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Anti-Inflammatory Activity of Diterpenoids from Celastrus orbiculatus in Lipopolysaccharide-Stimulated RAW264.7 Cells.

ABSTRACT: Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C. orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1-17, including undescribed podocarpane-type trinorditerpenoid (3), were purified from C. orbiculatus and their chemical structure were determined by high-resolution electrospray ionization mass (HRESIMS) and nuclear magnetic resonance (NMR) spectroscopic data. To investigate the anti-inflammatory activity of compounds 1-17, nitric oxide (NO) secretion was evaluated in LPS-treated murine macrophages, RAW264.7 cells. Among compounds 1-17, deoxynimbidiol (1) and new trinorditerpenoid (3) showed the most potent inhibitory effects (IC50: 4.9 and 12.6??M, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1?, IL-6, and tumor necrosis factor- (TNF-) ?. Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) ?B and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-?B (I?B), extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), and p38. Therefore, these results demonstrated that diterpenoids 1 and 3 obtained from C. orbiculatus may be considered a potential candidate for the treatment of inflammatory diseases.

SUBMITTER: Jang HJ

PROVIDER: S-EPMC7414338 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Anti-Inflammatory Activity of Diterpenoids from Celastrus orbiculatus in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Jang Hyun-Jae HJ Kim Kang-Hoon KH Park Eun-Jae EJ Kang Jeong A JA Yun Bong-Sik BS Lee Seung-Jae SJ Park Chan Sun CS Lee Soyoung S Lee Seung Woong SW Rho Mun-Chual MC

Journal of immunology research 20200730

Celastrus orbiculatus Thunb has been known as an ethnopharmacological medicinal plant for antitumor, anti-inflammatory, and analgesic effects. Although various pharmacological studies of C. orbiculatus extract has been reported, an anti-inflammatory mechanism study of their phytochemical constituents has not been fully elucidated. In this study, compounds 1-17, including undescribed podocarpane-type trinorditerpenoid (3), were purified from C. ...[more]

PMID: 32802895

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Project description:Background and purposeMushrooms are popular both as food and as a source of natural compounds of biopharmaceutical interest. Some mushroom-derived compounds such as beta-glucan have been shown to be immunostimulatory; this study explores the anti-inflammatory properties of hispidin analogues derived from the mushroom, Inonotus xeranticus. We sought to identify the molecular mechanism of action of these hispidin analogues by determining their effects on lipopolysaccharide (LPS)-mediated inflammatory responses in a macrophage cell line.Experimental approachThe production of inflammatory mediators was determined by Griess assay, reverse transcription-PCR and ELISA. The inhibitory effect of davalliactone on LPS-induced activation of signalling cascades was assessed by western blotting, immunoprecipitation and direct kinase assay.Key resultsIn activated RAW264.7 cells, davallialactone strongly downregulated LPS-mediated inflammatory responses, including NO production, prostaglandin E2 release, expression of proinflammatory cytokine genes and cell surface expression of co-stimulatory molecules. Davallialactone treatment did not alter cell viability or morphology. Davallialactone was found to exert its anti-inflammatory effects by inhibiting a signalling cascade that activates nuclear factor kappa B via PI3K, Akt and IKK, but not mitogen-activated protein kinases. Treatment with davallialactone affected the phosphorylation of these signalling proteins, but not their level of expression. These inhibitory effects were not due to the interruption of toll-like receptor 4 binding to CD14. In particular, davallialactone strongly inhibited the LPS-induced phosphorylation and kinase activity of Src, implying that Src may be a potential pharmacological target of davallialactone.Conclusions and implicationsOur data suggest that davallialactone, a small molecule found in edible mushrooms, has anti-inflammatory activity. Davallialactone can be developed as a pharmaceutically valuable anti-Src kinase agent.

Dataset Information

Anti-Inflammatory Activity of Diterpenoids from Celastrus orbiculatus in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Publications

Anti-Inflammatory Activity of Diterpenoids from <i>Celastrus orbiculatus</i> in Lipopolysaccharide-Stimulated RAW264.7 Cells.

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