Anthocyanins Prevent AAPH-Induced Steroidogenesis Disorder in Leydig Cells by Counteracting Oxidative Stress and StAR Abnormal Expression in a Structure-Dependent Manner.

Testosterone deficiency may increase the risk of sexual dysfunction and the failure of spermatogenesis. Oxidative stress that is derived from the destruction of homeostasis, disease, and exposure to contaminants can damage the steroidogenicity process in Leydig cells, resulting in a reduction in testosterone synthesis. Anthocyanins are a group of innoxious antioxidants widely recognized in food sources, and are an ideal candidate to relieve oxidative stress-related steroidogenesis disorder. However, there is still a major gap in our knowledge of the structure-function relationship of anthocyanin on the activity mentioned above. In the present study, four anthocyanins including cyanidin-3-glucoside (Cy-3-glu), delphinidin-3-glucoside (Dp-3-glu), pelargonidin-3-glucoside (Pg-3-glu), and cyanidin-3,5-diglucoside (Cy-3,5-diglu) were applied to reverse testosterone generation after employing 2,2'-Azobis(2-amidinopropane)-dihydrochloride (AAPH) as the inducer of oxidative stress in R2C cells. The results demonstrated that all four kinds of anthocyanins can inhibit ROS generation, alleviate mitochondrial membrane potential damage, and contribute to increased testosterone. Among them, Cy-3,5-diglu with diglycoside performed best on antioxidative ability and improved cell dysfunction and upregulated the expression of the steroidogenic acute regulatory protein (StAR). The molecular docking further revealed the direct combination between anthocyanins and StAR, suggesting that anthocyanins with monosaccharide were more likely to interact with StAR than with diglycoside. Taken together, these data indicate that recipient R2C cells under oxidative stress submitted to anthocyanins exhibited improved steroidogenesis in a structure-dependent manner. Anthocyanins could be considered the ideal ingredients against oxidative stress-induced testosterone deficiency.

Novel cascade reaction-based fluorescent cyanine chemosensor for cysteine detection and bioimaging in living system.

Precise detection of intracellular Cys will be helpful to accurately assess the physiological functions in the physiological and pathological processes. Herein, a new probe Meoeth-Cy-OBz-oCl capable of Cys sensing with high selectivity over other mercaptoamino-acid molecules including Hcy and GSH was developed. The studies on sensing mechanism supported thiols-induced SNAr substitution-rearrangement cascade reaction which allowed discriminating Cys from Hcy/GSH. And its preferential fluorescence response of Meoeth-Cy-OBz-oCl to intracellular Cys was also achieved by means of fluorescence imaging in HeLa cells. Besides, Meoeth-Cy-OBz-oCl was confirmed possessing mitochondria-targeting ability in living cells. In addition, fluorescence imaging in BALB/c mice revealed that Meoeth-Cy-OBz-oCl could visually monitor the variation of Cys in vivo.

Effects of cyanidin-3-O-glucoside on 3-chloro-1,2-propanediol induced intestinal microbiota dysbiosis in rats.

Gastrointestinal studies suggested that balanced gut microbial community contribute to a healthy gut. Our previous studies have suggested that cyanidin-3-O-glucoside (C3G) can alleviate food contaminant 3-Chloro-1,2-propanediol (3-MCPD) induced testis injury and improve the spermatogenesis in rats. To the best of our knowledge, the effects of 3-MCPD exposure and C3G intervention on intestinal microbiota have not been studied. In the present study, male Wistar rats were used to investigate the effects of C3G and 3-MCPD on microbiota composition. After 3-MCPD treatment, the small intestinal showed histopathological alterations, including villus atrophy, necrosis, decreased number of epithelial cells and cellular infiltration. Supplementation of C3G brings the small intestine closer to normal histology. Meanwhile, 3-MCPD exposure significantly changed the diversity and composition of gut microbiota. At the phylum level, Cyanobacteria and Firmicutes were enriched in 3-MCPD groups, while Actinobacteria and Proteobacteria were decreased. Supplementation of C3G significantly increased the relative abundance of Lachnospiraceae_NK4A136_group and Actinobacteria, indicating that C3G may regulate the communities of gut microbiota towards a beneficial orientation. Our results indicate that C3G may protect the intestinal mucosa damage caused by 3-MCPD, and appropriate dose of C3G restrains gut microbial dysbiosis caused by 3-MCPD, which is a potential way to promote gut healthy.

The target cells of anthocyanins in metabolic syndrome.

Metabolic syndrome develops to several related chronic diseases, such as obesity, cardiovascular disease, hypertension, diabetes, and fatty liver disease. Diseases are outcomes of various cells dysfunction, which are especially acting with a network in metabolic syndrome. Anthocyanins are natural edible pigments widely existed in dark-colored fruits, vegetables, and grains. Epidemiological investigation and nutritional intervention of anthocyanins have exhibited broad-spectrum biological effects that they can benefit patients with metabolic syndrome related chronic diseases. Whereas the underlying mechanisms and the effects of anthocyanins on critical cells in chronic metabolic diseases are complex and elusive. Therefore, this review summarizes the studies about the effects of anthocyanins on various metabolism related chronic diseases, and mainly focuses on the effects and underlying molecular mechanisms on critical cells. We confirmed that anthocyanins are efficient on adipocytes, endothelial cells, inflammatory cells, hepatocytes, intestinal cells and gut microbiota, but lack of evidence on platelets, skeletal muscle cells, hepatic stellate cells and pancreatic beta cells. Additionally, we discussed the structure-function relationship of anthocyanins and the metabolites. This review summarizes the development of studies on anthocyanins with its target cells in metabolic syndrome, and discusses the unclear aspects of the anthocyanins research work, which is necessary for the future clinical application.

Cyanidin-3- O-glucoside at Low Doses Protected against 3-Chloro-1,2-propanediol Induced Testis Injury and Improved Spermatogenesis in Male Rats.

In recent decades, the capability of mankind spermatogenesis is declining due to various threats. Anthocyanins as colorful polyphenols possess beneficial functions for the organisms, including Leydig cells, but their effects on male spermatogenesis remain underexplored. In our study, the protective effect of cyanidin-3- O-glucoside (C3G) was investigated on the 3-chloro-1,2-propanediol (3-MCPD) caused rat spermatogenic disorders. At low doses, C3G improved the number and motility of the sperms, alleviating the seminiferous tubule injury. Interestingly, C3G showed no influence on sexual hormone but increased the androgen receptor expression. Meanwhile, C3G reduced the oxidative stress and number of apoptotic cells and promoted the integrity of the blood-testis barrier in the testis. Additionally, C3G mediated the activation of p-ERK, p-JNK, and p53, which are related to the protection of Sertoli cells and spermatogenesis. In conclusion, C3G protected against the 3-MCPD caused testis damage and spermatogenic disorders under appropriate doses, which indicates the potential protection of anthocyanins on male reproduction.

Recent advances of medical foods in China: The opportunities and challenges under standardization.

Malnutrition with high incidence in hospitalized patients in China has brought a significant burden of disease. Although many clinical studies have demonstrated the importance of nutritional for patients with malnutrition, the application of medical foods in China is still restricted. For the classification, limits, production and registration of medical foods, the Chinese government newly enacted a series of regulations. In this review, comparing the policy, researches, and product variety of medical foods in China with other countries, although the current status of the development of medical foods in China is still far behind that of developed countries, some of regulations are stricter than those of many other countries or organizations. The medical foods in China are divided into four categories, the nutrients and environmental contaminants are limited to ensure the safety. As a prospect, the development of medical foods in China is expected to get out of the predicament of lack of emphasis, shortage of supply, backward of local processing technology and the imperfect management system. After all, in view of the huge population and the increasing demand of nutrition in China, there must be a very good prospect for the future development of the medical foods industry in China.

Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported.

Cyanidin-3-O-Glucoside Protects against 1,3-Dichloro-2-Propanol-Induced Reduction of Progesterone by Up-regulation of Steroidogenic Enzymes and cAMP Level in Leydig Cells.

1,3-Dichloro-2-propanol (1,3-DCP) is a food processing contaminant and has been shown to perturb male reproductive function. Cyanidin-3-O-glucoside (C3G), an anthocyanin antioxidant, is reported to have protective effects on many organs. However, it remains unclear whether C3G protects against chemical-induced reproductive toxicity. The present study was therefore to investigate the intervention of C3G on 1,3-DCP-induced reproductive toxicity in R2C Leydig cells. Results demonstrated that C3G inhibited the 1,3-DCP-induced cytotoxicity and cell shape damage with the effective doses being ranging from 10 to 40 µmol/L. In addition, 1,3-DCP (2 mmol/L) exposure significantly increased the ROS level and mitochondrial membrane potential damage ratio, leading to a decrease in progesterone production, while C3G intervention reduced the ROS level, and increased the progesterone production after 24 h treatment. Most importantly, C3G intervention could up-regulate the cyclic adenosine monophosphate (cAMP) level and protein expression of steroidogenic acute regulatory protein and 3ß-hydroxysteroid dehydrogenase. It was concluded that C3G is effective in reducing 1,3-DCP-induced reproductive toxicity via activating steroidogenic enzymes and cAMP level.