Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model

Abstract

BackgroundAtopic dermatitis (AD) is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP) has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO), a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway.ObjectiveTo explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model.MethodsWe utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD.ResultsANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin.ConclusionTaken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP.

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

“…Besides, it can also decrease thymic stromal lymphopoietin (TSLP) in skin lesions. Further study showed that andrographolide suppressed the RIP2/Caspase‐1/NF‐κB pathway, thereby blocking TSLP levels in HMC‐1 cell lines 191 …”

“…Further study showed that andrographolide suppressed the RIP2/Caspase-1/NF-κB pathway, thereby blocking TSLP levels in HMC-1 cell lines. 191 Exposure of skin to ultraviolet (UV) radiation gives rise to skin oxidative stress and inflammation, as well as consequent premature aging. 192 In a UV-induced skin photoaging mouse model, andrographolide was found to resist skin thickness, wrinkles, loss of elasticity, and loss of water content, presumably by reducing oxidative stress and inflammatory responses.…”

Andrographolide, a natural anti-inflammatory agent: An Update

“…In a murine model of malaria infection, andrographolide significantly decreased the levels of proinflammatory cytokine IFN-γ and improved the levels of anti-inflammatory cytokines IL-10 and IL-4, and the mechanism may have partly involved the regulation of serine/threonine kinase and GSK3β and inhibition of the NF-κB pathway ( Hassan et al, 2019 ). In mast cells and mice with atopic dermatitis, andrographolide can inhibit the expression of thymic interstitial lymphopoietin by inhibiting Caspase-1/RIP2/NF-κB activity and inhibit the inflammatory response to treat idiopathic dermatitis ( Li et al, 2016 ). In imiquimod-induced mouse psoriasis, andrographolide inhibited the generation of proinflammatory cytokines such as IL-23 and IL-1b and induced the autophagic proteolysis of MyD88, which controlled MyD88-dependent cytokine activation and alleviated psoriasis ( Shao et al, 2016 ).…”