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1.
Poult Sci ; 99(2): 801-811, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32029162

RESUMO

Guduchi (Tinospora cordifolia) is a well-recognized and widely distributed traditional plant that is used successfully in Indian Ayurveda medicine. T. cordifolia has shown many promising biological activities, such as antioxidative, antimicrobial, antihyperglycemic, anti-inflammatory, osteoprotective, hepatoprotective, antidiarrheal, and antistress effects. Guduchi is a rich source of protein and micronutrients, such as iron, zinc, copper, calcium, phosphorus, and manganese. It also contains many secondary plant metabolites, such as terpenes, alkaloids, flavonoids, steroids, and glycosides. Based on previous studies in poultry, the supplementation levels of Guduchi range from 1 to 5 g/kg of diet (different sources, such as powder, extracts, roots, and leaves, have been used). It was suggested that this variation in supplementation levels depends on different factors, including the extraction method, the supplementation proposed, the method of supplementation (either in feed or drinking water), and the species and physiological status of the birds. Generally, dietary supplementation of poultry broilers with T. cordifolia yielded positive impacts on growth performance, body gains (increased by 4.8%), dressing percentage (increased by 7.1%), meat quality traits, and the shelf life of the meat. In addition, T. cordifolia exerted a palliative effect on the general health status of the birds through reducing live enzymes and plasma uric acids and enhancing the immune response, as indicated by the leukocyte count, hemagglutinin titer, interleukin activity, and mortality levels. Further investigations concluded that T. cordifolia showed strong antimicrobial effects against Escherichia coli and Salmonella enteritidis, with subsequent reductions in mortality. Moreover, T. cordifolia showed an ability to improve humoral and cell-mediated immunity against Newcastle disease, infectious anemia, gout, and aflatoxicosis. The current review discusses many beneficial properties of T. cordifolia, although the lack of pharmacological trials limits the use of this extract in poultry. Further research should be performed regarding the composition of the active compound, the possible mechanisms of action, and the effective doses to fully understand the activities and benefits of T. cordifolia as a growth performance improvement supplement.


Assuntos
Galinhas/metabolismo , Patos/metabolismo , Fenômenos Fisiológicos da Nutrição , Extratos Vegetais/metabolismo , Tinospora/química , Perus/metabolismo , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Humanos , Medicina Ayurvédica , Extratos Vegetais/administração & dosagem , Distribuição Aleatória
2.
J Ethnopharmacol ; 248: 112356, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31669668

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora sinensis Lour. (Merr.) belongs to the family Menispermaceae and its stem extract have been used traditionally in broad aspects of therapeutic remedies including debility, dyspepsia, fever, jaundice, ulcer, bronchitis, urinary disease, skin disease, liver disease and diabetes. AIM OF THE STUDY: The aim of the study was to evaluate the protective effects of methanol extract of stem of Tinospora sinensis (METS) on streptozotocin induced pancreatic islet cell injuries of diabetic rats and its correlation to its phytochemical profiles. MATERIALS AND METHODS: A high-performance liquid chromatography technique (HPLC) was used to identify and quantify the major phytochemicals present in the METS. Diabetic rats were administered with METS at a dose of (100, 200 and 400 mg/kg respectively orally) and standard drug Metformin (300 mg/kg) was given orally to group serving positive control. Effect of the METS on glucose homeostasis, oxidative stress, antioxidant status, histopathology of pancreas and also on intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis, cell cycle of pancreatic islet cells were studied in diabetic rats. RESULTS: The major phytochemicals identified and quantified by HPLC in the extract were berberine, caffeic acid, myricetin and ferulic acid. This result showed that methanol extract exhibited good antioxidant effect. The methanol extract of the plant prevented the diabetogenic effect of STZ and significantly lowered the fasting blood glucose level, glycated haemoglobin and increased insulin and C-peptide level in treated rats. METS reduced apoptosis of STZ treated islet cells by significantly decreasing pro-inflammatory cytokines (TNFα, IL6), intracellular ROS generation, lipid peroxidation, nitric oxide (NO) production and increasing mitochondrial membrane potential and sub-G0 peak area, enzymatic and nonenzymatic antioxidants. CONCLUSION: The results revealed that the methanol extract of the stem of the plant possesses protective effects against diabetes and associated complications.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Diabetes Mellitus Experimental/prevenção & controle , Hipoglicemiantes/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Tinospora , Animais , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Hemoglobina A Glicada/metabolismo , Hipoglicemiantes/isolamento & purificação , Mediadores da Inflamação/metabolismo , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Estreptozocina , Tinospora/química
3.
J Pharm Biomed Anal ; 178: 112894, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31606561

RESUMO

Tinospora species are morphologically similar. Several cases of human toxicity have been reported in association with T. crispa. A chemical fingerprint was developed to differentiate T. crispa from its closely related species and to quantitate its major furanoditerpenes namely as borapetosides B, C and F. The rapid, sensitive and repeatable method was established using ultra-high performance liquid chromatography coupled with photodiode array and single quadrupole electrospray mass spectrometry detectors using a flavonoid, two alkaloids, an amide and six diterpenoids. Qualitative and quantitative determination was performed by UHPLC-UV and confirmed by MS. The intra-day RSD for replicates was between 0.9 and 6.8% and inter-day RSD was between 1.2 and 9.1%. Recovery was 97-103 %. The method is useful to achieve decisiveness in not only identifying but also differentiating T. crispa from T. sinensis and other closely related Tinospora species. Seventeen Tinospora plant samples and seventeen dietary supplements claiming T. crispa, T. sinensis and T. cordifolia were analyzed. The newly developed and validated method successfully resulted in the conclusive identification of two dietary supplements to be mislabeled.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Suplementos Nutricionais/análise , Tinospora/química , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
Molecules ; 24(22)2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31752124

RESUMO

Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 µg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 µg/mL, respectively) as compared to gallic acid and the tool compound "galantamine hydrobromide" (IC50 7.89 and 1.45 µg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with π-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.


Assuntos
Inibidores da Colinesterase/farmacologia , Extratos Vegetais/farmacologia , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Sinergismo Farmacológico , Humanos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Tinospora/química
5.
Int J Immunopathol Pharmacol ; 33: 2058738419855567, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31663444

RESUMO

Berberine (BBR) is a natural active principle with potential antitumor activity. The compound targets multiple cell signaling pathways, including proliferation, differentiation, and epithelial-mesenchymal transition. The aim of this study was to elucidate the mechanisms behind the anticancer activity of BBR by comparing the effects of purified BBR with those of the extract of Tinospora cordifolia, a medicinal plant that produces this metabolite. The expression levels of a panel of 44 selected genes in human colon adenocarcinoma (HCA-7) cell line were quantified by real-time polymerase chain reaction (PCR). BBR treatment resulted in a time- and dose-dependent down regulation of 33 genes differently involved in cell cycle, differentiation, and epithelial-mesenchymal transition. The trend was confirmed across the two types of treatment, the two time points, and the different absolute dosage of BBR. These findings suggest that the presence of BBR in T. cordifolia extract significantly contributes to its antiproliferative activity.


Assuntos
Antineoplásicos/farmacologia , Berberina/química , Neoplasias do Colo/tratamento farmacológico , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tinospora/química , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colo/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Plantas Medicinais/química
6.
Curr Pharm Biotechnol ; 20(12): 1055-1063, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31333126

RESUMO

OBJECTIVE: The present study was aimed to evaluate the effect of the aqueous extract of Tinospora cordifolia (AETC) against cyclophosphamide-induced immunosuppression and systemic Candida albicans infection in a murine model. METHODS: The protective effect of AETC against cyclophosphamide-induced leukopenia was evaluated by quantitative and qualitative analysis of the leukocytes. The immune-stimulating potential of AETC on macrophages was assessed by determining the levels of secreted cytokines. To determine the direct antifungal activity, AETC or fluconazole was administered to C. albicans infected mice. The efficacy of treatment was assessed by determining the survival rate, kidney fungal burden, the organ index and liver inflammation parameters. RESULTS: Cyclophosphamide administration resulted in substantial depletion of leukocytes, whereas AETC treatment induced the recovery of leukocytes in cyclophosphamide-injected mice. Moreover, AETC treatment of macrophages resulted in enhanced secretion of IFN-γ, TNF-α and IL-1ß. C. albicans infected mice treated with AETC at the doses of 50 and 100 mg/kg exhibited 40% and 60% survival rate, whereas the mice treated with fluconazole at a dose of 50 mg/kg showed 20% survival rate. Like survival data, the fungal load was found to be the lowest in the kidney tissues of mice treated with AETC at a dose of 100 mg/kg. Interestingly, mice infected with C. albicans demonstrated improvement in the organ indices and liver functioning after AETC treatment. CONCLUSION: These results suggest that AETC may potentially be used to rejuvenate the weakened immune system and eliminate systemic candidiasis in mice.


Assuntos
Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase/imunologia , Fluconazol/uso terapêutico , Extratos Vegetais/uso terapêutico , Tinospora/química , Animais , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Ciclofosfamida/farmacologia , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Rim/efeitos dos fármacos , Rim/microbiologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Extratos Vegetais/isolamento & purificação , Fator de Necrose Tumoral alfa/imunologia
7.
Fitoterapia ; 137: 104247, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247217

RESUMO

A new sesquiterpene glycoside and a new amide have been isolated from the stems of Tinospora sinensis. Their structures were established by 2D NMR spectroscopic techniques (1H,1H-COSY, NOESY, HSQC and HMBC) and mass spectrometry. The isolated compounds were subjected to evaluate neuroprotective activities in vitro. The pre-treatment of two new compounds can significantly ameliorate damage of oxidative stress induced by Aß25-35 and improve PC12 cells survival.


Assuntos
Amidas/farmacologia , Glicosídeos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Tinospora/química , Amidas/isolamento & purificação , Animais , Glicosídeos/isolamento & purificação , Estrutura Molecular , Células PC12 , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Sesquiterpenos/isolamento & purificação , Tibet
8.
Phytomedicine ; 61: 152831, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31035042

RESUMO

BACKGROUND: Tinospora cordifolia (Willd.) Miers is known for its therapeutic value in Indian traditional medicine for treating diabetes, rheumatoid arthritis, jaundice and cardiac diseases. However, information regarding its protective role against inflammatory diseases at the molecular level is limited. PURPOSE: The objective of the present work is to study the antioxidant and anti-inflammatory effect of alcoholic and water extracts of T. cordifolia (Willd.) Miers leaves in activated human monocytic THP-1 cells. STUDY DESIGN/METHODS: Phytochemical analyses of the dry leaf extracts of T. cordifolia (Willd.) Miers prepared using the solvents alcohol (TCAE) or water (TCWE) are performed employing spectrophotometric methods for estimating total phenolic and flavonoid content, and the plant material was authenticated by detecting T. cordifolia (Willd.) Miers metabolite biomarkers using LC-MS/MS. Arachidonic acid (AA)- and lipopolysaccharide (LPS)-activated human monocytic (THP-1) cells were used as experimental models to investigate the antioxidant and anti-inflammatory activities of the plant extracts. Arachidonic acid (AA)-induced reactive oxygen species (ROS) in THP-1 cells were monitored by confocal microscopy/spectrofluorimetry and transcript of antioxidant enzyme catalase (CAT), by quantitative real time PCR. Lipopolysaccharide (LPS)-induced proinflammatory marker like TNF-α at transcription and protein levels in THP-1 cells were measured by quantitative real-time PCR or ELISA respectively. Further, the effect of T. cordifolia (Willd.) Miers extracts on LPS-induced NF-κB translocation, and IκB and P-IκB protein levels, were studied by immunoblotting and confocal microscopy. RESULTS: T. cordifolia (Willd.) Miers extracts exhibited significant amounts of total phenolic and flavonoid content, and LC-MS/MS analyses detected tinosponone, a TC-specific clerodane-derived diterpene. Both types of extracts attenuated AA-induced ROS generation via enhancing catalase enzyme activity in THP-1 cells. Real time PCR and ELISA experiments revealed that the elevated levels of LPS-induced TNF-α was remarkably attenuated in THP-1 cells pretreated with T. cordifolia (Willd.) Miers extracts. Western blot and confocal microscopy showed that the alcoholic extract's anti-inflammatory activity by attenuating NF-κB translocation into the nucleus in LPS-activated THP-1 cells via the inhibition of IκB degradation in the cytosol. CONCLUSION: Our findings suggest that T. cordifolia (Willd.) Miers dry leaf extracts possess antioxidant and anti-inflammatory properties via upregulation of antioxidant enzymes and attenuation of NF- κB nuclear translocation in activated human monocytic (THP-1) cells, therefore the present study supports our proposed molecular basis for the traditional use of T. cordifolia (Willd.) Miers for treating various inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/farmacologia , Monócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Tinospora/química , Anti-Inflamatórios não Esteroides/química , Antioxidantes/química , Antioxidantes/metabolismo , Linhagem Celular , Avaliação Pré-Clínica de Medicamentos , Enzimas/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , Lipopolissacarídeos/toxicidade , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética , Extratos Vegetais/análise , Extratos Vegetais/química , Plantas Medicinais/química , Fator de Necrose Tumoral alfa/metabolismo
9.
Phytomedicine ; 57: 271-281, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30802713

RESUMO

BACKGROUND: The stems of Tinospora sinensis (Lour.) Merr commonly named "Kuan-Jin-Teng" in Chinese, have been used to treat rheumatoid arthritis as a Tibetan medicine. PURPOSE: The effects of the EtOAc fraction of ethanolic extract from the stems of T. sinensis (KJT) on the pro-inflammatory cytokines and MAPK pathway were studied in collagen-induced arthritis (CIA) model. STUDY DESIGN: Anti-arthritic activity of KJT was investigated in CIA model. METHODS: The chemical constituents of KJT were analyzed by LC-MS and HPLC. The CIA model was established with injecting the bovine CII emulsified in Freund's adjuvant in Wistar rats. Several doses of KJT (50.0, 100.0 and 200.0 mg/kg) were administrated via oral gavage to CIA rats daily for 4 weeks. The anti-arthritic activity of KJT was investigated by clinical arthritis scoring, paw swelling inspection and hyperalgesia measurement, as well as radiological and histological analysis in CIA rats. The impacts of KJT on the activation of MAPK pathway, production of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-17) in ankle joints, serum, and spleen in CIA rats were examined by western blot, immunohistochemical staining, ELISA, and quantitative real-time PCR respectively. Lastly, the effects of KJT on production of the nitric oxide (NO) and pro-inflammatory cytokines as well as the regulation of the phosphorylation of p38 and Erk were detected in lipopolysaccharide (LPS)-stimulated RAW264.7 murine macrophage cells. RESULTS: KJT significantly alleviated the paw swelling, hyperalgesia and arthritic severity, and reduced the synovial tissue proliferation and inflammatory cell infiltration in the CIA rats. Moreover, KJT suppressed the production of TNF-α, IL-1ß, and IL-17 in ankle joints, serum, and spleen and reversed the up-regulation of the phosphorylation of p38 and Erk in CIA rats. KJT was also demonstrated to inhibit the production of NO and pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), and phosphorylation of p38 and Erk in LPS-stimulated RAW264.7 cells. CONCLUSION: These results suggest the mechanisms of KJT performing its anti-arthritis effect may be attributed to inhibiting the production of pro-inflammatory cytokines and down-regulating the MAPK signaling pathway.


Assuntos
Artrite Experimental/tratamento farmacológico , Citocinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Reumatoide/tratamento farmacológico , Colágeno/toxicidade , Regulação para Baixo/efeitos dos fármacos , Edema/tratamento farmacológico , Edema/patologia , Adjuvante de Freund/efeitos adversos , Masculino , Medicina Tradicional Tibetana , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Tinospora/química
10.
J Indian Soc Pedod Prev Dent ; 37(1): 39-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804306

RESUMO

Introduction: Microbes are considered as the primary etiological agents in endodontic diseases. Ways of reducing these agents are root canal debridement and antibacterial filling materials. One of the factors in determining the success of endodontic treatment previously was sealing root canals with materials possessing potent bactericidal effect. Due to cytotoxic reactions of sealers and their inability to eliminate bacteria completely from dentinal tubules, trend to use natural plants extracts have been introduced. Aim: To compare antimicrobial activity of endodontic sealers added to herbal extracts. Materials and Method: Three sealers mixed with three herbal extracts were evaluated against seven strains of bacteria at various time intervals using Agar Diffusion Test. The mean zones of inhibition were measured. Statistical Analysis: All statistical analysis was performed using the SPSS 15 statistical software version, Chicago. Intergroup comparison was evaluated using Kruskal Walls test along with Mann Whitney U test. The Intragroup comparison was evaluatd using Friedman test along with Wilcoxon test. Results: Statistically significant zones of bacterial growth inhibition were observed largest with Zinc Oxide Eugenol based sealer when mixed with Glycyrrhiza glabra (Licorice) followed in descending order by zinc oxide eugenol based sealer mixed with Tinospora cordifolia (Guduchi) and Mimusops elengi (Bakul) respectively. Conclusion: Zinc Oxide Eugenol based sealer with herbal extracts produced largest inhibitory zones followed in descending order by Resin based sealer and Calcium hydroxide along with three herbal extracts respectively.


Assuntos
Anti-Infecciosos/farmacologia , Cavidade Pulpar/microbiologia , Extratos Vegetais/farmacologia , Materiais Restauradores do Canal Radicular/farmacologia , Bacteroides fragilis/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Glycyrrhiza/química , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Mimusops/química , Peptostreptococcus/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Streptococcus/efeitos dos fármacos , Tinospora/química , Cimento de Óxido de Zinco e Eugenol/farmacologia
11.
Complement Ther Med ; 42: 286-291, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30670256

RESUMO

INTRODUCTION: Species of Tinospora are used as herbal remedies for the treatment of various diseases with very few toxic effects having been reported. Tinospora cordifolia (TCF) has been reported to effectively prevent hepatotoxicity. However, there are an increasing number of cases revealing that Tinospora crispa (TCP) might have the negative effect of inducing hepatotoxicity. Because of the similar leaves, people may mistake TCP for TCF, and consume it with the purpose of protecting liver function. OBJECTIVE: Find out the misusing level of TCP and TCF and which chemical compound in TCP might induce hepatotoxicity. METHODS: We report two cases of acute fulminant hepatitis associated with chronic use of TCP. Given that the two herbs were misidentified in these two reports, we investigated the frequency of erroneous identification by using three keywords ("Guduchi", "Tinospora cordifolia", "Tinospora crispa") to search images from the Google Images database. To further clarify the influence of liver function between TCP and TCF, we searched PubMed (up to 29 July 2018) for relevant publications on clinical trials or case reports. RESULTS: Based on web review, over 35 percent of websites failed to accurately identify these two herbs. The different effects on liver function between TCP and TCF were compared through literature review. It indicated that TCF exerted liver protection, TCP had a contrary effect, suggesting its cis-Clerodane-type furano-diterpenoids might be an important factor of inducing hepatotoxicity. CONCLUSIONS: We concluded that people might cause hepatic injury or even death without correctly identifying these two Tinospora species.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Hepatite/etiologia , Fígado/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/efeitos adversos , Tinospora , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Hepatite/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Especificidade da Espécie , Tinospora/química , Tinospora/classificação
12.
Chem Biol Interact ; 299: 120-130, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30543781

RESUMO

Approximately 15% of globally diagnosed breast cancers are designated as triple negative breast cancer (TNBC). In this study, we investigated the effect of the natural compound, Bis(2- ethyl hexyl) 1H-pyrrole-3,4-dicarboxylate (TCCP), purified from Tinospora cordifolia on MDA-MB-231, a TNBC cell line. The pro-apoptotic nature of TCCP on MDA-MB-231 was determined by assessing various apoptotic markers. ROS generation, intracellular calcium, mitochondrial membrane potential (ΔΨm), MPTP, cardiolipin peroxidation and caspase activity were determined fluorometrically. BAX, BCL-2, cytochrome c, caspases, and p53 protein expressions were determined by immunoblotting. Further, the effect of TCCP on DNA and cell death was determined by DNA fragmentation assay, annexin-V staining, and cell cycle analysis. TCCP treatment caused endogenous ROS generation, increase in intracellular calcium and phosphorylation of p53 in a concentration-dependent manner, which was reverted upon pre-treatment with pifithrin-µ. This led to the downstream altered expression of Bcl-2 and Bax proteins, mitochondrial membrane depolarization, MPTP, and cardiolipin peroxidation. TCCP induced cytochrome c release into the cytosol, caspase activation, ultimately resulting in DNA fragmentation. Further, induction of apoptosis and morphological alterations were evident from the phosphatidylserine externalization and increase in sub G1 population. The in vivo Ehrlich ascites tumor (EAT) mouse study revealed the effectiveness of TCCP in reducing the tumor burden and resulted in a ~2 fold increase in mice survival with minimal hepato-renal toxicity. Overall, TCCP was shown to be efficient in inducing ROS and mitochondrial-mediated apoptosis by restoring p53 activity in MDA-MB-231 cells and also induced EAT cell death in vivo thereby inhibiting tumor proliferation.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Pirróis/química , Espécies Reativas de Oxigênio/metabolismo , Tinospora/química , Proteína Supressora de Tumor p53/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Taxa de Sobrevida , Tinospora/metabolismo
13.
Parasitol Int ; 68(1): 57-59, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30343056

RESUMO

During Plasmodium malaria parasite infection in a human, the intraerythrocytic stages lead to the clinical manifestations of the disease, especially hypoglycemia. Hypoglycemia is a recognized feature of severe malaria and linked with a high risk of mortality for children. Hence, the present study aimed to investigate the protective effect of T. crispa stem extract on hypoglycemia induced by P. berghei infection tested with a mouse model. ICR mice were inoculated with 1 × 107 parasitized erythrocytes of P. berghei ANKA (PbANKA) by intraperitoneal injection and given 50, 100, and 200 mg/kg of ethanolic extract for 4-consecutive days. The results showed that T. crispa stem extract exerted a protective effect (100%) on hypoglycemia induced by PbANKA infection at doses of 100 and 200 mg/kg. A significantly (p < .05) prolonged mean survival time (28.0 ±â€¯1.9 days) of the extract treated mice was also observed. Additionally, no effect on blood glucose levels was seen in normal mice treated with all doses of extract. It can be concluded that T. crispa stem extract may have beneficial properties in protecting against hypoglycemia, and in increasing survival time during malaria infection.


Assuntos
Hipoglicemia/tratamento farmacológico , Malária/complicações , Extratos Vegetais/administração & dosagem , Caules de Planta/química , Plasmodium berghei/fisiologia , Tinospora/química , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Eritrócitos/parasitologia , Etanol/química , Humanos , Hipoglicemia/etiologia , Hipoglicemia/prevenção & controle , Malária/parasitologia , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico
14.
Environ Sci Pollut Res Int ; 26(15): 14712-14716, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-29869741

RESUMO

Tinospora crispa stem aqueous extractions for various time durations were determined regarding their total phenolic content and their larvicidal abilities. The results revealed that the total phenolic content in 1-, 3-, 5-, 10-, and 24-h extracts were 8.26, 8.43, 13.57, 12.52, and 12.43 mg/g gallic acid equivalent, respectively. The 5-h extract of T. crispa was evaluated against Culex quinquefasciatus mosquito larva in concentrations 3.125, 6.25, 12.5, and 25 mg/l, by determining the lethal concentration (LC) within 24 h and by histopathological analysis. The 24-h LC50 and LC90 values were 16.95 and 30.12 mg/l, respectively. The histopathological lesions after exposure to 50% of the 24-h LC50 were observed primarily in the midgut of the larva. The lesions observed were for the example epithelial cells lifting from the basement membrane, cell elongation protruding into the lumen, brush border disrupting with absent microvilli, and vesicle appearance. The present study indicated that the aqueous extract of this herb may have a suitable property for a larvicidal natural product and may replace harmful chemical pesticides.


Assuntos
Culex/efeitos dos fármacos , Inseticidas/química , Larva/efeitos dos fármacos , Tinospora/química , Animais , Culex/química , Inseticidas/análise , Larva/química
15.
J Pharm Biomed Anal ; 165: 213-223, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30553111

RESUMO

TongFengTangSan (TFTS), a traditional Tibetan medicine comprising of Tinospora sinensis (TS), Terminalia chebula Retz (TC) and Trogopterori faeces (TF), is used to treat joint diseases like gout, gout arthritis, swelling, pain etc. Despite the significant therapeutic effects of TFTS, its pharmacological components have not been analyzed so far. Therefore, the chemical composition of the effective part of TFTS was analyzed by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS). The results show that the ethanol extract (EE) of TFTS was more effective in reducing the serum uric acid (SUA) and XOD (Serum and Liver) levels in a hyperuricemic rats model compared to the TFTS raw powder (RP). UHPLC-Q-TOF-MS/MS identified a total of 106 compounds in the positive and negative ion mode, of which 87 were from TC, 13 from TS and 6 from TF. In addition, 106 compounds contained 57 tannins, 6 triterpenoids, 10 alkaloids, 7 flavonoids, 22 organic acids and 4 phenylpropanoids. The preliminary results indicate that the EE of TFTS includes the active anti hyperuricemic substances. The present study first investigated the efficacy and the active components of TFTS in hyperuricemic treatment, and further summarized the diagnostic ion and neutral loss patterns of MS/MS cracking of tannic compounds. These findings lay the foundation for the further study and clinical application of TFTS.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Hiperuricemia/tratamento farmacológico , Medicina Tradicional Tibetana/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Etanol/química , Masculino , Materia Medica/análise , Materia Medica/química , Materia Medica/farmacologia , Ratos , Ratos Sprague-Dawley , Terminalia/química , Tinospora/química , Ácido Úrico/sangue
16.
Tuberculosis (Edinb) ; 113: 81-90, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30514517

RESUMO

Plethora of clinical and scientific information obtained in recent past has strengthened the idea that targeting critical constituents of host immune system may have beneficial outcomes for the treatment of tuberculosis. Macrophages being the primary host for Mycobacterium tuberculosis, offer an attractive target for modulation. Owing to their negligible toxicity, plant derived polysaccharides with the ability to activate macrophages; are suitable candidates for immunomodulation. In the present study, effects of polysaccharide rich extract (PRE) isolated from Tinospora cordifolia, on the survival of intracellular MTB strains and activation of macrophages were investigated. PRE treatment up regulated the expression of pro-inflammatory cytokines such as IL-ß, TNF-α, IL-6, IL-12, and IFN-γ in RAW 264.7 cell line. Up regulation in the expression of NOS2 was observed along with concomitant enhanced nitric oxide production post PRE treatment. Surface expression of MHC-II and CD-86 was up regulated after PRE treatment. Above results suggested the classical activation of macrophages by PRE treatment. Furthermore, PRE treatment led to the activation of all the three classes of MAPK i.e p38, ERK and JNK MAPKs. Further, PRE up regulated the expression of cytokines, NOS-2, MHC-II and CD-86 in MTB infected macrophages. PRE treatment inhibited the intracellular survival of drug resistant MTB in macrophages which was partially attributed to PRE mediated NO induction. Thus our data demonstrate classical activation of macrophages by PRE treatment and killing of intracellular MTB by NO induction.


Assuntos
Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Tinospora , Animais , Antituberculosos/isolamento & purificação , Antígeno B7-2/metabolismo , Citocinas/metabolismo , Farmacorresistência Bacteriana/genética , Antígenos de Histocompatibilidade Classe II/metabolismo , Interações Hospedeiro-Patógeno , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Viabilidade Microbiana/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidade , Óxido Nítrico Sintase Tipo II/metabolismo , Extratos Vegetais/isolamento & purificação , Polissacarídeos/isolamento & purificação , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Tinospora/química
17.
BMC Complement Altern Med ; 18(1): 268, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30285727

RESUMO

BACKGROUND: Glutamate, the major excitatory neurotransmitter of CNS acts as a neurotoxin at higher concentrations. Prolonged activation of glutamate receptors results in progressive neuronal damage by aggravating calcium influx, inducing mitochondrial damage and oxidative stress. Excitotoxic cell death is associated with the pathogenesis of various neurodegenerative disorders such as trauma, brain injury and neurodegenerative diseases. The current study was designed to investigate the neuroprotective and neuroregenerative potential of Tinospora cordifolia against glutamate-induced excitotoxicity using primary cerebellar neuronal cultures as a model system. METHODS: Monosodium salt of glutamate was used to induce neurotoxic injury in primary cerebellar neurons. Four extracts including Hexane extract, Chloroform extract, Ethyl acetate, and Butanol extract were obtained from fractionation of previously reported aqueous ethanolic extract of T. cordifolia and tested for neuroprotective activity. Out of the four fractions, Butanol extract of T. cordifolia (B-TCE) exhibited neuroprotective potential by preventing degeneration of neurons induced by glutamate. Expression of different neuronal, apoptotic, inflammatory, cell cycle regulatory and plasticity markers was studied by immunostaining and Western blotting. Neurite outgrowth and migration were also studied using primary explant cultures, wound scratch and gelatin zymogram assay. RESULTS: At molecular level, B-TCE pretreatment of glutamate-treated cultures normalized the stress-induced downregulation in the expression of neuronal markers (MAP-2, GAP-43, NF200) and anti-apoptotic marker (Bcl-xL). Further, cells exposed to glutamate showed enhanced expression of inflammatory (NF-κB, AP-1) and senescence markers (HSP70, Mortalin) as well as the extent of mitochondrial damage. However, B-TCE pretreatment prevented this increase and inhibited glutamate-induced onset of inflammation, stress and mitochondrial membrane damage. Furthermore, B-TCE was observed to promote regeneration, migration and plasticity of cerebellar neurons, which was otherwise significantly inhibited by glutamate treatment. CONCLUSION: These results suggest that B-TCE may have neuroprotective and neuroregenerative potential against catastrophic consequences of glutamate-mediated excitotoxicity and could be a potential therapeutic candidate for neurodegenerative diseases.


Assuntos
Ácido Glutâmico/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Tinospora/química , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Cerebelo/citologia , Cerebelo/efeitos dos fármacos , Cerebelo/fisiologia , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
18.
Molecules ; 23(10)2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30301176

RESUMO

Fifty-seven compounds were purified from the stems of Tinospora sinensis, including three new compounds characterized as a lignan (1), a pyrrole alkaloid (11), and a benzenoid (17), respectively. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among the isolates, fifteen compounds were examined for their anti-inflammatory potential in vitro. The results showed that several compounds displayed moderate inhibition of N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release.


Assuntos
Alcaloides/farmacologia , Lignanas/farmacologia , Elastase Pancreática/metabolismo , Pirróis/farmacologia , Alcaloides/química , Citocalasina B/antagonistas & inibidores , Citocalasina B/toxicidade , Humanos , Lignanas/química , Estrutura Molecular , Neutrófilos/efeitos dos fármacos , Neutrófilos/enzimologia , Elastase Pancreática/biossíntese , Elastase Pancreática/efeitos dos fármacos , Caules de Planta/química , Pirróis/química , Superóxidos/antagonistas & inibidores , Superóxidos/toxicidade , Tinospora/química
19.
Fitoterapia ; 131: 127-133, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30339924

RESUMO

Two new cadinane sesquiterpene glucosides (1, 2), two new phenylpropanoid glycosides (3, 4), and two new diterpenoid glucosides (5, 6), as well as 6 known compounds were isolated from the stems of Tinospora sinensis. The structures of these compounds were elucidated by extensive spectroscopic analysis and chemical methods. The absolute configuration of compound 1 was determined by timedependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations and in situ dimolybdenum CD method. All the isolated compounds except for compounds 7, 11 and 12 were evaluated for their anti-neuroinflammatory effect by inhibiting the nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine BV-2 microglial cells, and compound 4 showed anti-neuroinflammatory activity with IC50 values 42.90 µM in vitro assay.


Assuntos
Glucosídeos/isolamento & purificação , Glicosídeos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Tinospora/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Linhagem Celular , China , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Camundongos , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Caules de Planta/química , Sesquiterpenos Policíclicos , Sesquiterpenos/farmacologia
20.
Sci Rep ; 8(1): 13520, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30202067

RESUMO

Tinospora crispa is a popular traditional herbal plant commonly used throughout the world for treatment of various diseases, in particular type 2 diabetes mellitus. We report here a new case of toxic hepatitis in a 57-year old male patient in the French West Indies following the consumption of two aqueous extracts of fresh Tinospora crispa stems. It thus differs from two previously reported cases that concerned the chronic intake of powdered dry stems delivered in solid oral dosage forms (i.e. pellets and tablets). Liquid Chromatography-Diode Array Detection-Mass Spectrometry (LC/DAD/MS) analyses were performed on an aqueous extract of the offending sample that mimics the swallowed preparation. They revealed the presence of species-specific molecular marker borapetoside C (1) and thus enabled an unambiguous phytochemical identification. The exploration of tandem MS/MS data obtained by ultra-high performance liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-ESI-QTOF-HRMS) allowed the identification of 17 additional cis-clerodane-type furanoditerpenoid lactones, analogues of 1. These results support the hypothesis that the mechanisms underlying hepatotoxicity of Tinospora crispa are the same as those encountered with furanoditerpenoids-containing plants such as Teucrium chamaedrys or Dioscorea bulbifera. In the context of type 2 diabetes treatment, we recommend that Tinospora crispa intake should be more closely monitored for signs of hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Diterpenos Clerodânicos/toxicidade , Extratos Vegetais/efeitos adversos , Tinospora/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Caules de Planta/química , Caules de Planta/toxicidade , Tinospora/química
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