Sleep disturbances have been the hallmark of the recent coronavirus disease 2019 pandemic. Studies have shown that once sleep is disrupted, it can lead to psychological and physical health issues which can, in turn, disrupt circadian rhythm and induce further sleep disruption. As consumers are trying to establish healthy routines, nutritional and preclinical safety investigation of fermented hispidin-enriched Sanghuangporus sanghuang mycelia (GKSS) as a novel food material for spontaneous sleep in Sprague-Dawley rats is conducted for the first time. Results showed that the nutritional analysis of GKSS including moisture, ash, crude lipid, crude protein, carbohydrate, and energy were found to be 2.4 ± 0.3%, 8.0 ± 2.5%, 1.7 ± 0.3%, 22.9 ± 1.2%, 65.1 ± 3.1%, and 367.1 ± 10.2 kcal/100 g respectively. In the 28-day repeated-dose oral toxicity study, only Sprague-Dawley male rats receiving 5 g/kg showed a slight decrease in feed consumption at week 3, but no associated clinical signs of toxicity or significant weight loss were observed. Although a significant reduction of the platelet count was found in mid- and high-dose GKSS treated male groups, such changes were noted to be within the normal range and were not correlated with relative spleen weight changes. Hence, the no observed adverse effect level (NOAEL) of GKSS was identified to be higher than 5 g/kg in rats. After the safety of GKSS is confirmed, the sleep-promoting effect of GKSS ethanolic extract enriched with hispidin was further assessed. Despite 75 mg/kg of GKSS ethanolic extract does not affect wakefulness, rapid eye movement (REM) sleep and non-REM (NREM) sleep, GKSS ethanolic extract at 150 mg/kg significantly decreased wakefulness and enhanced NREM and REM sleep. Interestingly, such effects seem to be mediated through anti-inflammatory activities via NF-E2-related factor-2 (Nrf2) signaling pathway. Taken together, these findings provide the preliminary evidence to studies support the claims suggesting that GKSS contained useful phytochemical hispidin could be considered as and is safe to use as a functional food agent or nutraceutical for relieving sleep problems mediated by Nrf2 pathway, which the results are useful for future clinical pilot study.

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-1β, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae (C. cicadae), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae, exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.

Oral cancers, hepatocellular carcinoma, and colorectal cancers are the three most common cancers, leading to 18,000 cases of cancer-related mortality in Taiwan per year. To bridge the gap towards clinical translation, we developed a circulating tumor cell (CTC) organoid culture workflow that efficiently expands CTC from patients to test Antrodia Cinnamomea mycelium-derived bioactive compounds. Three ACM-derived bioactive compounds were evaluated for tumor chemosensitization characteristics. Significant and consistent cytotoxic/5-FU sensitizing effects of GKB202 were found on 8 different patient-derived tumors. Acute toxicity profile and hepatic metabolism of GKB202 in rats suggest GKB202 is rapidly cleared by liver and is well tolerated up to the dose of 20 mg/kg. This comprehensive study provides new evidence that liquid fermentation of Antrodia cinnamomea mycelium (ACM) contains bioactive compounds that lead to effective control of CTC, especially when combined with 5-FU. Together, these data suggest ACM-derived GKB202 may be considered for further clinical investigation in the context of 5-FU-based combination therapy.

Osteoporosis, a significant bone disease predominantly affecting elderly and postmenopausal women, leads to increased bone fragility and fracture risk, presenting a major public health concern with substantial socioeconomic implications. This study investigated the therapeutic potential of Lactobacillus strains, known for their immunomodulatory properties, in an ovariectomy-induced osteoporosis mouse model. Among three tested strains Lactobacillus casei GKC1, Lactobacillus rhamnosus GKLC1, and Lactobacillus johnsonii GKJ2, GKC1 demonstrated superior efficacy in promoting osteogenesis-related gene expression, including alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (RUNX2). In ovariectomized mice (n = 8/group), both live and heat-inactivated GKC1 (57 mg/kg) and fermented GKC1 (1000 mg/kg) were administered orally for 28 days, with alendronate (2.5 mg/kg) serving as a positive control. The treatment significantly improved bone mineral density and femoral microstructure parameters compared to the ovariectomized control group. For the first time, heat-inactivated GKC1 exhibited superior anti-inflammatory effects through reduction of IL-17A and enhanced bone microstructural integrity, suggesting its potential as a safe and effective therapeutic agent for postmenopausal osteoporosis management. These findings provide compelling evidence for the development of postbiotic-based interventions in osteoporosis treatment, offering a promising alternative to conventional therapeutics.

Background: Disuse atrophy is a frequent cause of muscle atrophy, which can occur in individuals of any age who have been inactive for a prolonged period or immobilization. Additionally, acute diseases such as COVID‐19 can cause frequent sequelae and exacerbate muscle wasting, leading to additional fatigue symptoms. It is necessary to investigate potent functional nutrients for muscle reinforcement in both disuse atrophy and fatigue to ensure better physical performance.Methods: The effects of Sanghuangporus sanghuang SS‐MN4 mycelia were tested on two groups of 6‐week‐old male mice—one with disuse atrophy and the other with fatigue. The disuse atrophy group was divided into three sub‐groups: a control group, a group that underwent hind limb casting for 7 days and then recovered for 7 days and a group that was administered with SS‐MN4 orally for 14 days, underwent hind limb casting for 7 days and then recovered for 7 days. The fatigue group was divided into two sub‐groups: a control group that received no SS‐MN4 intervention and an experimental group that was administered with SS‐MN4 orally for 39 days and tested for exhaustive swimming and running on Day 31 and Day 33, respectively. RNA sequencing (RNA‐seq) and western blot analysis were conducted on C2C12 cell lines to identify the therapeutic effects of SS‐MN4 treatment.Results: In a disuse atrophy model induced by hind limb casting, supplementing with 250 mg/kg of SS‐MN4 for 14 days led to 111.2% gastrocnemius muscle mass recovery and an 89.1% improvement in motor function on a treadmill (P < 0.05). In a fatigue animal model, equivalent SS‐MN4 dosage improved swimming (178.7%) and running (162.4%) activities (P < 0.05) and reduced blood urea nitrogen levels by 18% (P < 0.05). SS‐MN4 treatment also increased liver and muscle glycogen storage by 34.36% and 55.6%, respectively, suggesting a higher energy reserve for exercise. RNA‐seq and western blot studies from the C2C12 myotube showed that SS‐MN4 extract upregulates Myh4 and helps sustain myotube integrity against dexamethasone damage.Conclusions: Supplementation of SS‐MN4 (250‐mg/kg body weight) with hispidin as active compound revealed a potential usage as a muscle nutritional supplement enhancing muscle recovery, fast‐twitch fibre regrowth and fatigue resistance.