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Due to its complex pathogenesis, the prevention and therapization of Alzheimer's disease (AD) remains a serious challenge. Crocin, the main compound isolated from Crocus sativus L., demonstrates various pharmacological activities including anti‑apoptotic properties. The present study investigated the neuroprotective effect of crocin and the underlying mechanisms. In l‑glutamate‑damaged HT22 cells, 3‑h crocin pretreatment strongly enhanced the HT22 cell viability, reduced the apoptotic rate, mitigated mitochondrial dysfunction, suppressed intracellular reactive oxygen species (ROS) accumulation and Ca2+ overload compared with untreated cells. Additionally, crocin significantly decreased the expression levels of Bax, Bad and cleaved caspase‑3 and increased the expression levels of B‑cell lymphoma‑extra large, phosphorylated (P‑) protein kinase B and P‑mammalian target of rapamycin compared with untreated cells. In mice with AD induced by d‑galactose and aluminum trichloride, crocin substantially improved the cognition and memory abilities of the mice as measured by their coordination of movement in an open field test, and reduced their escape time in the Morris water maze test compared with untreated mice. Biochemical analysis confirmed that crocin was able to reduce the Aβ1‑42 content in the mouse brains, increase the levels of glutathione peroxidase, superoxide dismutase, acetylcholine and choline acetyltransferase, and reduce the levels of ROS and acetylcholinesterase in the serum, cerebral cortex and hypothalamus compared with untreated mice. Immunohistochemical analysis demonstrated that crocin reduced Aβ1‑42 deposition in the hippocampus of the brains of treated mice compared with untreated mice. In conclusion, crocin demonstrates good prospects in the treatment of AD through the oxidative stress‑associated apoptosis signaling pathway.

Evodiamine (Evo), a major alkaloid compound isolated from the dry unripened fruit of Evodia fructus, has a wide range of pharmacological activities. The present study sought to explore the neuroprotective effects of Evo in l-glutamate (l-Glu)-induced apoptosis of HT22 cells, and in a d-galactose and aluminum trichloride-developed Alzheimer’s disease (AD) mouse model. Evo significantly enhanced cell viability, inhibited the accumulation of reactive oxygen species, ameliorated mitochondrial function, increased the B-cell lymphoma-2 protein content, and inhibited the high expression levels of Bax, Bad, and cleaved-caspase-3 and -8 in l-Glu-induced HT22 cells. Evo also enhanced the phosphorylation activities of protein kinase B and the mammalian target of rapamycin in the l-Glu-induced HT22 cells. In the AD mouse model, Evo reduced the aimless and chaotic movements, reduced the time spent in the central area in the open field test, and decreased the escape latency time in the Morris water maze test. Evo reduced the deposition of amyloid beta 42 (Aβ42) in the brain, and increased the serum level of Aβ42, but showed no significant effects on Aβ40. In addition, six weeks of Evo administration significantly suppressed oxidative stress by modulating the related enzyme levels. In the central cholinergic system of AD mice, Evo significantly increased the serum levels of acetylcholine and choline acetyltransferase and decreased the level of acetylcholinesterase in the serum, hypothalamus, and brain. Our results provide experimental evidence that Evo can serve as a neuroprotective candidate for the prevention and/or treatment of neurodegenerative diseases.

Alzheimer's disease (AD) is prone to onset and progression under oxidative stress conditions. Hericium coralloides (HC) is an edible medicinal fungus that contains various nutrients and possesses antioxidant properties. In the present study, the nutritional composition and neuroprotective effects of HC on APP/PS1 mice were examined. Behavioral experiments showed that HC improved cognitive dysfunction in APP/PS1 mice. Immunohistochemical and Western blotting results showed that HC reduced the levels of p-tau and amyloid-β deposition in the brain. By altering the composition of the gut microbiota, HC promoted the growth of short-chain fatty acid-producing bacteria and suppressed the growth of Helicobacter. Metabolomic results showed that HC decreased D-glutamic acid and oxidized glutathione levels. In addition, HC reduced the levels of reactive oxygen species, enhanced the secretion of superoxide dismutase, catalase, and glutathione peroxidase, inhibited the production of malondialdehyde and 4-hydroxynonenal, and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Collectively, HC demonstrated antioxidant activity by activating Nrf2 signaling and regulating gut microbiota, further exerting neuroprotective effects. This study confirms that HC has the potential to be a clinically effective AD therapeutic agent and offers a theoretical justification for both the development and use of this fungus. [ABSTRACT FROM AUTHOR]

Auricularia delicate (ADe), an edible fungus belonging to the family Auriculariaceae and order Auriculariales, possesses antimicrobial, hepatoprotective, and antioxidant effects. In this study, after systematic analysis of its composition, ADe was administered to high-fat-diet (HFD)-fed mice to investigate its anti-obesity effect. ADe significantly controlled body weight; alleviated hepatic steatosis and adipocyte hypertrophy; reduced aspartate aminotransferase, total cholesterol, insulin, and resistin; and increased adiponectin levels in HFD-fed mice serum. Based on intestinal microbiota and lipidomics analysis, ADe treatment regulated the composition and abundance of 49 intestinal microorganisms and influenced the abundance of 8 lipid species compared with HFD-fed mice. Based on a correlation analysis of the intestinal microbiota and lipids, Coprococcus showed significant negative associations with ceramide (d18:0 20:0+O), phosphatidylserine (39:4), sphingomyelin (d38:4), and zymosterol (20:2). Moreover, ADe treatment decreased the levels of ROS and MDA and increased the levels of Nrf2, HO-1, and three antioxidant enzymes in HFD-fed mice livers. Collectively, the anti-obesity effect of ADe involves the regulation of oxidative stress and is mediated by the intestinal microbiota. Hence, this study provides a reference for the application of ADe as a candidate food for obesity. [ABSTRACT FROM AUTHOR]

The purified polysaccharides from Hericium erinaceus fermented mycelium entitled with PHEB was analyzed and it was mainly composed of six glycosidic bonds. It has been confirmed to show the relieving activity against Alzheimer's Disease (AD)- just as behaviors of B6C3-Tg (APPswePSEN1d E9)/Nju double transgenic [Genotype: (Appswe)T, (Psen1) T] (APP/PS1) mice. Six-week PHEB administration significantly improved the cognitive behavior of mice. Brain injury, amyloid beta deposition and tau hyperphosphorylation were alleviated in PHEB-treated AD mice without changes in other tissues. PHEB alleviated the oxidative stress in brains of AD mice via regulation the Nrf2 and its downstream kinase, which further improved the cholinergic system function. Proteomics and bioinformatics analysis showed that the therapeutic effect of PHEB is achieved by regulating calcium homeostasis mediated by oxidative stress. Furthermore, PHEB regulated the CaMK II/IV to achieve the calcium homeostasis in brains; and ultimately to show the anti-AD property. • The polysaccharide (PHEB) is first purified from Hericium erinaceus mycelium. • Clear structure of PHEB with the molecular weight of 36.1 kDa has been confirmed. • PHEB has the anti-Alzheimer's disease activities in APP/PS1 mice. • Oxidative stress-mediated calcium homeostasis is related to anti-AD effect of PHEB. [ABSTRACT FROM AUTHOR]

EuOCP3, with a molecular weight of 38.1 kDa, is an acidic polysaccharide purified from Eucommia ulmoides Oliver cortex. Herein, we determined that the main backbone of EuOCP3 was predominantly composed of →4)-α-Gal p A-(1 → 4)-α-Gal p A-(1→, →4)-α-Gal p A-(1 → 5)-α-Ara f -(1→, →4)-α-Gal p A-(1 → 2)-α-Rha p -(1→, and →4)-α-Gal p A-(1 → 5)-α-Ara f -(1 → 2)-α-Rha p -(1 → repeating blocks, which were connected by →2,3,5)-α-Ara f -(1→. The side chains, substituted at C-2 and C-5 of →2,3,5)-α-Ara f -(1→, contained T-β-Ara f → and T-β-Ara f → 4)-α-Gal p A-(1 → residues. In dexamethasone (Dex)-induced osteoporosis (OP) mice, EuOCP3 treatment restored cortical bone thickness, increased mineralized bone area, enhanced the number of osteoblasts, and decreased the number of osteoclasts on the surface of cortical bone. Combining analysis of gut microflora, serum metabolite profiles, and biological detection results, we demonstrated that EuOCP3 regulated the abundance of specific species within the gut microflora, such as g_Dorea and g_Prevotella , and ameliorated oxidative stress. In turn, enhancement of osteogenic function and restoration of bone metabolism via the extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway was indicated. The current findings contribute to understanding the potential of EuOCP3 in anti-OP treatment. [Display omitted] [ABSTRACT FROM AUTHOR]