Anti-Inflammatory Activity of Diterpenoids fromCelastrus orbiculatusin 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 μM, respectively) on lipopolysaccharide- (LPS-) stimulated NO releases as well as proinflammatory mediators, such as inducible nitric oxide (iNOS), cyclooxygenase- (COX-) 2, interleukin- (IL-) 1β, IL-6, and tumor necrosis factor- (TNF-) α. Its inhibitory activity of proinflammatory mediators is contributed by suppressing the activation of nuclear transcription factor- (NF-) κB and mitogen-activated protein kinase (MAPK) signaling cascades including p65, inhibition of NF-κB (IκB), 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.

Effect of Celastrus Orbiculatus Extract on proliferation and apoptosis of human Burkitt lymphoma cells

“…Additionally, COE promotes apoptosis by regulating cell proliferation, migration, invasion, apoptosis, autophagy, and cycle distribution. These findings suggest that COE may be a potential therapeutic agent for the treatment of various cancers ( Qian et al, 2012 ; Zhang et al, 2012 ; Li et al, 2014 ; Yang et al, 2016 ; Wang et al, 2017a ; Wang et al, 2018 ; Jang et al, 2020 ). In this study, we demonstrated that COE could also interfere with Burkitt lymphoma cells and inhibit their proliferation.…”

A Comprehensive Review of the Classification, Sources, Phytochemistry, and Pharmacology of Norditerpenes

“…Compounds 494 – 496 and 500 demonstrated moderate inhibitory activities against NF-κB activation in RAW264.7 macrophages, with IC 50 values of 15, 25, 19, and 4 μM, respectively [ 149 , 150 , 151 ]. Compound 8 was the most effective compound in inhibiting LPS-induced nitric oxide (NO) production (IC 50 = 3.56 μM) in T. orientalis .…”

Anti-Inflammatory Activity of Extracts and Pure Compounds Derived from Plants via Modulation of Signaling Pathways, Especially PI3K/AKT in Macrophages

“…The NF-κB pathway and additionally ERK1/2 and JNK were inhibited by Aster incisus [ 109 ] and Fructus sophorae [ 110 ] extracts; ERK1/2 and p38 were attenuated by Hibiscus syriacus [ 111 ] and Rodgersia podophylla [ 112 ] extracts; JNK and p38 were decreased by Populus deltoides [ 113 ] and Xanthii fructus [ 114 ] extracts in macrophage cell lines. Furthermore, deoxynimbidiol and trinorditerpenoid, diterpenoids from Celastrus orbiculatus [ 115 ], torilin, a sesquiterpene obtained from Torilis japonica [ 96 ], shikonofuran E, a phenolic compound isolated from Onosma paniculatum [ 116 ], scandoside, an iridoid from Hedyotis diffusa [ 117 ], bellidifolin, a xanthone from Swertia chirayita [ 118 ], 1-carbomethoxy-β-carboline, an alkaloid from Portulaca oleracea [ 119 ] and strictosamide, an alkaloid from Nauclea officinalis [ 120 ] inhibited both NF-κB and MAPK signaling ( Figure 3 ).…”