Hispidin

Anticancer activity of hispidin via reactive oxygen species-mediated apoptosis in colon cancer cells.[Pubmed:25075033]

Anticancer Res. 2014 Aug;34(8):4087-93.

Few studies have been performed on the anticancer activity of Hispidin, a phenolic compound produced from the medicinal mushroom Phellinus linteus. Herein, we studied Hispidin-induced apoptosis, which is associated with the generation of reactive oxygen species (ROS) in colon cancer cells. Hispidin was found to reduce cell viability both in mouse and human colon cancer cells. Apoptotic cell morphological changes were observed by microscopy, and apoptosis was assessed in Hispidin-treated cells using a biochemical method. The results showed accumulation of the sub-G1 cell population and increase in early apoptosis in a dose-dependent manner. In addition, Hispidin induced apoptosis through up-regulation of both intrinsic and extrinsic apoptotic pathways. Although the molecular mechanism underlying Hispidin-induced apoptosis is known to involve the generation of ROS, however Hispidin did not show any apoptosis in the pre-treatment with a ROS scavenger, N-acetyl-L-cysteine. In conclusion, Hispidin induces both intrinsic and extrinsic apoptotic pathways mediated by ROS in colon cancer cells, thereby suggesting that Hispidin could be a promising new anticancer agent.

Anti-inflammatory activity of mushroom-derived hispidin through blocking of NF-kappaB activation.[Pubmed:25355452]

J Sci Food Agric. 2015 Sep;95(12):2482-6.

BACKGROUND: Hispidin, a polyphenol compound mainly derived from the valuable medicinal mushroom Phellinus species, has been found to possess distinct biological effects. However, the anti-inflammatory potential of Hispidin still remains uncharacterized. RESULTS: In this study, the effects of Hispidin on activation of nuclear factor kappa B (NF-kappaB) and the subsequent production of inducible nitric oxide synthase (iNOS) were determined in the lipopolysaccharide (LPS)-induced macrophage RAW 264.7 cells. Our data indicated that Hispidin inhibits transcriptional activity of NF-kappaB in a dose-dependent manner. Hispidin also attenuated LPS-induced NF-kappaB nuclear translocation and associated inhibitor of kappa B (IkappaB-alpha) degradation. Furthermore, Hispidin deceased iNOS protein expression and the generation of reactive oxygen species (ROS) in the LPS-induced cells, but did not affect phosphorylation of mitogen-activated protein kinases. CONCLUSION: These findings suggest that Hispidin exhibits anti-inflammatory activity through suppressing ROS mediated NF-kappaB pathway in mouse macrophage cells.

Hispidin derived from Phellinus linteus affords protection against acrylamide-induced oxidative stress in Caco-2 cells.[Pubmed:24877638]

Chem Biol Interact. 2014 Aug 5;219:83-9.

Acrylamide (AA), a well-known toxicant, has attracted numerous attentions for its presumably carcinogenesis, neurotoxicity and cytotoxicity. Oxidative stress was considered to be associated with acrylamide cytotoxicity, but the link between oxidative stress and acrylamide cytotoxicity is still unclear. In the present study, Hispidin produced from the edible fungus Phellinus linteus displayed dramatically antioxidant activities against DPPH radicals, ABTS radicals, ferric reducing and hydroxyl radicals, as well as superoxide anion radicals. Moreover, the cytoprotective effect of Hispidin against AA-induced oxidative stress was verified upon Caco-2 cells according to evaluate the cell viability, intracellular ROS, mitochondrial membrane potential (MMP) and glutathione (GSH) in the presence or absence of AA (5 mM) in a dose-dependent manner. Collectively, our results demonstrated for the first time that Hispidin was able to inhibit AA-induced oxidative stress, which might have implication for the dietary preventive application.

Cytoprotective effect of hispidin against palmitate-induced lipotoxicity in C2C12 myotubes.[Pubmed:25826786]

Molecules. 2015 Mar 27;20(4):5456-67.

It is well known that Phellinus linteus, which produces Hispidin and its derivatives, possesses antioxidant activities. In this study, we investigated whether Hispidin has protective effects on palmitate-induced oxidative stress in C2C12 skeletal muscle cells. Our results showed that palmitate treatment in C2C12 myotubes increased ROS generation and cell death as compared with the control. However, pretreatment of Hispidin for 8 h improved the survival of C2C12 myotubes against palmitate-induced oxidative stress via inhibition of intracellular ROS production. Hispidin also inhibited palmitate-induced apoptotic nuclear condensation in C2C12 myotubes. In addition, we found that Hispidin can suppress cleavage of caspase-3, expression of Bax, and NF-kappaB translocation. Therefore, these results suggest that Hispidin is capable of protecting C2C12 myotubes against palmitate-induced oxidative stress.

The protective effect of hispidin against hydrogen peroxide-induced apoptosis in H9c2 cardiomyoblast cells through Akt/GSK-3beta and ERK1/2 signaling pathway.[Pubmed:25128810]

Exp Cell Res. 2014 Oct 1;327(2):264-75.

Hispidin, a phenolic compound from Phellinus linteus (a medicinal mushroom), has been shown to possess strong anti-oxidant, anti-cancer, anti-diabetic, and anti-dementia properties. However, the cardioprotective efficacy of Hispidin has not yet been investigated. In the present study, we investigated the protective effect of Hispidin against oxidative stress-induced apoptosis in H9c2 cardiomyoblast cells and neonatal rat ventricular myocytes. While the treatment of H9c2 cardiomyoblast cells with hydrogen peroxide caused a loss of cell viability and an increase in the number of apoptotic cells, Hispidin significantly protected the cells against hydrogen peroxide-induced cell death without any cytotoxicity as determined by XTT assay, LDH release assay, Hoechst 33342 assay, and Western blotting of apoptosis proteins such as caspase-3, Bax, and Bcl-2. Our data also shows that Hispidin significantly scavenged intracellular ROS, and markedly enhanced the expression of antioxidant enzymes such as heme oxygenase-1 and catalase, which was accompanied by the concomitant activation of Akt/GSK-3beta and ERK1/2 phosphorylation in H9c2 cardiomyoblast cells. The effects of Hispidin on Akt and ERK phosphorylation were abrogated by LY294002 (a PI3K/Akt inhibitor) and U0126 (an ERK1/2 inhibitor). The effect of Hispidin on GSK-3b activities was also blocked by LY294002. Furthermore, inhibiting the Akt/GSK-3beta and ERK1/2 pathway by these inhibitors significantly reversed the Hispidin-induced Bax and Bcl-2 expression, apoptosis induction, and ROS production. These findings indicate that Hispidin protects against apoptosis in H9c2 cardiomyoblast cells exposed to hydrogen peroxide through reducing intracellular ROS production, regulating apoptosis-related proteins, and the activation of the Akt/GSK-3beta and ERK1/2 signaling pathways.