Hypothalamic astrocyte NAD+ salvage pathway mediates the coupling of dietary fat overconsumption in a mouse model of obesity.

Nicotinamide adenine dinucleotide (NAD)+ serves as a crucial coenzyme in numerous essential biological reactions, and its cellular availability relies on the activity of the nicotinamide phosphoribosyltransferase (NAMPT)-catalyzed salvage pathway. Here we show that treatment with saturated fatty acids activates the NAD+ salvage pathway in hypothalamic astrocytes. Furthermore, inhibition of this pathway mitigates hypothalamic inflammation and attenuates the development of obesity in male mice fed a high-fat diet (HFD). Mechanistically, CD38 functions downstream of the NAD+ salvage pathway in hypothalamic astrocytes burdened with excess fat. The activation of the astrocytic NAMPT-NAD+-CD38 axis in response to fat overload induces proinflammatory responses in the hypothalamus. It also leads to aberrantly activated basal Ca2+ signals and compromised Ca2+ responses to metabolic hormones such as insulin, leptin, and glucagon-like peptide 1, ultimately resulting in dysfunctional hypothalamic astrocytes. Our findings highlight the significant contribution of the hypothalamic astrocytic NAD+ salvage pathway, along with its downstream CD38, to HFD-induced obesity.

[Formula: see text], a Rare Protopanaxatriol-Type Ginsenoside Fraction from Black Ginseng, Suppresses Inflammatory Gene iNOS via the Iinhibition of p-STAT-1 and NF-[Formula: see text]B.

Black ginseng (BG), which is ginseng that has been steamed and dried nine times, and its main protopanaxatriol-type ginsenosides Rg4, Rg6, Rh4, and Rg2 have been reported to exhibit various forms of biological activity, including antiseptic, antidiabetic, wound-healing, immune-stimulatory, and anti-oxidant activity. The aim of the this study was to examine the effects of [Formula: see text] (a rare protopanaxatriol-type ginsenoside fraction; Rg2, Rg4, Rg6, Rh1, and Rh4) on heme oxygenase-1 (HO-1) induction and on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-)2 in lipopolysaccharide (LPS)-activated human pulmonary artery endothelial cells (HPAECs). [Formula: see text] was tested to determine its effect on iNOS protein expression and inflammatory markers (interleukin [IL]-1[Formula: see text] and tumor necrosis factor [TNF]-[Formula: see text] in the lung tissue of LPS-treated mice. The results showed that [Formula: see text] induced the expression of HO-1, reduced LPS-activated NF-[Formula: see text]B-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, which contributed to the inhibition of STAT-1 phosphorylation. In particular, [Formula: see text] induced the translocation of Nrf2 from the cytosol to the nucleus by increasing Nrf2-ARE activity and decreased IL-1[Formula: see text] production in LPS-activated HPAECs. This reduction in iNOS/NO expression due to [Formula: see text] was reversed by siHO-1 RNA transfection. In LPS-treated mice, [Formula: see text] significantly reduced lung tissue iNOS protein levels and TNF-[Formula: see text] levels in the bronchoalveolar lavage fluid. In conclusion, these findings indicate that [Formula: see text] has a critical anti-inflammatory effect due to its ability to regulate iNOS via the inhibition of p-STAT-1 and NF-[Formula: see text]B, and thus it may be suitable for the treatment of inflammatory disease.

Inhibitory effects of compounds isolated from Dioscorea batatas Decne peel on particulate matter-induced pulmonary injury in mice.

Particulate matter 2.5 (PM2.5), with an aerodynamic diameter of ≤2.5 µm, is the primary air pollutant that plays a key role associated with lung injury produced by loss of vascular barrier integrity. Dioscorea batatas Decne (Chinese yam), a perennial plant belonging to Dioscoreaceae family, is widely cultivated in tropical and subtropical regions across Asia. Both aerial parts and root of D. batatas are consumed for nutritional and medicinal purposes. The aim of this study was to (1) identify the bioactive compounds present in D. batatas peel which may be responsible for inhibition of PM2.5-induced pulmonary inflammation in mice and (2) examine in vitro mechanisms underlying the observed effects of these compounds on mouse lung microvascular endothelial cells. The measured parameters include permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology. Two phenanthrene compounds, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2) were isolated from D. batatas peels. Both these phenanthrene compounds exhibited significant scavenging activity against PM2.5-induced ROS and inhibited ROS-induced activation of p38 mitogen-activated protein kinase. In addition, enhancement of Akt pathway, involved in the maintenance of endothelial integrity, was noted. These phenanthrene compounds also reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid obtained from PM2.5-induced lung tissues. Evidence thus indicates that phenanthrene compounds derived from D. batatas may exhibit protective effects against PM2.5-induced inflammatory lung injury and vascular hyperpermeability in mice.

Suppressive effects of collismycin C on polyphosphate-mediated vascular inflammatory responses.

Human endothelial cells-derived polyphosphate (PolyP) is one of the pro-inflammatory mediators as suggested by the previous reports. 2,2'-bipyridine containing natural products are generally accepted to have antimicrobial, cytotoxic and anti-inflammatory properties. This study was undertaken to investigate whether a 2,2'-bipyridine containing natural product, collismycins C, can modulate PolyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. After HUVECs or mice were activated with PolyP, cells or mice were post-treated with collismycins C. The anti-inflammatory activities of collismycins C were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in PolyP-activated HUVECs and mice. In addition, the beneficial effects of collismycins C on survival rate in PolyP-injected mice. Collismycins C inhibits PolyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, PolyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by collismycins C in HUVECs. These anti-inflammatory functions of collismycins C were confirmed in PolyP injected mice. In conclusion, based on the anti-inflammatory effects of collismycins C in PolyP-mediated septic response, collismycins C have therapeutic potential for various systemic inflammatory diseases.

Sequential Fenton oxidation and hydrothermal treatment to improve the effect of pretreatment and enzymatic hydrolysis on mixed hardwood.

Sequential Fenton oxidation (FO) and hydrothermal treatment were performed to improve the effect of pretreatment and enzymatic hydrolysis of mixed hardwood. The molar ratio of the Fenton reagent (FeSO4·7H2O and H2O2) was 1:25, and the reaction time was 96h. During the reaction, little or no weight loss of biomass was observed. The concentration of Fe(2+) was determined and was found to increase continuously during FO. Hydrothermal treatment at 190-210°C for 10-80min was performed following FO. Sequential FO and hydrothermal treatment showed positive effects on pretreatment and enzymatic hydrolysis. Xylose concentration in the hydrolysate was as high as 14.16g/L when FO-treated biomass was treated at 190°C, while its concentration in the raw material was 3.72g/L. After 96h of enzymatic hydrolysis, cellulose conversion in the biomass obtained following sequential treatment was 69.58-79.54%. In contrast, the conversion in the raw material (without FO) was 64.41-67.92%.