Alzheimer’s disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and ‘eumetabolic’ activities may possess superior efficacies compared to less pluripotent remedies.

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Diabetes mellitus (DM) is a kind of chronic and metabolic disease, which can cause a number of diseases and severe complications. Network pharmacology approach is introduced to study DM, which can combine the drugs, target proteins and disease and form drug-target-disease networks. Network pharmacology has been widely used in the studies of the bioactive compounds and action mechanisms of natural products for the treatment of DM due to the multi-components, multi-targets, and lower side effects. This review provides a balanced and comprehensive summary on network pharmacology from current studies, highlighting different bioactive constituents, related databases and applications in the investigations on the treatment of DM especially type 2. The mechanisms related to type 2 DM, including α-amylase and α-glucosidase inhibitory, targeting β cell dysfunction, AMPK signal pathway and PI3K/Akt signal pathway are summarized and critiqued. It suggests that the network pharmacology approach cannot only provide a new research paradigm for natural products, but also improve the current antidiabetic drug discovery strategies. Furthermore, we put forward the perspectives on the reasonable applications of network pharmacology for the therapy of DM and related drug discovery.

Normal aging is a complex process that affects every organ system in the body, including the taste system. Thus, we investigated the effects of the normal aging process on taste bud morphology, function, and taste responsivity in male mice at 2, 10, and 18 months of age. The 18-month-old animals demonstrated a significant reduction in taste bud size and number of taste cells per bud compared with the 2- and 10-month-old animals. The 18-month-old animals exhibited a significant reduction of protein gene product 9.5 and sonic hedgehog immunoreactivity (taste cell markers). The number of taste cells expressing the sweet taste receptor subunit, T1R3, and the sweet taste modulating hormone, glucagon-like peptide-1, were reduced in the 18-month-old mice. Concordant with taste cell alterations, the 18-month-old animals demonstrated reduced sweet taste responsivity compared with the younger animals and the other major taste modalities (salty, sour, and bitter) remained intact.

Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase Cβ2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds.

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Black soybean seed coat extract (BSSCE) is a rich source of anthocyanins with multiple health effects. This study was aimed at investigating the composition and hypoglycemic and hypolipidemic effects of BSSCE in vitro and in a high-fat diet and streptozotocin (STZ)-induced diabetic mice. The anthocyanins of BSSCE were identified as cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, and peonidin-3-O-glucoside by HPLC-MS. Results demonstrated that BSSCE exhibited strong inhibitory activities for α-amylase, potent inhibition activity against lipid accumulation in HepG2 cells and protection effect on HO-induced oxidative stress-damaged HepG2 cells. The food and water intake, body weight loss, blood glucose and insulin level of BSSCE treatment group were found to be significantly reduced when compared with those of diabetic mice group (p < 0.05). The fasting blood glucose level and insulin level of the BSSCE 400 mg kg group mice significantly decreased by 47.97% and 46.49%, respectively. The oral glucose tolerance and activities of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) notably improved (p < 0.05). BSSCE could also ameliorate the atherogenic dyslipidaemia of diabetic mice by remarkably decreasing the content of total cholesterol (T-CHO), total triglyceride (TG), and non-esterified fatty acid (NEFA) and increasing the content of high-density lipoprotein cholesterol (HDL-c) (p < 0.05). BSSCE could protect against liver, kidney and pancreas damages in diabetic mice. This study suggested that cyanidin-3-O-glucoside contributed to BSSCE-induced hypoglycemia and hypolipidemia effects in type 2 diabetes mellitus (T2DM), and BSSCE might be a promising functional food or medicine for T2DM treatment.

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