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Deciphering the mechanism of Tinospora cordifolia extract on Th17 cells through in-depth transcriptomic profiling and in silico analysis

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dc.contributor.authorNandan, Amrita
dc.contributor.authorSharma, Vishwas
dc.contributor.authorBanerjee, Prodyot
dc.contributor.authorSadasivam, Kannan
dc.contributor.authorVenkatesan, Subramanian
dc.contributor.authorPrasher, Bhavana
dc.date.accessioned2023-09-19T13:23:22Z
dc.date.available2023-09-19T13:23:22Z
dc.date.issued09-01-2023
dc.description.abstractNaive CD4+ T cells differentiate into effector (Th1, Th2, Th17) cells and immunosuppressive (Treg) cells upon antigenic stimulation in the presence of a specific cytokine milieu. The T cell in vitro culture system provides a very efficient model to study compounds’ therapeutic activity and mechanism of action. Tinospora cordifolia (Willd.) Hook.f. & Thomson (Family. Menispermaceae) is one of the widely used drugs in Ayurveda (ancient Indian system of medicine) for various ailments such as inflammatory conditions, autoimmune disorders, and cancer as well as for promoting general health. In vitro and in vivo studies on immune cells comprising dendritic cells, macrophages, and B cells suggest its immune-modulating abilities. However, to date, the effect of T. cordifolia on individual purified and polarized T cell subsets has not been studied. Studying drug effects on T cell subsets is needed to understand their immunomodulatory mechanism and to develop treatments for diseases linked with T cell abnormalities. In this study, we examined the immunomodulatory activity of T. cordifolia on primary CD4+ T cells, i.e., Th1, Th17, and iTreg cells. An aqueous extract of T. cordifolia was non-cytotoxic at concentrations below 1500 µg/ml and moderately inhibited the proliferation of naive CD4+ T cells stimulated with anti-CD3ε and anti-CD28 for 96 h. T. cordifolia treatment of naive CD4+ T cells differentiated under Th17-polarizing conditions exhibited reduced frequency of IL-17 producing cells with inhibition of differentiation and proliferation. For the first time, in-depth genome-wide expression profiling of T. cordifolia treated naive CD4+ T cells, polarized to Th17 cells, suggests the broad-spectrum activity of T. cordifolia. It shows inhibition of the cytokine-receptor signaling pathway, majorly via the JAK-STAT signaling pathway, subsequently causing inhibition of Th17 cell differentiation, proliferation, and effector function. Additionally, the molecular docking studies of the 69 metabolites of T. cordifolia further substantiate the inhibitory activity of T. cordifolia via the cytokine-receptor signaling pathway. Furthermore, in vitro polarized Th1 and iTreg cells treated with T. cordifolia extract also showed reduced IFN-γ production and FoxP3 expression, respectively. This study provides insight into the plausible mechanism/s of anti-inflammatory activity of T. cordifolia involving T cells, mainly effective in Th17-associated autoimmune and inflammatory diseases.
dc.identifier.doi10.3389/fphar.2022.1056677
dc.identifier.scopus2-s2.0-85146870895
dc.identifier.urihttps://apicris.irins.org/handle/IITM2023/16648
dc.relation.ispartofseriesFrontiers in Pharmacology
dc.sourceFrontiers in Pharmacology
dc.subjectayurveda
dc.subjectguduchi
dc.subjectimmunomodulatory
dc.subjectmolecular docking
dc.subjectsignaling pathway
dc.subjectTh17 cells
dc.subjectTinospora cordifolia
dc.titleDeciphering the mechanism of Tinospora cordifolia extract on Th17 cells through in-depth transcriptomic profiling and in silico analysis
dc.typeJournal
dspace.entity.typePublication
oaire.citation.volume13
person.affiliation.cityChennai
person.affiliation.cityChennai
person.affiliation.cityNew Delhi
person.affiliation.cityAllahabad
person.affiliation.id60025757
person.affiliation.id60022800
person.affiliation.id60019199
person.affiliation.id128123871
person.affiliation.nameIndian Institute of Technology Madras
person.affiliation.nameCentral Leather Research Institute India
person.affiliation.nameCouncil of Scientific and Industrial Research India
person.affiliation.nameIndependent Researcher
person.identifier.scopus-author-id31967803200
person.identifier.scopus-author-id58275086900
person.identifier.scopus-author-id58079042900
person.identifier.scopus-author-id57961978700
person.identifier.scopus-author-id58078542600
person.identifier.scopus-author-id25226093200
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