585 nm light-emitting diodes inhibit melanogenesis through upregulating H19/miR-675 axis in LEDs-irradiated keratinocytes by paracrine effect.

BACKGROUND: 585 nm light-emitting diodes have been proven to suppress melanogenesis in melanocytes. However, whether LEDs will influence normal human epidermal keratinocytes (NHEKs) and paracrine effect of LEDs-irradiated NHEKs in melanogenesis remains unknown. OBJECTIVE: To elucidate the possible mechanisms in vitro of anti-melanogenic activity of 585 nm LEDs on paracrine effect of NHEKs and its exosomes. METHODS: NHEKs irradiated with different fluences of 585 nm LEDs were evaluated the cell viability by CCK8 assay. Irradiated medium of NHEKs was co-cultured with melanocytes. Melanin content, tyrosinase activity and melanogenic enzymes activities were detected. Exosomes from NHEKs medium were isolated and characterized by electron microscopy and nanoparticle tracking analysis. The expression changes of H19 and its encoded exosomal miR-675 were analyzed. RESULTS: Irradiation with 585 nm LEDs from 0 J/cm2 to 20 J/cm2 had no cytotoxic effect on NHEKs. After co-cultured with irradiated medium of NHEKs, melanin content and tyrosinase activity were reduced and the melanogenic activities were downregulated on both mRNA and protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). H19 and its derived exosomal miR-675 from NHEKs, which has been proven relevant to melanogenesis, were significantly upregulated after irradiation. Furthermore, H19 knockdown and miR-675 inhibition in NHEKs could attenuate the inhibition effect of 585 nm LEDs on melanogenesis. CONCLUSIONS: This study demonstrated that 585 nm LEDs could inhibit melanogenesis via the up-regulation of H19 and its derived exosomal miR-675 from NHEKs, which was considered as a novel paracrine factor in regulating melanogenesis.

Astragaloside IV Attenuates Myocardial Ischemia-Reperfusion Injury from Oxidative Stress by Regulating Succinate, Lysophospholipid Metabolism, and ROS Scavenging System.

Astragaloside IV is one of the main active ingredients isolated from Astragalus membranaceus. Here we confirmed its protective effect against cardiac ischemia-reperfusion (I/R) injury and aimed to investigate the potential molecular mechanisms involved. Pretreatment of ex vivo and in vivo I/R-induced rat models by astragaloside IV significantly prevented the ratio of myocardium infarct size, systolic and diastolic dysfunction, and the production of creatine kinase and lactate dehydrogenase. Metabolic analyses showed that I/R injury caused a notable reduction of succinate and elevation of lysophospholipids, indicating excessive reactive oxygen species (ROS) generation driven by succinate's rapid reoxidization and glycerophospholipid degradation. Molecular validation mechanistically revealed that astragaloside IV stimulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) released from Kelch-like ECH-associated protein 1 (Keap1) and translocated to the nucleus to combine with musculoaponeurotic fibrosarcoma (Maf) to initiate the transcription of antioxidative gene heme oxygenase-1 (HO-1), which performed a wide range of ROS scavenging processes against pathological oxidative stress in the hearts. As expected, increasing succinate and decreasing lysophospholipid levels were observed in the astragaloside IV-pretreated group compared with the I/R model group. These results suggested that astragaloside IV ameliorated myocardial I/R injury by modulating succinate and lysophospholipid metabolism and scavenging ROS via the Nrf2 signal pathway.

Danshen injection prevents heart failure by attenuating post-infarct remodeling.

ETHNOPHARMACOLOGICAL RELEVANCE: Danshen Injection (DSI) is a traditional Chinese medicine extracted from Danshen, prepared from the dried root and rhizome of Salvia miltiorrhiza Bunge. Danshen is an ancient antipyretic traditional Chinese medicine which is mostly used to improve blood circulation and dispel blood stasis. Danshen decoction or liquor-fried Danshen (with grain-based liquor) which is cool in nature is traditionally used to 'cool the blood' and reduce the swelling of sores and abscesses. AIM OF STUDY: The present study aimed to examine the effect and mechanism of DSI in LAD induced heart injury. MATERIALS AND METHODS: One day after LAD surgery, adult male Sprague-Dawley rats were randomized to 3 groups: MI group; DSI group (1.5ml/kg/d, intramuscular); and Valsartan group (10mg/kg/d, intragastric). Echocardiography and hemodynamic measurements (Pressure-Volume loop) were performed to evaluate cardiac function. Pathological methods (Masson, and Sirus red staining) were used to check myocardial fibrosis. Western blotting assay was used to detect the protein expression of MMP-2. RT-PCR was used to detect the gene expression of MMP-9, MPO, iNOS, Bcl-2 and Bax. RESULTS: DSI administration to LAD rats resulted in improved cardiac functions, hemodynamic parameters and normalized ventricular mass. Furthermore, DSI-treated group demonstrated potential regulation of myocardial collagen I and III deposition associated with MMP-2 expression. Also, DSI administration decreased gene expression of iNOS, MPO and MMP-9, and increased Bcl-2/Bax ratio. CONCLUSION: Myocardial fibrosis, cardiac hypertrophy, hemodynamic deterioration as well as systolic and diastolic dysfunctions which characterize a failing hearts were significantly prevented by DSI. Our study may provide future directions to focus on the anti-hypertrophic mechanisms of DSI and pathological roles played by MMP-2 in myocardial hypertrophy. Meanwhile, DSI also performed the effect of anti-inflammation by the way of decreasing iNOS and MPO. The way Danshen Injection increasing Bcl-2/Bax presented the possibility that it may has the effect of inhibiting cell death.

Danzhi Qing'e (DZQE) activates AMPK pathway and regulates lipid metabolism in a rat model of perimenopausal hyperlipidaemia.

What is the central question of this study? Does Danzhi Qing'e (DZQE) regulate lipid metabolism and improve ovarian function in a rat model of perimenopausal hyperlipidaemia, and could this effect be mediated through the AMPK pathway? What is the main finding and its importance? We revealed that DZQE is a pharmacotherapy that could activate the AMPK pathway to improve ovarian function and lipid metabolism during perimenopause complicated with hyperlipidaemia syndrome in an animal model. Thus, this study provides a novel therapeutic option for treating perimenopausal syndrome and highlights the therapeutic potential of DZQE in perimenopausal rats. Menopause is an important event in a woman's life. During perimenopause, accompanied by development of osteoporosis and dyslipidaemia, ovarian function gradually declines. Dyslipidaemia is a risk factor for cardiovascular disorders, cerebrovascular disease and breast cancer in postmenopausal women. All of these contribute to impairment of liver function, particularly fatty liver disease, because liver dysfunction is associated with ovarian dysfunction and hyperlipidaemia. The aim of this study was to define a therapeutic approach to improve ovarian function and attenuate lipid accumulation in order to prevent perimenopause-induced ovarian dysfunction and hyperlipidaemia. Four-week-old female Wistar rats were injected i.p. with 4-vinylcyclohexene diepoxide (4-VCD) and fed with a high-fat diet (HFD) to serve as a model of perimenopause complicated with hyperlipidaemia. The 4-VCD induces perimenopause, while the HFD causes hyperlipidaemia. Five days after administration of 4-VCD, the 4-VCD + HFD-treated rats were assessed daily for oestrous cycle stage by vaginal cytology. Rats were then assigned into groups, in which 2.5, 5.0 or 10.0 g kg-1 Danzhi Qing'e (DZQE) or estradiol valerate was administered intragastrically for 8 weeks. Expression levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestrogen and testosterone measured by enzyme-linked immunosorbent assay served as biomarkers for perimenopause and ovarian dysfunction. The expression levels of AMPK and acetyl-CoA carboxylase in the liver were determined with Western blotting, and aspartate aminotransferase and alanine aminotransferase were analysed using an automated biochemical analyser to examine liver function. The DZQE improved ovarian function by upregulating oestrogen and testosterone concentrations in serum and downregulating FSH and LH serum concentrations. Moreover, DZQE reduced serum concentrations of triglyceride, total cholesterol and low-density lipoprotein in a dose-dependent manner to regulate lipid levels during perimenopause. Furthermore, DZQE increased AMPK at both the transcriptional and translational levels and decreased the expression of SREBP-1c gene as well as its downstream target gene, fatty acid synthase. Danzhi Qing'e improved dyslipidaemia during menopause and also had an effect on liver function. Danzhi Qing'e is an effective Chinese herbal compound, which improves ovarian function and lipid metabolism in perimenopause complicated with hyperlipidaemia at least in part through the AMPK pathway.