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1.
Rapid Commun Mass Spectrom ; 36(24): e9411, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36195983

RESUMO

RATIONALE: Helwingia japonica (HJ), a traditional medicinal plant, is commonly used for the treatment of dysentery, blood in the stool, and scald burns. Three major HJ species, Helwingia japonica (Thunb.) Dietr. (QJY), Helwingia himalaica Hook. f. et Thoms. ex C. B. Clarke, and Helwingia chinensis Batal., share great similarities in both morphology and chemical constituents. The discrimination of medicinal plants directly affects their pharmacological and clinical effects. Here, we solved the taxonomy uncertainty of these three HJ species and explored the discrimination and study of other traditional medicines (TMs). METHODS: First, the anti-inflammatory effects of the three HJ species were compared using lipopolysaccharide (LPS)-induced inflammatory responses in mouse leukemia cells of monocyte macrophage (RAW) 264.7 cells. Then, plant metabolomics were performed in 48 batches of samples to discover chemical markers for discriminating different HJ species. Finally, network pharmacology was applied to explore the linkages among constituents, targets, and signaling pathways. RESULTS: In vitro experiments showed that the QJY exhibited the most potential anti-inflammatory activities. Meanwhile, 172 compounds were tentatively identified and eight metabolites with higher relative content in QJY were designated as chemical markers to distinguish QJY and the other two species. According to the property of absorbed in vivo, threonic acid, arginine, and tyrosine were selected to construct a component-target-pathway network. The network pharmacology analysis confirmed that the chemotaxonomy differentiation was consistent with the bioactive assessment. CONCLUSIONS: The present study demonstrates that bioactivity evaluation integrated with plant metabolomics and network pharmacology could be used as an effective approach to discriminate different TMs and discover the active compounds.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Camundongos , Animais , Farmacologia em Rede , Metabolômica , Anti-Inflamatórios/farmacologia , Células RAW 264.7 , Medicamentos de Ervas Chinesas/metabolismo
2.
J Ethnopharmacol ; 299: 115654, 2022 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-36058477

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lung cancer is one of the most common malignant tumours and has become the leading cause of cancer-related deaths worldwide. Abnormal microcirculation during tumour growth leads to intermittent hypoxia (IH), which is responsible for promoting cancer cell proliferation and migration. Patients with advanced lung cancers show deficiency of both Qi and Yin Syndrome (DQYS) in TCM, and studies have confirmed that IH exposure is related to DQYS. Shashen-Maidong Decoction (SMD), has been widely applied clinically targeting DQYS and has a long history for treating lung cancer by nourishing the body's "zheng qi" and resisting "xie qi". However, whether SMD could be beneficial to lung cancer under IH conditions remains unclear. AIM OF THE STUDY: This study aimed to clarify the effects and mechanism of SMD on non-small cell lung cancer (NSCLC) growth under IH conditions. MATERIALS AND METHODS: C57 mice were injected subcutaneously into the right axilla with Lewis lung cancer (LLC) cells and exposed to IH conditions (21%-5% O2, 5 min/cycle, 8 h/day) for 21 days. SMDs were orally treated with different concentrations (2.6, 5.2 or 10.4 g/kg/day) 30 min before IH exposure. Tumour proliferation and migration were assessed by HE and IHC staining, and oxidative stress was assessed by DHE staining and MDA or SOD detection. IL-6, IL-1ß and TNF-α levels were assessed by IHC staining, and the IL-6/JAK2/STAT3 signalling pathway was detected by western blotting. RESULTS: Our results showed that SMD treatment inhibited tumour growth and liver metastasis in LLC-bearing mice exposed to IH, decreased Ki67, CD31, VEGF, and MMP-2, and increased E-cadherin expression in tumourt tissue. SMD reduced ROS production, increased SOD levels and SOD-2 expression, and decreased MDA levels and NOX-2 expression. SMD decreased IL-6, IL-1ß and TNF-α levels, reduced IL-6 expression and inhibited JAK2 and STAT3 phosphorylation. Additionally, SMD treatment improved DQYS and liver and kidney function in LLC-bearing mice under IH conditions. CONCLUSION: Our research suggests that SMD treatment can inhibit tumour growth in mice exposed to IH. The antitumour effect of SMD may be related to attenuated oxidative stress and inflammation through inactivation of the IL-6/JAK2/STAT3 signalling pathway under IH conditions.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Pulmonares , Animais , Caderinas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Hipóxia/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Interleucina-6/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
3.
J Ethnopharmacol ; 298: 115679, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36058481

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shi Wei Ru Xiang powder (SWR) is a traditional Tibetan medicinal formula with the effect of dispelling dampness and dispersing cold. In clinical practice, SWR is generally used for the treatment of hyperuricemia (HUA). However, its exact pharmacological mechanism remains unclear. AIMS OF THE STUDY: To preliminarily elucidate the regulatory effects and possible mechanisms of SWR on hyperuricemia using network pharmacology and experimental validation. MATERIALS AND METHODS: A mouse model of hyperuricemia was used to evaluate the alleviating effect of SWR on hyperuricemia. The major components of SWR were acquired by UPLC-Q/TOF-MS. The potential molecular targets and associated signaling pathways were predicted through network pharmacology. The mechanism of action of SWR in ameliorating hyperuricemia was further investigated by pharmacological evaluation. RESULTS: Mice with hyperuricemia and renal dysfunction were ameliorated by SWR. The 36 components of SWR included phenolic acids, terpenoids, alkaloids and flavonoids were identified. Network pharmacological analysis showed the involvement of the above compounds, and 115 targets were involved to treat hyperuricemia, involving multiple biological processes and different signaling pathways. Pharmacological experiments validated that SWR ameliorated hyperuricemic nephropathy in mice by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, nuclear factor kappaB (NF-κB) signaling pathway and NOD-like receptor signaling pathway. CONCLUSION: MAPK signaling pathway, NF-κB signaling pathway and NOD-like receptor signaling pathway play important roles in the therapeutic effects of SWR on hyperuricemia.


Assuntos
Medicamentos de Ervas Chinesas , Hiperuricemia , Animais , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Medicina Tradicional Tibetana , Camundongos , NF-kappa B , Proteínas NLR , Farmacologia em Rede , Pós/uso terapêutico
4.
J Ethnopharmacol ; 298: 115610, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35973632

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Niu Huang Jie Du prescription (NHJD) is a traditional Chinese medicine (TCM) widely used in patients suffering from excessive inner fire toxin (Huo Du Nei Sheng) syndrome, such as sore throat, gingival swelling, and pain, mouth and tongue sores, etc. This formula contains realgar (As4S4) which is one of the 28 toxic medicinal materials promulgated by the Chinese Ministry of Health. Many studies reported its toxicity on the liver and kidney, and the detoxification effect of NHJD. However, its detoxification mechanism is still unclear. AIM OF THE STUDY: To clarify the detoxification mechanism of NHJD to realgar, this study evaluated the detoxification effect of NHJD on realgar exposure in mice, and analyzed differences in mRNA expression profiles in liver tissues and associated functional predictions. MATERIAL AND METHODS: ICR mice were administered with NHJD, realgar, and CMC-Na as blank control for 12 weeks, respectively. Liver injury was evaluated by histopathologic examination and liver mRNA gene were sequenced by Illumina. Differentially expressed gene, functionally enrichment and protein association network analysis were conducted. RESULTS: 43 genes were screened out, among which 15 genes in the realgar group were decreased, but the extent of the decline has been restored in the NHJD group. The remaining 28 genes have exactly the opposite trends. Functional module analysis revealed that those detoxification function-related genes were primarily for positive regulation of glutathione metabolism, P450 on the metabolism of exogenous compounds, oxidative stress and immune-related, etc. CONCLUSIONS: The results indicated that realgar mainly causes liver damage by changing the common enzymes of drug metabolism, especially the expression of genes related to CYPs, GSTs family, oxidative stress, and complement immunity, while the TCM prescription NHJD has a regulatory effect on the abnormal expression of corresponding genes. Our results will provide some clues for the detoxification mechanism of arsenic-containing TCM prescriptions.


Assuntos
Arsenicais , Medicamentos de Ervas Chinesas , Animais , Arsenicais/farmacologia , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado , Medicina Tradicional Chinesa/métodos , Camundongos , Camundongos Endogâmicos ICR , Prescrições , RNA/metabolismo , RNA/farmacologia , RNA Mensageiro/metabolismo , Sulfetos/farmacologia
5.
J Ethnopharmacol ; 298: 115649, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987410

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xuanbai-Chengqi decoction (XBCQ) is a traditional Chinese medicine (TCM) compound used in the treatment of pulmonary infection in China. Despite the popular usage of XBCQ, its underlying protective roles and the associated molecular mechanisms with the gut-lung axis in influenza remain unclear. AIM OF THE STUDY: We aimed to explore the protective effects and the underlying mechanism of XBCQ efficacy on lung and intestine injuries induced by influenza A virus as well as to identify the main active components through integrated network pharmacology, intestinal flora analysis and pathway validation. MATERIALS AND METHODS: The potential active components and therapeutic targets of XBCQ in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including components screening, targets prediction and bioinformatics analysis. Inflammatory cytokines and pathway proteins were assayed to validate the results of network pharmacology. Then the mechanism of XBCQ alleviating lung and intestine injuries was further explored via intestinal flora analysis. The important role of Rhubarb in the formula was verified by removing Rhubarb. RESULTS: XBCQ could significantly improve the survival rate in IAV-infected mice. The network pharmacology results demonstrated that JUN, mitogen-activated protein kinase (MAPK), and tumor necrosis factor (TNF) are the key targets of XBCQ that can be useful in influenza treatment as it contains the core components luteolin, emodin, and aloe-emodin, which are related to the pathways of TNF, T-cell receptor (TCR), and NF-κB. Verification experiments demonstrated that XBCQ could significantly alleviate the immune injury of the lungs and the gut of the mice, which is attributable to the inhibition of the release of inflammatory cytokines (such as TNF-α, IL-6, and IL-1ß), the downregulation of the protein expression levels of Toll-like receptors-7 (TLR7), MyD88, and p-NF-κB65, and the reduction in the relative abundance of Enterobacteriaceae and Proteus, while an increase in that of Firmicutes and Lachnospiraceae. The overall protective role of XBCQ contributing to the treatment of the lungs and the gut was impaired when Rhubarb was removed from XBCQ. CONCLUSIONS: Our results suggest that the efficacy of XBCQ is related to the inhibition of the immune injury and remodeling of the intestinal flora, wherein Rhubarb plays an important role, which cumulatively provide the evidence applicable for the treatment of viral pneumonia induced by a different respiratory virus with XBCQ.


Assuntos
Medicamentos de Ervas Chinesas , Emodina , Microbioma Gastrointestinal , Vírus da Influenza A , Influenza Humana , Infecções por Orthomyxoviridae , Rheum , Animais , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Emodina/farmacologia , Humanos , Influenza Humana/complicações , Pulmão , Camundongos , Farmacologia em Rede
6.
J Ethnopharmacol ; 298: 115631, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35987411

RESUMO

BACKGROUND: Coronary heart disease (CHD) and depression are very common and often co-existing disorders. Xiong-Pi-Fang (XPF), a therapeutic classical traditional Chinese medicine (TCM) formula, has shown satisfactory efficacy in treating CHD associated with depression. However, its mechanism of action is still unknown. PURPOSE: To employ a systematic pharmacology approach for identifying the action mechanisms of XPF in treating CHD associated with depression. METHODS: We used a systematic pharmacology approach to identify the potential active mechanisms of XPF in treating CHD with depression. Potential active compounds in XPF and the diseases targets were screened using relevant databases to build corresponding pathways, following the experiments that were conducted to confirm whether the presumptive results of systemic pharmacology were correct. RESULTS: Network pharmacology predicted 42 key targets and 20 signaling pathways involved in XPF-mediated treatment, with IL-6/JAK2/STAT3/HIF-1α/VEGF-A pathway significantly affected. The common influences were hypothalamic-pituitary-adrenal axis (HPA axis) and glucocorticoid signaling, validated through chronic unexpected mild stress (CUMS) with isoprenaline (ISO) for inducing CHD within the depression model in rats. In addition, XPF intake reduced depressive-like behaviors and improved ECG ischemic changes. Furthermore, XPF exerted some anti-inflammatory effects by inhibiting the interleukin-6 (IL-6) induced phosphorylation of janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3), ultimately downregulating hypoxia-inducible factor 1-α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) activation. The dysfunctional HPA axis feedback loop was also regulated, which enhanced the glucocorticoid receptor (GR) expression. In contrast, it improved glucocorticoid resistance by reducing the mineralocorticoid receptor expression. CONCLUSIONS: Suppressing IL-6 release and maintaining the HPA feedback loop balance could be the primary mechanism of XPF against CHD with depression. The significance of the IL-6 and HPA axis identified indicates their potential as essential targets for CHD therapy with depression.


Assuntos
Doença das Coronárias , Medicamentos de Ervas Chinesas , Animais , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Sistema Hipotálamo-Hipofisário , Interleucina-6/metabolismo , Farmacologia em Rede , Sistema Hipófise-Suprarrenal , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
J Ethnopharmacol ; 298: 115589, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35926779

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Penthorum chinense Pursh (PCP, Saxifragaceae) is an edible plant and frequently-used Chinese herbal medicine, and is commonly used as Miao medicine in China. It showed well effect on alcoholic liver injury (ALI), but studies on its active ingredients and mechanisms against ALI remain at the starting stage. AIM OF THE STUDY: This work aims to explore the active ingredients and pharmacological mechanisms of PCP against ALI. MATERIALS AND METHODS: First, network pharmacology was applied to decipher the potential active ingredients and pharmacological mechanisms of PCP against ALI by ingredient identification, ADMET evaluation, target identification, network construction and analysis, protein-protein interaction (PPI) analysis, and gene enrichment analysis. Second, molecular docking was used to explore the interaction between key active ingredient and hub protein of PCP against ALI. Then, the ingredient analysis of PCP aqueous extract and semiquantitative analysis of key active ingredient were carried out on HPLC-DAD. Subsequently, mice with ALI were used to investigate the therapeutic effect or verify the predicted mechanisms of PCP or key active ingredient against ALI by analyzing body weight, liver index, ALT and AST activities in serum and liver tissues, oxidation related indices (SOD activity, GSH level and MDA level) in liver tissues, histopathology of liver tissues (oil red O, hematoxylin-eosin and DAB-TUNEL staining), and changes of related proteins (PI3K, Akt, p-Akt, Bax and Bcl-2) in liver tissues with the aid of Western blot. RESULTS: Network pharmacology showed that the active ingredients and related genes of PCP against ALI comprised 10 ingredients and 52 genes. Based on the result of ingredient analysis of PCP aqueous extract, quercitrin was identified as the key active ingredient of PCP against ALI. PPI analysis indicated that AKT1 was the hub gene of PCP against ALI, and molecular docking suggested that there were good interaction between quercetin and Akt1 protein. Gene enrichment analysis showed that the pivotal molecular mechanism of PCP against ALI might be to inhibit hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. PCP and quercitrin showed anti-ALI effect by offsetting weight loss and increase of liver index, and reversing the imbalance of oxidative stress and histopathological changes of liver tissues (abnormal fatty acid metabolism, hepatic cord swelling and inflammatory cell infiltration) in mice with ALI. PCP caused the decrease of DAB-TUNEL-positive cells, upregulated the anti-apoptotic proteins (PI3K, Akt and p-Akt) levels and the ratio of p-Akt/Akt, and downregulated pro-apoptotic protein (Bax) level and the ratio of Bax/Bcl-2 in liver tissues of mice with ALI, indicating that the mechanism of PCP against ALI involved in inhibiting hepatocyte apoptosis via activation of PI3K-Akt signaling pathway. CONCLUSION: PCP and quercitrin showed well anti-ALI effect. The key active ingredient of PCP against ALI was identified as quercitrin. The underlying pharmacological mechanisms of PCP against ALI may be related to PI3K-Akt signaling pathway-mediated inhibition of hepatocyte apoptosis. This work provided new evidence to support the application of PCP in treatment of ALI, and a research basis for the research and development of functional foods or drugs against ALI from PCP.


Assuntos
Medicamentos de Ervas Chinesas , Proteínas Proto-Oncogênicas c-akt , Animais , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado , Camundongos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
8.
Food Funct ; 13(16): 8542-8557, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35880684

RESUMO

Cistanches Herba (CH), as a nutritional and functional supplement used in food and health care products for centuries, consists of the stems of Cistanche deserticola and C. tubulosa. Our previous studies confirmed that the stems of C. tubulosa exerted advantageous antidepressant effect. However, whether the difference in the phytochemical compositions between the stems of C. deserticola and C. tubulosa would lead to diverse bioavailability and accompanying antidepressant effects remain unclear, as well as their specific bioactive compounds and underlying mechanism. In this study, a series of comparative studies showed that the antidepressant activity of C. tubulosa extract (CTE) was stronger than that of the C. deserticola extract (CDE), which was accompanied with the discovery of 10 differential markers from 52 identified compounds between CTE and CDE, and different pharmacokinetic behaviors of 9 prototype and 4 metabolites belonging to the glycosides between the CTE-treated and CDE-treated group in normal and depressive rats were simultaneously found by a validated UPLC-QTRAP-MS/MS method. Subsequently, network pharmacology prediction, in vitro and in vivo experiment verification from these differential markers further revealed that 7 compounds were confirmed to contribute to the antidepressant action of CH by inhibiting neuronal apoptosis mediated by mitochondrial function and activation of the AKT/GSK3ß signaling pathway, synchronously indicating most of those, with higher bioavailability in vivo after CTE administration, that were responsible for the stronger antidepressant effect of CTE over CDE. Hence, the integrated analysis of phytochemical composition, pharmacokinetics, and network pharmacology provide new insights into the applications of CH from different botanical origins against depression.


Assuntos
Cistanche , Medicamentos de Ervas Chinesas , Animais , Antidepressivos/farmacologia , Cistanche/química , Cistanche/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Glicosídeos , Farmacologia em Rede , Compostos Fitoquímicos/metabolismo , Ratos , Espectrometria de Massas em Tandem
9.
Metab Syndr Relat Disord ; 20(8): 480-488, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35862014

RESUMO

Introduction: Berberine is derived from rhizoma coptidis, a well-known Traditional Chinese herbal Medicine that has been found to be effective in the treatment of type 2 diabetes mellitus in recent years. The aim of the present study was to investigate the effects of berberine on a gestational diabetes mellitus (GDM) rat model and the related mechanisms. Methods: GDM was induced in Sprague-Dawley rats using a high-fat diet before and during pregnancy. Berberine (100 mg/kg/day) was administered from the 7th to 20th day of pregnancy. Insulin resistance (IR), glucose tolerance, and maternal, fetal, and placental weight were determined. Liver histopathological analysis, as well as analysis of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), inhibitor kappa B kinaseß (IKKß), nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1), and protein kinase B (AKT), was performed at the end of pregnancy. Results: Treatment of GDM rats with berberine markedly decreased IR, the number of dead and absorptive fetuses, maternal body weight gain, and fetal and placental weight compared with GDM without berberine. Furthermore, berberine decreased CRP and TNF-α levels, IKKß expression, NF-κB P65 nuclear translocation, and changed the phosphorylation of JNK, IRS-1, and AKT in the liver of GDM rats. Conclusions: Berberine improved IR and maternal-fetal outcomes of GDM rats, possibly through modulation of IKK/NF-κB, JNK, and IRS-1/AKT signaling pathways in the liver. Therefore, berberine may be a potential GDM treatment.


Assuntos
Berberina , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Medicamentos de Ervas Chinesas , Resistência à Insulina , Animais , Feminino , Gravidez , Ratos , Berberina/farmacologia , Berberina/metabolismo , Proteína C-Reativa/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Gestacional/tratamento farmacológico , Diabetes Gestacional/metabolismo , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Glucose/metabolismo , Quinase I-kappa B/metabolismo , Quinase I-kappa B/farmacologia , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/farmacologia , Fígado/metabolismo , NF-kappa B/metabolismo , NF-kappa B/farmacologia , Placenta/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
10.
Phytomedicine ; 103: 154239, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35716541

RESUMO

BACKGROUND: Depression is a prevalent emotion disorder which is thought to be due to neuronal structural alterations and/or functional impairment within specific brain regions. Several studies have shown that microRNAs are involved in the pathogenesis of depression. As a Chinese herbal formula, Xiaoyaosan (XYS) could have antidepressive effects, although the mechanisms associated with microRNAs are poorly understood. PURPOSE: In this study, we investigated whether inhibition of the miR-200a/b-3p/NR3C1 pathway in the prefrontal cortex is involved in the anti-neuronal apoptosis and anti-stress effects of XYS and then further delineated the underlying mechanism. METHODS: To evaluate the efficacy of XYS in relieving stress behaviors and altering the expression of miRNAs involved in the regulation of these behaviors in vivo, a chronic unpredictable mild stress (CUMS) rodent model and RNA-seq were performed. Primary cortical neurons were used to evaluate the molecular function of miR-200a/b-3p and detect the in vitro neuroprotective function of paeoniflorin, which is one of the main components of XYS. To investigate the function of miR-200a/b-3p in stress behaviors, stereotactic microinjection of AAV2/9-Syn-miR-200a/b-3p was performed to deliver the treatment to the rat mPFC. RESULTS: XYS reduced the anxiety and depression-like behaviors associated with chronic stress and reduced the expression of miR-200a/b-3p and neuronal apoptosis in the prefrontal cortex (PFC). The overexpression of miR-200a/b-3p in primary cortical neurons reduced the expression of the target gene NR3C1, increased the protein expression of cleaved caspase-3 and Bax, and decreased the anti-apoptotic protein Bcl-2. One of the active ingredients of XYS, paeoniflorin, can inhibit miR-200a/b-3p-mediated apoptosis of primary neurons and abnormal expression of apoptosis-related proteins. After overexpressing miR-200a/b-3p in vivo (vmPFC), the rats eventually showed significant anxiety-like behaviors similar to those caused by chronic stress. CONCLUSION: Our findings indicate that XYS can inhibit the CUMS-induced expression of miR-200a/b-3p, regulate miR-200a/b-3p/NR3C1 signaling in the PFC caused by chronic stress, and reduce neuronal apoptosis and stress-related behaviors.


Assuntos
Medicamentos de Ervas Chinesas , MicroRNAs , Animais , Apoptose , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Receptores de Glucocorticoides/metabolismo
11.
Biomed Pharmacother ; 151: 113076, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35550529

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease that may progress to nonalcoholic steatohepatitis (NASH), hepatic tissue fibrosis, liver cirrhosis, and hepatocellular carcinoma. In this study, we investigated the effects of Pien Tze Huang (PTH), a well-known traditional Chinese herbal formula with liver protective effect, in methionine-choline deficient diet (MCD)- and high-fat diet (HFD)-induced NASH mouse models. Our results showed that PTH could exert hepatoprotective effects by improving liver weight and steatosis and reducing the fibrosis and serum levels of alanine transaminase (ALT) and aspartate transaminase (AST) in both animal models. The effects of PTH was accompanied with the reduction of infiltrated macrophages, the inhibition of the expression of cytokines, and the induction of adiponectin expression. Mechanistically, we found that PTH could inhibit the activation of proinflammatory transcription factor nuclear factor-κB (NF-κB) by preventing the degradation of inhibitor of κBα (IκBα). These results demonstrate that PTH can improve NAFLD largely due to its suppression of the NF-κB inflammatory pathway.


Assuntos
Medicamentos de Ervas Chinesas , Hepatopatia Gordurosa não Alcoólica , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fibrose , Fígado , Cirrose Hepática/metabolismo , Metionina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1790-1801, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534249

RESUMO

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-ß-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.


Assuntos
Cistanche , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas em Tandem/métodos
13.
J Ethnopharmacol ; 291: 115156, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35245628

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: LongShengZhi capsule (LSZ), a traditional Chinese medicine, is used for treatment of patients with vascular diseases. LSZ reduced doxorubicin-induced heart failure by reducing production of reactive oxygen species and inhibiting inflammation and apoptosis. AIM OF THE STUDY: This study was to explore whether LSZ could alleviate cardiac remodeling via upregulation of microRNA (miR)-150-5p and the downstream target. Cardiac remodeling was induced by Ang II in vivo and in vitro. RESULTS: LSZ attenuated Ang II-induced cardiac hypertrophy and fibrosis in rats, and in primary cardiomyocytes (CMs) and primary cardiac fibroblasts (CFs). MiR-150-5p was downregulated in Ang II-induced rat heart, CMs and CFs, and these decreases were reserved by LSZ. In vivo overexpression of miR-150-5p by transfection of miR-150-5p agomiR protected Ang II-induced cardiac hypertrophy and fibrosis in rats. Meanwhile, its overexpression also reversed Ang II-induced upregulation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and ß-myosin heavy chain (ß-MHC) in rat hearts and primary CMs, as well as upregulation of collagen I, collagen III and transforming growth factor-ß (TGF-ß) in rat hearts and primary CFs. Matrix metalloproteinase 14 (MMP14) was validated as the target gene of miR-150-5p, which was overexpressed in Ang II-induced rat heart, rat primary CMs and primary CFs. Notably, overexpression of MMP14 induced cardiac remodeling, and reversed the protective role of miR-150-5p in downregulating Ang II-induced upregulation of hypertrophy and fibrosis markers in vitro. CONCLUSION: Collectively, LSZ protects Ang II-induced cardiac dysfunction and remodeling via upregulation of miR-150-5p to target MMP14. Administration of LSZ, upregulation of miR-150-5p or targeting of MMP14 may be strategies for cardiac remodeling therapy.


Assuntos
Medicamentos de Ervas Chinesas , Metaloproteinase 14 da Matriz , MicroRNAs , Remodelação Ventricular , Angiotensina II/farmacologia , Animais , Cardiomegalia/induzido quimicamente , Cardiomegalia/tratamento farmacológico , Cardiomegalia/patologia , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fibrose , Metaloproteinase 14 da Matriz/genética , MicroRNAs/genética , Miócitos Cardíacos , Ratos , Regulação para Cima , Remodelação Ventricular/efeitos dos fármacos
14.
Anal Biochem ; 643: 114580, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35149001

RESUMO

The pharmacodynamics, 1H NMR metabolomics and endogenous network pharmacology strategy approaches were integrated to investigate the preventive mechanism of Gushudan (GSD) on kidney-yang-deficiency-syndrome (KYDS) rats in this study. Firstly, the KYDS rat model was achieved by hydrocortisone induction, and the efficacy of GSD on KYDS model rats was assessed by the pharmacodynamic indicators. Next, the comprehensive untargeted serum metabolic profile of rats was obtained in 1H NMR metabolomics study, 29 potential biomarkers closely associated with KYDS were identified, which were mainly involved in carbohydrate metabolism, amino acid metabolism and intestinal flora metabolism. In addition, the potential biomarkers-targets-pathways-disease metabolic network was further investigated for deeper understanding the preventive effects of GSD on KYDS rats and its mechanism, which was further obtained for the important targets related to biomarkers and diseases such as NOS3, PTGS2 and CXCL8, and important metabolic pathways such as glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, and microbial metabolism in diverse environments. Finally, compared with our previous anti-osteoporosis study of GSD, it suggested that some similar metabolic pathways, which would provide some scientific reference of the existence of the kidney-bone axis under the traditional Chinese medicine (TCM) theory of "kidney dominates bone".


Assuntos
Medicamentos de Ervas Chinesas/análise , Nefropatias/metabolismo , Metabolômica , Deficiência da Energia Yang/metabolismo , Animais , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Nefropatias/sangue , Nefropatias/diagnóstico , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Ratos , Ratos Sprague-Dawley , Deficiência da Energia Yang/sangue , Deficiência da Energia Yang/diagnóstico
15.
Artigo em Inglês | MEDLINE | ID: mdl-35032891

RESUMO

In traditional Chinese medicine (TCM), components with identical nuclei often share structural similarity, indicating the possibility of similar second-level mass spectrometry (MS/MS) fragments. High-resolution product-ion filter (HRPIF) technique can be utilized to identify metabolites, with similar fragments, in vivo. In principle, this technique applies to TCM; however, its application has been restricted due to the limitations of traditional MS/MS data acquisition. Therefore, a novel analysis strategy, based on data-dependent acquisition (DDA) and data-independent acquisition (DIA) datasets, has been developed for the determination of template product ions and efficient non-targeted identification of TCM-related components in vivo by HRPIF and background subtraction (BS). This DDA-DIA combination strategy, taking Rhei Radix et Rhizoma as a test case, identified 71 anthraquinone prototype components in vitro (36 of which were discovered for the first time), and 45 related components in vivo, confirming glucuronidation and sulfation as the main reactions. The developed strategy could rapidly identify TCM-related components in vivo with high sensitivity, indicating the immense importance of this novel HRPIF data mining technology in TCM analysis.


Assuntos
Mineração de Dados/métodos , Medicamentos de Ervas Chinesas/metabolismo , Rheum/química , Rizoma/química , Administração Oral , Animais , Antraquinonas/administração & dosagem , Antraquinonas/sangue , Antraquinonas/química , Antraquinonas/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Masculino , Estrutura Molecular , Plasma/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
16.
J Ethnopharmacol ; 288: 114994, 2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35033623

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gualou-Xiebai-Banxia decoction (GXBD) was a classical traditional Chinese medicine formula for the treatment of coronary heart disease. However, the current study on the chemical and metabolite profiles of GXBD did not follow the ancient prescription and extraction method, which hindered the discovery of effective compounds and quality control. MATERIALS AND METHODS: In this study, we prepared GXBD by ancient prescription and extraction methods, and then analysed the chemical components and xenobiotics of GXBD in vivo using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry and in-house software. RESULTS: 49 chemical constituents were preliminarily identified, including 7 terpenoids, 6 flavonoids, 5 alkaloids, 17 organic acids, 8 steroids and steroidal saponins, 2 nucleosides and 4 other types of compounds, of which 10 constituents were confirmed unambiguously with authentic standards. Moreover, 129 metabolites were tentatively identified, including 83 metabolites in plasma, 39 metabolites in urine, 25 metabolites in bile and 9 metabolites in feces. Our study speculated that luteolin, adenosine, vanillic acid and curbitacin B might be possible effective components of GXBD for the treatment of coronary heart disease. Dehydration, deglycosylation, dehydrogenation, acetylation and taurine regulation were the main biotransformation reactions of GXBD. CONCLUSION: Our results provided an important basis for the discovery of effective compounds and quality control of GXBD. In addition, in-house software was an useful tool for identifcation of metabolites.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Espectrometria de Massas/métodos , Animais , Medicamentos de Ervas Chinesas/metabolismo , Masculino , Controle de Qualidade , Ratos , Ratos Sprague-Dawley
17.
Rapid Commun Mass Spectrom ; 36(4): e9219, 2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-34740284

RESUMO

RATIONALE: Panax ginseng (PG) and American ginseng (AMG) are both medicinal plants of the Panax genus in the Acanthopanax family. Although PG and AMG have similar components of ginsenosides, there are many differences of their bioactivities. In this study, the biochemical mechanisms of different bioactivities of PG and AMG were explored by researching the differential metabolites in plasma after administration of each of PG and AMG. METHODS: In order to explore the material basis of differential bioactivities, two groups of mice were administrated orally with PG and AMG, and the method of metabolomics was used to identify the differential metabolites in plasma. Then network pharmacology was used based on the differential metabolites. Afterward, the metabolite-target-pathway network of PG and AMG was constructed; thus the pathways related to different bioactivities were analyzed. RESULTS: Through principal component analysis and orthogonal projections to latent structures discriminant analysis, there were 10 differential metabolites identified in the PG group and 8 differential metabolites identified in the AMG group. Based on network pharmacology, the differential metabolites were classified and related to differential bioactivities of PG and AMG. In the PG group, there were 6 metabolites related to aphrodisiac effect and exciting the nervous system, and 5 metabolites associated with raised blood pressure. In the AMG group, 5 metabolites were classified as having the effect of inhibiting the nervous system, and 6 metabolites were related to antihypertensive effect. CONCLUSIONS: This study explored the material basis of the differential biological activities between PG and AMG, which is significant for the research of PG and AMG use and to promote human health.


Assuntos
Medicamentos de Ervas Chinesas/química , Panax/metabolismo , Animais , Medicamentos de Ervas Chinesas/metabolismo , Ginsenosídeos/sangue , Ginsenosídeos/química , Metabolômica , Camundongos , Panax/química , Panax/classificação , Plantas Medicinais/química , Plantas Medicinais/metabolismo , Plasma/química , Análise de Componente Principal
18.
Anal Biochem ; 642: 114480, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34813769

RESUMO

Shen Gui capsule (SGC) has been demonstrated to have a significant treatment effect for coronary heart disease (CHD). Nevertheless, the holistic therapeutic mechanism of SGC in vivo remain poorly interpreted. We aimed to systematically explore the preventive effect and mechanism of SGC on CHD rats using plasma metabolomics strategy. Rat CHD model was established by left anterior descending coronary artery ligation (LAD). Echocardiography, histological analyses of the myocardium and biochemical assays on serum were used to confirm the successful establishment of the CHD model and therapeutic effects of SGC. Then, UHPLC-MS/MS-based plasma metabolomics was combined with multivariate data analysis to screen potential pharmaco biomarkers associated with SGC treatment in the LAD-induced rat CHD model. After SGC treatment, 12 abnormal metabolites considered as potiential pharmaco biomarkers recovered to near normal levels. These biomarkers were involved in several metabolic pathways, including fat and protein metabolism, phenylalanine metabolism, neuroactive ligand-receptor interaction, androgen receptor signaling pathway, and estrone metabolism.These results suggested that SGC achieves therapeutic action on CHD via regulating various aspects of the body such as energy metabolism, neurological disturbances and inflammation, and thus plays a significant role in the treatment of CHD and its complications. The study is useful to systematically understand and analyze the mechanism of SGC's "multipie pathways, multiple levels, multiple targets" prevention and treatment of CHD.


Assuntos
Doença das Coronárias/tratamento farmacológico , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Animais , Cápsulas , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Análise Multivariada , Ratos , Espectrometria de Massas em Tandem
19.
Biomed Chromatogr ; 36(1): e5235, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34553391

RESUMO

Dingkun Dan (DKD), a reputable traditional Chinese medicine formula, has been used to treat gynecological diseases and showed significant clinical effects since ancient times. However, the application and development of DKD are seriously hampered by the unclear active substances. Structural characterization of compounds absorbed in vivo and their corresponding metabolites is significant for clarifying the pharmacodynamic material basis. In this study, an integrated strategy using ultra-performance liquid chromatography, coupled with quadrupole time-of-flight mass spectrometry and UNIFI™ software, was used to identify prototypes and metabolites after oral administration of DKD in rats. As a result, a total of 261 compounds, including 140 prototypes and 121 metabolites, were tentatively characterized in rat plasma, urine, and feces. The metabolic pathways of prototypes have been studied to clarify their possible transformation process in vivo. Moreover, an in vitro metabolism study was applied for verifying the metabolites under simulating the metabolic environment in vivo. This first systematic metabolic study of DKD is important for elucidating the metabolites and metabolic pathways and could provide a scientific basis for explaining the integrative mechanism in further pharmacology study.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/metabolismo , Espectrometria de Massas/métodos , Administração Oral , Alcaloides/análise , Alcaloides/química , Alcaloides/metabolismo , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Flavonoides/análise , Flavonoides/química , Flavonoides/metabolismo , Redes e Vias Metabólicas , Ratos , Saporinas/análise , Saporinas/química , Saporinas/metabolismo
20.
J Ethnopharmacol ; 291: 115157, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35247474

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence and mortality of bronchial asthma are increasing, and respiratory syncytial virus (RSV) is widely regarded as the common cause of clinical exacerbation of asthma. Ma-Xing-Gan-Shi decoction (MXGSD), a classic traditional Chinese medicine prescription, is well-known for treating respiratory diseases, while the mechanism of effecting on RSV-exacerbated asthma remains to be explored. AIM OF THE STUDY: In this study, we investigated the mechanism by which MXGSD exerts a protective effect on asthma exacerbated by RSV in vivo and in vitro. MATERIALS AND METHODS: MXGSD is composed of four Chinese medicine, including Ephedra intermedia Schrenk & C.A.Mey. (herbaceous stem, 27g), Prunus armeniaca L. (dry seed, 27g), Glycyrrhiza uralensis Fisch. (radix and rhizome, 18g), and Gypsum fibrosum (main component: CaSO4·2H2O, 54g). In the present study, the exacerbated asthmatic mice model with the treatment of OVA plus RSV was replicated, and accompanied by the TMT proteomic analysis and further experimental investigations. Then, the protective effect of MXGSD (13.2, 6.6, 3.3 g/kg/d, 7d) on the mice treated by OVA plus RSV, and the mechanism of regulating TRPV1 was explored. In addition, the intracellular Ca2+ concentration of 16HBE cells pretreated with MXGSD medicated serum was also tested after stimulation with the TRPV1 agonist capsaicin. RESULTS: The results suggested that MXGSD could reduce the levels of inflammation cells, airway hyperresponsiveness, and pathological damage of lung tissue. TMT quantitative proteomics analysis and further experimental exploration revealed that MXGSD could reduce the levels of IL-4, IL-13, PGE2, and SP in BAL and down-regulate the expression of TRPV1 mRNA and protein in lung tissue. Furthermore, 16HBE cells stimulated by capsaicin showed an increased intracellular Ca2+ concentration, while the pretreatment of MXGSD medicated serum could reduce it. CONCLUSION: MSGSD showed a protective effect on RSV-exacerbated asthma, which may be related to its regulation of TRPV1 expression and reduction of Th2 cytokines and neurogenic inflammatory mediators. It may provide an objective basis and reference for the clinical application of MXGSD.


Assuntos
Asma , Medicamentos de Ervas Chinesas , Infecções por Vírus Respiratório Sincicial , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Proteômica , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sinciciais Respiratórios/metabolismo , Canais de Cátion TRPV/metabolismo
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