Therapeutic properties of Isoliquiritigenin with molecular modeling studies: Investigation of anti-pancreatic acinar cell tumor and as HMG-CoA reductase inhibitor for treatment of hypercholesterolemia

IntroductionIsoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels.Material and methodsHMG-CoA Reductase activity according to the method described by Takahashi S. et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with X-RAY diffraction method (PDB ID: 1HWK) was obtained from the PDB database.ResultsIn our study, inhibition result of Isoliquiritigenin on HMG-CoA reductase showed lower value IC50 = 193.77±14.85 µg / mL. For a better understanding of biological activities and interactions, the molecular docking study was accomplished. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to the HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the properties of Isoliquiritigenin against common human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47 were evaluated.ConclusionsThe treated cells with Isoliquiritigenin were assessed by MTT assay for 48h about the cytotoxicity and anti-human pancreatic acinar cell tumor properties on normal (HUVEC) and human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47. The IC50 of Isoliquiritigenin were 262, 389, and 211 µg/mL against 266-6, TGP49, and TGP47 cell lines, respectively.

Enhanced 3-Hydroxypropionic Acid Production From Acetate via the Malonyl-CoA Pathway in Corynebacterium glutamicum

Acetate is an economical and environmental-friendly alternative carbon source. Herein, the potential of harnessing Corynebacterium glutamicum as a host to produce 3-hydroxypropionic acid (3-HP) from acetate was explored. First, the expression level of malonyl-CoA reductase from Chloroflexus aurantiacus was optimized through several strategies, strain Cgz2/sod-N-C* showed an MCR enzyme activity of 63 nmol/mg/min and a 3-HP titer of 0.66 g/L in flasks. Next, the expression of citrate synthase in Cgz2/sod-N-C* was weakened to reduce the acetyl-CoA consumption in the TCA cycle, and the resulting strain Cgz12/sod-N-C* produced 2.39 g/L 3-HP from 9.32 g/L acetate. However, the subsequent deregulation of the expression of acetyl-CoA carboxylase genes in Cgz12/sod-N-C* resulted in an increased accumulation of intracellular fatty acids, instead of 3-HP. Accordingly, cerulenin was used to inhibit fatty acid synthesis in Cgz14/sod-N-C*, and its 3-HP titer was further increased to 4.26 g/L, with a yield of 0.50 g 3-HP/g-acetate. Finally, the engineered strain accumulated 17.1 g/L 3-HP in a bioreactor without cerulenin addition, representing the highest titer achieved using acetate as substrate. The results demonstrated that Corynebacterium glutamicum is a promising host for 3-HP production from acetate.

Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β-conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investigation. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels.

An Update on New Cholesterol Inhibitor: Bempedoic Acid

: An increase in the level of cholesterol day by day is easily seen in most people just because of poor life style, food with high cholesterol, lack of physical work, etc. There are lots of molecules available, which lower down the cholesterol level. In this field a new molecule has been introduced that is bimpedoic acid. Researches indicate that bempedoic acid has the same mechanism of action as statins, which means that it also inhibits the HMG-CoA reductase enzyme. This letter to the editor is my best collection of published scientific data on bempedoic acid till now. It also includes the chemistry, pharmacodynamic and pharmacokinetic parameters of the mentioned new molecule.