Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry.

For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at multiple stages have yet to be explored. Thus, this study systematically identifies and assesses the inhibitory effect of GKPL on the SARS-CoV-2 virus. Initially, the concentrations and contact times of GKPL against SARS-CoV-2 pseudovirus were assessed in HepG2 cells. Subsequently, utilizing the Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry method, potential biomarkers in the fungal extract were discerned. Metabolomic analysis identified 18 compounds in GKPL, with hispidin and hypholomine B present in the highest amounts. These compounds were isolated using chromatographic techniques and further identified through 1D NMR spectroscopic and mass spectrometry analysis. Hispidin and hypholomine B were found to inhibit the infection of SARS-CoV-2 pseudovirus by reducing angiotensin-converting enzyme 2 gene expression in HepG2, thereby decreasing viral entry. Moreover, hispidin and hypholomine B effectively block the spike receptor-binding domain, while hypholomine B, for the first time, showed significant inhibition of 3CL protease. This suggests that GKPL, enriched with hispidin and hypholomine B, has the potential to be used as an active ingredient against SARS-CoV-2.

Lactobacillus plantarum GKM3 and Lactobacillus paracasei GKS6 Supplementation Ameliorates Bone Loss in Ovariectomized Mice by Promoting Osteoblast Differentiation and Inhibiting Osteoclast Formation.

Osteoporosis, an imbalance in the bone-forming process mediated by osteoblasts and the bone-resorbing function mediated by osteoclasts, is a bone degenerative disease prevalent among the aged population. Due to deleterious side effects of currently available medications, probiotics as a potential treatment of osteoporosis is an appealing approach. Hence, this study aims to evaluate the beneficial effects of two novel Lactobacilli strain probiotics on bone health in ovariectomized (OVX) induced osteoporotic mice model and its underlying mechanisms. Forty-five 9-week-old Institute of Cancer Research (ICR) mice underwent either a sham-operation (n = 9) or OVX (n = 36). Four days after the operation, OVX mice were further divided into four groups and received either saline alone, Lactobacillus plantarum GKM3, Lactobacillus paracasei GKS6 or alendronate per day for 28 days. After sacrifice by decapitation, right distal femur diaphysis was imaged via micro-computed tomography (MCT) and parameters including bone volume/tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), and bone mineral density (BMD) were measured. Moreover, GKM3 and GKS6 on RANKL-induced osteoclast formation and osteoblast differentiation using in vitro cultures were also investigated. The results showed that both probiotics strains inhibited osteoporosis in the OVX mice model, with L. paracasei GKS6 outperforming L. plantarum GKM3. Besides this, both GKS6 and GKM3 promoted osteoblast differentiation and inhibited RANKL-induced osteoclast differentiation via the Bone Morphogenetic Proteins (BMP) and RANKL pathways, respectively. These findings suggested that both strains of Lactobacilli may be pursued as potential candidates for the treatment and management of osteoporosis, particularly in postmenopausal osteoporosis.

Thirteen-Week Oral Toxicity Evaluation of Erinacine AEnriched Lion's Mane Medicinal Mushroom, Hericium erinaceus (Agaricomycetes), Mycelia in Sprague-Dawley Rats.

Recently, erinacine A-enriched Hericium erinaceus (EAHE) mycelia have demonstrated therapeutic efficacy in animal models of neurodegenerative disease, including Alzheimer and Parkinson disease. Despite promising results from animal models, there have been no reports on its toxicity after long-term consumption. Hence, the present study was designed to evaluate the safety of EAHE mycelia through a 13-week subchronic rodent feeding study. Following 13 weeks of EAHE mycelia feeding at dosages of 0, 875, 1750, and 2625 mg/kg body weight in both male and female Sprague-Dawley rats, findings revealed neither any mortalities nor noticeable toxicological effects in all the rats during the investigation period. Physiological parameters including body weight and feed consumption patterns were unaffected by EAHE mycelia administration. The hematological and biochemical parameters as well as histopathological studies revealed no significant differences between the treatment and control groups. Conclusively, the obtained results suggested that EAHE mycelia could be relatively unharmful when used over an extended period, supporting its safe use in food preparation.

Effects of Deinococcus spp. supplement on egg quality traits in laying hens.

To counter the ill effects of synthetic dyes, bacterial pigment production as an alternative is now one of the promising and emerging fields of research. This study was conducted to evaluate the applicability of Deinococcus genus on the egg quality traits in laying hens. In study I, 24 single comb White Leghorn layers were fed with various 1 wt % Deinococcus bacterial strains for 10 d. In study II, 84 brown Hendrix layers were fed with one of 4 diets containing 0, 0.2, 1, or 5 wt % Deinococcus sp. GKB-Aid 1995 powder for 12 wk. In study III, 60 White Leghorn laying hens were fed either with or without 1 wt % Deinococcus sp. GKB-Aid 1995 powder, 1 wt % Deinococcus sp. GKB-Aid 1995 granules, or 1 wt % Deinococcus sp. GKB-Aid 1995 oily granules for 10 successive d. In all of the experiments, feeding Deinococcus powder did not affect egg quality traits except for the yolk color. In particular, supplementation with all Deinococcus powder treatments changed the yolk color (P < 0.05) in study I, with the best pigmentation score obtained by D. grandis and Deinococcus sp. GKB-Aid 1995. Moreover, longer supplementation of Deinococcus sp. GKB-Aid 1995 in study II had a significant effect on feed conversion ratio. With these findings under consideration, the present study suggests that the Deinococcus species, especially Deinococcus sp. GKB-Aid 1995, can be an excellent candidate for improving egg yolk color in laying hens.

Characterization and safety evaluation of a Deinococcus member as feed additive for hens.

As previous studies mainly focus on understanding the mechanisms of radioresistance in Deinococcus bacteria, the present study aimed at characterizing and verifying the safety use of the GKB-Aid 1995 strain, a member of the radiation-resistant bacterial genus Deinococcus, as an ingredient in feed supplements. Using Vitek 2 system and 16S rRNA gene sequencing, GKB-Aid 1995 most resembles Deinococcus grandis. The Ames test, in vitro chromosomal test, in vivo micronucleus test and acute toxicity test were performed subsequently for its safety evaluation. As there is a possibility that the pigment of GKB-Aid 1995 can pass from feed to eggs intended for human consumption, an acute toxicity test was also carried out in pigmented egg yolk. The results confirmed that GKB-Aid 1995 was non-genotoxic in three genotoxicity experiments, and the LD50 of GKB-Aid 1995 and the pigmented egg yolk in ICR mice was greater than 10 and 12 g kg(-1) body weight, respectively. Overall, these data indicate that GKB-Aid 1995 is a non-toxic substance with no genotoxicity and is therefore safe to be used as a feed supplement or feed additive. This study suggests there is potential in developing GKB-Aid 1995 as an animal feed additive intended to enhance yolk coloration to meet the demand of consumers.

Genotoxicity profile of erinacine A-enriched Hericium erinaceus mycelium.

Hericium erinaceus (H. erinaceus) has a long history of usage in traditional Chinese medicine for the treatment of gastric disorders. Recently, it has become a well-established candidate in causing positive brain and nerve health-related activities by inducing nerve growth factor (NGF) from its bioactive ingredient, erinacine A. This active compound, which exists only in fermented mycelium but not in its fruiting body, increases NGF levels in astroglial cells in vitro as well as catecholamine and NGF levels in vivo. With increasing recognition of erinacine A in H. erinaceus (EAHE) mycelium improving neurodegenerative diseases, numerous products are being marketed based on these functional claims. To our knowledge, there have been no reports on the mutagenicity of EAHE prior to this paper. Hence, the present study was undertaken to determine the mutagenicity and genotoxicity effects of EAHE mycelium conducted in three standard battery of tests (reverse mutation, chromosomal aberration, and micronuclei tests) according to the latest guidelines in order to meet all international regulatory requirements and provide information on the safety of this new and promising natural remedy. Our results have indicated that EAHE mycelium did not significantly increase the number of revertant colonies in the bacterial reverse mutation test nor induce higher frequency of aberrations in the chromosome aberration test. Moreover, no statistically significant EAHE mycelium-related increase was observed in the incidence of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. In conclusion, the three standard battery of tests suggested that EAHE mycelium was devoid of mutagenicity and genotoxicity in the tested doses and experimental conditions.