Immunomodulatory Activities of Medicinal Mushroom<i>Grifola frondosa</i>Extract and Its Bioactive Constituent

Wu, Shu-Jing; Lu, Tzy-Ming; Lai, Min-Nan; Ng, Lean‐Teik

doi:10.1142/s0192415x13500109

Cited by 25 publications

(12 citation statements)

References 26 publications

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“…For example, G. lucidum extractions were reported to have hepatoprotective effects and induce apoptosis of HepG2 cells 23. EP is a natural product present in G. lucidum , which has been shown to regulate various biological processes including oxidation,12 inflammation,24 and tumor cell growth 25…”

Section: Discussionmentioning

confidence: 99%

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Tan¹,

Pan²,

Liu³

et al. 2017

OTT

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Ergosterol peroxide (EP), a sterol derived from medicinal mushrooms, has been reported to exert antitumor activity in several tumor types. However, the role of EP toward ovarian cancer cells has not been investigated. In this study, we analyzed the cytotoxicity of EP in various cell lines representing high-grade serous ovarian cancer and low-grade serous ovarian cancer, respectively. Although EP showed no significant inhibition of the viability of normal ovarian surface epithelial cells, it impaired the proliferation and invasion capacities of tumor cells in a dose-dependent manner. We further figured out key modulators involved in its antitumor effects by quantitative reverse transcription polymerase chain reaction, ELISA, and Western blot. The nuclear β-catenin was down-regulated upon EP treatment, subsequently reducing the Cyclin D1 and c-Myc expression levels. Meanwhile, the protein level of protein tyrosine phosphatase SHP2 was up-regulated in EP treated cells, whereas Src kinase activity was inhibited. Both activation of SHP2 phosphatase and inhibition of Src kinase decreased the phosphorylation level of transducer and activator of STAT3 protein, which was implicated in oncogenesis. On the other hand, EP remarkably inhibited the expression and secretion of VEGF-C, implying its involvement in counteracting tumor angiogenesis. Moreover, EP treatment showed comparable cytotoxic effect with β-catenin knock-down or STAT3 inhibition. Taken together, our results demonstrated that EP showed antitumor effects toward ovarian cancer cells through both β-catenin and STAT3 signaling pathways, making it a promising candidate for drug development.

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Section: Discussionmentioning

confidence: 99%

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Tan¹,

Pan²,

Liu³

et al. 2017

OTT

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“…Natural sterols such ergosterol peroxide significantly blocked MyD88 and VCAM-1 expression, and cytokine (IL-1β, IL-6 and TNF-α) production in LPS-stimulated cells. It also effectively inhibited NF-kB activation [62]. The possible activity of LSEE may be due to the presence of glucosinolates, flavonoids and natural sterols.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model

Raish

Ahmad

Alkharfy

et al. 2016

BMC Complement Altern Med

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BackgroundFulminant hepatic failure (FHF) is clinical syndrome with very poor prognosis and high mortality there is urgent need for the development of safe and non-toxic hepatoprotective agents for the adequate management of hepatitis. Hepatoprotective effect of the Lepidium sativum ethanolic extract (LSEE) was assessed by D-galactosamine-induced/lipopolysaccharide (400 mg/kg and 30 μg/kg) liver damage model in rats.MethodsHepatoprotective activity of LSEE (150 and 300 mg/kg) and silymarin on D-GalN/LPS induced FHF in rat was assessed using several liver function enzyme parameters. Antioxidant properties as antioxidant stress enzymes were assessed in hepatic Liver as well as mRNA expression of cytokines genes such as TNF-α, IL-6, and IL-10 and stress related genes iNOS and HO-1 were determined by RT-PCR. Protein expression of apoptotic genes were evaluated through western blot. MPO and NF-κB DNA-binding activity was analyzed by ELISA. The magnitude of hepatic impairment was investigated through histopathological evaluation.ResultsMarked amelioration of hepatic injuries by attenuation of serum and lipid peroxidation has been observed as comparable with silymarin (25 mg/kg p.o). D-GalN/LPS induced significant decrease in oxidative stress markers protein level, and albumin. LSEE significantly down-regulated the D-GalN/LPS induced pro-inflammatory cytokines TNFα and IL-6 mRNA expression in dose dependent fashion about 0.47 and 0.26 fold and up-regulates the IL-10 by 1.9 and 2.8 fold, respectively. While encourages hepatoprotective activity by down-regulating mRNA expression of iNOS and HO-1. MPO activity and NF-κB DNA-binding effect significantly increased and was mitigated by LSEE in a dose-dependent style as paralleled with silymarin.ConclusionOur data suggests that pretreatment of LSEE down regulates the caspase 3 and up-regulates the BCl2 protein expression. The above findings revealed that Lepidium sativum has significant hepatoprotective activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-016-1483-4) contains supplementary material, which is available to authorized users.

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“…The 5α,8α-endoperoxides belong to a group of oxidized sterols derivatives resulting from the addition of an oxygen to a 5,7-diene system in the molecule of the precursor sterol [6]. Ergosterol peroxide is the best-known representative of this class, displaying anti-inflammatory properties that are associated to its capacity to inhibit the production of pro-inflammatory mediators and the activation of nuclear factor kappa B (NF-κB) signaling pathway [7]. The cholesterol derivative 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) is another oxidized sterol that has been found in different species of sea hares [8,9], sea urchins, and cone snails [10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Pereira

Jiménez

et al. 2019

Marine Drugs

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Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.

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Immunomodulatory Activities of Medicinal MushroomGrifola frondosaExtract and Its Bioactive Constituent

Cited by 25 publications

References 26 publications

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Ergosterol peroxide inhibits ovarian cancer cell growth through multiple pathways

Hepatoprotective activity of Lepidium sativum seeds against D-galactosamine/lipopolysaccharide induced hepatotoxicity in animal model

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

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