Celastrus orbiculatus Thunb. Decreases Athero‐Susceptibility in Lipoproteins and the Aorta of Guinea Pigs Fed High Fat Diet

Abstract

Celastrus orbiculatus Thunb. (COT), a traditional Chinese herb, has anti-inflammatory and anti-oxidative properties. In this study, we examined the protective effect of COT on the initiation of atherosclerosis induced by high fat diet and explored the underlying mechanisms. We established guinea pig models of hyperlipidemia and treated them with three dosages of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. Plasma lipid analysis indicated that COT decreased total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B100 (apoB100) and apolipoprotein E (apoE) levels and increased high density lipoprotein cholesterol (HDL-C) level. The analysis of the hepatic gene involving cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of LDL receptor (LDL-R), scavenger receptor class B type 1 (SR-B1), cholesterol 7α-hydroxylase A1 (CYP7A1) and the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Oil red O staining showed COT significantly reduced lipid deposition in the arterial wall. Moreover, ELISA assay revealed COT lowered the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in plasma. Meanwhile, the level of Nitric oxide (NO) in plasma was increased by COT. Immunohistochemistry and Western blot analysis showed the expression of CD68 and active NF-kB p65 proteins in the arterial wall was decreased by COT. The content of Malondialdehyde (MDA) and activity of Superoxide dismutase (SOD) in plasma were determined and the data indicated COT suppressed oxidative stress reaction. These results reveal that administration of COT decreases athero-susceptibility through lowering plasma lipid, attenuating inflammation, and suppressing oxidative stress in guinea pig fed high fat diet.

Chinese Herbal Compounds for the Prevention and Treatment of Atherosclerosis: Experimental Evidence and Mechanisms

“…Zhang et al [ 54 ] using a plasma lipid analysis approach found Celastrus orbiculatus Thunb Extract (COT), a compound derived from the Chinese herb Celastrus orbiculatus Thunb , to decrease total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B100 (apoB100), and apolipoprotein E (apoE) levels and to increase the level of HDL cholesterol (HDL-C). Quantitative real-time PCR revealed that COT upregulated the mRNA abundance of LDL receptor (LDL-R), scavenger receptor class B type 1 (SR-B1), cholesterol 7 α -hydroxylase A1 (CYP7A1), and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) [ 54 ]. Choi et al reported that extract from the herb Cynanchum wilfordii treatment in HFCD-fed rats lessened LDL cholesterol and triglyceride levels and elevated HDL cholesterol [ 40 ].…”

“…Recently, the research of Napagoda et al indicated that the ethnopharmacological use of Plectranthus zeylanicus extract constituted an anti-inflammatory remedy [ 101 ]. Zhang et al found that Celastrus orbiculatus Thunb (COT) lowered the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and TNF- α in plasma [ 54 ]. Wang et al discovered that Artemisinin , a compound derived from the Chinese herb Artemisia annua , inhibited the secretion and mRNA levels of TNF- α , interleukin (IL)-1 β , and IL-6 in a dose-dependent manner in THP-1 human monocytes.…”

Anti-Inflammatory Activity of Diterpenoids fromCelastrus orbiculatusin Lipopolysaccharide-Stimulated RAW264.7 Cells

“…NO assay was carried out for measurements of NO release using a previously reported method [34]. Briefly, RAW264.7 cells were plated at 1 × 10 5 cell density in 96-well microplate and cultured for 24 h. Compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) were pretreated with increasing dose concentrations (0.5, 1, 5, 10, 25, 50, and 100 μM) and then stimulated with LPS (1 μg/mL, Sigma-Aldrich, St. Louis, MO, USA) for 18 h. The mixture of cell supernatant (100 μL) and Griess reagent (1% sulfanilamide +0.1% N-(1-naphthyl)ethylenediamine (Sigma-Aldrich, St. Louis, MO, USA)) in 5% phosphoric acid was recorded at 550 nm using a microplate reader (Varioskan LUX, Thermo Fisher Scientific Inc., Waltham, MA, USA). The percentage inhibition and logarithmic concentrations were presented as a graph using GraphPad Prism 5 ( Fig.…”

“…C. orbiculatus has been traditionally prescribed as a herbal remedy for bacterial infection, insecticidal, and rheumatoid arthritis [3,4]. Previous pharmacological studies has shown that these extracts containing diverse phytochemical components such as sesquiterpenoids, diterpenoids, tri-terpenoids, alkaloids, flavonoids, and phenolic compounds [5][6][7][8][9][10] exhibit various biological activity such as antitumor [11][12][13][14], antioxidant [9], antinociceptive [15], antiatherosclerosis [16], neuroprotective [17], and anti-inflammatory [18] effects. Although a variety of biological activities of C. orbiculatus extracts reported in the literatures, whether any phytochemical component contributes to their biological mechanisms other than celastrol, which is the main triterpenoid compound of C. orbiculatus [19,20], has been discussed limitedly so far.…”

“…In current study, the chemical structures of phytochemical constituents (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) isolated from C. orbiculatus were determined by spectroscopic data including NMR and ESI-MS. Among components obtained from C. orbiculatus, compounds 1 and 3, both of which are podocarpane trinorditerpenoids, exhibited most potent inhibitory activity against LPS-treated NO release, and their anti-inflammatory activity was explored through underlying molecular mechanisms including NF-κB and MAPK signaling pathway.…”