Nutritional Agonists of PPAR-γ: An Immunomodulatory Approach to Control Cytokine Storm in Covid19 Patients

Recent examinations express that multi organ failure is seen in Corona virus infected patients with different pathway. It has been shown in contemplates that increased levels of cytokines like IL-1B and INF gamma were observed. It is called as cytokine storm with higher convergences of CCL2 and CXCL10. The cytokine storm is trailed by our immune system attacking own body which thus may cause numerous organ abnormalities and conclusive outcome being death. There is currently no specific treatment for viral illness, and this methodology is an optional path for focusing on specific qualities that may diminish cytokine storm. In such manner Peroxisome Proliferators Activated Receptors (PPARs) have a place with group of transcription factors which are known to manage the inflammatory mechanisms in body. This immunomodulatory approach is intended to focus PPAR-gamma ligands and their molecular docking studies. The activation or increased expression levels of PPAR gamma because of chosen agonists may reduce the cytokine storm in the covid patients. Thus, this is one such fascinating way to deal with neutralization of the cytokines exorbitantly elevated by use of substances like pomegranate, lemon grass and so on to activate PPARs reliably.

MicroRNA29a Reverts the Activated Hepatic Stellate Cells in the Regression of Hepatic Fibrosis through Regulation of ATPase H+ Transporting V1 Subunit C1

Activated hepatic stellate cells (aHSCs) play a key role in liver fibrosis. During the regression of fibrosis, aHSCs are transformed into inactivated cells (iHSCs), which are quiescent lipid-containing cells and express higher levels of lipid-related genes, such as peroxisome proliferators-activated receptors gamma (PPARγ). Here, we investigated the role of MicroRNA29a (Mir29a) in the resolution of liver fibrosis. Mir29a and lipid-related genes were up-regulated after the recovery of CCl4-induced liver fibrosis in mice. PPARγ agonist rosiglitazone (RSG) promoted de-differentiation of aHSCs to iHSCs and up-regulated MIR29a expression in a human HSC cell line LX-2. MIR29a mimics in vitro promoted the expression of lipid-related genes, while decreased the expression of fibrosis-related genes. MIR29a inhibitor showed the reverse effects. ATPase H+ transporting V1 subunit C1 (Atp6v1c1) was increased in liver fibrosis, while down-regulated after the recovery in mice, and negatively regulated by MIR29a in LX-2 cells. Knockdown of ATP6V1C1 by siRNA decreased alpha-smooth muscle actin (α-SMA) and increased lipid-related genes expression. Simultaneous addition of MIR29a mimics and ATP6V1C1 siRNA further increased RSG promoted expression of lipid-related proteins in vitro. Collectively, MIR29a plays an important role during the trans-differentiation of aHSCs in the resolution of liver fibrosis, in part, through regulation of ATP6V1C1.

DESIGN OF NEW PEROXISOME PROLIFERATORS GAMMA ACTIVATED RECEPTOR AGONISTS (PPARγ) VIA QSAR BASED MODELING

The Peroxisome proliferators-activated receptors (PPARs) are one of the nuclear fatty acid receptors, which contain a type II zincfinger DNA binding pattern and a hydrophobic ligand binding pocket. These receptors are thought to play an essential role in metabolic diseasessuch as obesity, insulin resistance, and coronary artery disease. Therefore Peroxisome Proliferators-Activated Receptor (PPARγ) activators havedrawn great recent attention in the clinical management of type 2 diabetes mellitus, prompting several attempts to discover and optimize newPPARγ activators. Objective: The aim of the study was to finding new selective human PPARγ (PPARγ) modulators that are able to improveglucose homeostasis with reduced side effects compared with TZDs and identify the specific molecular descriptor and structural constraint toimprove the agonist activity of PPARγ analogs. Material and Method: Software’s that was used for this study include S.P. Gupta QSARsoftware (QSAR analysis), Valstat (Comparative QSAR analysis and calculation of L-O-O, Q2, r2, Spress), BILIN (Comparative QSAR analysisand calculation of Q2, r, S, Spress, and F), etc., allowing directly performing statistical analysis. Then multiple linear regression based QSARsoftware (received from BITS-Pilani, India) generates QSAR equations. Result and Discussion: In this study, we explored the quantitativestructure–activity relationship (QSAR) study of a series of meta-substituted Phenyl-propanoic acids as Peroxisome Proliferators Gamma activatedreceptor agonists (PPARγ).The activities of meta-substituted Phenyl-propanoic acids derivatives correlated with various physicochemical, electronic and steric parameters.Conclusion: The identified QSAR models highlighted the significance of molar refractivity and hydrophobicity to the biological activity.

Antidiabetic Activity of Polysaccharides from Tuberous Root ofLiriope spicatavar.proliferain KKAy Mice

Tuberous root ofLiriope spicatavar.proliferahas been widely used as a traditional Chinese medicine for the treatment of diabetes. The present study investigated the antidiabetic effect and the potential mechanisms of two new polysaccharides (LSP1, LSP2) and the total polysaccharides (TLSP), isolated from the tuberous roots. Upon the intragastric administration in obese insulin-resistant diabetic KKAy mice for 28 days, TLSP, LSP1, and LSP2 all caused a remarkable decrease of fasting blood glucose and significant improvement of insulin resistance and serum lipid metabolism in diabetic mice. In addition, liver histological analysis showed that TLSP, LSP1, and LSP2 significantly ameliorated the hepatocyte hypertrophy and decreased the lipid accumulation in the mice liver. Further experiments suggested that TLSP, LSP1, and LSP2 effectively inhibited hepatic gluconeogenesis and increased hepatic glycolysis and hepatic glycogen content. Furthermore, the mechanistic analysis showed the increased expression of insulin-receptorαsubunit, insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and peroxisome proliferators-activated receptorsγ. These results suggested that TLSP, LSP1, and LSP2 manifest strong antidiabetic activity, therefore hold a great promise for therapeutic application in diabetic therapy and other related metabolic disorders.

Dual PPARα/γAgonism Normalizes Lipoprotein Profile of Renal Dyslipidemia

Chronic kidney disease (CKD) is characterised by specific lipoprotein abnormalities and insulin resistance. Dual activation of the peroxisome proliferators-activated receptors (PPAR)αandγcan significantly improve insulin sensitivity. The aim of the study was to investigate the effects of a dual PPARα/γagonist on lipoprotein abnormalities in patients with CKD. One mg of the dual PPARα/γagonist tesaglitazar was given once daily during six weeks to CKD patients, and to healthy subjects. Plasma lipids, apolipoproteins (apo) and discrete lipoprotein subclasses were measured at baseline and end of treatment. In the CKD patients apoA-I increased significantly by 9%, and apoB decreased by 18%. There was an increase of apoC-III in HDL by 30%, and a parallel decrease of apoC-III in VLDL + LDL by 13%. Both the apoB-containing cholesterol-rich and the triglyceride-rich subclasses decreased significantly. With the exception of ApoC-III,all plasma lipids apolipoproteins and lipoprotein subclasses were reduced by treatment down to similar levels as the baseline levels of a healthy group of reference subjects. This study suggests that by improving insulin sensitivity a dual PPARα/γagonist has the potential to normalise most of the lipoprotein abnormalities in patients with CKD.

PPARs Signaling and Cancer in the Gastrointestinal System

Nowadays, the study of the peroxisome proliferators activated receptors (PPARs) as potential targets for cancer prevention and therapy has gained a strong interest. From a biological point of view, the overall responsibility of PPARs in cancer development and progression is still controversial since several studies report both antiproliferative and tumor-promoting actions for these signaling molecules in human cancer cells and animal models. In this paper, we discuss PPARs functions in the context of different types of gastrointestinal cancer.

Lipid Mediators in Acne

Multiple factors are involved in acne pathogenesis, and sebum secretion is one of the main ones. The role sebum plays in acne development has not been completely elucidated yet; however, increasing amounts of data seem to confirm the presence of alterations in sebum from acne patients. Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid. Furthermore, particular attention has been focused on squalene peroxide that seems to be able to induce an inflammatory response beyond cytotoxicity and comedones formation. Moreover, recent data suggest that lipid mediators are able to interfere with sebocytes differentiation and sebogenesis through the activation of pathways related to peroxisome proliferators-activated receptors. Understanding the factors and mechanisms that regulate sebum production is needed in order to identify novel therapeutic strategies for acne treatment.