Psoriasis is a skin disease that is characterized by a high degree of inflammation caused by immune dysfunction. (R)-salbutamol is a bronchodilator for asthma and was reported to alleviate immune system reactions in several diseases. In this study, using imiquimod (IMQ)-induced mouse psoriasis-like dermatitis model, we evaluated the therapeutic effects of (R)-salbutamol in psoriasis in vivo, and explored the metabolic pathway involved. The results showed that, compared with IMQ group, (R)-salbutamol treatment significantly ameliorated psoriasis, reversed the suppressive effects of IMQ on differentiation, extreme keratinocyte proliferation, and infiltration of inflammatory cells. Enzyme-linked immunosorbent assays (ELISA) showed that (R)-salbutamol markedly reduced the plasma levels of IL-17. Cell analysis using flow cytometry showed that (R)-salbutamol decreased the proportion of CD4+ Th17+ T cells (Th17), whereas it increased the percentage of CD25+ Foxp3+ regulatory T cells (Tregs) in the spleens. (R)-salbutamol also decreased the weight ratio of spleen to body. Furthermore, untargeted metabolomics showed that (R)-salbutamol affected three metabolic pathways, including (i) arachidonic acid metabolism, (ii) sphingolipid metabolism, and (iii) glycerophospholipid metabolism. These results demonstrated that (R)-salbutamol can alleviate IMQ-induced psoriasis through regulating Th17/Tregs cell response and glycerophospholipid metabolism. It may provide a new use of (R)-salbutamol in the management of psoriasis.
Garcinia species are widely used for their slimming effects via increased fat burning and suppression of satiety. However, scientific evidence for the biological effects of Garcinia atroviridis (GA) is lacking. We investigated the phytochemical composition, safety profiles, and antioxidant and antiobesity effects of methanolic extracts of Garcinia atroviridis (MeGa) in obese female rats. Repeated dose toxicity studies were conducted according to the OECD guidelines. Upon sacrifice, haematological, biochemical, lipid profile, and serum-based metabolomics analyses were performed to evaluate metabolic expression changes and their related pathways. MeGa contains several phytochemical groups and GA fruit acids. MeGa was found to be nontoxic in both male and female rats with an oral lethal dose (LD50) of 2000 mg/kg. After 9 weeks of treatment, MeGa-treated obese rats had lower weight gain and better lipid profiles (cholesterol and triglyceride), which correlated with the altered metabolic pathways involved in the metabolism of lipid (glycerophospholipid) and biosynthesis of unsaturated fatty acid. In addition, MeGa caused differential metabolism pathways of arachidonic acid and tryptophan that affect the inflammatory response and suppression of appetite. We concluded that MeGa is safe, and its slimming effects are due to the differential metabolism of lipids.
Cell impurities are an emerging nucleating molecular barriers having the capability in disordering the metabolic chain reactions of proteolysis, glycolysis and lipolysis. Their massive effects induced by copolymer crystal growth in compaction with metal and mineral transients are extended as well as in damaging DNA and mRNA structure motif and other molecular assembly e.g. histones structure unites. Their polycrystalline packing modes, polydispersity and their tendency to surface and interface adhesion prompted us in structuring scaffold biomaterials enriched with biopeptides, layered by phospho-glycerides ester-forms. The interface tension of the formed map is flexible and dependent to the surface exposure and its collapse modes to the surrounding molecular ligands. Thus, the attempts in increasing surface exposure e.g. the viscoelastic of structured lipopeptides and types of formed network structures interplays an extra- conjugating biomolecules having a least cytotoxicity effects to cells constituents. Disulfides molecules are selected to be the key regulatory element in rejoining both lipidic and proteic moieties by disordering atoms status via chemical ionization using organic catalyst. The insertion of methionine based peptidic chain at the lateral surfaces of scaffold biomaterials enhances the electron-meta-static motions by raising a molecular disordering status at distinct regions of the map e.g. epimerization into a nonpolar side that helps the chemical conjunction of disulfide groups with the esterified phosphoglycerides mono-layers. These effects in turn are accomplished by the formation of meso-sphere nonpolar- vesicles. The oxidation of disulfide group would alter the ordering of initial molecules by raising a newly molecular disorders to the map with high polarity to surface regions. In the same time indicates a continuation in the crystallization growth factor via a low chemical lesions between the impurities and a supersaturation in the intra-atomic distances with maximum cross linking to the deformed ligand with scaffold biomaterials.
Sepsis is a severe inflammatory disorder that can lead to multiple organ injury. Isosteviol sodium (STV-Na) is a terpenoid derived from stevioside that exerts anti-inflammatory, antioxidant and antiapoptotic activities. However, the influence of STV-Na on sepsis remains unknown. Here, we assessed the potential effects of STV-Na on sepsis and multiple organ injury induced by lipopolysaccharide (LPS). We found that STV-Na increased the survival rate of mice treat with LPS, significantly improved the functions of the heart, lung, liver, and kidney, reduced the production of inflammatory cytokines and decreased macrophage infiltration. Moreover, Multiorgan metabolomics analysis demonstrated that glutathione metabolism, purine metabolism, glycerophospholipid metabolism and pantothenate and CoA biosynthesis, were significantly altered by STV-Na. This study provides novel insights into the metabolite changes of multiple organ injury in septic mice, which may help characterize the underlying mechanism and provide an improved understanding of the therapeutic effects of STV-Na on sepsis.