Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Stromal cell-derived factor-1 (SDF-1) (CXC chemokine ligand-12)/CXC chemokine receptor 4 (CXCR4) is involved in the carcinogenesis of human gastric cancer, where it stimulates angiogenesis and favors metastasis of tumor cells to distant organs. In addition, resistin is suggested to be an important link between obesity and the development of gastric cancer. Resistin has identified as an important player in inflammatory responses, and emerged as a mediator in inflammation-associated cancer. A limited number of studies have investigated the association of resistin and SDF-1 with gastric cancer. Herein, we investigated the molecular mechanisms by which resistin influences the expression of SDF-1 in gastric carcinoma cells.

Background: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Methods: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Results: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. Conclusion: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

The C-reactive protein-to-albumin ratio is a proven prognostic predictor of nasopharyngeal carcinoma. However, the role of the C-reactive protein-to-albumin ratio in other head and neck cancers remains unclear. This meta-analysis explored the prognostic value of the C-reactive protein-to-albumin ratio in head and neck cancers. A systematic search was conducted. Outcomes of interest included overall survival, disease-free survival, and distant metastasis–free survival. The hazard ratio with 95% confidence interval was pooled using a random-effects model. A total of 11 publications from the literature were included, allowing for the analysis of 7080 participants. Data pooling demonstrated that pretreatment C-reactive protein-to-albumin ratio had a hazard ratio of 1.88 (95% CI: 1.49−2.37, p < 0.001) for predicting overall survival, 1.91 (95% CI: 1.18−3.08, p = 0.002) for disease-free survival, and 1.46 (95% CI: 1.08−1.96, p = 0.001) for distant metastasis–free survival. Subgroup analysis showed that the C-reactive protein-to-albumin ratio is a significant prognostic marker for various head and neck cancers. An elevated pretreatment C-reactive protein-to-albumin ratio predicts a worse prognosis for patients with head and neck cancers. Therefore, the C-reactive protein-to-albumin ratio could serve as a potential prognostic biomarker facilitating treatment stratification.

Erinacine S, the new bioactive diterpenoid compound isolated from the ethanol extract of the mycelia of Hericium erinaceus, displays great health-promoting properties. However, the effects of erinacine S on inductive apoptosis in cancer cells such as gastric cancer and its molecular mechanisms remain unclear. Our results demonstrated that erinacine S treatment significantly induces cell apoptosis with increased ROS production in gastric cancer cells, but not in normal cells. Significantly, erinacine S also showed its inhibitory effects on tumor growth in an in vivo xenograft mouse model. Furthermore, immunohistochemical analyses revealed that erinacine S treatment significantly increases the FasL and TRAIL protein, whereas it decreases the levels of PCNA and cyclin D1 in the gastric cancer xenograft mice. Consistently, in AGS cells, erinacine S treatment not only triggers the activation of extrinsic apoptosis pathways (TRAIL, Fas-L and caspase-8, -9, -3), but it also suppresses the expression of the anti-apoptotic molecules Bcl-2 and Bcl-XL in a time-dependent manner. In addition, erinacine S also causes cell cycle G1 arrest by the inactivation of CDKs/cyclins. Moreover, our data revealed that activation of the ROS-derived and AKT/FAK/PAK1 pathways is involved in the erinacine S-mediated transcriptional activation of Fas-L and TRAIL through H3K4 trimethylation on their promoters. Together, this study sheds light on the anticancer effects of erinacine S on gastric cancer and its molecular mechanism in vitro and in vivo.

CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino) phenyl]ethanone) is a major active agent of Camptotheca acuminata’s alkaloid derivative, and its anti-tumorigenic activity, a valuable biological property of the agent, has been reported in many types of cancer. In this study, we researched the novel CIL-102-induced protein for either the induction of cell apoptosis or the inhibition of cell migration/invasiveness in colorectal cancer cells (CRC) and their molecular mechanism. Firstly, our data showed that CIL-102 treatment not only increased the cytotoxicity of cells and the production of Reactive Oxygen Species (ROS), but it also decreased cell migration and invasiveness in DLD-1 cells. In addition, many cellular death-related proteins (cleavage caspase 9, cleavage caspase 3, Bcl-2, and TNFR1 and TRAIL) and JNK MAPK/p300 pathways were increased in a time-dependent manner. Using the proteomic approach with a MALDI-TOF-TOF analysis, CIL-102-regulated differentially expressed proteins were identified, including eight downregulated and 11 upregulated proteins. Among them, upregulated Endoplasmic Reticulum resident Protein 29 (ERP29) and Fumarate Hydratase (FUMH) by CIL-102 were blocked by the inhibition of ROS production, JNK activity, and p300/CBP (CREB binding protein) signaling pathways. Importantly, the knockdown of ERP29 and FUMH expression by shRNA abolished the inhibition of cell migration and invasion by CIL-102 in DLD-1 cells. Together, our findings demonstrate that ERP29 and FUMH were upregulated by CIL102 via ROS production, JNK activity, and p300/CBP pathways, and that they were involved in the inhibition of the aggressive status of colorectal cancer cells.