RESUMO
Diesun Miaofang (DSMF) is a traditional herbal formula, which has been reported to activate blood, remove stasis, promote qi circulation and relieve pain. DSMF holds a great promise for the treatment of traumatic injury in an integrative and holistic manner. However, its underlying mechanisms remain to be elucidated. In the present study, a systems pharmacology model, which integrated cluster ligands, human intestinal absorption and aqueous solution prediction, chemical space mapping, molecular docking and network pharmacology techniques were used. The compounds from DSMF were diverse in the clusters and chemical space. The majority of the compounds exhibited drug-like properties. A total of 59 compounds were identified to interact with 16 potential targets. In the herb-compound-target network, the majority of compounds acted on only one target; however, a small number of compounds acted on a large number of targets, up to a maximum of 12. The comparison of key topological properties in compound-target networks associated with the above efficacy intuitively demonstrated that potential active compounds possessed diverse functions. These results successfully explained the polypharmacological mechanism underlying the efficiency of DSMF for the treatment of traumatic injury as well as provided insight into potential novel therapeutic strategies for traumatic injury from herbal medicine.
Assuntos
Medicamentos de Ervas Chinesas/química , Análise por Conglomerados , Bases de Dados de Compostos Químicos , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Mucosa Intestinal/metabolismo , Medicina Tradicional Chinesa , Solubilidade , Cicatrização/efeitos dos fármacosRESUMO
Huoxue Huayu (HXHY) has been widely used in traditional Chinese medicine (TCM) as a key therapeutic principle for osteoarthritis (OA), and related herbs have been widely prescribed to treat OA in the clinic. The aims of the present study were to explore a multi-target therapy for OA using 10 common HXHY herbs and to investigate their potential applications for treatment of other diseases. A novel computational simulation approach that integrates chemical structure, ligand clusters, chemical space and druglikeness evaluations, as well as docking and network analysis, was used to investigate the properties and effects of the herbs. The compounds contained in the studied HXHY herbs were divided into 10 clusters. Comparison of the chemical properties of these compounds to those of other compounds described in the DrugBank database indicated that the properties of the former are more diverse than those of the latter and that most of the HXHY-derived compounds do not violate the 'Lipinski's rule of five'. Docking analysis allowed for the identification of 39 potential bioactive compounds from HXHY herbs and 11 potential targets for these compounds. The identified targets were closely associated with 49 diseases, including neoplasms, musculoskeletal, nervous system and cardiovascular diseases. Ligandtarget (LT) and ligandtargetdisease (LTD) networks were constructed in order to further elucidate the pharmacological effects of the herbs. Our findings suggest that a number of compounds from HXHY herbs are promising candidates for multtarget therapeutic application in OA and may exert diverse pharmacological effects, affecting additional diseases besides OA.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite/tratamento farmacológico , Análise por Conglomerados , Bases de Dados Factuais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Humanos , Ligantes , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/uso terapêuticoRESUMO
OBJECTIVE: To investigate the effect of prim-O-glucosylcimifugin and 4'-O-p-D-glucosyl-5-O-methylvisa-mminol con on the proliferation of smooth muscle cell stimulated by TNF-alpha. METHOD: The primary cell culture method of smooth muscle cell (SMC) was established by attachment-block. The SMC was identificated by immunochemistry method, and the growth curve was drawn by cytometry. The third generation of SMC was adopted in the experiment. The effect of prim-O-glucosylcimif-ugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con on the proliferation and cell cycle of SMC was investigated by MTT and flow cytometry respectively. RESULT: TNF-alpha of 5 micro g x L(-1) can stimulate the proliferation of SMC and increase the proportion of G2 phase and S phase in cell cycle which has great significant difference (P < 0.01) compared with control. The three dose groups of prim-O-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisammin-ol con can inhibit the proliferation of SMC and increase the proportion of G0/G1 phase, which has great significant difference (P < 0.01) compared with model group. CONCLUSION: Prim-O-glucosylcimifugin and 4'-O-beta-D-glucosyl-5-O-methylvisamminol con can inhibit the proliferation of SMC stimulated by TNF-alpha.
Assuntos
Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Monossacarídeos/farmacologia , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Xantenos/farmacologia , Animais , Células Cultivadas , Feminino , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To observe the protective effects of catechin morphon (GCG and EGCG) on hypoxia-reoxygenation induced injury in myocardial cells and to explore the mechanisms. METHOD: In cultured neonatal rat cardiomyocytes, we investigated the preconditioning protection by GCG and EGCG on the spontaneous beating, the survival rate, the release of LDH, MDA, SOD, GSH-Px and the ATP enzyme activity of cardiomyocyte cellular membrane in cultured rat cardiomyocytes treated during the reoxygenation 1h following hypoxia 3 h. The blocking agent of protien kinase C staurosporine (10 nmol x L(-1)) or the deactivator of Gi/o protein pertussis toxin (PTX, 200 microg x mL(-1)) were added before the catechin treatment. RESULTS: Preconditioning by GCG and EGCG increased the spontaneous beating and the survival rate, and decreased the release of LDH and MDA with the rise of SOD and ATP enzyme activity. Inhibition of PKC by staurosporine and Gi/o protein by PTX abolished the protection by catechin with the reduction of the beating, survival rate and activity of SOD, and the increase of the release of LDH and MDA. The results indicated that the activation of signal transduction pathway from PKC and Gi/o protein seemed to be involved in the cardioprotection of preconditioning by GCG and EGCG. CONCLUSION: The protection by GCG and EGCG on hypoxia-reoxygenation injury in cultured neonatal rat cardiomyocytes is found, which is related with scavenging of free radicals, and PKC Gi/o signal transduction pathway.
Assuntos
Catequina/química , Catequina/farmacologia , Hipóxia/complicações , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Oxigênio/metabolismo , Animais , Cardiotônicos/química , Cardiotônicos/farmacologia , Catequina/análogos & derivados , Feminino , Radicais Livres/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Quinase C/metabolismo , Proteínas/metabolismo , Ratos , Transdução de Sinais/efeitos dos fármacos , Taxa de SobrevidaRESUMO
OBJECTIVE: To observe the antioxidant effects of water extract of Carthamus tinctorius on ox-LDL induced injury in rat cardiac microvascular endothelial cell and detecting oxygen derived free radicals (OFR) to explore the antioxidant mechanisms. METHOD: By using the third generation of rat cardiac microvascular endothelial cells (rCMEC), the protection of water extract of C. tinctorius was investigated after ox-LDL (100 mg x L(-1) induced damage. The supernatant was collected for detecting lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XOD), glutathione peroxidase (GSH-Px), nitric oxide (NO), nitric oxide synthase (NOS) activity, and cell suspension was collected for detecting reactive oxygen species (ROS) by electron spin resonance (ESR). RESULT: Water extract of C. tinctorius increased the rCMEC survival rate, reduced LDH, MDA and XOD levels, and improved SOD, GSH-Px and NOS activity, while in the cell suspension ROS signal decreased significantly. CONCLUSION: Water extract of C. tinctorius has antioxidation. The mechanisms are likely related with scavenging of free radicals, enhancing its clearance, enhancing endogenous antioxidant activity.