RESUMO
BACKGROUND: Syringin, a phenylpropanoid glycoside, has exhibited numerous biological properties including inhibitory activities against various immune and inflammatory disorders. In this study, syringin isolated from Tinospora crispa was evaluated for its ability to down-regulate activated nuclear factor-kappa B (NF-κB), phosphoinositide-3-kinase-Akt (PI3K-Akt) and mitogen-activated protein kinases (MAPKs) signal transducing networks in U937 macrophages activated by lipopolysaccharide. METHODS: The attenuating effects of syringin on the productions of prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α), and the expressions of signaling molecules of the signaling pathways were investigated by using ELISA, Western blot, and qRT-PCR. RESULTS: Syringin downregulated the NF-κB, MAPKs, and PI3K-Akt signal networks by significantly reducing PGE2 production in the macrophages via suppression of COX-2 gene and protein expression levels. It also reduced TNF-α and IL-1ß secretion and their mRNA expression, suppressed phosphorylation of NF-κB (p65), IKKα/ß, and IκBα, and restored ability of IκBα to degrade. Syringin dose-dependently attenuated Akt, p38 MAPKs, JNK, and ERK phosphorylation. Also, the expression of corresponding upstream signaling molecules toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) were down-regulated in response to syringin treatment. CONCLUSION: The suppressive effect of syringin on the inflammatory signaling molecules in MyD88-dependent pathways suggested it's potential as a drug candidate for development into an agent for treatment of various immune-mediated inflammatory disorders.
Assuntos
Glucosídeos , Lipopolissacarídeos , Macrófagos , Fator 88 de Diferenciação Mieloide , NF-kappa B , Fenilpropionatos , Transdução de Sinais , Tinospora , Humanos , Fator 88 de Diferenciação Mieloide/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Tinospora/química , Glucosídeos/farmacologia , Fenilpropionatos/farmacologia , NF-kappa B/metabolismo , Células U937 , Dinoprostona/metabolismo , Interleucina-1beta/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Ciclo-Oxigenase 2/genética , Mediadores da Inflamação/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Receptor 4 Toll-Like/metabolismoRESUMO
Three neo-clerodane diterpenoids, including two new tinocordifoliols A (1) and B (2) and one known tinopanoid R (3), were isolated from the ethyl acetate-soluble fraction of the 70% ethanol extract of Tinospora cordifolia stems. The structures were elucidated by various spectroscopic methods, including one dimensional (1D) and 2D-NMR, high resolution-electrospray ionization (HR-ESI)-MS, and electronic circular dichroism (ECD) data. The T. cordifolia extract and all isolated compounds 1-3 possessed arginase I inhibitory activities. Among them, 3 exhibited moderate competitive inhibition of human arginase I (IC50 = 61.9 µM). Furthermore, docking studies revealed that the presence of a ß-substituted furan in 3 may play a key role in the arginase I inhibitory activities.
Assuntos
Arginase , Diterpenos Clerodânicos , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Caules de Planta , Tinospora , Tinospora/química , Arginase/antagonistas & inibidores , Arginase/metabolismo , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Humanos , Caules de Planta/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/isolamento & purificação , Relação Estrutura-Atividade , Estrutura Molecular , Conformação Molecular , Relação Dose-Resposta a DrogaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The increasing incidence of osteoarthritis (OA), especially among the elderly population, highlights the need for more efficacious treatments that go beyond mere symptomatic relief. Tinospora crispa (L.) Hook. f. & Thomson (TC) boasts a rich traditional heritage, widespread use in Ayurveda, traditional Chinese medicine (TCM), and diverse indigenous healing practices throughout Southeast Asia for treating arthritis, rheumatism, fever, and inflammation. AIM OF THE STUDY: This study investigates the anti-inflammatory and chondroprotective potential of TC stem extracts, including ethanolic TC extract (ETCE) and aqueous TC extract (ATCE), in modulating OA pathogenesis through in vitro and in vivo approaches. MATERIALS AND METHODS: The study utilized LC-MS/MS to identify key compounds in TC stem extracts. In vitro experiments assessed the antioxidative and anti-inflammatory properties of ETCE and ATCE in activated macrophages, while an in vivo monoiodoacetate (MIA)-induced OA rat model evaluated the efficacy of ETCE treatment. Key markers of oxidative stress, such as superoxide dismutase (SOD) and catalase (CAT), were assessed alongside pro-inflammatory cytokines TNF-α and IL-1ß, and matrix-degrading enzymes, matrix metalloproteinase (MMP 13 and MMP 3), to evaluate the therapeutic effects of TC stem extracts on OA. RESULTS: Chemical profiling of the extracts was conducted using LC-MS/MS in positive ionization, identifying seven compounds, including pseudolaric acid B, stylopine, and reticuline, which were reported for the first time in this species. The study utilized varying concentrations of TC stem extracts, specifically 6.25-25 µg/mL for in vitro assays and 500 mg/kg for in vivo studies. Our findings also revealed that both ETCE and ATCE exhibit dose-dependent reduction in reactive oxygen species (41%-52%) and nitric oxide (NO) levels (50% and 72%), with ETCE displaying superior antioxidative efficacy and marked anti-inflammatory properties, significantly reducing TNF-α and IL-6 at concentrations above 12.5 µg/mL. In the MIA-induced OA rat model, ETCE treatment notably outperformed ATCE, markedly lowering TNF-α (1.91 ± 0.37 pg/mL) and IL-1ß (26.30 ± 3.68 pg/mL) levels and effectively inhibiting MMP 13 and MMP 3 enzymes. Furthermore, macroscopic and histopathological assessments, including ICRS scoring and OARSI grading, indicate that TC stem extracts reduce articular damage and proteoglycan loss in rat knee cartilage. These results suggest that TC stem extracts may play a role in preventing cartilage degradation and potentially alleviating inflammation and pain associated with OA, though further studies are needed to confirm these effects. CONCLUSION: This study highlights the potential of TC stem extracts as a novel, chondroprotective therapeutic avenue for OA management. By targeting oxidative stress, pro-inflammatory cytokines, and cartilage-degrading enzymes, TC stem extracts promise to prevent cartilage degradation and alleviate inflammation and pain associated with OA.
Assuntos
Anti-Inflamatórios , Antioxidantes , Osteoartrite , Estresse Oxidativo , Extratos Vegetais , Tinospora , Animais , Tinospora/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Osteoartrite/tratamento farmacológico , Osteoartrite/induzido quimicamente , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Masculino , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Camundongos , Ratos Sprague-Dawley , Ratos , Células RAW 264.7 , Condrócitos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Caules de Planta/química , Citocinas/metabolismo , Ácido Iodoacético , Artrite Experimental/tratamento farmacológicoRESUMO
Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2-12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b, 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions.
Assuntos
Agentes de Imunomodulação , Compostos Fitoquímicos , Tinospora , Tinospora/química , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Animais , Camundongos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/isolamento & purificação , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Interleucina-6RESUMO
The present study aimed to determine the genoprotective activity and safety of Moringa oleifera leave and Tinospora cordifolia stem extracts against cyclophosphamide (CP)-induced genotoxicity utilizing Swiss albino mice. Animals were divided into 14 groups for subacute treatment with either M. oleifera or T. cordifolia extracts daily for 28 days. The extract doses selected were 100, 200 or 400 mg/kg b.w administered orally alone or combined with CP (50 mg/kg b.w. intraperitoneally daily for 5 days). Analyses performed included the comet assay, micronucleus test (MN) in bone marrow cells and sperm head abnormality assay (SHA). M. oleifera and T. cordifolia extracts induced no significant genotoxic effects on somatic and germ cells. In contrast, for all cells examined M. oleifera and T. cordifolia extracts inhibited DNA damage initiated by CP. Taken together data demonstrated that both plant extracts did not exhibit marked genotoxic effects but displayed potential chemoprotective properties against CP-induced genotoxicity in Swiss mice.
Assuntos
Ciclofosfamida , Dano ao DNA , Testes para Micronúcleos , Moringa oleifera , Extratos Vegetais , Folhas de Planta , Tinospora , Animais , Tinospora/química , Camundongos , Ciclofosfamida/toxicidade , Moringa oleifera/química , Extratos Vegetais/farmacologia , Masculino , Folhas de Planta/química , Dano ao DNA/efeitos dos fármacos , Ensaio Cometa , Caules de Planta/química , Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Mutagênicos/toxicidade , Antimutagênicos/farmacologiaRESUMO
Nanoemulsions are gaining interest in a variety of products as a means of integrating easily degradable bioactive compounds, preserving them from oxidation, and increasing their bioavailability. However, preparing stable emulsion compositions with the desired characteristics is a difficult task. The aim of this study was to encapsulate the Tinospora cordifolia aqueous extract (TCAE) into a water in oil (W/O) nanoemulsion and identify its critical process and formulation variables, like oil (27-29.4 mL), the surfactant concentration (0.6-3 mL), and sonication amplitude (40% to 100%), using response surface methodology (RSM). The responses of this formulation were studied with an analysis of the particle size (PS), free fatty acids (FFAs), and encapsulation efficiency (EE). In between, we have studied a fishbone diagram that was used to measure risk and preliminary research. The optimized condition for the formation of a stable nanoemulsion using quality by design was surfactant (2.43 mL), oil concentration (27.61 mL), and sonication amplitude (88.6%), providing a PS of 171.62 nm, FFA content of 0.86 meq/kg oil and viscosity of 0.597 Pa.s for the blank sample compared to the enriched TCAE nanoemulsion with a PS of 243.60 nm, FFA content of 0.27 meq/kg oil and viscosity of 0.22 Pa.s. The EE increases with increasing concentrations of TCAE, from 56.88% to 85.45%. The RSM response demonstrated that both composition variables had a considerable impact on the properties of the W/O nanoemulsion. Furthermore, after the storage time, the enriched TCAE nanoemulsion showed better stability over the blank nanoemulsion, specially the FFAs, and the blank increased from 0.142 to 1.22 meq/kg oil, while TCAE showed 0.266 to 0.82 meq/kg.
Assuntos
Emulsões , Tamanho da Partícula , Extratos Vegetais , Tinospora , Água , Emulsões/química , Extratos Vegetais/química , Tinospora/química , Água/química , Sonicação , Nanopartículas/química , Óleos/química , Tensoativos/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Dengue is one of the most prevalent mosquito-borne viral infections. Moreover, due to the absence of appropriate curative and preventive measures against it, the mortality rate is increasing alarmingly. However, remarkable docking and clinical advances have been achieved with plant-based natural and conventional therapeutics. Tinospora cordifolia is one of the highly explored panaceas at the local level for its effective anti-dengue formulations. AIM OF THE STUDY: The present article aims for critical assessment of the data available on the anti-dengue therapeutic use of T. cordifolia. Efforts have also been made on the clinical and in-silico anti-dengue efficacy of this plant. The phytochemistry and the antiviral machinery of the plant are also emphasized. MATERIALS AND METHODS: The present article is the outcome of the literature survey on the anti-dengue effect of T. cordifolia. A literature survey was conducted from 2011 to 2024 using different databases with appropriate keywords. RESULTS: The present study confirms the anti-dengue potential of T. cordifolia. The plant can suppress the initiation of 'cytokine storm', vascular leakage and inhibition of various structural and NS proteins to exert its anti-dengue potential. Berberine and magnoflorine phytocompounds were highly explored for their anti-dengue potential. CONCLUSIONS: The present study concluded that T. cordifolia serves as an effective therapeutic agent for treating dengue. Further in-silico and clinical studies are needed so that stable, safe and efficacious anti-dengue drug can be developed. Besides, a precise antiviral mechanism of T. cordifolia against DENV infection is still needed.
Assuntos
Antivirais , Dengue , Compostos Fitoquímicos , Extratos Vegetais , Tinospora , Tinospora/química , Dengue/tratamento farmacológico , Humanos , Antivirais/farmacologia , Antivirais/uso terapêutico , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Animais , Vírus da Dengue/efeitos dos fármacosRESUMO
Tinospora sinensis (T. sinensis), whose Tibetan name is "Lezhe", as a traditional medicine, is widely distributed in China, India and Sri Lanka. It is used for the treatment of rheumatic arthralgia, sciatica, lumbar muscle strain and bruises. Research over the previous decades indicated that T. sinensis mainly contains terpenes, lignans, alkaloids, phenol glycosides and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, analgesic, immunosuppressive, anti-aging, anti-radiation, anti-leishmania and liver protection have been reported. However, the scholar's research on the pharmacodynamic material basis of T. sinensis is relatively weak. Data regarding many aspects such as links between the traditional uses and bioactivities, pharmacokinetics, and quality control standard of active compositions is still limited and need more attention. This review reports a total of 241 compounds, the ethnopharmacology and clinical application of T. sinensis, covering the literature which were searched by multiple databases including Web of Science, PubMed, Google Scholar, Science Direct, CNKI and other literature sources from 1996 to date, with a view to provide a systematic and insightful reference and lays a foundation and inspiration for the application and further in-depth research of T. sinensis resources.
Assuntos
Compostos Fitoquímicos , Tinospora , Tinospora/química , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Medicina Tradicional , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificaçãoRESUMO
Background: The potential molluscicidal extracts, obtained from indigenous plants Cannabis sativa, Acacia nilotica, and Tinospora cordifolia, were tested for toxicity against freshwater pulmonate snail Lymnaea acuminata, an intermediate host of Fasciola hepatica. The organic extracts had a significant effect on young snails. Materials and Methods: All organic extracts and column-purified fractions gave median lethal concentrations (19-100.05 mg/L; 24 h) that fell well within the threshold level of 100 mg/L, set for a potential molluscicide by the World Health Organization. Results: The toxicity of T. cordifolia stem acetone extract (96 h LC50: 16.08 mg/L) was more pronounced compared with C. sativa leaf ethanol extract (96 h LC50: 16.32 mg/L) and A. nilotica leaf ethanol extract (96 h LC50: 24.78 mg/L). ß-caryophyllene, gallic acid, and berberine were characterized and identified as active molluscicidal components. Co-migration of ß-caryophyllene (retardation factor [Rf] 0.95), gallic acid (Rf 0.30), and berberine (Rf 0.23) with column-purified parts of Cannabis sativa, Acacia nilotica, and Tinospora cordifolia on thin-layer chromatography demonstrates same Rf value, that is, 0.95, 0.30, and 0.23, respectively. Conclusion: This study indicates that these extracts thus represent potential plant-derived molluscicides that are worthy of further investigations.
Assuntos
Acacia , Cannabis , Moluscocidas , Extratos Vegetais , Tinospora , Animais , Tinospora/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Acacia/química , Moluscocidas/farmacologia , Cannabis/química , Folhas de Planta/química , Lymnaea/efeitos dos fármacos , Fasciola/efeitos dos fármacos , Caramujos/parasitologia , Caramujos/efeitos dos fármacosRESUMO
Clerodane diterpenes are a class of secondary metabolites that can be classified into four types according to the configuration of the H3-19/H-10-H3-17/H3-20 fragment, i.e., trans-cis (TC), trans-trans (TT), cis-cis (CC), and cis-trans (CT). Tinotufolins A-C and E (1a-3a and 5a), isolated from the leaves of Tinospora crispa, were previously elucidated as CT-type clerodanes; however, our established 13C NMR-based empirical rules and density functional theory calculations suggested that these clerodanes belong to the CC type. Therefore, tinotufolins A-F (1-6) were reisolated from the leaves of T. crispa, along with an undescribed compound 7 and known compounds 8-11, and their structures were established by extensive spectroscopic analyses. The structures of tinotufolins A-C and E were revised to CC-type 1-3 and 5, and undescribed compound 7 was established as a CC-type clerodane. The present study demonstrates that empirical rules and calculations can efficiently identify and revise erroneous structures in clerodane diterpenes.
Assuntos
Diterpenos Clerodânicos , Folhas de Planta , Tinospora , Folhas de Planta/química , Tinospora/química , Diterpenos Clerodânicos/química , Diterpenos Clerodânicos/isolamento & purificação , Estrutura Molecular , Teoria da Densidade FuncionalRESUMO
BACKGROUND: The sympatric occurrence of the species that often resulted in different gatherings of plant material, ambiguous history on traditional use, and taxonomic flux due to similarities within the Tinospora (Menispermaceae) taxa are some of the reasons that triggered the necessity to develop robust analytical methods for efficient QC, especially to recognize dry and powder forms. OBJECTIVE: To develop novel HPTLC-based fingerprinting of two closely resembling Tinospora species followed by HPTLC-MS analysis and identification of compounds differentiating Tinospora crispa (TCP) and Tinospora cordifolia (TCR) and a rapid and quantitative assessment by HPLC with a photodiode array detector (HPLC-PDA) with MS/MS characterization of specific TCP and TCR analytical markers. METHODS: An HPTLC-based method was developed using chloroform-toluene-methanol-formic acid (7 + 4 + 2 + 0.2, by volume). The TCP compounds could be distinguished and isolated using successive column chromatography with complete characterization. Further these used in the reverse phase (RP)-HPLC-PDA coupled with LC-ESI (electrospray ionization)-MS/MS to quantify and confirmation in TCP and TCR. RESULTS: The fingerprinting showed distinct bands in TCP stems, confirmed as clerodane- furanoditerpenoids with indirect profiling by the HPTLC-MS technique. Systematic isolation confirmed these compounds as borapetosides B and E. Thus, the RP-HPLC-PDA method was developed for these borapetosides B and E, with tinosporide to differentiate these two species. The quantitation method was well validated with good linearity (r2 >0.99) with sensitive LOD (0.49-3.71 mcg/mL) and LOQ (1.48-11.23 mcg/mL) with recoveries of 92.34-96.19%. CONCLUSION: A novel, validated HPLC-PDA method showed good resolution and reliability (up to 1% adulteration) in quantification for targeted major analytical markers from TCP to differentiate TCR. Thus, HPTLC and HPLC-PDA-based techniques are helpful with MS/MS-based characterization to identify and quantify these analytical markers from TCP (borapetoside B and E) and TCR (tinosporide) in dry and powder form. HIGHLIGHTS: This article reports on the systemic use of HPTLC-MS for separating and identifying analytical markers in Tinospora species, distinguishing TCR and TCP with quantitative HPLC-PDA and MS/MS assessment.
Assuntos
Espectrometria de Massas em Tandem , Tinospora , Tinospora/química , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Pós , Extratos Vegetais/química , Receptores de Antígenos de Linfócitos TRESUMO
Twenty-six clerodane diterpenoids have been isolated from T. sagittata, a plant species of traditional Chinese medicine Radix Tinosporae, also named as "Jin Guo Lan". Among them, there are eight previously undescribed clerodane diterpenoids (tinotanoids A-H: 1-8), and 18 known diterpenoids (9-26). The absolute configurations of compounds 1, 2, 5, 8, 13, 17 and 20 were determined by single-crystal X-ray diffraction. Compound 1 is the first example of rotameric clerodane diterpenoid with a γ-lactone ring which is constructed between C-11 and C-17; meanwhile, compounds 3 and 4 are two pairs of inseparable epimers. Compounds 2, 12 and 17 demonstrated excellent inhibitory activity on NO production against LPS-stimulated BV-2 cells with IC50 values of 9.56 ± 0.69, 9.11 ± 0.53 and 11.12 ± 0.70 µM, respectively. These activities were significantly higher than that of the positive control minocycline (IC50 = 23.57 ± 0.92 µM). Moreover, compounds 2, 12 and 17 dramatically reduced the LPS-induced upregulation of iNOS and COX-2 expression. Compounds 2 and 12 significantly inhibited the levels of pro-inflammatory cytokines TNF-α, IL-1ß and IL-6 that were increased by LPS stimulation.
Assuntos
Diterpenos Clerodânicos , Menispermaceae , Tinospora , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Tinospora/química , Lipopolissacarídeos/farmacologia , Raízes de Plantas/química , Estrutura MolecularRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AIM: The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. METHODS: Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. RESULTS: The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20ß-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20ß-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. CONCLUSION: T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.
Assuntos
Neuralgia , Tinospora , Ratos , Animais , Paclitaxel , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Tinospora/química , Epóxido Hidrolases , Simulação de Acoplamento Molecular , Neuralgia/induzido quimicamente , Neuralgia/tratamento farmacológico , Analgésicos/farmacologia , Analgésicos/uso terapêuticoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora crispa (L.) Hook. f. & Thomson stem (TCS) has long been used as folk medicine for the treatment of diabetes mellitus. Previous study revealed that TCS possesses multi-ingredients and multi-targets characteristic potential as insulin sensitizer activity. However, its mechanisms of action and molecular targets are still obscure. AIM OF THE STUDY: In the present study, we investigated the effects of TCS against insulin resistance in muscle cells through integrating in vitro experiment and identifying its active biomarker using metabolomics and in molecular docking validation. MATERIALS AND METHODS: We used centrifugal partition chromatography (CPC) to isolate 33 fractions from methanolic extract of TCS, and then used UHPLC-Orbitrap-HRMS to identify the detectable metabolites in each fraction. We assessed the insulin sensitization activity of each fraction using enzyme-linked immunosorbent assay (ELISA), and then used confocal immunocytochemistry microscopy to measure the translocation of glucose transporter 4 (GLUT4) to the cell membrane. The identified active metabolites were further simulated for its molecular docking interaction using Autodock Tools. RESULTS: The polar fractions of TCS significantly increased insulin sensitivity, as measured by the inhibition of phosphorylated insulin receptor substrate-1 (pIRS1) at serine-312 residue (ser312) also the increasing number of translocated GLUT4 and glycogen content. We identified 58 metabolites of TCS, including glycosides, flavonoids, alkaloids, coumarins, and nucleotides groups. The metabolomics and molecular docking simulations showed the presence of minor metabolites consisting of tinoscorside D, higenamine, and tinoscorside A as the active compounds. CONCLUSIONS: Our findings suggest that TCS is a promising new treatment for insulin resistance and the identification of the active metabolites in TCS could lead to the development of new drugs therapies for diabetes that target these pathways.
Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tinospora , Humanos , Insulina/metabolismo , Simulação de Acoplamento Molecular , Tinospora/química , Músculo Esquelético , Glucose/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológicoRESUMO
Natural products with curative properties are gaining immense popularity in scientific and food research, possessing no side effects in contrast to other drugs. Guduchi, or Tinospora cordifolia, belongs to the menispermaceae family of universal drugs used to treat various diseases in traditional Indian literature. It has received attention in recent decades because of its utilization in folklore medicine for treating several disorders. Lately, the findings of active phytoconstituents present in herbal plants and their pharmacological function in disease treatment and control have stimulated interest in plants around the world. Guduchi is ethnobotanically used for jaundice, diabetes, urinary problems, stomachaches, prolonged diarrhea, skin ailments, and dysentery. The treatment with Guduchi extracts was accredited to phytochemical constituents, which include glycosides, alkaloids, steroids, and diterpenoid lactones. This review places emphasis on providing in-depth information on the budding applications of herbal medicine in the advancement of functional foods and nutraceuticals to natural product researchers.
Assuntos
Plantas Medicinais , Tinospora , Tinospora/química , Extratos Vegetais/química , Plantas Medicinais/química , Suplementos NutricionaisRESUMO
BACKGROUND: Tinospora cordifolia Miers. (TC) (Giloya/Guduchi) is a native Indian herb, reported for its wide array of medicinal activities including immunomodulatory activity. However, the exact pharmacological mechanism of TC as an immunomodulatory agent remains unclear. Central to this, to the best of our knowledge, no study has explored the immunoadjuvant potential of TC in response to the Japanese encephalitis (JE) vaccines. PURPOSE: The study aims to explore the immunoadjuvant potential of TC ethanolic extract in response to the JE vaccine and illustrates its potential mechanism of immunomodulation using an integrated approach of network pharmacology and in-vivo experimental study. STUDY DESIGN AND METHODS: Initially, the extract was prepared and the components of TC were identified through high-resolution liquid chromatography mass spectrometry (HR-LC/MS). The compounds were then screened for network pharmacology analysis. Next, the drug and disease targets were identified and the network was constructed using Cytoscape 3.7.2 to obtain different signalling pathways of TC in JEV. We then evaluated the immunoadjuvant potential of TC ethanolic extract in mice immunized with inactivated JE vaccine (SA-14-14-2 strain). BALB/c mice were supplemented with TC extract (30 and 100 mg/kg, i.g.), daily for 56 days, marked with immunization on 28th day of the study, by JE vaccine. Blood was collected for flow cytometry and haematological analysis (total and differential cell counts). The surface expression of immune-cell markers (CD3+, CD4+, CD19+, CD11c+, CD40+) were evaluated on day 0 (pre-immunization), day 14 and 28 post-immunization. Additionally, inflammatory cytokines (IFN-γ+/IL-17A+) were evaluated post-14 and 28 days of immunization. RESULTS: The HR-LC/MS analysis identified the presence of glycosides, terpenoids, steroids and alkaloids in the TC extract. Through network analysis, 09 components and 166 targets were obtained, including pathways that involve toll-like receptor signalling, pattern-recognition receptor signalling, cytokine receptor and cytokine mediated signalling, etc. The in-vivo results showed that preconditioning with TC ethanolic extract significantly elevated the haematological variables (leucocyte count) as well as the surface expression of CD markers (B and T cell subsets) on day 0 (pre-immunization), day 14 and 28 post-immunization. Furthermore, preconditioning of TC demonstrated a dose-dependant augmentation of immune cells (CD3+, CD4+, CD19+, CD11c+) and inflammatory cytokines (IFN-γ+/IL-17A+) on day 14 and 28 post-immunization when compared to vaccine alone group. CONCLUSION: Results showed that preconditioning with TC extract before immunization might play a potential role in enhancing the cell-mediated as well as humoral immunity. Altogether, the combinatorial approach of network pharmacology and in-vivo animal experimentation demonstrated the immunoadjuvant potential of TC in response to JEV vaccine.
Assuntos
Vacinas contra Encefalite Japonesa , Tinospora , Camundongos , Animais , Tinospora/química , Interleucina-17 , Farmacologia em Rede , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Citocinas/metabolismo , Adjuvantes Imunológicos/farmacologia , ImunidadeRESUMO
Seven previously undescribed diterpenoids, tinocrisposides A-D (1-4) and borapetic acids A (5), B (6), and C (7), together with 16 known compounds, were isolated from the stem of Tinospora crispa (Menispermaceae). The structures of the new isolates were elucidated by spectroscopic and chemical methods. The ß-cell protective effect of the tested compounds was examined on insulin-secreting BRIN-BD11 cells under dexamethasone treatment. Diterpene glycosides 12, 14-16, and 18 presented a substantial protective effect on BRIN-BD11 cells treated with dexamethasone in a dose-dependent manner. Compounds 4 and 17 with two sugar moieties exhibited clear protective effects on ß-cells.
Assuntos
Diterpenos , Tinospora , Glicosídeos/farmacologia , Glicosídeos/química , Tinospora/química , Diterpenos/farmacologia , DexametasonaRESUMO
Tinospora cordifolia (Guduchi or Gurjo), a herbaceous vine or climbing deciduous shrub, is consider as an important medicine in the Ayurvedic system of medication, which is available in India, China, Myanmar, Bangladesh and Srilanka. Menispermaceae is the family of this compound. T. cordifolia have a variety of properties to treat various ailments such as fevers, jaundice, diabetes, dysentery, urinary infections, and skin diseases. This compound has been subjected to many chemicals, pharmacological, pre-clinical, or clinical investigations and some new therapeutic potential effects have been indicated. This review aims to summarize the critical information concerning in areas of chemical constituents, chemical structure, and pharmacokinetic activities such as anti-diabetic, anticancer, immune-modulatory, antivirus (especially in silico study about COVID-19), antioxidant, antimicrobial, hepatoprotective and its effect on cardiovascular and neurological disorders as well as rheumatoid arthritis. This traditional herb needs more experimental study on the clinical, pre-clinical study, and clinical efficacy of these compounds for the prevention and treatment of COVID-19 and needs large-scale clinical studies to prove the clinical efficacy of this compound, especially in stress-related diseases and other neuronal disorders.
Assuntos
COVID-19 , Tinospora , Humanos , Tinospora/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Antioxidantes/farmacologia , Antioxidantes/químicaRESUMO
This is a 54-year-old woman from Germany of central European origin who developed an acute hepatitis while orally taking Ayurvedic herbal remedies, among those was the medicinal herb Tinospora cordifolia. She took the plant powders from July 1, 2021, to October 1, 2021, with the intention of relieving the symptoms of her subjectively irritated gastrointestinal tract. The patient's main symptoms of acute hepatitis were progressively increasing general fatigue, nausea, and exhaustion. During an inpatient hospital admission from November 4, 2021, to November 9, 2021, she was under clinical observation, but no specific therapeutic measures were deemed necessary; however, blood chemistry showed an acute toxic hepatitis. There was no clinical or laboratory evidence of acute liver failure. Aminotransferase values decreased to normal values on December 14, 2021, by themselves. This case report contributes to the ongoing discussion about the potential risks of triggering an acute hepatitis due to the intake of herbal remedies from the Tinospora genus in rare cases, differentiating other involved risk factors. The case also shows that causality assignments are not trivial in the context of multivariate clinical scenarios. In the case of known hepatic metabolism-associated risk factors, T. cordifolia should be used with more caution based on available case reports. At the same time, no hasty and exaggerated prejudgments should be made about this medicinal herb, which has been very successfully used in traditional South Asian systems of medicine for many centuries.
Assuntos
Hepatite , Falência Hepática Aguda , Fitoterapia , Extratos Vegetais , Tinospora , Humanos , Pessoa de Meia-Idade , Hepatite/tratamento farmacológico , Hepatite/etiologia , Falência Hepática Aguda/induzido quimicamente , Extratos Vegetais/efeitos adversos , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Tinospora/química , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , FemininoRESUMO
Tinospora cordifolia and Actinidia deliciosa are the widely used plant in Ayurvedic systems of medicine. Both plants are well known for their immunomodulatory activity. In the current study, in silico exploration was performed using advanced computational techniques such as molecular docking and molecular dynamics simulation approach. Bioactive molecules from the Tinospora cordifolia and Actinidia deliciosa were docked against the Human IL-2. Out of all the docked bioactive molecules, Pygenic acid-B (PubChem CID:146157192) showed the highest negative binding affinity.