Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1β and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression.

Retinal diseases are a leading cause of visual loss and blindness, affecting a significant proportion of the population worldwide and having a detrimental impact on quality of life, with consequent economic burden. The retina is highly metabolically active, and a number of retinal diseases are associated with metabolic dysfunction. To better understand the pathogenesis underlying such retinopathies, new technology has been developed to elucidate the mechanism behind retinal diseases. Metabolomics is a relatively new “omics” technology, which has developed subsequent to genomics, transcriptomics, and proteomics. This new technology can provide qualitative and quantitative information about low-molecular-weight metabolites (M.W. < 1500 Da) in a given biological system, which shed light on the physiological or pathological state of a cell or tissue sample at a particular time point. In this article we provide an extensive review of the application of metabolomics to retinal diseases, with focus on age-related macular degeneration (AMD), diabetic retinopathy (DR), retinopathy of prematurity (ROP), glaucoma, and retinitis pigmentosa (RP).

Retinitis pigmentosa (RP) is a group of visual disorders caused by mutations in over 70 genes. RP is characterized by initial degeneration of rod cells and late cone cell death, regardless of genetic abnormality. Rod cells are the main consumers of oxygen in the retina, and after the death of rod cells, the cone cells have to endure high levels of oxygen, which in turn leads to oxidative damage and cone degeneration. Gypenosides (Gyp) are major dammarane-type saponins of Gynostemma pentaphyllum that are known to reduce oxidative stress and inflammation. In this project we assessed the protective effect of Gyp against cone cell death in the rpgrip1 mutant zebrafish, which recapitulate the classical pathological features found in RP patients. Rpgrip1 mutant zebrafish were treated with Gyp (50 µg/g body weight) from two-months post fertilization (mpf) until 6 mpf. Gyp treatment resulted in a significant decrease in cone cell death compared to that of untreated mutant zebrafish. A markedly low level of reactive oxygen species and increased expression of antioxidant genes were detected in Gyp-incubated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Similarly, the activities of catalase and superoxide dismutase and the level of glutathione were significantly increased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Gyp treatment also decreased endoplasmic reticulum stress in rpgrip1 mutant eyes. Expression of proinflammatory cytokines was also significantly decreased in Gyp-treated mutant zebrafish eyes compared to that of untreated mutant zebrafish. Network pharmacology analysis demonstrated that the promotion of cone cell survival by Gyp is possibly mediated by multiple hub genes and associated signalling pathways. These data suggest treatment with Gyp will benefit RP patients.

Atherosclerosis is a chronic vascular disease characterized by failure to resolve inflammation and forming plaque within the arterial wall. Atherosclerosis and its related cardiovascular diseases are the major causes of death worldwide. Our previous preliminary study showed that anthocyanin-rich extract (ACNE) from Xinjiang wild cherry plum (Prunus divaricata Ledeb) fruit peels exhibited anti-atherosclerotic effect. However, the potential mechanism of this health-beneficial effect remains unclear. Here, network pharmacology combined with molecular docking was used to tentatively address this issue. The ACNE mainly contains cyanidin, cyanidin 3-glucoside (Cy3Glu), Cyanidin 3-(6’’-acetylglucoside) (Cy3AcGlu), cyanidin 3-galactoside (Cy3Gal), cyanidin 3-xyloside (Cy3Xyl), and cyanidin 3-rutinoside (Cy3Rut). Seven key targets, EGFR, VEGFA, HSP90AA1, SRC, HIF1A, CXCR4 and IGF1R were identified from core protein-protein interaction (PPI) network. Anthocyanins interacting on key targets were initially demonstrated by molecular docking, particularly Cy3Rut and Cy3Xyl having highest affinity with most key targets. Biological function analysis suggested that key targets were involved in several biological processes, including positive regulation of cell migration, positive regulation of phosphorylation, inflammatory response, response to hypoxia, etc. The significantly enriched pathways, such as HIF-1 signaling pathway, calcium signaling pathway, macrophage stimulating protein MSP signaling network map, were closely related to atherosclerosis. Altogether, based on the comprehensive analysis and discussion, we revealed that TLR4/EGFR and IGF1R-CXCL12/CXCR4 pathways were at least partially implicated in the anti-atherosclerotic effects of anthocyanins through affecting inflammation, endothelial homeostasis, and foam cell formation. This study served as a theoretical basis for further validating the underlying anti-atherosclerotic mechanism of anthocyanins via in vitro and in vivo experiments.

Background: Hepatic lipid metabolism disorder has been linked to a wide range of diseases. Aspalathin is a flavonoid enriched in rooibos tea and has shown capacity to protect against hyperlipidemia, oxidative stress and inflammation. In the current study, we investigated the functional role of aspalathin in regulating liver metabolism and gut microbiota in the context of a high-fat diet (HFD). Methods: Male mice were fed a control diet or HFD, then HFD-fed animals were treated with or without aspalathin-rich extract (ASE). Hepatic neutral lipids were detected using oil red O staining and a colorimetric assay. Expression of cholesterol metabolism-, lipogenesis- and fatty acid β-oxidation-associated genes was measured. Gut microbiota was analyzed using 16S rRNA sequencing and bioinformatic approaches. Results: HFD-fed mice had markedly higher levels of triglycerides and cholesteryl esters and downregulated expression of cholesterol metabolism-, transport- and lipogenesis-related genes in the liver. ASE administration counteracted HFD-induced effects. In addition, HFD altered the composition, diversity and metabolic pathways of the gut microbiota. The richness of beneficial bacteria, particularly the butyrate-producing bacteria, was significantly decreased. The altered metabolic pathways are involved in the metabolism of carbohydrates, lipids, amino acids and nucleotides, as well as mitochondrial function. ASE treatment reversed most of the alterations back to the characteristics of the control group. Conclusions: Our results demonstrated the potential of ASE improving liver lipid metabolism and gut microbiota in the scenario of a high-fat diet, providing insights into future studies on the mechanism of ASE regulating lipid metabolism disorder.