Dyslipidemia is a lifestyle-related (physical inactivity or obesity) disease; therefore, dietary foods that can easily be consumed in daily life is important to prevent dyslipidemia. Ergosterol, a precursor of vitamin D2, is a fungal sterol present in the membranes of edible mushrooms and other fungi. Ergosterol is converted to brassicasterol by 7-dehydrocholesterol reductase (DHCR7), a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3) into cholesterol. Previously, we reported that ergosterol increases 7-dehydrocholesterol, decreases cholesterol levels by competitive effect of DHCR7, and reduces DHCR7 mRNA and protein levels in human HepG2 hepatoma cells. Here, we investigated the effects of long-term high ergosterol intake on the cholesterol, vitamin D2, and D3 biosynthetic pathways of rats fed a high-fat and high-sucrose (HFHS) diet using gas chromatography–mass spectrometry and liquid chromatography with tandem mass spectrometry. In HFHS rats, oral ergosterol administration for 14 weeks significantly decreased plasma low-density lipoprotein cholesterol, total bile acid, and cholesterol precursor (squalene and desmosterol) levels and increased 7-dehydrocholesterol levels compared to HFHS rats without ergosterol. Ergosterol, brassicasterol, and vitamin D2 were detected, cholesterol levels were slightly decreased, and levels of vitamin D3 and its metabolites were slightly increased in rats fed HFHS with ergosterol. These results showed that ergosterol increased vitamin D2 levels, inhibited the cholesterol biosynthetic pathway, and possibly promoted vitamin D3 biosynthesis in vivo. Therefore, daily ergosterol intake may aid in the prevention of dyslipidemia.
Inflammatory bowel disease (IBD) is a worldwide issue, and the increased incidence has brought a heavy burden to patients and society. Gut microbiota is involved in the pathogenesis of IBD, and targeting the microbiota, such as probiotics, has emerged as a potential therapy for the treatment of IBD. Here, the effect of Bifidobacterium animalis subsp. lactis LKM512 (LKM512), an anti-aging probiotic, on dextran sulfate sodium salt (DSS)-induced IBD in larval zebrafish was determined. Supplementation of LKM512 promoted the survival rate of the larvae, together with increased locomotor activities and body length. In addition, LKM512 treatment enhanced mucus secretion and alleviated intestinal injury, and these results were associated with the upregulation of mucin-related and inflammatory markers. Moreover, LKM512 increased the diversity of the microbiota and ameliorated the dysbiosis by increasing the abundance of Bacteroidetes and Firmicutes and reducing the abundance of Proteobacteria. Specifically, the abundance of beneficial bacteria, including the SCFAs-producing genera Lachnospiraceae_NK4A136_group, Muribaculaceae, and Alloprevotella, was increased by LKM512, while the abundance of harmful genera, such as Pseudomonas, Halomonas, and Escherichia-Shigella, was reduced by LKM512. Consistent with these findings, the microbial functions related to metabolism were partly reversed by LKM512, and importantly, fermentation of short-chain fatty acids-related functions were enhanced by LKM512. Therefore, LKM512 might be one potential probiotic for the prevention and treatment of IBD, and further studies that clarify the mechanism of LKM512 would promote the application of LKM512.
The involvement of serotonin (5-HT) and/or noradrenaline in acute pruriceptive processing in the central nervous system (CNS) has been reported using antidepressants, such as milnacipran, a serotonin and noradrenaline reuptake inhibitor, and mirtazapine, a noradrenergic and specific serotonergic antidepressant; however, the roles of 5-HT receptor family in acute pruriceptive processing have not been fully elucidated in the CNS. In the present study, scratching behavior induced by chloroquine (CQ) was ameliorated by milnacipran or mirtazapine, and these effects were reversed by SB207266, a 5-HT4 antagonist, or SB258585, a 5-HT6 antagonist, but not by SB258585, a 5-HT5 antagonist. Moreover, CQ-induced scratches were mitigated by intrathecal injection of 5-HT4 agonists, such as BIMU8 and ML10302, and the 5-HT6 agonist, WAY208466. Conversely, histamine-induced scratches were not affected by the 5-HT4 agonists or a 5-HT6 agonist. Similarly, the amelioration of histamine-induced scratches by these antidepressants was not reversed by the 5-HT4, 5-HT5, or 5-HT6 receptor antagonist. Therefore, 5-HT is involved in the amelioration of CQ-induced scratches by milnacipran and mirtazapine, and 5-HT4, 5-HT5, and 5-HT6 receptors play differential roles in acute pruriceptive processing after administration of CQ or histamine.
Osmundacetone (DHBAc) is an antioxidant compound that has been shown to have neuroprotective and immunomodulatory activities. However, few studies have estimated its effect on cerebral ischemia-reperfusion (I/R) injury. In this study, we investigated the protective effect of DHBAc on the brain tissue of rats with cerebral I/R injury. Rats were respectively given nimodipine (NI), low dose (L-DHBAc) and high dose (H-DHBAc) Osmundacetone, and they were killed under anesthesia after 24 hours of reperfusion. And neurological impairment scores, cerebral infarct size and cerebral pathological changes were respectively detected, and mRNA expression of recombinant kelch like ECH associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), protein expression levels of caspase3, cleaved caspase3, heme oxygenase-1 (HO-1) and quinone oxidoreductase1 (NQO1) in ischemic brain tissue were measured. Compared with the I/R group, neurological impairment scores of the DHBAc groups were significantly decreased, and their infarct sizes were significantly smaller. DHBAc could improve the pathological status of brain tissue with cerebral I/R injury, including reducing number of inflammatory cells and area of vacuoles and restoring number of normal neurons. Expression levels of Keap1 mRNA and proteins of cleaved caspase3 were significantly decreased in the DHBAc groups than those of the I/R group, while expression levels of Nrf2 mRNA, HO-1 and NQO1 proteins were remarkably increased. The effect of H-DHBAc was similar to those of NI. These results suggest that DHBAc could mitigate damage to brain tissue in rats with cerebral I/R injury.
Psoriasis is classically regarded as a Th1 response-dominant disease believed to be antagonized by the Th2 response, which is responsible for allergic diseases, such as atopic dermatitis. The roles of these responses in psoriasis and the relationship between psoriasis and atopic dermatitis have received increasing attention because it is estimated that more than one million patients are concomitantly affected by psoriasis and atopic dermatitis. To address this, we attempted to determine the characteristics of imiquimod-induced psoriasiform lesions in mice with a concomitant allergic response after co-application of the unrelated allergen ovalbumin onto the skin. Imiquimod cream containing ovalbumin was successively applied to the right back skin of hairless HR female mice. Psoriasiform scores were determined for 11 days, and then, the resected skin thickness, spleen weight, and serum antibody levels were examined. In some experiments, mice were allowed free access to ovalbumin-containing water for 10 days before skin application to induce oral tolerance. Imiquimod cream induced psoriasis, and its severity increased upon simultaneous ovalbumin treatment. Increases in anti-ovalbumin IgG2a levels, a Th1 response indicator, and IgG1 and IgE levels, Th2 response indicators, were mediated by ovalbumin addition. Oral tolerance against ovalbumin effectively decreased ovalbumin-exacerbated imiquimod-induced psoriasis, in parallel with a decrease in levels of anti-ovalbumin antibodies. These results suggest that the concomitant allergic response induced by ovalbumin application exacerbates imiquimod-induced psoriasis. This implies that allergic responses to unrelated allergens might exacerbate psoriasis in humans and that modulating such responses could be an effective new approach to treat psoriasis.
This study examined the effects of 1,8-cineole on reducing oxidative stress injury and restoring mitochondrial function in oxygen-glucose deprivation and reoxygenation (OGD/R) HT22 cells via the nuclear factor erythrocyte 2 related factor 2 (Nrf2) pathway. The optimal concentration of 1,8-cineole to reduce OGD/R injury was screened via cell morphology, cell survival rate, and lactate dehydrogenase (LDH) leakage rate. Oxidative damage was observed by measuring superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), catalase (CAT) activities, and reactive oxygen species (ROS), glutathione (GSH), protein carbonyl, malondialdehyde (MDA), lipid peroxidation (LPO) content, and 8-hydroxy-2 deoxyguanosine (8-OHDG) expression. Mitochondrial function was observed by mitochondrial membrane potential (MMP) and ATPase activity. Nrf2 pathways were observed by the expression levels of total Nrf2, nucleus Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), the mRNA levels of HO-1 and NQO1. Among different concentrations of 1,8-cineole for promoting HT22 cell proliferation and attenuated OGD/R injury, 10 μmol/L 1,8-cineole was the best. After 1,8-cineole treatment, SOD, GSH-PX, and CAT activities and GSH content increased, while ROS, MDA, LPO, protein carbonyl, and 8-OHDG levels decreased. 1,8-Cineole could restore MMP and increase mitochondrial enzyme activity. It could also increase the total Nrf2, nucleus Nrf2, NQO1, and HO-1, and Nrf2 inhibitor brusatol reduced the effect of 1,8-cineole. Immunofluorescence assay showed that 1,8-cineole could facilitate the transfer of Nrf2 into the nucleus. 1,8-cineole increased the mRNA levels of NQO1 and HO-1. The above results showed that 1,8-cineole could alleviate OGD/R-induced oxidative damage and restores mitochondrial function by activating the Nrf2 signal pathway.
Neuropathic pain is one of the most intractable diseases. The lack of effective therapy measures remains a critical problem due to the poor understanding of the cause of neuropathic pain. The aim of this study was to investigate the effect of dexmedetomidine (Dex) in trigeminal neuropathic pain and the underlying molecular mechanism in order to identify possible therapeutic targets. We used a chronic constriction injury (CCI) model of mice to investigate whether Dex prevents neuropathic pain and the inflammation response. The α 2-adrenoceptors (α2AR) inhibitor BRL44408 and adenovirus for knocking down High mobility group box 1 (HMGB1) was administrated to confirm whether Dex exert its effect through targeting α2AR and HMGB1. The results indicated that Dex significantly inhibited CCI induced neuropathic pain through targeting α2AR and HMGB1. Dex inhibited the inflammatory response through decreasing the release and the mRNA expression of IL-1β, IL-6, and TNF-ɑ while increasing that of IL-10. Moreover, Dex participates in the regulation of HMGB1, Toll-like receptor 4 (TLR4), NFκb (p-65) expression and the phosphorylation of IκB-ɑ. In conclusion, Dex could relieve neuropathic pain through α2AR and HMGB1 and attenuate inflammation response.