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1.
Zhongguo Zhong Yao Za Zhi ; 48(21): 5915-5931, 2023 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-38114188

RESUMO

This study used UPLC-TQ-MS technology to replicate a Henoch-Schonlein purpura(HSP) model in rats by administering warm drugs by gavage and injecting ovalbumin with Freund's complete adjuvant emulsion. The distribution differences and characteristics of eight major components(ferulic acid, caffeic acid, neochlorogenic acid, cryptochlorogenic acid, benzoyl oxypaeoniflorin, tracheloside, loganin, and paeoniflorin) in rat liver, lung, heart, spleen, and kidney tissues were determined after oral administration of the Liangxue Tuizi Mixture at a dose of 42 g·kg~(-1) in both normal physiological and HSP states at 0.5, 1, 2, 6, and 12 hours. The results showed that the distribution patterns of the eight components of Liangxue Tuizi Mixture in the tissues of normal and HSP model rats were different. The main component, paeoniflorin, in Moutan Cortex and Paeoniae Radix Alba had higher content in all tissues. The eight components were predominantly distributed in the liver, lung, and kidney tissues, followed by spleen and heart tissues.


Assuntos
Vasculite por IgA , Ratos , Animais , Vasculite por IgA/tratamento farmacológico , Monoterpenos , Administração Oral , Espectrometria de Massa com Cromatografia Líquida
2.
Chin Med ; 18(1): 102, 2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37592331

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Psoralea corylifolia Linn. (BGZ) is a commonly used traditional Chinese medicine (TCM) for the treatment of kidney-yang deficiency syndrome (Yangsyn) with good curative effect and security. However, BGZ was also reported to induce liver injury in recent years. According to TCM theory, taking BGZ may induce a series of adverse reactions in patients with kidney-yin deficiency syndrome (Yinsyn), which suggests that BGZ-induced liver damage may be related to its unreasonable clinical use. AIM OF THE STUDY: Liver injury caused by TCM is a rare but potentially serious adverse drug reaction, and the identification of predisposed individuals for drug-induced liver injury (DILI) remains challenging. The study aimed to investigate the differential responses to BGZ in Yangsyn and Yinsyn rat models and identify the corresponding characteristic biomarkers. MATERIALS AND METHODS: The corresponding animal models of Yangsyn and Yinsyn were induced by hydrocortisone and thyroxine + reserpine respectively. Body weight, organ index, serum biochemistry, and Hematoxylin and Eosin (HE) staining were used to evaluate the liver toxicity effect of BGZ on rats with Yangsyn and Yinsyn. Transcriptomics and metabonomics were used to screen the representative biomarkers (including metabolites and differentially expressed genes (DEGs)) changed by BGZ in Yangsyn and Yinsyn rats, respectively. RESULTS: The level changes of liver organ index, alanine aminotransferase (ALT), and aspartate aminotransferase (AST), suggested that BGZ has liver-protective and liver-damaging effects on Yangsyn and Yinsyn rats, respectively, and the results also were confirmed by the pathological changes of liver tissue. The results showed that 102 DEGs and 27 metabolites were significantly regulated related to BGZ's protective effect on Yangsyn, which is mainly associated with the glycerophospholipid metabolism, arachidonic acid metabolism, pantothenate, and coenzyme A (CoA) biosynthesis pathways. While 28 DEGs and 31 metabolites, related to the pathway of pantothenate and CoA biosynthesis, were significantly regulated for the BGZ-induced liver injury in Yinsyn. Furthermore, 4 DEGs (aldehyde dehydrogenase 1 family member B1 (Aldh1b1), solute carrier family 25 member 25 (Slc25a25), Pim-3 proto-oncogene, serine/threonine kinase (Pim3), out at first homolog (Oaf)) and 4 metabolites (phosphatidate, phosphatidylcholine, N-Acetylleucine, biliverdin) in the Yangsyn group and 1 DEG [galectin 5 (Lgals5)] and 1 metabolite (5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxylate) in Yinsyn group were significantly correlated to the ALT and AST levels of BGZ treated and untreated groups (receiver operating characteristic (ROC) ≥ 0.9). CONCLUSIONS: Yinsyn and Yangsyn are the predisposed syndromes for BGZ to exert liver damage and liver protection respectively, which are mainly related to the regulation of amino acid metabolism, lipid metabolism, energy metabolism, and metabolism of cofactors and vitamins. The results further suggest that attention should be paid to the selection of predisposed populations when using drugs related to the regulation of energy metabolism, and the Yinsyn/Yangsyn animal models based on the theory of TCM syndromes may be a feasible method for identifying the susceptible population to receive TCM.

3.
Zhongguo Zhong Yao Za Zhi ; 48(9): 2480-2489, 2023 May.
Artigo em Chinês | MEDLINE | ID: mdl-37282877

RESUMO

Qualitative and quantitative analysis of 2-(2-phenylethyl) chromones in sodium chloride(NaCl)-treated suspension cells of Aquilaria sinensis was conducted by UPLC-Q-Exactive-MS and UPLC-QQQ-MS/MS. Both analyses were performed on a Waters T3 column(2.1 mm×50 mm, 1.8 µm) with 0.1% formic acid aqueous solution(A)-acetonitrile(B) as mobile phases at gradient elution. MS data were collected by electrospray ionization in positive ion mode. Forty-seven phenylethylchromones was identified from NaCl-treated suspension cell samples of A. sinensis using UPLC-Q-Exactive-MS, including 22 flindersia-type 2-(2-phenylethyl) chromones and their glycosides, 10 5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones and 15 mono-epoxy or diepoxy-5,6,7,8-tetrahydro-2-(2-phenylethyl) chromones. Additionally, 25 phenylethylchromones were quantitated by UPLC-QQQ-MS/MS. Overall, the rapid and efficient qualitative and quantitative analysis of phenylethylchromones in NaCl-treated suspension cells of A. sinensis by two LC-MS techniques, provides an important reference for the yield of phenylethylchromones in Aquilariae Lignum Resinatum using in vitro culture and other biotechnologies.


Assuntos
Cromonas , Thymelaeaceae , Cloreto de Sódio , Cromatografia Líquida , Flavonoides , Espectrometria de Massas em Tandem
4.
Zhongguo Zhong Yao Za Zhi ; 48(12): 3327-3344, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37382017

RESUMO

Ultra-performance liquid chromatography-quadrupole time of fight/mass spectrometry(UPLC-Q-TOF-MS) and UNIFI were employed to rapidly determine the content of the components in Liangxue Tuizi Mixture. The targets of the active components and Henoch-Schönlein purpura(HSP) were obtained from SwissTargetPrediction, Online Mendelian Inheritance in Man(OMIM), and GeneCards. A "component-target-disease" network and a protein-protein interaction(PPI) network were constructed. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the targets by Omishare. The interactions between the potential active components and the core targets were verified by molecular docking. Furthermore, rats were randomly assigned into a normal group, a model group, and low-, medium-, and high-dose Liangxue Tuizi Mixture groups. Non-targeted metabolomics was employed to screen the differential metabolites in the serum, analyze possible metabolic pathways, and construct the "component-target-differential metabolite" network. A total of 45 components of Liangxue Tuizi Mixture were identified, and 145 potential targets for the treatment of HSP were predicted. The main signaling pathways enriched included resistance to epidermal growth factor receptor tyrosine kinase inhibitors, phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT), and T cell receptor. The results of molecular docking showed that the active components in Liangxue Tuizi Mixture had strong binding ability with the key target proteins. A total of 13 differential metabolites in the serum were screened out, which shared 27 common targets with active components. The progression of HSP was related to metabolic abnormalities of glycerophospholipid and sphingolipid. The results indicate that the components in Liangxue Tuizi Mixture mainly treats HSP by regulating inflammation and immunity, providing a scientific basis for rational drug use in clinical practice.


Assuntos
Vasculite por IgA , Animais , Ratos , Vasculite por IgA/tratamento farmacológico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Metabolômica
5.
Zhongguo Zhong Yao Za Zhi ; 47(1): 176-187, 2022 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-35178925

RESUMO

This study was designed to explore the alleviating effect and mechanism of Glycyrrhizae Radix et Rhizoma against Psora-leae Fructus-induced liver injury based on network pharmacology and cell experiments. The active components of Glycyrrhizae Radix et Rhizoma and Psoraleae Fructus were first retrieved from the Encyclopedia of Traditional Chinese Medicine(ETCM), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), Comparative Toxicogenomics Database(CTD), and literature and further screened by SwissADME. The obtained 25 potential toxic components of Psoraleae Fructus and 29 flavonoids in Glycyrrhizae Radix et Rhizoma were input into the SwissTargetPrediction for target predication. A total of 818 targets related to liver injury were screened out based on GeneCards and MalaCards, and 91 common targets of Psoraleae Fructus, Glycyrrhizae Radix et Rhizoma, and liver injury were obtained from Venny. STRING was applied for constructing the PPI network, and Metascape for analyzing the biological processes and signaling pathways that common targets participated in. Cytoscape was used to construct the component-target-disease network and component-target-pathway network for Glycyrrhizae Radix et Rhizoma against Psoraleae Fructus-induced liver injury. The predicted core targets were proto-oncogene tyrosine-protein kinase(SRC), phosphatidylinositol 4,5-bisphosphate 3-kinase subunit alpha(PIK3 CA), RAC-alpha serine/threonine-protein kinase(AKT1), etc, with PI3 K-AKT signaling pathway, MAPK signaling pathway, apoptosis, Toll-like receptor signaling pathway, and NF-κB signaling pathway mainly involved. Following the scree-ning of the main toxic and pharmacodynamic components, the pharmacodynamic effects were investigated by cell experiments. The results showed that licochalcone A was mainly responsible for alleviating coryfolin-induced liver injury, licochalcone B for coryfolin-and psoralidin-induced liver injury, and echinatin for corylifolinin-and bakuchiol-induced liver injury. The preliminary revealing of the alleviating effect of Glycyrrhizae Radix et Rhizoma on Psoraleae Fructus-induced liver injury and the prediction of related mechanisms will provide reference for further mechanism research and reasonable clinical compatibility.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/farmacologia , Glycyrrhiza , Humanos , Medicina Tradicional Chinesa , Farmacologia em Rede
6.
Zhongguo Zhong Yao Za Zhi ; 47(24): 6763-6779, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36604926

RESUMO

UPLC-TQ/MS was employed to determine the content of 8 main components(psoralen, isopsoralen, psoralenoside, isopsoralenoside, bavachin, psoralidin, corylin, and neobavaisoflavone) in tissues of normal and lipopolysaccharide(LPS)-induced model rats 0.5, 1, 2, 6, and 12 h after intragastric administration of 3.6 g·kg~(-1) ethanol extract of Psoraleae Fructus. The distribution characteristics of the 8 main components in the different tissues(liver, kidney, spleen, heart, and lung) were studied and compared. The results showed that the distribution behaviors of the components varied among different tissues. At different time points, the components presented wide and uneven distribution in the body. Liver and kidney had higher content of the components, followed by spleen, heart, and lung. In both normal and LPS-induced model rats, the content of the 8 main components was higher in liver and kidney and varied significantly among different tissues. The content of psoralen in the tissues of LPS-induced model rat was significantly higher than that of the normal group 12 h after administration. The reason may be that the modeling slowed down the absorption and distribution of psoralen. The LPS-induced model rats had higher content of psoralenoside and isopsoralenoside in the liver tissue than the normal rats, which indicated that the modeling increased the absorption and distribution of psoralenoside and isopsoralenoside in the liver tissue. Further, it is hypothesized that psoralenoside and isopsoralenoside may be toxic substances of Psoraleae Fructus-induced liver injury.


Assuntos
Furocumarinas , Psoralea , Ratos , Animais , Lipopolissacarídeos , Etanol , Extratos Vegetais , Ficusina
7.
Ann Palliat Med ; 10(11): 11415-11429, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34872267

RESUMO

BACKGROUND: The etiology and pathogenesis of cough are complex. As a Chinese patent medicine that has been on the market, ErtongKe (ETK) granules have a good effect in treating acute and chronic cough in children. The purpose of this research was to determine the bioactive components and possible action mechanisms of ETK in the treatment of cough using an integrated network pharmacology method. METHODS: The Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss target prediction databases were used to screen the potential components and associated targets of ETK. The Genecards database was then used to gather targets interacting with cough. An analysis of the signaling pathways associated with ETK for cough treatment was carried out using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analysis methods. Cytoscape 3.8.1 was used to design the protein-protein interaction (PPI) and compound-target-pathway networks. Finally, the important genes and active components of ETK were confirmed using Auto Dock vina and Discovery studio software. RESULTS: Total 242 active components of ETK were screened, 1,173 potential targets related to the ingredients and 4,400 targets related to cough were collected separately. Moreover, 600 candidate targets and 39 signaling pathways were determined. We also screened out the following core components, including tuberostemonone, quercetin, kaempferol, praeruptorin E, stigmasterol, oroxylin A, and other potentially active ingredients. At the same time, 8 core targets, including JUN, PIK3CA, PIK3R1, MAPK14, EGFR, SRC, AKT1, and MAPK1, and 20 key pathways, including the cAMP signaling pathway, calcium signaling pathway, and PI3K-Akt signaling pathway among others, were also selected. All the 8 core targets were verified by molecular docking. CONCLUSIONS: This research established that ETK exerts anti-cough activity by modulating several targets and pathways through multiple components. Additionally, the pooled results shed light on ETK compounds being investigated as potential antitussives.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Criança , Tosse/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Tecnologia
8.
J Biotechnol ; 309: 85-91, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31926180

RESUMO

Ascomycete fungi Cordyceps are widely used in traditional Chinese medicine, and numerous investigations have been carried out to uncover their biological activities. However, primary researches on the physiological effects of Cordyceps were committed using crude extracts. At present, there are only a few compounds which were comprehensively characterized from Cordyceps, partial owing to the low production. In order to scientifically take advantage of Cordyceps, we used the strategy of genome mining to discover bioactive compounds from Cordyceps militaris. We found the putative biosynthetic gene cluster of the acyl-CoA:cholesterol acyltransferase inhibitor beauveriolides in the genome of C. militaris, and produced the compounds by heterologous expression in Aspergillus nidulans. Production of beauveriolide I and III also was detected in both ferment mycelia and fruiting bodies of C. militaris. The possible biosynthetic pathway was proposed. Our studies unveil the active compounds of C. militaris against atherosclerosis and Alzheimer's disease and provide the enzyme resources for the biosynthesis of new cyclodepsipeptide molecules.


Assuntos
Anticolesterolemiantes/metabolismo , Cordyceps/genética , Cordyceps/metabolismo , Depsipeptídeos/biossíntese , Depsipeptídeos/genética , Esterol O-Aciltransferase/efeitos dos fármacos , Acil Coenzima A/metabolismo , Doença de Alzheimer , Anticolesterolemiantes/farmacologia , Aspergillus nidulans/genética , Aterosclerose , Vias Biossintéticas/genética , Clonagem Molecular , Depsipeptídeos/química , Depsipeptídeos/isolamento & purificação , Carpóforos/metabolismo , Regulação Fúngica da Expressão Gênica , Medicina Tradicional Chinesa , Família Multigênica
9.
Mol Neurobiol ; 54(10): 8404-8418, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27933584

RESUMO

Myelin-associated inhibitors, such as NogoA, myelin-associated glycoprotein (MAG), and oligodendrocyte myelin glycoprotein (OMgp), play a pivotal role in the lack of neuroregeneration in multiple sclerosis, an inflammatory demyelinating disease of the central nervous system (CNS). Matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory agent, has shown beneficial effects in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, the underlying mechanisms of MAT-induced EAE amelioration are not fully understood. In the present study, we show that MAT treatment suppressed ongoing EAE, and this effect correlated with an increased expression of growth-associated protein 43, an established marker for axonal regeneration. MAT treatment significantly reduced the levels of NogoA, its receptor complex NgR/p75NTR/LINGO-1, and their downstream RhoA/ROCK signaling pathway in the CNS. In contrast, intracellular cyclic AMP (cAMP) levels and its protein kinase (protein kinase A (PKA)), which can promote axonal regrowth by inactivating the RhoA, were upregulated. Importantly, adding MAT in primary astrocytes in vitro largely induced cAMP/PKA expression, and blockade of cAMP significantly diminished MAT-induced expression of PKA and production of BDNF, a potent neurotrophic factor for neuroregeneration. Taken together, our findings demonstrate that the beneficial effects of MAT on EAE can be attributed not only to its capacity for immunomodulation, but also to its directly promoting regeneration of the injured CNS.


Assuntos
Alcaloides/uso terapêutico , Encefalomielite Autoimune Experimental/tratamento farmacológico , Encefalomielite Autoimune Experimental/metabolismo , Inibição Neural/fisiologia , Proteínas Nogo/metabolismo , Quinolizinas/uso terapêutico , Transdução de Sinais/fisiologia , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células Cultivadas , Feminino , Cobaias , Camundongos , Inibição Neural/efeitos dos fármacos , Proteínas Nogo/antagonistas & inibidores , Quinolizinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento , Matrinas
10.
Zhonghua Nan Ke Xue ; 16(9): 856-9, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-21171274

RESUMO

OBJECTIVE: To study the clinical efficacy of vardenafil on erectile dysfunction (ED) patients with kidney-yang deficiency, kidney-yin deficiency or liver-qi stasis. METHODS: Based on the syndromes of Traditional Chinese Medicine, 124 ED patients were divided into Groups A (kidney-yang deficiency, n=44), B (kidney-yin deficiency, n=41) and C (liver-qi stasis, n = 39). All the patients were treated with vardenafil at 5 mg daily for 8 weeks, and the therapeutic effects were evaluated by comparing the scores on IIEF-5 and Erection Quality Scale (EQS) before and after the treatment. RESULTS: After vardenafil treatment, the IIEF-5 and EQS scores of the ED patients were markedly increased, with statistically significant differences among the three groups (P < 0.01). The success rate of sexual intercourse was significantly improved in Groups A, B (P < 0.01) and C (P < 0.05). And the hardness of penile erection was enhanced by 81.82%, 73.17% and 43.59% respectively in the three groups of patients. CONCLUSION: Vardenafil is more effective for ED patients with kidney-yang or kidney-yin deficiency than for those with liver-qi stasis.


Assuntos
Disfunção Erétil/tratamento farmacológico , Imidazóis/uso terapêutico , Piperazinas/uso terapêutico , Vasodilatadores/uso terapêutico , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Sulfonas/uso terapêutico , Triazinas/uso terapêutico , Dicloridrato de Vardenafila , Deficiência da Energia Yang/tratamento farmacológico , Deficiência da Energia Yin/tratamento farmacológico
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