Pharmacological Basis for Use of Armillaria mellea Polysaccharides in Alzheimer's Disease: Antiapoptosis and Antioxidation.

Armillaria mellea, an edible fungus, exhibits various pharmacological activities, including antioxidant and antiapoptotic properties. However, the effects of A. mellea on Alzheimer's disease (AD) have not been systemically reported. The present study aimed to explore the protective effects of mycelium polysaccharides (AMPS) obtained from A. mellea, especially AMPSc via 70% ethanol precipitation in a L-glutamic acid- (L-Glu-) induced HT22 cell apoptosis model and an AlCl3 plus D-galactose- (D-gal-) induced AD mouse model. AMPSc significantly enhanced cell viability, suppressed nuclear apoptosis, inhibited intracellular reactive oxygen species accumulation, prevented caspase-3 activation, and restored mitochondrial membrane potential (MMP). In AD mice, AMPSc enhanced horizontal movements in an autonomic activity test, improved endurance times in a rotarod test, and decreased escape latency time in a water maze test. Furthermore, AMPSc reduced the apoptosis rate, amyloid beta (Aß) deposition, oxidative damage, and p-Tau aggregations in the AD mouse hippocampus. The central cholinergic system functions in AD mice improved after a 4-week course of AMPSc administration, as indicated by enhanced acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations, and reduced acetylcholine esterase (AchE) levels in serum and hypothalamus. Our findings provide experimental evidence suggesting A. mellea as a neuroprotective candidate for treating or preventing neurodegenerative diseases.

Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.

Calf Spleen Extractive Injection (CSEI), extracted from the spleen of healthy cows (within 24 hours of birth), is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. This study evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, BMNCs and a mouse model of cyclophosphamide (CTX)-induced hematopoietic suppression. CSEI promoted the proliferation and differentiation of CHRF and K562 cells, activated hematopoietic- and proliferation-related factors RSK1p90, ELK1 and c-Myc, and facilitated the expression of differentiation- and maturation-related transcription factors GATA-1, GATA-2. In the mice with hematopoietic suppression, 3 weeks of CSEI administration enhanced the bodyweights and thymus indices, suppressed the spleen indices and strongly elevated the production of HSPCs, neutrophils and B cells in bone marrow, ameliorated bone marrow cellularity, and regulated the ratio of peripheral blood cells. Proteome profiling combined with ELISA revealed that CSEI regulated the levels of cytokines, especially G-CSF and its related factors, in the spleen and plasma. Additional data revealed that CSEI promoted phosphorylation of STAT3, which was stimulated by G-CSF in both mice spleen and cultured BMNCs. Taken together, CSEI has the potential to improve hematopoietic function via the G-CSF-mediated JAK2/STAT3 signaling pathway.

Paecilomyces tenuipes extract prevents depression-like behaviors in chronic unpredictable mild stress-induced rat model via modulation of neurotransmitters.

The medicinal fungus Paecilomyces tenuipes exhibits a variety of pharmacological effects, including antidepressive effects. The chronic unpredictable mild stress (CUMS)­induced rat model has served an important role in studies involving antidepressants screening. The aim of the present study was to evaluate the antidepressant­like activity of P. tenuipes N45 aqueous extract (PTNE) in a CUMS­induced rat model of behavioral despair depression. Following 4 weeks of PTNE treatment, behavioral tests were conducted to investigate the antidepressant­like activities, and the levels of neurotransmitters and hormones in blood and hypothalamus were measured. The results demonstrated that PTNE treatment significantly increased movement in the forced running test, whereas the immobility time was reduced in the hotplate test and the forced swim test in depression­model rats. PTNE treatment was able to normalize the levels of hormones and neurotransmitters in serum and hypothalamus of CUMS rats. The data demonstrated that PTNE treatment may be a potential pharmaceutical agent in treatment­resistant depression, and the effects of PTNE may be partly mediated through normalizing the levels of neurotransmitters.

Antifatigue Effects of Antrodia cinnamomea Cultured Mycelium via Modulation of Oxidative Stress Signaling in a Mouse Model.

Antrodia cinnamomea, a folk medicinal mushroom, has numerous biological effects. In this study, we aim to assess whether the antifatigue effects of A. cinnamomea mycelia (AC) and its underlying mechanisms are related to oxidative stress signaling using behavioral mouse models and biochemical indices detection. Mice were orally treated with AC at doses of 0.1, 0.3, and 0.9 g/kg for three weeks. AC had no effect on the spontaneous activities of mice indicating its safety on central nervous system. Furthermore, results obtained from weight-loaded forced swimming test, rotary rod test, and exhausted running test confirmed that AC significantly enhanced exercise tolerance of mice. Biochemical indices levels showed that these effects were closely correlated with inhibiting the depletion of glycogen and adenosine triphosphate stores, regulating oxidative stress-related parameters (superoxide dismutase, glutathione peroxidase, reactive oxygen species, and malondialdehyde) in serum, skeletal muscle, and liver of mice. Moreover, the effects of AC may be related with its regulation on the activations of AMP-activated protein kinase, protein kinase B, and mammalian target of rapamycin in liver and skeletal muscle of mice. Altogether, our data suggest that the antifatigue properties of AC may be one such modulation mechanism via oxidative stress-related signaling in mice.

Tricholoma matsutake Aqueous Extract Induces Hepatocellular Carcinoma Cell Apoptosis via Caspase-Dependent Mitochondrial Pathway.

Tricholoma matsutake, one of widely accepted functional mushrooms, possesses various pharmacological activities, and its antitumor effect has become an important research point. Our study aims to evaluate the cytotoxicity activities of T. matsutake aqueous extract (TM) in HepG2 and SMMC-7721 cells. In in vitro experiments, TM strikingly reduced cell viability, promoted cell apoptosis, inhibited cell migration ability, induced excessive generation of ROS, and caused caspases cascade and mitochondrial membrane potential dissipation in hepatocellular carcinoma cells. In in vivo experiments, 14-day TM treatment strongly suppressed tumor growth in HepG2 and SMMC-7721-xenografted nude mice without influence on their body weights and liver function. Furthermore, TM increased the levels of cleaved poly-ADP-ribose polymerase (PARP), Bad, and Bax and reduced the expressions of B-cell lymphoma 2 (Bcl-2) in treated cells and tumor tissues. All aforementioned results suggest that caspase-dependent mitochondrial apoptotic pathways are involved in TM-mediated antihepatocellular carcinoma.

The Neuroprotective Properties of Hericium erinaceus in Glutamate-Damaged Differentiated PC12 Cells and an Alzheimer's Disease Mouse Model.

Hericium erinaceus, an edible and medicinal mushroom, displays various pharmacological activities in the prevention of dementia in conditions such as Parkinson's and Alzheimer's disease. The present study explored the neuroprotective effects of H. erinaceus mycelium polysaccharide-enriched aqueous extract (HE) on an l-glutamic acid (l-Glu)-induced differentiated PC12 (DPC12) cellular apoptosis model and an AlCl3 combined with d-galactose-induced Alzheimer's disease mouse model. The data revealed that HE successfully induced PC12 cell differentiation. A 3 h HE incubation at doses of 50 and 100 µg/mL before 25 mM of l-Glu effectively reversed the reduction of cell viability and the enhancement of the nuclear apoptosis rate in DPC12 cells. Compared with l-Glu-damaged cells, in PC12 cells, HE suppressed intracellular reactive oxygen species accumulation, blocked Ca2+ overload and prevented mitochondrial membrane potential (MMP) depolarization. In the Alzheimer's disease mouse model, HE administration enhanced the horizontal and vertical movements in the autonomic activity test, improved the endurance time in the rotarod test, and decreased the escape latency time in the water maze test. It also improved the central cholinergic system function in the Alzheimer's mice, demonstrated by the fact that it dose-dependently enhanced the acetylcholine (Ach) and choline acetyltransferase (ChAT) concentrations in both the serum and the hypothalamus. Our findings provide experimental evidence that HE may provide neuroprotective candidates for treating or preventing neurodegenerative diseases.