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Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways.

ABSTRACT: Psoriasis is a chronic inflammatory skin disease that affects approximately 2% of worldwide population, and causing long-term troubles to the patients. Therefore, it is urgent to develop safe and effective therapeutic drugs. Catalpol is a natural iridoid glucoside, that has several remarkable pharmacological effects, however, whether catalpol can alleviated psoriasis has not been explored. The goal of the present work is to study the role of catalpol in psoriasis in vivo and in vitro. Imiquimod-induced psoriasis-like mice were applied with different concentrations of catalpol for 8 consecutive days. The severity degree of psoriasis was estimated and the skin pathological changes were detected by H&E staining. Also, TNF-α-stimulated keratinocytes were treated with different concentrations of catalpol, then the oxidative stress and inflammation factors, as well as the expression of SIRT1 and activation of NF-kB and MAPK pathways were measured. The results showed that catalpol reduced the erythema, scaling, ear thickness, and changed pathological phenotypes in the lesioned skin region in mice. Treatment with catalpol significantly suppressed the oxidative stress and inflammatory reactions in vivo and in vitro, as reflected by the decreased secretion or expression of oxidative stress indicators and proinflammatory factors. Furthermore, the SIRT1 was up-regulated and the NF-κB and MAPKs signaling pathways were suppressed by the treatment of catalpol in vivo and in vitro. In summary, our data suggested that catalpol may have a therapeutic property of psoriasis by ameliorating oxidative stress and inflammation partly through SIRT1 mediated suppression of NF-κB and MAPKs pathways. Abbreviation: CAT: catalase; ELISA: enzyme-linked immunosorbent assay; GSH: glutathione; HRP: horseradish peroxidase; IMQ: imiquimod; JNK: c-Jun NH 2-terminal kinases; MAPKs: mitogen-activated protein kinases; MDA: malondialdehyde; NC: negative control group; NF-kB: nuclear factor kappa B; PASI: psoriasis area and severity index; PVDF: polyvinylidene difluoride membranes; qRT-PCR: quantitative real time polymerase chain reaction; ROS: reactive oxygen species; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SIRT1: silent information regulator 1; SOD: Cu/Zn superoxide dismutase.

SUBMITTER: Liu A

PROVIDER: S-EPMC8806253 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo investigate the role and regulatory mechanisms of fargesin, one of the main components of Magnolia fargesii, in macrophage reprogramming and crosstalk across cartilage and synovium during osteoarthritis (OA) development.MethodsTen-week-old male C57BL/6 mice were randomized and assigned to vehicle, collagenase-induced OA (CIOA), or CIOA with intra-articular fargesin treatment groups. Articular cartilage degeneration was evaluated using the Osteoarthritis Research Society International (OARSI) score. Immunostaining and western blot analyses were conducted to detect relative protein. Raw264.7 cells were treated with LPS or IL-4 to investigate the role of polarized macrophages. ADTC5 cells were treated with IL-1β and conditioned medium was collected to investigate the crosstalk between chondrocytes and macrophages.ResultsFargesin attenuated articular cartilage degeneration and synovitis, resulting in substantially lower Osteoarthritis Research Society International (OARSI) and synovitis scores. In particular, significantly increased M2 polarization and decreased M1 polarization in synovial macrophages were found in fargesin-treated CIOA mice compared to controls. This was accompanied by downregulation of IL-6 and IL-1β and upregulation of IL-10 in serum. Conditioned medium (CM) from M1 macrophages treated with fargesin reduced the expression of matrix metalloproteinase-13, RUNX2, and type X collagen and increased Col2a1 and SOX9 in OA chondrocytes, but fargesin alone did not affect chondrocyte catabolic processes. Moreover, fargesin exerted protective effects by suppressing p38/ERK MAPK and p65/NF-κB signaling.ConclusionsThis study showed that fargesin switched the polarized phenotypes of macrophages from M1 to M2 subtypes and prevented cartilage degeneration partially by downregulating p38/ERK MAPK and p65/NF-κB signaling. Targeting macrophage reprogramming or blocking the crosstalk between macrophages and chondrocytes in early OA may be an effective preventive strategy.

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Catalpol ameliorates psoriasis-like phenotypes via SIRT1 mediated suppression of NF-κB and MAPKs signaling pathways.

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