Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis

Huang, Chi‐Chang; Lin, Kun-Ju; Cheng, Ya‐Wen; Hsu, Chih‐An; Yang, Sien–Sing; Shyur, Lie‐Fen

doi:10.1016/j.jnutbio.2012.01.013

Cited by 51 publications

(38 citation statements)

References 37 publications

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“…Deoxyelephantopin (DOE), a sesquiterpne lactone from Elephantopus scaber , exerts many beneficial effects including hepatoprotective, 13 antiprotozoal, 14 and wound healing 15 . DOE has been reported to have anticancer effect 16, 17, 18, 19, 20.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Kabeer

Rajalekshmi

Nair

et al. 2017

Integrative Medicine Research

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BackgroundDeoxyelephantopin (DOE) is a natural bioactive sesquiterpene lactone from Elephantopus scaber, a traditionally relevant herb in Chinese and Indian medicine. It has shown promising anticancer effects against a broad spectrum of cancers.MethodsWe examined the effect of DOE on growth, autophagy, apoptosis, cell cycle progression, metastasis, and various molecular signaling pathways in cancer cells, and endeavored to decipher the molecular mechanisms underlying its effect. The cytotoxicity of DOE was examined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) and colony formation assays. The antimetastatic potential of DOE was identified by wound closure, as well as invasion and migration assays. The expression of mRNAs and proteins related to cytotoxicity in cancer cells induced by DOE was investigated using reverse transcription-polymerase chain reaction, flow cytometry, and Western blot analysis.ResultsDOE showed significant cytotoxicity and induced apoptosis in cancer cells. DOE promoted the autophagy of HCT 116 and K562 cells. DOE arrested cell cycle progression in the G2/M phase. DOE treatment caused activation of caspase-8, -9, -3 and -7, reactive oxygen species production, and cleavage of cleavage of poly-ADP-ribose polymerase (PARP), the markers of apoptosis. Moreover, apoptosis induction was associated with mitochondrial permeability and endoplasmic reticulum stress. Treatment of cancer cells with DOE inhibited mitogen-activated protein kinases, nuclear factor-kappa B, phosphatidylinositol 3-kinase (PI3K/Akt), and β-catenin signaling. Furthermore, treatment of DOE increased the expression of p53, phospho-Jun amino-terminal kinases (p-JNK), and p-p38 and decreased the expression of phospho-signal transducer and activator of transcription 3 (p-STAT3) and phospho-mammalian target of rapamycin (p-mTOR) in cancer cells. DOE downregulated matrix metalloproteinase (MMP-2) and MMP-9, urokinase-type plasminogen activator (uPA), and urokinase-type plasminogen activator receptor (uPAR) mRNA levels in cancer cells.ConclusionThese findings concluded that DOE may be useful as a chemotherapeutic agent against cancer.

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Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Kabeer

Rajalekshmi

Nair

et al. 2017

Integrative Medicine Research

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“…Moreover, E. scaber was also reported as the source of a number of sesquiterpene lactones, such as compounds 4 and 5 , which have shown significant contribution to the anti-inflammatory activity of plants [50]. Some of the sesquiterpenes from the genus Elephantopus have demonstrated significant anti-inflammatory as well as hepatoprotective activities and are being considered as drug lead compounds [3]. Based on the above analysis, we hypothesize that Zhuang people use this plant to treat headaches, bronchitis, and hepatitis,due to its anti-inflammatory and antioxidant effects.…”

Section: Discussionmentioning

confidence: 99%

“…Previous bioactivity studies on E. scaber demonstrated that the extracts or compounds from this species have antibiosis, antivirus, and cytotoxicity activities [2]. The sesquiterpene lactones in particular have been explored for their anti-inflammatory and hepatoprotective activities [3], which partially proved the traditional knowledge of E. scaber .…”

Section: Introductionmentioning

confidence: 99%

Bioactivities of Compounds from Elephantopus scaber, an Ethnomedicinal Plant from Southwest China

Wang

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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Elephantopus scaber is an ethnomedicinal plant used by the Zhuang people in Southwest China to treat headaches, colds, diarrhea, hepatitis, and bronchitis. A new δ-truxinate derivative, ethyl, methyl 3,4,3′,4′-tetrahydroxy-δ-truxinate (1), was isolated from the ethyl acetate extract of the entire plant, along with 4 known compounds. The antioxidant activity of these 5 compounds was determined by ABTS radical scavenging assay. Compound 1 was also tested for its cytotoxicity effect against HepG2 by MTT assay (IC50 = 60 μM), and its potential anti-inflammatory, antibiotic, and antitumor bioactivities were predicted using target fishing method software.

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“…(2) Previous studies have demonstrated that expression of HO-1 is rapidly up-regulated in the liver after administration of GalN/LPS. (1) This represents an adaptive response to the oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

“…(2,5,6) Several studies have demonstrated that GalN/LPS challenge leads to increased NF-κB activation. (2,5,6) MAPK cascades also participate in many LPS-induced macrophage inflammatory processes, such as cell death, proliferation and inflammation. Although the involvement of the MAPK pathway in TNF-α regulation is firmly documented, the detailed mechanism is still unknown.…”

Section: Discussionmentioning

confidence: 99%

BRP, a polysaccharide fraction isolated from Boschniakia rossica, protects against galactosamine and lipopolysaccharide induced hepatic failure in mice

Ji-shu

Jin

Qiu

et al. 2014

J. Clin. Biochem. Nutr.

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The aim of this study was to investigate the hepatoprotective effect of BRP, a polysaccharide fraction isolated from Boschniakia rossica, against galactosamine and lipopolysaccharide induced fulminant hepatic failure. Mice were injected with a single dose of galactosamine/lipopolysaccharide with or without pretreatment of BRP. Results showed marked reduction of hepatic necrosis, serum marker enzymes and levels of tumor necrosis factor-α and interleukin-6 in BRP pretreated mice when compared with galactosamine/lipopolysaccharide-challenged mice. Mice pretreated with BRP decreased the activation of caspases-3 and caspase-8, and showed a reduced level of DNA fragmentation of liver cells. BRP also reduced hepatic lipid peroxidation, increased potential of hepatic antioxidative defense system, and reduced hepatic nitric oxide level which was elevated by galactosamine/lipopolysaccharide injection. Immunoblot analysis showed down-regulation of inducible nitric oxide synthase and cyclooxygenase-2 proteins of liver tissues in BRP pretreated group when compared with galactosamine/lipopolysaccharide-challenged group. Furthermore, treatment with galactosamine/lipopolysaccharide markedly increased toll-like receptor 4, nuclear level of nuclear factor-κB, and phosphorylation of both extracellular signal-regulated kinase and c-Jun N-terminal kinase in liver tissues. However, these increases were attenuated by pretreatment with BRP. The results suggest that BRP alleviates galactosamine/lipopolysaccharide-induced liver injury by enhancing antioxidative defense system, suppressing inflammatory responses and reducing apoptotic signaling.

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Hepatoprotective effect and mechanistic insights of deoxyelephantopin, a phyto-sesquiterpene lactone, against fulminant hepatitis

Cited by 51 publications

References 37 publications

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Molecular mechanisms of anticancer activity of deoxyelephantopin in cancer cells

Bioactivities of Compounds from Elephantopus scaber, an Ethnomedicinal Plant from Southwest China

BRP, a polysaccharide fraction isolated from Boschniakia rossica, protects against galactosamine and lipopolysaccharide induced hepatic failure in mice

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