RESUMO
Ancient Chinese medicine literature and modern pharmacological studies show that Sophora tonkinensis Gagnep. (ST) has a protective effect on the heart. A biolabel research based on omics and bioinformatics and experimental validation were used to explore the application value of ST in the treatment of heart diseases. Therapeutic potential, mechanism of action, and material basis of ST in treating heart diseases were analyzed by proteomics, metabolomics, bioinformatics, and molecular docking. Cardioprotective effects and mechanisms of ST and active compounds were verified by echocardiography, HE and Masson staining, biochemical analysis, and ELISA in the isoproterenol hydrochloride-induced myocardial ischemia (MI) mice model. The biolabel research suggested that the therapeutic potential of ST for MI may be particularly significant among the heart diseases it may treat. In the isoprenaline hydrochloride-induced MI mice model, ST and its five active compounds (caffeic acid, gallic acid, betulinic acid, esculetin, and cinnamic acid) showed significant protective effects against echocardiographic changes and histopathological damages of the ischemic myocardial tissue. Meanwhile, they showed a tendency to correct mitochondrial structure and function damage and the abnormal expression of 12 biolables (DCTN1, DCTN3, and SCARB2, etc.) in the vesicle-mediated transport pathway, inflammatory cytokines (IL-1ß, IL-6, and IL-10, etc.), and low density lipoprotein receptor (LDLR). The biolabel research identifies a new application value of ST in the treatment of heart diseases. ST and its active compounds inhibit mitochondrial impairments, inflammation, and LDLR deficiency through regulating the vesicle-mediated transport pathway, thus achieving the purpose of treating MI.
Assuntos
Isquemia Miocárdica , Sophora , Camundongos , Animais , Sophora/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Isquemia Miocárdica/tratamento farmacológico , Inflamação/tratamento farmacológico , Isoproterenol/uso terapêutico , Receptores de LDLRESUMO
In traditional Chinese medicine, Herba Lysimachiae (HL) is mainly used to treat rheumatic arthralgia. Current pharmacological studies also showed that HL has therapeutic potential for synovial diseases. HL is an oral drug, whose compounds need to enter the blood circulation before reaching the injured tissue, thus potentially causing activity or toxicity to the blood system. In this study, the biolabel-led research pattern was used to analyze the serum profile after HL intervention, based on which the safety and efficacy of HL were explored. Metabonomics and proteomics were combined to analyze the biolabels responsible for the interventions of HL in serum. Bioinformatics databases were used to screen for the material basis that may interfere with biolabels. Omics analysis showed that differentially expressed proteins (19) and metabolites (5) were identified and considered as the potential biolabels, which were involved in 8 biochemical processes (platelet activation and aggregation, blood glucose release, immune and inflammatory regulation, oxidative stress, endoplasmic reticulum stress, tumor progression, blood pressure regulation, and uric acid synthesis). Thirty-one compounds may be the material basis to interfere with 11 biolabels. The present research reveals that the potential activities and toxicities of HL can be explored based on the biolabel-led research pattern.
Assuntos
Medicamentos de Ervas Chinesas , Proteômica , Animais , Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Metabolômica , RatosRESUMO
Previous studies have shown that Sophorae Tonkinensis radix et rhizome (ST) can be used to treat some lung diseases. However, the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST treatment of lung diseases remain unclear. Thus, the aim of this study was to carry out an integrated analysis based on the biolabel-led research pattern. Proteomics and metabonomics were applied to explore the biolabels responsible for the effect of ST on lung tissue. Based on the biolabels, a bioinformatics database was used to topologically analyze the therapeutic potentials, therapeutic advantages, mechanism of action, and material basis of ST in treating lung diseases. Four human lung-cancer cell models were used to validate the results of the biolabel analysis. In total, 45 proteins and 3 metabolites were significantly enriched in 13 pathways and were considered as biolabels. Bioinformatics revealed that the therapeutic potentials of ST involved a variety of lung diseases, especially lung neoplasms. Under the mediation of 40 biolabels, 29 compounds may be the material basis of ST in treating lung diseases. In a verification experiment, ST had a significant inhibitory effect on the H226 cell line (lung squamous cell carcinoma), which ranks first in morbidity and mortality among lung cancers in China. Additionally, five biolabels (CPS1, CKM, CPT1B, COX5B, and COX4I1) were involved in the anti-lung cancer mechanism of ST and 3 compounds (gallic acid, betulinic acid, and caffeic acid). These findings indicate that the biolabel-led research pattern was helpful in achieving the objectives of this study.
Assuntos
Medicamentos de Ervas Chinesas , Pneumopatias , Sophora , Linhagem Celular Tumoral , Biologia Computacional , Desenho de Fármacos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Pneumopatias/tratamento farmacológico , Rizoma/química , Sophora/químicaRESUMO
The root and rhizome of Sophora tonkinensis Gagnep. (ST) are widely used for the treatment of tonsillitis, sore throats, and heat-evil-induced diseases in traditional Chinese medicine. However, the clinical application of ST is relatively limited due to its toxicity. The mechanism and material basis of ST-induced pulmonary toxicity are still unclear. In the present research, integrated omics and bioinformatics analyses were used to investigate the toxic mechanism and material basis of ST in lung tissue. Proteomics and metabonomics were integrated to analyze the differentially expressed proteins and metabolites. Joint pathway analysis was used to analyze the significantly dysregulated pathways. PubChem and the Comparative Toxicogenomics Database were applied for the screen of toxic targets and compounds. Integrated omics revealed that 323 proteins and 50 metabolites were differentially expressed after treating with ST, out of which 19 proteins and 1 metabolite were significantly enriched in seven pathways. Bioinformatics showed that 15 compounds may indirectly affect the expression of 9 toxic targets of ST. Multiple toxic targets of ST-induced pulmonary injury were found in the study, whose dysregulation may trigger pulmonary cancer, dyspnea, and oxidative stress. Multiple compounds may be the toxic material basis in response to these effects.
Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Pulmão , Metaboloma/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Sophora , Animais , Bases de Dados Genéticas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/metabolismo , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Pulmão/química , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Proteoma/análise , ProteômicaRESUMO
Herba Lysimachiae inhibits synovial damage in osteoarthritis via regulating two bio labels (integrin alpha 2b/beta 3). However, the relevant active ingredients are still unknown. Here, the active ingredients of herbal medicines were analyzed based on the liquid chromatography-tandem mass spectrometry technology and public bioinformatics platforms. The liquid chromatography-tandem mass spectrometry technology was used for compound analysis, and public databases (PubChem BioAssay and STRING) were applied to establish the links between herbal compounds and both bio labels, and identify which herbal compounds may regulate these bio labels. Subsequently, the osteoarthritis model was used to confirm the results. Totally, ninety compounds in Herba Lysimachiae were identified based on the liquid chromatography-tandem mass spectrometry technology. Bioinformatics analysis showed that five compounds (myricetin, fisetin, esculetin, 7-hydroxycoumarin-4-acetic acid, and caffeic acid) may synergistically regulate bio labels through 11 targets, which may be the active ingredients of Herba Lysimachiae for osteoarthritis treatment. In the verification experiments, five compounds markedly suppressed the overexpression of bio labels in the synovium of the osteoarthritis model. In conclusion, the present study effectively and rapidly analyzed the active ingredients of Herba Lysimachiae for osteoarthritis treatment.
Assuntos
Biologia Computacional , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/uso terapêutico , Osteoartrite/tratamento farmacológico , Primulaceae/química , Animais , Cromatografia Líquida , Ácido Iodoacético , Masculino , Osteoartrite/induzido quimicamente , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em TandemRESUMO
Previous research has demonstrated that Herba Lysimachiae (HL) exerts the dual effects on platelet aggregation in the synovium, which may contribute to its protection against synovial lesions under different situations. However, the mechanism is unclear. In the present experiment, a biolabel research based on metabonomics was used to mine the information about the intervention of HL on synovium at the metabolite level, which may help to analyze the regulation of HL on synovial platelet aggregation and its possible treatment in synovial diseases. Synovial metabolic profiling was analyzed using a Shimadzu Nexera UHPLC LC-30A system and an AB SCIEX Triple TOF 4600 mass spectrometer. Enzyme-linked immunosorbent assay (ELISA) was used to verify the biolabels analysis results in the healthy and osteoarthritis rats. Totally, thirteen common metabolites were differentially expressed after treating with HL, and implicated in 2 key pathways (arachidonic acid metabolism and glycerophospholipid metabolism). ELISA showed that HL regulated the expression of prostaglandins E1 and E2 in synovial tissues of the healthy and osteoarthritis rats. This study reveals that HL may regulate synovial platelet aggregation through prostaglandin E1/E2. Additionally, HL is suitable for treating synovial diseases, especially osteoarthritis, which may be associated with platelet aggregation, apoptosis, inflammation, angiogenesis, and carcinogenesis processes.
Assuntos
Metaboloma/efeitos dos fármacos , Osteoartrite/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Primulaceae , Prostaglandinas/metabolismo , Animais , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Metabolômica , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/metabolismoRESUMO
In traditional Chinese medicine theory, Sophorae Tonkinensis radix et rhizome (ST) has the effects of treating tonsillitis, sore throats, and heat-evil-induced diseases. However, the utilization of ST is relatively restricted owing to its toxicity. The previous studies have made some progress on the mechanism and material basis of ST-induced hepatotoxicity, but there is still no significant breakthrough. In this study, integrated omics and bioinformatics analyses were used to investigate the mechanism and material basis of ST-induced hepatotoxicity. Integrated omics were used to analyze the differentially expressed proteins and metabolites, based on which the significantly dysregulated pathways were analyzed by using MetaboAnalyst. Bioinformatics was applied to screen the toxic targets and material basis. Integrated omics revealed that 254 proteins and 42 metabolites were differentially expressed after the treatment with ST, out of which 7 proteins were significantly enriched in 3 pathways. Bioinformatics showed that 20 compounds may interfere with the expression of 7 toxic targets of ST. Multiple toxic targets of ST-induced hepatotoxicity were found in the study, whose dysregulation may trigger hepatocyte necrosis/apoptosis, liver metastasis, and liver cirrhosis. Multiple compounds may be the toxic material basis in response to these effects.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Medicamentos de Ervas Chinesas , Sophora , Doença Hepática Induzida por Substâncias e Drogas/genética , Biologia Computacional , Medicamentos de Ervas Chinesas/toxicidade , RizomaRESUMO
Sophora tonkinensis Gagnep. (ST) (Fabaceae) is distributed chiefly in south-central and southeast China and Vietnam. In traditional Chinese medicine theory, the root and rhizome of ST are toxic and mainly used in the treatment of pharyngeal and laryngeal diseases. Modern studies provide new insights into the pharmacological and toxicological aspects of ST. The pharmacological and toxicological properties of ST were reviewed in this paper based on the literature from Google Scholar and CNKI, and the bioinformatics platforms were applied to explore the pharmacological and toxicological potentials of ST. The results of the literature analysis showed that ST has hepatoprotective, immunomodulatory, and anticancer effects and produces obvious toxicity to the liver and nervous and cardiovascular system. The results of bioinformatics showed that the compounds from ST may be applied to the treatment of cancer and digestive and nervous system diseases and show the possibility to cause hematotoxicity, neurotoxicity, and immunotoxicity. The present review demonstrates that attention should be paid to the potential toxicity of ST in the treatment of diseases and provides the reference for the subsequent pharmacological toxicological studies on the mechanism and chemical basis of ST.
Assuntos
Medicina Tradicional Chinesa , Extratos Vegetais , Sophora/química , Sophora/toxicidade , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidadeRESUMO
Osteoarthritis (OA) is a common chronic articular degenerative disease, and characterized by articular cartilage degradation, synovial inflammation/immunity, and subchondral bone lesion, etc. The disease affects 2-6% of the population around the world, and its prevalence rises with age and exceeds 40% in people over 70. Recently, increasing interest has been devoted to the treatment or prevention of OA by herbal medicines. In this paper, the herbal compounds with anti-OA activities were reviewed, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 43 herbal compounds were analyzed, which mainly target the damaged joints (e.g. cartilage, subchondral bone, and synovium, etc.) and circulatory system to improve the pathogenesis of OA. Through cheminformatics analysis, over half of these compounds have good drug-likeness properties, and the pharmacokinetic behavior of these components still needs to be further optimized, which is conducive to the enhancement in their drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-OA drug discovery, which may be worthy of further investigation and development.
RESUMO
Some previous studies have demonstrated that Herba Lysimachiae (HL) has a certain protective effect on synovial lesion. But the synovial diseases HL is suitable for treating have remained unclear, as well as the mechanisms involved. To investigate the therapeutic potentials of HL in synovial diseases based on the biolabel-led research pattern. Label-free quantitative proteomics analysis was used to screen the potential biolabels responsible for the intervention of HL on synovium. The effects of HL on the joint swelling and synovial platelet aggregation in osteoarthritis model was applied to confirm the biolabels analysis results. Totally, 140 common proteins were differentially expressed after treatment with HL, out of which 23 were involved in 4 key pathways and considered as the potential biolabels responsible for the interventions of HL on synovium. Biolabels analysis showed that HL increased the levels of the proteins promoting platelet aggregation in physiological situations. The potential biolabels and their related pathways were mainly associated with the pathogenesis of osteoarthritis. In osteoarthritis model, HL inhibited the joint swelling and the overexpression of Itga2b and Itgb3 in synovium to some extent. This study reveals that HL is suitable to treat osteoarthritis. Additionally, HL may produce the dual effects on platelet aggregation in synovium.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Primulaceae/química , Proteoma/efeitos dos fármacos , Proteômica/métodos , Membrana Sinovial , Animais , Cromatografia Líquida , Modelos Animais de Doenças , Masculino , Osteoartrite/metabolismo , Ratos , Ratos Sprague-Dawley , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismoRESUMO
Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5-1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug-likeness properties will be further studied and developed. Therefore, the herbal compounds with anti-RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug-likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti-inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug-likeness properties. Most of the compounds can be an alternative and valuable source for anti-RA drug discovery.
Assuntos
Artrite Reumatoide/tratamento farmacológico , Quimioinformática/métodos , Medicina Herbária/métodos , Plantas Medicinais/química , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate the neuro-protective effects of Acanthopanax senticosus Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson's disease (PD). METHODS: The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg i.p) once a day for 5 days. The control group received an equal volume of saline (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC). RESULTS: After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly (P<0.05). EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential (both P<0.05), which was supported by an ultra-structural level analysis. The changes in reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins expressions (parkin, Pink1, DJ-1, α-synuclein, and Lrrk2) reverted to near normal levels (all P<0.05), based on the results of immune-histological and Western blotting observations. CONCLUSIONS: The neuro-protective effects of EAS are linked to protecting mice against MPTP-induced mitochondrial dysfunction and structural damage. Therefore, EAS is a promising candidate for the prevention or treatment of mitochondrial neurodegenerative disorders, such as PD.
Assuntos
Eleutherococcus , Intoxicação por MPTP/tratamento farmacológico , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mesencéfalo/efeitos dos fármacos , Dilatação Mitocondrial/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/uso terapêuticoRESUMO
OBJECTIVES: This study was aimed to explore the chemical basis of the rhizomes and aerial parts of Dioscorea nipponica Makino (DN). METHODS: The pharmacokinetic profiles of the compounds from DN were calculated via ACD/I-Lab and PreADMET program. Their potential therapeutic and toxicity targets were screened through the DrugBank's or T3DB's ChemQuery structure search. KEY FINDINGS: Eleven of 48 compounds in the rhizomes and over half of the compounds in the aerial parts had moderate or good human oral bioavailability. Twenty-three of 48 compounds in the rhizomes and 40/43 compounds from the aerial parts had moderate or good permeability to intestinal cells. Forty-three of 48 compounds from the rhizomes and 18/43 compounds in the aerial parts bound weakly to the plasma proteins. Eleven of 48 compounds in the rhizomes and 36/43 compounds of the aerial parts might pass across the blood-brain barrier. Forty-three 48 compounds in the rhizomes and 18/43 compounds from the aerial parts showed low renal excretion ability. The compounds in the rhizomes possessed 391 potential therapeutic targets and 216 potential toxicity targets. Additionally, the compounds from the aerial parts possessed 101 potential therapeutic targets and 183 potential toxicity targets. CONCLUSIONS: These findings indicated that combination of cheminformatics and bioinformatics may facilitate achieving the objectives of this study.
Assuntos
Biologia Computacional , Dioscorea/química , Extratos Vegetais/química , Animais , Disponibilidade Biológica , Barreira Hematoencefálica/metabolismo , Feminino , Humanos , Absorção Intestinal , Camundongos , Componentes Aéreos da Planta/química , Extratos Vegetais/farmacocinética , Extratos Vegetais/toxicidade , Rizoma/química , Distribuição TecidualRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Ciwujia (CWJ), one of the most commonly used Chinese materia medicas (CMMs), is derived from the roots, rhizomes, and stems of Acanthopanax senticosus harms (AS). CWJ has been used for the treatment of various central nervous system (CNS) and peripheral system diseases. Drug-likeness prediction can help to analyze the absorption, distribution, metabolism, and excretion (ADME) processes of the compounds in CWJ, as well as their potential therapeutic and toxic effects, which is of significance in the confirmation of the active material bases of CWJ. MATERIALS AND METHODS: The ADME properties of the compounds were calculated through web based PreADMET program and ACD/I-Lab 2.0. The potential therapeutic and toxicity targets of these compounds were screened by the ChemQuery tool in DrugBank and T3DB. RESULTS: 14/39 compounds had moderate or good oral bioavailability (OB). 29/39 compounds bound weakly to the plasma proteins. 18/39 compounds might pass across the blood-brain barrier (BBB). Most of these compounds showed low renal excretion ability. 25/39 compounds had 99 structurally similar drugs and 158 potential therapeutic targets. Additionally, 17/39 compounds had 53 structurally similar toxins and 126 potential toxicity targets. CONCLUSION: Our study suggests that these compounds have a certain drug-likeness potentials, which are also likely to be the material bases of CWJ. These results may provide a reference for the safe use of CWJ and the expansion of its application scope.
Assuntos
Eleutherococcus/química , Materia Medica/análise , Barreira Hematoencefálica , Biologia ComputacionalRESUMO
α-Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α-synuclein overexpression and toxicity. Identifying the RNAs related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non-coding RNAs (lncRNAs) and mRNAs was undertaken in control non-transgenic and human α-synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α-synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti-α-synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α-synuclein group, which may cause potential neurotoxicity analogous to α-synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α-synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions.
Assuntos
Eleutherococcus/química , Extratos Vegetais/farmacologia , alfa-Sinucleína/genética , Animais , Eleutherococcus/efeitos adversos , Humanos , Corpos de Lewy , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , TranscriptomaRESUMO
To study the potential effect of Dioscorea nipponica(DN) in intervening peripheral system of rats based on metabolomic analysis. The identification of the potential intervention targets of DN in peripheral system may facilitate its safe application and therapeutic potential exploitation. Totally 20 male SD rats were randomly divided into the blank group and the DN-treated groups, with 10 rates in each group. The DN-treated group was orally administrated with DN extracts once a day for 5 days, with the dose of 80 mg x kg(-1) (equivalent to 15 g crude drug in human), and the blank group was given equal volume of saline once a day for 5 days. Heart, liver, spleen, lung, and kidney tissues and serum samples were collected from each rat 24 h later after the last administration. The ultra-performance liquid chromatography/quadrupole time-of-flight-mass spectrometry based metabolomics was used to investigate the effect of DN in intervening peripheral system of rats. After the treatment with DN, 5 modulated metabolites in heart tissue, 6 in liver tissue, 5 in spleen tissue, 3 in lung tissue, 5 in kidney tissue and 6 in serum sample were identified and considered as the potential intervention targets of DN. Effect of DN in regulating some endogenous metabolites was beneficial for protecting peripheral system, while that in other endogenous metabolites produced potential toxicity to peripheral system. The metabolomic analysis revealed the coexistence of protective and toxic effects of DN on peripheral system, which may be a practical guidance for its safe application and beneficial to the expansion of its application scope.
Assuntos
Dioscorea/química , Medicamentos de Ervas Chinesas/farmacologia , Rim/química , Fígado/química , Pulmão/química , Animais , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Metabolômica , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
Acanthopanax senticosus is extensively used to treat various nervous and cerebrovascular diseases in traditional medicinal systems in China and Russia. Ultrahigh-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry coupled with pattern recognition methods was used to investigate the effects of A. senticosus on the peripheral system in rats. The analysis of possible pathways influenced by A. senticosus was performed with MetaboAnalyst and Cytoscape software. After treatment with A. senticosus, 21 modulated metabolites in heart tissue, 20 in liver tissue, 14 in spleen tissue, 17 in lung tissue, 16 in kidney tissue, and 12 in a serum sample were identified and considered potential biomarkers of A. senticosus treatments. The regulation of some endogenous metabolites by A. senticosus could be beneficial for the treatment of several peripheral system diseases, such as hypertension, cancer, and oxidative stress, etc. However, there were also some upregulated endogenous metabolites producing potential toxicity to the peripheral system. A metabonomic analysis revealed that protection and toxicity coexisted in the effects of A. senticosus on the peripheral system, which may be a practical guide for its safe use and beneficial to the expansion of its application.
Assuntos
Eleutherococcus/química , Metabolômica , Extratos Vegetais , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Espectrometria de Massas , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Baço/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus Harms (AS), also called "Ciwujia" in Chinese and "Siberian ginseng" in the Siberian Taiga region, is the herb used in traditional medicinal systems of China, Russia, Japan and Korea for the treatment of various nervous and cerebrovascular diseases. AIM OF THE STUDY: Our pre-study has showed that AS can significantly suppress α-synuclein overexpression and toxicity. Neuronal protein α-synuclein is a key player in the development of neurodegenerative diseases called α-synucleinopathies. Identifying the potential biomarkers related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. METHODS AND RESULTS: Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods was integrated to examine the cerebral metabolic signature of human α-synuclein transgenic mice and the effects of AS on central nervous system (CNS) in pathology and physiology. Totally, 17 differentially expressed metabolites in wild type (WT) group and 26 in A30P mutant (A30P) group were identified and considered as potential biomarkers. Among them, 11 endogenous metabolites in WT+AS group and 18 in A30P+AS group were involved in the anti-α-synucleinopathies mechanism of AS. However, western blot and metabolomics analysis showed the effects of AS on CNS in physiology were opposite to those in pathology, which may cause potential neurotoxicity. CONCLUSIONS: This study demonstrated that endogenous metabolites perturbation was involved in the pathogenesis of α-synucleinopathies and AS produced the dual effects on pathological and physiological CNS.
Assuntos
Eleutherococcus , Mesencéfalo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , alfa-Sinucleína/metabolismo , Animais , Biomarcadores/metabolismo , Masculino , Mesencéfalo/metabolismo , Metabolômica , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Raízes de Plantas , alfa-Sinucleína/genéticaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Acanthopanax senticosus harms (AS), also called "Ciwujia" in Chinese and "Siberian ginseng" in the Siberian Taiga region, is the herb used in traditional medicinal systems in China and Russia, which has been applied to the treatment of various nervous and cerebrovascular diseases, such as depression, mental fatigue, and transient global cerebral ischemia. The previous research works usually tended to focus on the neuroprotective effects of AS, but ignored its additional effects that are not entirely beneficial to the nervous system. Therefore, to discover the potential intervention targets of AS and evaluate their roles in the nervous system are the urgent problems. MATERIALS AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-QTOF-MS) coupled with pattern recognition methods were integrated to investigate the metabolic profiles of AS-treated rats. The analysis of possible pathways influenced by AS was performed by ingenuity pathway analysis (IPA) with MetPA. RESULTS: Treated with AS, 16 modulated metabolites were identified and considered as the potential intervention targets of AS, out of which 3 metabolites had protective effects on the nervous system, whereas 7 metabolites showed the neurotoxicity. CONCLUSION: These results may reveal that the effects of AS on nervous system had two sides, and it could not only exert the neuroprotection but also produce some potential neurotoxicity.
Assuntos
Eleutherococcus/efeitos adversos , Eleutherococcus/química , Metaboloma/efeitos dos fármacos , Sistema Nervoso/efeitos dos fármacos , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/farmacologia , Animais , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Masculino , Espectrometria de Massas/métodos , Metabolômica/métodos , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Extract of Acanthopanax senticosus harms (EAS) has been shown to have neuroprotective effects on Parkinson's disease (PD) cell model against α-synuclein overexpression and toxicity. However, studies of its anti-PD mechanism are challenging, owing to the complex pathophysiology of PD, and complexity of EAS with multiple constituents acting on different proteomic pathways. Here, we have investigated the proteomic profiles and potential biomarkers in a cell model of A53T mutant α-synuclein (A53T-α-Syn) overexpression after treatment of EAS. Using an iTRAQ (isobaric tags for relative and absolute quantitation)-based proteomics research approach, we identified 3425 modulated proteins, out of which 84 were found to be altered by A53T-α-Syn and considered as potential biomarkers. After treatment with EAS, the group showed the tendency to correct the abnormal expressions of 16 proteins out of 84 potential biomarkers, which were associated with the formation of Lewy body, mitochondrial energy metabolism, protein synthesis and apoptosis, etc. This study indicated that EAS might be a promising candidate for prevention or treatment of PD by regulating the related proteomic pathways in A53T-α-Syn transgenic SH-SY5Y cells.