group rats were measured and compared every week.Enzyme-linked immunosorbent assay(ELISA)was used to test plasma renin,angiotensin II(Ang II),and aldosterone(Ald)levels,and hematoxylin-eosin(HE)staining was used to observe pathological damage to the renal vessels in each group of rats.Western blot and reverse transcription real-time quantitative PCR(RT-PCR)were used to detect the protein and mRNA expression levels of PI3 K,AKT1,BAX,and Bcl-2,respectively.Results A total of 4123 hypertension targets were obtained from related databases.From the TCMSP and chemical databases,78 active components of PYJYF and the corresponding 401 drug targets were retrieved.Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF.The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases.GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF,as well as molecular biological processes,such as the regulation of blood pressure,renin-angiotensin-aldosterone system(RAAS),angiotensin-mediated ligand reactions,and biological stimulation of cardiomyocyte apoptosis.KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension.In animal experiments,PYJYF reduced the protein and m RNA levels of PI3 K,Akt,and Bax and upregulated the expression of the protein and m RNA levels of Bcl-2,reduced plasma renin,Ang II,and Ald levels,improved the hyperactivity of RAAS,and significantly reduced SBP in SHRs.Conclusion PYJYF is effective for hypertension therapy that acts through multiple compounds and targets.The possible underlying molecular mechanism includes regulating the PI3 K/Akt signaling pathway to suppress RAAS,increasing the ratio of Bcl-2/Bax proteins,and inhibiting apoptosis,thereby mediating the repair of renal and renal vascular damage caused by hypertension.These findings warrant further research for use in clinical settings.展开更多
文摘Orphanin FQ（OFQ） or nociceptin is a novel neuropeptide consisting of 17 amino acids. This peptide has a primary structure reminiscent of that of opioid peptide but exhibits an opposite effect to make animals hyperreactive. The effect of this new peptide on cardiovascular function are not completely known. The present study was conducted to investigate the effect of intravenous bolus injection of orphanin FQ on mean arterial blood presure （MABP） in conscious stroke-prone spontaneously hypertensive rats (SHRsp). Adult male SHRsp and Wistar normotensive rats （250～300 g body weight, 2. 5～3 months old） were used in this study. The MABP was measured in the conscious state by a tail-cuff method. In SHRsp model, intravenous bolus injection of orphanin FQ or Tyr1-orphanin FQ （0. 5 mg/kg） induced a prolonged and marked reduc- tion in MABP. The maximum changes in MABP were -30. 2±4. 2 mmHg by orphanin FQ and -28. 2± 4. 7 mmHg by Tyr1-orphanin FQ at 10 min after administration,and this effect lasted over 30 min. The Phe1→Tyr substitution in orphanin FQ was found to retain almost fully hypotensive activity. Pretreatment of SHRsp with naloxone-HCI（60 μg/kg）, 5 min before the injection of orphanin FQ, did not block the hy- potensive effect of orphanin FQ. Therefore, opioid receptors could not account for the hypotensive effect of orphanin FQ in SHRsp. In Wistar rats, intravenous bolus injection of the same dose of orphanin FQ did not cause a change in MABP. These observations suggest that orphanin FQ is a novel hypotensive peptide and may have some role in the regulation of blood pressure in SHRsp, rather than in normotensive rats. The ex-act underlying mechanisms are waiting to be clarified.
文摘In order to observe the therapeutic effects of Huanglian Fire-Purging Mixture (黄连清降合剂) on primary hypertension, 46 cases of primary hypertension in the treatment group were treated with Huanglian Fire-Purging Mixture to clear away heat from the liver, relieve mental stress, purge fire and remove toxin;and the other 26 cases of primary hypertension in the control group were treated with Niuhuang Bolus for Lowering Blood Pressure (牛黄降压丸). The effect in the treatment group was obviously superior to that in the control group (P＜0.05). The Huanglian Fire-Purging Mixture shows noticeable effects 3-6 hours after medication. The mixture can improve the clinical symptoms, the left ventricular diastolic function and myocardial ischemia, correct dyslipoproteinemia and dysglycemia, and reduce blood viscosity. And it is safe and with no obvious adverse reactions.
基金funding support from the National Natural Science Foundation of China(No.81874464)National Major New Drug Development Project(No.2019ZX09301-103)Provincial Department of Graduate Research Innovation Project of Hunan(No.CX20190565)。
文摘Objective This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula(平阳降压方,PYJYF)in treating hypertension,based on network pharmacology,and to verify the subsequent predictions through animal experiments.Methods The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM),Encyclopedia of Traditional Chinese Medicine(ETCM),and Drug Bank databases and available literature.The hypertension target genes were screened based on Therapeutic Target Database(TTD),GeneCards,Online Mendelian Inheritance in Man(OMIM),UniProt,and relevant literature.The component-disease-target network intersection target genes were inputted into the STRING database,and the key target genes were selected according to the degree algorithm.Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension.To verify this prediction,we used PYJYF to intervene in spontaneously hypertensive rats(SHRs)and Wistar–Kyoto rats(WKY)as normal control,and the noninvasive tail artery manometry method was used to measure systolic blood pressure(SBP)in the rat tail before PYJYF intervention.After drug intervention,the SBP of each group rats were measured and compared every week.Enzyme-linked immunosorbent assay(ELISA)was used to test plasma renin,angiotensin II(Ang II),and aldosterone(Ald)levels,and hematoxylin-eosin(HE)staining was used to observe pathological damage to the renal vessels in each group of rats.Western blot and reverse transcription real-time quantitative PCR(RT-PCR)were used to detect the protein and mRNA expression levels of PI3 K,AKT1,BAX,and Bcl-2,respectively.Results A total of 4123 hypertension targets were obtained from related databases.From the TCMSP and chemical databases,78 active components of PYJYF and the corresponding 401 drug targets were retrieved.Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF.The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases.GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF,as well as molecular biological processes,such as the regulation of blood pressure,renin-angiotensin-aldosterone system(RAAS),angiotensin-mediated ligand reactions,and biological stimulation of cardiomyocyte apoptosis.KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension.In animal experiments,PYJYF reduced the protein and m RNA levels of PI3 K,Akt,and Bax and upregulated the expression of the protein and m RNA levels of Bcl-2,reduced plasma renin,Ang II,and Ald levels,improved the hyperactivity of RAAS,and significantly reduced SBP in SHRs.Conclusion PYJYF is effective for hypertension therapy that acts through multiple compounds and targets.The possible underlying molecular mechanism includes regulating the PI3 K/Akt signaling pathway to suppress RAAS,increasing the ratio of Bcl-2/Bax proteins,and inhibiting apoptosis,thereby mediating the repair of renal and renal vascular damage caused by hypertension.These findings warrant further research for use in clinical settings.
