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1.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3058-3065, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467696

RESUMO

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.


Assuntos
Corydalis , Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Tibetana , Simulação de Acoplamento Molecular , Isquemia Miocárdica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
2.
Zhongguo Zhong Yao Za Zhi ; 46(9): 2229-2236, 2021 May.
Artigo em Chinês | MEDLINE | ID: mdl-34047125

RESUMO

To establish a quantitative analysis of multi-components by single marker(QAMS) method for five flavonoids in Rhododendron anthopogonoides and verify its feasibility and applicability in the medicinal materials of R. anthopogonoides. With hyperoside as the internal reference, relative correction factors(RCF) of rutin, quercetin, quercitrin and kaempferol were established by high-performance liquid chromatography(HPLC) analysis. RCFs were used to calculate the content of each component, system durability and relative retention time. Simultaneously, QAMS and external standard method(ESM) were used to determine the content of five flavonoids in 12 batches of R. anthopogonoides from different origins. The results were statistically analyzed to verify the accuracy and feasibility. The fingerprints and cluster analysis data of R. anthopogonoides analyzed and discussed differences among the batches. According to the results, the RCFs of rutin, quercetin, quercetin and kaempferol in R. anthopogonoides were 1.242 6, 0.990 5, 0.535 0, and 0.781 3, respectively. The RCFs represented a good reproducibility under different experimental conditions. Besides, there was no significant difference between QAMS and ESM. Besides, the fingerprint and cluster analysis data showed the consistency between the classification and with the origin distribution of the herbs. In conclusion, the QAMS method shows a good stability and accuracy in the quality control of R. anthopogonoides.


Assuntos
Medicamentos de Ervas Chinesas , Rhododendron , Cromatografia Líquida de Alta Pressão , Flavonoides , Medicina Tradicional Tibetana , Reprodutibilidade dos Testes
3.
Bull Environ Contam Toxicol ; 107(3): 449-458, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33839798

RESUMO

Methylmercury presents potent neurotoxicity to humans. Fish consumption is the leading source of human exposure to methylmercury worldwide. However, the exposure source in Tibet remains poorly understood because of the scarcity of observational data on most Tibetan foods, although high mercury levels were recently detected in some traditional Tibetan medicines. Here, the results of field investigations show that the joint consumption of traditional Tibetan medicines (TTMs), fish, and rice constitutes a primary exposure pathway to methylmercury in Tibetans and that the probable daily intake of methylmercury is close to that for many coastal regions. People who are young and high-income may have higher methylmercury exposure levels mainly because of economic development and cultural exchanges among regions. Our analysis indicates that a large proportion of the Tibetan population are likely to face a high methylmercury exposure risk and that mercury-susceptible populations in Tibet should be attentive to consuming TTMs with fish.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Animais , Peixes , Contaminação de Alimentos/análise , Humanos , Medicina Tradicional Tibetana , Mercúrio/análise , Mercúrio/toxicidade , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/toxicidade , Tibet
4.
Biomater Sci ; 9(10): 3821-3829, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33881045

RESUMO

The Tibetan eighteen flavor dangshen pills (TEP) are composed of 18 traditional Tibetan medicines, which are commonly used in the treatment of skin diseases in the Tibetan medical system. They have anti-inflammatory and analgesic effects, and healing properties. However, TEP contain large doses and have strong side effects and low bioavailability. To improve the utilization rate of TEP in skin treatment, we prepared TEP powder and then introduced it into polyvinyl alcohol/chitosan (PVA/CS) hydrogels to treat diabetic wounds by slowly releasing the active ingredients of TEP. In vitro studies showed that TEP-loaded hydrogels can effectively and continuously release the active ingredients of TEP and have antibacterial and antioxidant properties. In addition, the hydrogel system was not cytotoxic to L929 cells, and significantly promoted the proliferation of HUVECs. Moreover, when the TEP-loaded hydrogel was applied to diabetic wounds in rats, it reduced the inflammatory response and improved collagen deposition, which in turn promoted skin healing. Our results indicate that TEP-loaded hydrogels may be a new formulation for the application of traditional Tibetan medicines for the treatment of chronic wounds.


Assuntos
Quitosana , Diabetes Mellitus , Animais , Preparações de Ação Retardada , Hidrogéis , Medicina Tradicional Tibetana , Álcool de Polivinil , Ratos , Cicatrização
5.
Phytomedicine ; 85: 153548, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33831690

RESUMO

BACKGROUND: Pterocephalus hookeri (C. B. Clarke) Höeck, a Tibetan medicine widely used for treatment of rheumatoid arthritis, was recorded in Chinese Pharmacopoeia (2020 version) with slight toxicity. The liver injury was observed in mice with administration of n-butanol extract (BUE) in our previously study. However, the toxic components and the mechanism were still unrevealed. PURPOSE: The present study was aimed to isolate and structural elucidate of the toxic compound pterocephin A (PA), as well as evaluate its liver toxicity and investigate its mechanism. METHODS: PA was isolated from the BUE of P. hookeri. Its structure was determined by analysis of HRMS, NMR and ECD data. L-02 cellular viability, LDH, ALT, AST, ROS, intracellular Ca2+ and the fluidity of cell membrane were assessed by multifunctional microplate reader. The PI staining, cell membrane permeability assessment, and mitochondrial fluorescence staining analysis were determined through the fluorescence microscope. Liver samples for mice were assessed by pathological and immunohistochemistry analysis. Expression levels of indicated proteins were measured by western blotting assays. RESULTS: PA was determined as a previously undescribed oleanolane-type triterpenoid saponin. In vitro study revealed PA significantly induced hepatotoxicity by inhibition of L-02 cell growth, abnormally elevation of ALT and AST. Mechanically, PA induced the damage of cell membrane, fragmentation of mitochondria, and subsequently increase of intracellular Ca2+ and ROS levels, which trigged by necroptosis with the activation of RIP1 and NF-κB signaling pathways. In vivo study confirmed PA could induce liver injury in mice with observation of the body weight loss, increasing of serum ALT and AST, and the histopathological changes in liver tissues. CONCLUSION: Our present study indicated that PA was an undescribed toxic constituent in P. hookeri to induce liver injury in mice by activation of necroptosis and inflammation. And the findings are of great significance for the clinical use safely of this herb.


Assuntos
Caprifoliaceae/química , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Necroptose , Saponinas/efeitos adversos , Triterpenos/efeitos adversos , Animais , Linhagem Celular , Feminino , Humanos , Inflamação , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Medicina Tradicional Tibetana , Camundongos , Estrutura Molecular , NF-kappa B/metabolismo , Compostos Fitoquímicos/efeitos adversos , Extratos Vegetais/efeitos adversos
6.
Fitoterapia ; 151: 104886, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33757847

RESUMO

Two undescribed sesamin-type sesquilignans ptehoosines A (1) and B (2), together with 4 known lignans (3-6), were isolated from Pterocephalus hookeri (C.B. Clarke) Höeck which was widely used as traditional Tibetan medicine for treatment of rheumatoid arthritis. Their structures were determined by HR-ESI-MS, NMR analysis and CD experiment. The in vitro antiangiogenic effect of all isolated compounds against human umbilical vein endothelial cells (HUVECs) were evaluated by CCK-8 assay. Among them, compound 1 exhibited significant proliferative inhibition on HUVECs with IC50 value of 32.82 ± 0.99 µM. Further in vitro study indicated 1 could arrest cell cycle at G0/G1 phase and reduce the migration of HUVECs. In vivo experiment exhibited 1 could inhibit tail vessels plexus in zebrafish. The above finding suggested that 1 was a promising lead compound against RA by inhibiting of angiogenesis.


Assuntos
Inibidores da Angiogênese/farmacologia , Caprifoliaceae/química , Dioxóis/farmacologia , Lignanas/farmacologia , Inibidores da Angiogênese/isolamento & purificação , Animais , Pontos de Checagem do Ciclo Celular , Dioxóis/isolamento & purificação , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Humanos , Lignanas/isolamento & purificação , Medicina Tradicional Tibetana , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Tibet , Peixe-Zebra
7.
Zhongguo Zhong Yao Za Zhi ; 46(2): 488-493, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645138

RESUMO

On the basis of literatures and standards relating to Tibetan medicine, the varieties, origin, standards and efficacy of Saxifragaceae plant used in Tibetan medicine were summarized. According to the findings, 75 species(including varieties) in 8 genera of Saxifragaceae plants, involving 21 varieties, are used in Tibetan medicine. Among them, 9 commonly used varieties, namely Songdi, Sedi, Yajima, Aoledansaierbao, Jiansidawu, Saiguo, Katuer, Sangdi, Maoqinghong, are recorded in Chinese Pharmacopoeia, Ministry Standards for Tibetan Medicine, Tibetan Medicine Standards and other local standards, accounting for 42.9% of the total number of varieties. Tibetan names, Tibetan translation of Chinese names, as well as original plant of Tibetan medicine varieties are quite different in relevant Tibetan medicine standards and literatures, which resulted in common phenomena of synonym and homonym. The standards of most varieties only involve characters, and microscopic, physical and chemical identification, with low quality standards. Based on the results of the analysis, this paper suggests strengthening surveys on herbal textual research, resources and current utilization of Saxifragaceae plants used in Tibetan medicine, summarizing the varieties, establishing improved quality standards, and perfor-ming a comparative study on therapeutic material basis and biological activity of different original plants, in order to promote rational use of these medicinal plant resources, and ensuring the accuracy, safety, and effectiveness of clinical medication.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Saxifragaceae , Grupo com Ancestrais do Continente Asiático , Humanos , Medicina Tradicional Tibetana , Padrões de Referência
8.
J Ethnopharmacol ; 272: 113953, 2021 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-33610711

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Ruteng (CRT) is a prescribed formulation based on the theory of Tibetan medicine for the treatment of yellow-water-disease. It is consisted with 7 medicinal material include Boswellia carterii Birdw (named "Ruxiang" in Chinese); Tinospora sinensis (Lour.) Merr. (named "Kuan-Jin-Teng" in Chinese), Cassia obtusifolia L (named "Jue-Ming-Zi" in Chinese); Abelmoschus manihot (L.) Medic (named "Huang-Kui-Zi" in Chinese); Terminalia chebula Retz. (named "He-Zi" in Chinese); Lamiophlomis rotata (Benth.) Kudo (named "Du-Yi-Wei" in Chinese) and Pyrethrum tatsienense (Bur. et Franch.) Ling (named "Da-Jian-Ju" in Chinese). They are widely distributed in Tibet area of China and have been used to treat rheumatism, jaundice, and skin diseases for centuries. AIM OF THE STUDY: The present study was conducted to investigate the anti-arthritis effect of CRT and to disclose the systems pharmacology-based dissection of mechanisms. MATERIALS AND METHODS: The chemical constituents in CRT were identified using HPLC method, and CRT candidate targets against RA were screened by network pharmacology-based analysis and further experimentally validated based on collagen-induced arthritis (CIA) rat model. Furthermore, therapeutic mechanisms and pathways of CRT were investigated. RESULTS: 391 potential targets (protein) were predicted against 92 active ingredients of 7 medicinal materials in CRT. Enrichment analysis and molecular docking studies also enforced the practiced results. X-ray based physiological imaging showed the attenuated effect of CRT on paw swelling, synovial joints and cartilage with improved inflammation in CIA rats. Moreover, the expression of biomarkers associated with RA such as MMP1, MMP3 and MMP13 and TNF-a, COX2 and iNOS are down-regulated in ankle joints, serum, or liver. CONCLUSION: In conclusion, CRT compound could attenuate RA symptoms and active ingredients of this compound could be considered for drug designing to treat RA.


Assuntos
Antirreumáticos/farmacologia , Antirreumáticos/uso terapêutico , Artrite Experimental/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Antirreumáticos/química , Artrite Experimental/sangue , Artrite Experimental/diagnóstico por imagem , Artrite Experimental/patologia , Colágeno/toxicidade , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/química , Articulações/diagnóstico por imagem , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Medicina Tradicional Tibetana , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Mapas de Interação de Proteínas , Ratos Wistar , Triterpenos/química
9.
J Ethnopharmacol ; 270: 113820, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33465441

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ershiwuwei Lvxue Pill (ELP, མགྲིན་མཚལ་ཉེར་ལྔ།), a traditional Tibetan medicine preparation, has been used hundreds of years for the clinical treatment of rheumatoid arthritis (RA) in the highland region of Tibet, China. However, the underlying mechanism of its therapeutic effect remains unclear. AIM OF THE STUDY: The present study aimed to investigate the potential pharmacological mechanisms of anti-arthritic effect of ELP. MATERIALS AND METHODS: The main chemical constituents of ELP were analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC-Q-TOF-MS). Forty-eight male Wistar rats (220 ± 20 g) were randomly divided into six groups: normal group, collagen-induced arthritis (CIA) group, methotrexate group (1.05 mg/kg), ELP groups (115, 230 and 460 mg/kg). CIA rat models were assigned to evaluate the anti-RA activity of ELP by determining the paws swelling, arthritis score, organ coefficients of spleen and thymus, and histopathological analysis of knee joints of synovial tissues. The levels of TNF-α, IL-10, IL-6 and IL-17 in serum were measured by ELISA. In addition, mRNA and protein expression levels associated with JAK2/STAT3 signaling pathway in synovial tissues of CIA rats were detected by qRT-PCR, immunohistochemistry and Western blot analyses. RESULTS: Fourteen main chemical constituents of ELP were quantitatively determined by UPLC-Q-TOF-MS analysis. Treatment with ELP reduced the paw swelling, arthritis score and organ coefficients of spleen and thymus. Histopathological examination revealed the protective effects of ELP on CIA rats with knee joint injury. The levels of serum pro-inflammatory cytokines (TNF-α, IL-6 and IL-17) were markedly reduced while the anti-inflammatory cytokine IL-10 was significantly increased with the treatment of ELP. Further investigations showed ELP down-regulated the mRNA and protein expression levels of Bcl-2, whereas up-regulated Bax, SOCS1 and SOCS3. Meanwhile, the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 proteins from synovial tissues were dramatically decreased with the treatment of ELP, whereas no changes of the mRNA and protein expression levels of JAK2 and STAT3 were observed. CONCLUSION: These results indicated that ELP reduced the severity of arthritis and joint swelling, suggesting an antirheumatic effect on CIA rats. The possible mechanism is related to inhibiting inflammatory response and inducing apoptosis in synovial tissues by regulating JAK2/STAT3 signaling pathway. However, further in vivo and in vitro investigations are still needed to clarify the underlying mechanism of ELP in treating RA.


Assuntos
Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Artrite Experimental/tratamento farmacológico , Janus Quinase 2/antagonistas & inibidores , Medicina Tradicional Tibetana , Extratos Vegetais/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antirreumáticos/química , Antirreumáticos/uso terapêutico , Artrite Experimental/metabolismo , Citocinas/metabolismo , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Articulações/patologia , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos Wistar , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
10.
J Ethnopharmacol ; 267: 113514, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33223115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhamnella gilgitica Mansf. et Melch. (སེང་ལྡེང་།, RG) is a traditional Tibetan medicinal plant that is currently grown throughout Tibet. According to the theory of Tibetan medicine, RG is efficient for removing rheumatism, reducing swelling, and relieving pain. Hence, it has been used for the treatment of rheumatoid arthritis (RA) in Tibet for many years. However, there are no previous reports on the anti-RA activities of ethyl acetate extract of RG (RGEA). AIM OF THE STUDY: This study aimed to explore the anti-RA effect and mechanism of RGEA on collagen-induced arthritis (CIA) in rats. MATERIALS AND METHODS: The CIA model was established in male Wister rats by intradermal injection of bovine type II collagen and Complete Freund's Adjuvant at the base of the tail and left sole, respectively. The rats were orally administered with RGEA (9.71, 19.43, or 38.85 mg/kg) for 23 days. The body weight, swelling volume, arthritis index score, thymus and spleen indices, and pathological changes were observed to evaluate the effect of RGEA on RA. Furthermore, the inflammatory cytokines in serum, such as interleukin1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin6 (IL-6), interleukin17 (IL-17), interferon-γ (INF-γ), interleukin4 (IL-4), and interleukin10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA) to explore the anti-inflammatory effects of RGEA. The terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was used to examine apoptosis. Finally, the protein and gene expression of B-cell lymphoma-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), Caspase3, janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling1 (SOCS1), and 3 (SOCS3) in synovial tissue were detected using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: After the treatment with RGEA, the body weight of rats was restored, both the arthritis index and paw swelling were suppressed, and spleen and thymus indices were decreased. RGEA reduced the inflammatory cells and synovial hyperplasia in the synovial tissue of the knee joint, and suppressed bone erosion. Meanwhile, RGEA decreased the levels of IL-1ß, IL-6, IL-17, TNF-α, and INF-γ, while increased the levels of IL-4 and IL-10. TUNEL fluorescence apoptosis results confirmed that RGEA obviously promoted the apoptosis of synovial cells. Further studies showed that RGEA inhibited the proteins and mRNAs expression of JAK2 and STAT3 as well as increased the proteins and mRNAs expression of SOCS1 and SOCS3. In addition, RGEA upregulated the expression of Bax and Caspase3, and downregulated the expression of Bcl-2. CONCLUSION: The anti-RA effectof RGEA might be related to the promotion of apoptosis and inhibition of inflammation, which regulated the JAK-STAT pathway.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/prevenção & controle , Janus Quinase 2/metabolismo , Articulações/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhamnaceae , Fator de Transcrição STAT3/metabolismo , Acetatos/química , Animais , Antirreumáticos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/enzimologia , Artrite Experimental/patologia , Colágeno Tipo II , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Janus Quinase 2/genética , Articulações/enzimologia , Articulações/patologia , Masculino , Medicina Tradicional Tibetana , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Rhamnaceae/química , Fator de Transcrição STAT3/genética , Transdução de Sinais , Solventes/química , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo
11.
J Ethnopharmacol ; 267: 113630, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33246118

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Previously, the phytochemical constituents of Biebersteinia heterostemon Maxim (BHM) and Arenaria kansuensis Maxim (AKM) were studied and the evaluation of anxiolytic effect based on their extracts was also investigated. The two traditional Tibetan herbs, BHM and AKM, have been widely used in Qinghai-Tibet Plateau for cardiopulmonary disorders and neuropsychiatric diseases. The anxiolytic activities of a number of agents mediated by α2/3-containing GABAA receptors (GABAARs) have been demonstrated through the genetic and pharmacological studies. Flavonoids, such as flavones and flavanols, are a class of ligands that act at GABAARs and exhibit anxiolytic effects in vivo. Here, the flavonoids are the predominant constituents isolated from BHM and AKM. And our purpose is to investigate structure-activity relationships of the flavonoid compounds with binding to BZ-S of GABAAR complexes, and to search for anxiolytic constituents that lack undesirable-effects such as sedation and myorelaxation. MATERIALS AND METHODS: The flavonoid constituents were separated and purified through the repeatedly silica gel or/and C18 column chromatography. The affinities of the compounds for BZ-S of GABAARs were detected by the radioreceptor binding assay with bovine cerebellum membranes, in which the different recombinant subunits-containing GABAARs were expressed in HEK 293T cells. The behavior tests, including elevated plus maze, locomotor activity, holeboard, rotarod and horizontal wire, were used to determine and evaluate the anxiolytic, sedative, and myorelaxant effects of these flavonoids. RESULTS: Eleven total flavonoid compounds were obtained from the Tibetan herbs (BHM and AKM). The flavones with 6-and/or 8-OMe possessed the most potent binding affinity to GABAARs, which were based on the result of structure-activity relationships analysis. Demethoxysudachitin (DMS, Ki = 0.59 µM), a flavone that binds to recombinant α1-3/5 subunit-containing GABAARs, was isolated from BHM, and exhibited high anxiolytic activity, without inducing sedation and myorelaxation. Moreover, the anxiolytic effect of DMS was antagonized by flumazenil, suggesting that a mode of action was mediated via the BZ-S of GABAARs. CONCLUSIONS: This present study indicated that the flavones, especially DMS, are novel GABAAR ligands and therapeutic potential candidates for anxiety.


Assuntos
Ansiolíticos/farmacologia , Arenaria (Planta) , Comportamento Animal/efeitos dos fármacos , Flavonoides/farmacologia , Geraniaceae , Extratos Vegetais/farmacologia , Receptores de GABA-A/efeitos dos fármacos , Animais , Ansiolíticos/química , Ansiolíticos/isolamento & purificação , Ansiolíticos/toxicidade , Arenaria (Planta)/química , Arenaria (Planta)/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/toxicidade , Geraniaceae/química , Geraniaceae/toxicidade , Células HEK293 , Humanos , Ligantes , Medicina Tradicional Tibetana , Camundongos Endogâmicos C57BL , Estrutura Molecular , Atividade Motora/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Ligação Proteica , Ratos , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismo , Relação Estrutura-Atividade
12.
J Ethnopharmacol ; 266: 113432, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33011367

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Veronica ciliata Fisch. is a traditional medical herb that present in more than 100 types of Tibetan medicine prescriptions, most of which are used for liver disease therapy. Iridoid glycosides have been identified as the major active components of V.ciliata with a variety of biological activities. AIMS OF THE STUDY: The aim of this study is to explore the protective effect and potential mechanism of n-Butanol extract (BE) and iridoid glycosides (IG) from V.ciliata against ɑ-naphthyl isothiocyanate (ANIT)-induced hepatotoxicity and cholestasis in mice. MATERIALS AND METHODS: Mice were intragastrically (i.g.) given BE and IG at different dose or positive control ursodeoxycholic acid (UCDA) once a day for 14 consecutive days, and were treated with ANIT to cause liver injury on day 12th. Serum levels of hepatic injury markers and cholestasis indicators, liver index and liver histopathology were measured to evaluate the effect of BE and IG on liver injury caused by ANIT. The protein levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B(NF-κB), interleukin-6 (IL-6), Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and the levels of oxidative stress indicators in liver tissue were investigated to reveal the underlying protective mechanisms of BE and IG against ANIT-induced hepatotoxicity and cholestasis. RESULTS: The n-Butanol extract (BE) and iridoid glycosides (IG) isolated from V.ciliata significantly decreased serum level of cholestatic liver injury markers aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), total bile acid (TBA), total bilirubin (TBIL), and direct bilirubin (DBIL) in ANIT-treated mice. Histopathology of the liver tissue showed that pathological damages were relieved upon BE and IG treatment. Meanwhile, the results indicated BE and IG notably restored relative liver weights, inhibited oxidative stress induced by ANIT through increasing hepatic level of superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and decreasing hepatic content of malondialdehyde (MDA). Western blot revealed that BE and IG inhibited the expression of pro-inflammatory factors TGF-α, IL-6 and NF-κB. Furthermore, the decreased protein expression of bile acid transporters NTCP, BSEP, MRP2 were upregulated by BE and IG in a dose-dependent manner. CONCLUSION: The results have demonstrated that BE and IG exhibited a dose-dependently protective effect against ANIT-induced liver injury with acute intrahepatic cholestasis in mice, which might be related to the regulation of oxidative stress, inflammatory response and bile acid transport. In addition, these findings pointed out that iridoid glycosides as main active components of V.ciliata play a critical role in hepatoprotective effect of V.ciliata.


Assuntos
Colestase/tratamento farmacológico , Glicosídeos Iridoides/farmacologia , Extratos Vegetais/farmacologia , Veronica/química , 1-Butanol/química , 1-Naftilisotiocianato , Animais , Ácidos e Sais Biliares/metabolismo , Transporte Biológico/efeitos dos fármacos , Colestase/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glicosídeos Iridoides/administração & dosagem , Glicosídeos Iridoides/isolamento & purificação , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Medicina Tradicional Tibetana , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem
13.
Zhongguo Zhong Yao Za Zhi ; 45(22): 5383-5392, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350197

RESUMO

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.


Assuntos
Medicamentos de Ervas Chinesas , Hipertensão , Anti-Hipertensivos , China , Humanos , Hipertensão/tratamento farmacológico , Medicina Tradicional Tibetana , Simulação de Acoplamento Molecular , Tecnologia
14.
Zhongguo Zhong Yao Za Zhi ; 45(21): 5273-5279, 2020 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-33350245

RESUMO

This paper aimed to investigate the protective effect and mechanism of the Tibetan medicine Ershiwuwei Songshi Pills on α-naphthalene isothiocyanate(ANIT)-induced cholestatic liver injury in rats based on the farnesol X receptor(FXR) signaling pathway. SD rats were randomly divided into blank group, model group, ursodeoxycholic acid(UDCA) group, Tibetan medicine Ershiwuwei Songshi Pills low, medium and high dose groups(0.09, 0.18, 0.36 g·kg~(-1)). A prophylactic dosing regimen was used in the experiment. From the 1 st to 4 th days, the UDCA group and the Tibetan medicine Ershiwuwei Songshi Pills suspension groups received prophylactic gavage administration; on the 5 th day, the blank control group was given an equal volume of olive oil blank reagent, and the remaining groups were given ANIT modeling reagent. Administration was continued on day 5 to 6 in each administration group. Forty-eight hours after modeling on the 7 th day, blood was collected from the femoral artery of rats. Serum alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), direct bilirubin(DBIL), total bilirubin(TBIL), and total bile acid(TBA) levels were detected, and liver histopathological changes were observed. The relative expression changes of FXR, SHP, CYP7 A1, MRP2, MRP3, NTCP, BSEP mRNA in liver tissues were detected by Real-time fluorescence quantitative method, and the expression changes of FXR, SHP, UGT2 B4 protein in liver tissues were detected by Western blot. The results showed that the Tibetan medicine Ershiwuwei Songshi Pills significantly reduced the levels of ALT, ALP, DBIL, TBIL and TBA in the serum of the ANIT mo-del rats(P<0.01, P<0.05), significantly up-regulated the mRNA expressions of SHP and NTCP(P<0.01, P<0.05), significantly down-regulated the mRNA expression of CYP7 A1 and MRP3(P<0.01, P<0.05); and significantly up-regulated the protein expressions of FXR and SHP(P<0.01, P<0.05). The Tibetan medicine Ershiwuwei Songshi Pills have an obvious protective effect on ANIT-induced cholestatic liver injury in rats, and its mechanism may be related to the bile acid metabolism mediated by the FXR signaling pathway.


Assuntos
Colestase , Medicina Tradicional Tibetana , Animais , Colestase/tratamento farmacológico , Colestase/genética , Fígado , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
15.
Biomed Pharmacother ; 131: 110723, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152910

RESUMO

Stroke is an acute cerebrovascular disease caused by the sudden rupture of cerebral blood vessels or vascular obstruction from brain tissue damage or dysfunction, thereby preventing blood flow into the brain. Cerebral ischemia-reperfusion injury (CI/RI), a common syndrome of ischemic stroke, is a complex pathological process whose physiological mechanism is still unclear. Qishiwei Zhenzhu pills (QSW), a famous Tibetan medicine preparation, has the effect of tranquilizing by heavy settling, dredging channels and activating collaterals, harmonizing Qi and blood, restoring consciousness, and inducing resuscitation. Here, we investigated the protective effect of QSW on CI/RI in rats and its potential mechanism. First, the volatile and liposoluble components in QSW were determined using gas chromatography-mass spectrometry (GCMS). After 24 h of CI/RI, the neuroprotective effect was determined by evaluating the neurological function, cerebral infarction, histopathology, and blood-brain barrier (BBB) function. Immunofluorescence, real-time quantitative PCR (RT-qPCR), and western blot (WB) were used to detect the expression of matrix metalloproteinase 9 (MMP-9), claudin-5, and occludin. Finally, GCMS metabonomics was used to identify different metabolites and analyze metabolic pathways. The results showed that 88 volatile components and 63 liposoluble components were detected in QSW. Following the experimental stroke operation, it was observed that rats administered QSW pretreatment had improved neurological function, reduced infarct volume (P < 0.01), increased Nissl bodies (P < 0.05), improved histopathology, and reduced BBB disruption. Immunofluorescence, RT-qPCR, and WB results showed that MMP-9 level in the brain tissue of the QSW pretreatment group had a decreasing trend and the expression of claudin-5 and occludin had a tendency to increase. Eleven metabolites related to lipid metabolism, fatty acid metabolism, and energy metabolism, were identified via GC-MS metabonomics. Our study shows that QSW preconditioning has a neuroprotective effect on CI/RI; however, its mechanism requires further study.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Isquemia Encefálica/prevenção & controle , Medicina Tradicional Tibetana , Metabolômica , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Barreira Hematoencefálica/ultraestrutura , Isquemia Encefálica/patologia , Claudina-5/genética , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/genética , Redes e Vias Metabólicas , Neurônios/ultraestrutura , Permeabilidade , Ratos , Ratos Sprague-Dawley
16.
Zhongguo Zhong Yao Za Zhi ; 45(18): 4423-4428, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33164372

RESUMO

In this study, the content of iridoids and flavonoids in Tibetan medicine "Lanhua Longdan" was determined simul-taneously by quantitative analysis of multi-components by single marker(QAMS), which was used to verify the feasibility and applicability of the method in the application of Lanhua Longdan quality evaluation. Using HPLC with two typical elements gentiopicroside and isoorientin as the internal reference, the relative correction factor(RCF) between the mand loganin acid, swertiamarin, sweroside, isoscoparin-2″-ß-D-glucopyranoside and isoscoparin was determined and then used, to calculate the content of several other components to achieve QAMS. At the same time, the external standard method(ESM) was used to determine the contents of these 7 components in the medicinal materials, and the differences were compared to verify the accuracy and feasibility of QAMS. The results showed that the RCF repeatability is good. There were no significant differences in the determination results of the contents of 12 batches of 4 varieties of Tibetan medicine Lanhua Longdan obtained by QAMS and ESM. Therefore, the QAMS can be used for the quality evaluation of Lanhua Longdan, and provides a reference for the quality evaluation of multi-index components of Lanhua Longdan. The results showed that the content of iridoid and flavonoid in the dried product should not be less than 0.6% and 0.8% respectively.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Tibetana , Cromatografia Líquida de Alta Pressão , Flavonoides , Iridoides
17.
Zhongguo Zhong Yao Za Zhi ; 45(19): 4792-4797, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33164447

RESUMO

"Shengdeng" is a traditional Tibetan medicine, which has many synonyms. It is complex in origin and serious in mi-xing. In order to clarify the origin of "Shengdeng" and its medicinal use, this paper makes a textual research on the name, variety and efficacy of "Shengdeng" by consulting Tibetan medicine classics such as The Four Medical Trantras and Jingzhu Materia Medica, combined with modern literature of Tibetan medicine. It is clear that the synonyms, primitive species, mainstream varieties and functions of Tibetan medicine "Shengdeng". The collation and analysis of the literature shows that "Shengdeng" has effects of treating rheumatism, drying "Huangshui", detumescence and relieving pain, and is mainly used for the treatment of rheumatoid arthritis in Tibetan medicine. Its original varieties include 14 species of plants belonging to 6 families: Spicaceae, Rhamnaceae, Cephalotaxus, Leguminosae, Hematoxylaceae and Taxaceae. Combined with the collection of legal standards at all levels, the distribution of resources and the application of clinical prescriptions, it is considered that the mainstream species of "Shengdeng" are Rhamnella gilgitica, Xanthoceras sorbifolia, Rhamnus parvifolia. As a substitute, Acacia catechu is also widely used in clinic. The literature review and variety textual research on Tibetan medicine "Shengdeng" is helpful to improve the safety, effectiveness and quality controllability of its clinical application, and provide scientific basis for its further standard setting, pharmacodynamics research, new drug development and so on.


Assuntos
Fabaceae , Plantas Medicinais , Rhamnaceae , Dessecação , Medicina Tradicional Tibetana
18.
Zhongguo Zhong Yao Za Zhi ; 45(15): 3631-3641, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32893552

RESUMO

Zha-xun is widely used in Tibetan medicine and is also an international traditional medicine. This study believes that the black organic matter constituting Zha-xun is mainly stored in the rocks. The exudation points of Zha-xun mostly distribute on the cliffs of high mountains, which makes it difficult to evaluate its resource distribution and storage area. This paper was aimed at the exudation environment of Tibetan medicine Zha-xun in Sichuan province and 6 ecological environmental factors of the Zha-xun were determined via the field investigation. Combining with these 6 factors as well as the GIS data of Sichuan province, ArcGIS software was used to extract ideal environmental factors which are suitable for exudation of Zha-xun, including geology types, geomorphological types, altitude, slope, vegetation types, and mean annual temperature. The spatial overlay analyses on the extracted environmental factors were carried out to predict the distribution area of Zha-xun in Sichuan province. Afterwards, field investigation was conducted to verify the prediction. The prediction showed that the exudation spots of Zha-xun in Sichuan province mainly located in 29 counties including 12 in Aba Prefecture, 15 in Ganzi Prefecture, and Muli County and Dechang County in Liangshan Prefecture. The deposit areas of Zha-xun were located in the Triassic, Devonian and Silurian strata and were basically distributed in 9 basins, including Dingqu River, Yalong River, Xianshui River, Dadu River, Suomo River, Minjiang River and Baishui River, characterized by a fragmented patch-like distribution along the mountain ranges, and the exudation spots of Zha-xun were mainly scattered among the rain-free cliffs' concavities of river valleys at a certain altitude. The prediction was consistent with the field investigation results, which suggested that it is possible and feasible to predict distribution of Zha-xun resources based on GIS-analysis. The study may provide a scientific basis for comprehensive investigations into Zha-xun's distribution and formation mechanism, thus promoting rational development and utilization of Zha-xun resources.


Assuntos
Sistemas de Informação Geográfica , Medicina Tradicional Tibetana , China , Geologia , Medicina Tradicional , Temperatura
19.
Zhongguo Zhong Yao Za Zhi ; 45(11): 2708-2713, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32627507

RESUMO

Appropriate producing areas can guarantee the quality of Tibetan medicine, but research on the suitable ecological factors and suitable producing areas of Tibetan medicinal plants is scarce. This paper used the Geographic Information System for Global Medicinal Plants(GMPGIS) to analyze the ecological suitability of Tibetan medicinal plants nationwide. For the first time, the range of ecological factors and main soil types of Tibetan medicinal plants were extracted, such as the average annual temperature-19.4-24.2 ℃, annual average precipitation 17-4 088 mm, annual average sunshine 124.2-171.6 W·m~(-2). The main soil types were black calcareous soil, thin layer soil, chestnut soil and so on. Based on 337 sampling points, the largest ecological similarity area of Tibetan medicine across the country was obtained through ecological similarity analysis. In addition to Tibet and Qinghai provinces and Tibetan Autonomous Prefectures in Sichuan, Gansu, and Yunnan provinces, Jiuquan city and Linxia county in Gansu province, Panzhihua and Ya'an in Sichuan province, and Xinjiang, Inner Mongolia, and Shanxi provinces also had larger suitable cultivation areas. In addition, by analyzing the current situation of Tibetan medicine industry, the research pointed out that there were some problems such as unreasonable development and utilization of resources, lack of standards and norms, weak basic research and imperfect industrial system, and made corresponding countermeasures for sustainable development of resources, formulation of standards and specifications, promotion of medicine through science and technology, expansion of domestic and foreign markets, etc. This study provided the basis for guiding the rational layout of production bases, introduction and breeding of plant Tibetan medicine nationwide, laying the foundation for the scientific and standardized production of high-quality Tibetan medicine, clarifying the development direction of Tibetan medicine industry, and providing ideas for the development strategy of Tibetan medicine and other national medicine industry.


Assuntos
Desenvolvimento Industrial , Medicina Tradicional Tibetana , China , Solo , Tibet
20.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2063-2072, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32495555

RESUMO

Bawei Chenxiang Powder is a traditional Tibetan folk medicine formula, consisting of resinous wood of Aquilaria sinensis, kernel of Myristica fragrans, fruit of Choerospondias axillaris, travertine, resin of Boswellia carterii or B. bhaw-dajiana, stem of Aucklandia lappa, fruit of Terminalia chebula(roasted), and flower of Gossampinus malabarica. It has the function of clearing heart heat, nourishing heart, tranquilizing mind, and inducing resuscitation, which has been used for the treatment of coronary heart disease and angina pectoris. Modern research shows that the medicine materials of this formula mainly contain terpenoids like sesquiterpenes and triterpenes and polyphenols like flavonoids, lignans, and tannins, displaying some pharmacological activities such as anti-myocardial ischemia, anti-cerebral ischemia, and spatial learning and memory promotion. This review summaries the traditional uses, chemical constituents, and pharmacological activities research progress, hopefully to provide a reference for clarification of its pharmacological active ingredients.


Assuntos
Medicamentos de Ervas Chinesas , Terminalia , Flavonoides , Medicina Tradicional Tibetana , Tibet
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