RESUMEN
The gut microbiota is considered an important factor in the progression of Alzheimer's disease (AD). Active research on the association between the metabolome and the gut microbiome is ongoing and can provide a large amount of beneficial information about the interactions between the microbiome and the metabolome. Previous studies have shown that the oligosaccharides from Morinda officinalis (OMO) can delay the progress of AD in model animals by regulating the diversity of the gut microbiome and metabolic components, and the correlation between the gut microbiome and metabolic components still needs to be further verified. This study applied a new two-level strategy to investigate and ensure the accuracy and consistency of the results. This strategy can be used to determine the association between the gut microbiome and serum metabolome in APP/PS1 transgenic mice and C57BL/6J male mice. The "4C0d-2 spp.-Cholesterol," "CW040 spp.-L-valine," "CW040 spp.-L-acetylcarnitine," "RF39 spp.-L-valine," "TM7-3 spp.-L-valine," and "TM7-3 spp.-L-acetylcarnitine" associations among specific "microbiota-metabolite" pairs were further identified based on univariate and multivariate correlation analyses and functional analyses. The key relevant pairs were verified by an independent oligosaccharide intervention study, and the gut microbiome and serum metabolome of the OMO intervention group were similar to those of the normal group. The results indicate that OMO can significantly suppress Alzheimer's disease by regulating the key microbiota-metabolite pairs. Therefore, this two-level strategy is effective in identifying the principal correlations in large datasets obtained from combinations of multiomic studies and further enhancing our understanding of the correlation between the brain and gut in patients with AD.
RESUMEN
Hericium erinaceus (HE), a traditional edible mushroom, is known as a medicine food homology to ameliorate gastrointestinal diseases. To investigate whether HE is clinically effective in alleviating inflammatory bowel disease (IBD), HE extracts (polysaccharide, alcoholic extracts and whole extracts were prepared using solvent extraction methods) were administrated for 2 weeks in rats with IBD induced by trinitro-benzene-sulfonic acid (TNBS) enema (150 mg/kg). Significant clinical and histological changes in IBD rats were identified, including damage activity, common morphous and tissue damage index scores in colonic mucosa and myeloperoxidase (MPO) activity. The damage activity, common morphous and tissue damage index scores in colonic mucosa (P <0.05) were improved, MPO activities were decreased. Inflammatory factors were also differentially expressed in colonic mucosa in IBD rats, including serum cytokines, Foxp3 and interleukin (IL)-10 were increased while NF-κB p65 and tumor necrosis factor (TNF)-α were decreased (P <0.05), and T cells were activated (P <0.05), especially in the alcohol extracts-treated group. We also found that the structure of gut microbiota of the H. erinaceus extracts-treated groups changed significantly by compared with the model group. Further studies revealed that the polysaccharides in HE extracts may play a prebiotic role, whereas the alcoholic extracts show bactericidin-like and immunomodulatory effects. Taken together, we demonstrated that H. erinaceus extracts could promote the growth of beneficial gut bacteria and improve the host immunity in vivo IBD model, which shows clinical potential in relieving IBD by regulating gut microbiota and immune system.
RESUMEN
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting approximately more than 5% of the population worldwide over the age 65, annually. The incidence of AD is expected to be higher in the next 10 years. AD patients experience poor prognosis and as a consequence new drugs and therapeutic strategies are required in order to improve the clinical responses and outcomes of AD. The purpose of the present study was to screen a certain number of potential compounds from herbal sources and investigate their corresponding mode of action. In the present study, the learning and memory effects of ethanol:water (8:2) extracts from Hericium erinaceus were evaluated on a dementia rat model. The model was established by intraperitoneal injection of 100 mg/kg/d D-galactose in rats. The results indicated that the extracts can significantly ameliorate the learning and memory abilities. Specific active ingredients were screened in vivo assays and the results were combined with molecular docking studies. Potential receptor-ligand interactions on the BACE1-inhibitor namely, 3-Hydroxyhericenone F (3HF) were investigated. The isolation of a limited amount of 3HF from the fruit body of H. erinaceus by chemical separation was conducted, and the mode of action of this compound was verified in NaN3-induced PC12 cells. The cell-based assays demonstrated that 3HF can significantly down-regulate the expression of BACE1 (p < 0.01), while additional AD intracellular markers namely, p-Tau and Aß1-42 were further down-regulated (p < 0.05). The data further indicate that 3HF can ameliorate certain mitochondrial dysfunction conditions by the reversal of the decreasing level of mitochondrial respiratory chain complexes, the calcium ion levels ([Ca2+]), the inhibiton in the production of ROS, the increase in the mitochondrial membrane potential and ATP levels, and the regulation of the expression levels of the genes encoding for the p21, COX I, COX II, PARP1, and NF-κB proteins. The observations suggest the use of H. erinaceus in traditional medicine for the treatment of various neurological diseases and render 3HF as a promising naturally occurring chemical constituent for the treatment of AD via the inhibition of the ß-secretase enzyme.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVENCE: Neurodegenerative diseases (NDs) caused by neurons and/or myelin loss lead to devastating effects on patients׳ lives. Although the causes of such complex diseases have not yet been fully elucidated, oxidative stress, mitochondrial and energy metabolism dysfunction, excitotoxicity, inflammation, and apoptosis have been recognized as influential factors. Current therapies that were designed to address only a single target are unable to mitigate or prevent disease progression, and disease-modifying drugs are desperately needed, and Chinese herbs will be a good choice for screening the potential drugs. Previous studies have shown that bajijiasu, a dimeric fructose isolated from Morinda officinalis radix which was used frequently as a tonifying and replenishing natural herb medicine in traditional Chinese medicine clinic practice, can prevent ischemia-induced neuronal damage or death. MATERIALS AND METHODS: In order to investigate whether bajijiasu protects against beta-amyloid (Aß25â35)-induced neurotoxicity in rats and explore the underlying mechanisms of bajijiasu in vivo, we prepared an Alzheimer׳s disease (AD) model by injecting Aß25-35 into the bilateral CA1 region of rat hippocampus and treated a subset with oral bajijiasu. We observed the effects on learning and memory, antioxidant levels, energy metabolism, neurotransmitter levels, and neuronal apoptosis. RESULTS: Bajijiasu ameliorated Aß-induced learning and memory dysfunction, enhanced antioxidative activity and energy metabolism, and attenuated cholinergic system damage. Our findings suggest that bajijiasu can enhance antioxidant capacity and prevent free radical damage. It can also enhance energy metabolism and monoamine neurotransmitter levels and inhibit neuronal apoptosis. CONCLUSION: The results provide a scientific foundation for the use of Morinda officinalis and its constituents in the treatment of various AD. Future studies will assess the multi-target activity of the drug for the treatment of AD.