Anti-inflammatory effects of three withanolides isolated from Physalis angulata L. in LPS-activated RAW 264.7 cells through blocking NF-κB signaling pathway.

Ethnopharmacological Relevance: Physalis angulata L. is commonly used in many countries as popular medicine for the treatment of a variety of diseases such as malaria, hepatitis, dermatitis and rheumatism. But the anti-inflammatory active constituents of this medicinal plant and their molecular mechanism are still not elucidated clearly.
Aim of the Study: The aim of the study is to isolate and identify a series of compounds from the ethanolic extract of Physalis angulata L., and to investigate the anti-inflammatory activities in vitro and the molecular mechanism of physagulin A, physagulin C, and physagulin H.
Materials and Methods: In order to further understand the anti-inflammatory mechanism of the three compounds, their potential anti-inflammatory activities were investigated in vitro in LPS-activated RAW 264.7 macrophage cells by Griess assay, ELISA, Western blot and immunofluorescence methods in the present study.
Results: Physagulin A, physagulin C, and physagulin H could not only inhibit the release of NO, PGE ₂ , IL-6 and TNF-α, but also could down-regulate the expression of iNOS and COX-2 proteins. Furthermore, physagulin A, physagulin C, and physagulin H could remarkably block the degradation of IκB-α and the nuclear translocation of NF-κB/p65 in LPS-activated RAW 264.7 cells. However, none of them could inhibit the phosphorylation of MAPKs family proteins ERK, JNK and p38. Thus, the anti-inflammatory actions of physagulin A, physagulin C, and physagulin H were mainly due to the significant inhibition of NF-κB signaling pathway rather than MAPKs signaling pathway.
Conclusions: All the results clearly showed that physagulin A, physagulin C, and physagulin H demonstrated potent anti-inflammatory activity and can be used as novel NF-κB inhibitors. They are potential to be developed as an alternative or complementary agents for inflammatory diseases.
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