HMG-CoA Reductase Activity Research Articles

In Silico and In Vitro Analysis of Tacca Tubers (Tacca leontopetaloides) from Banyak Island, Aceh Singkil Regency, Indonesia, as Antihypercholesterolemia Agents

Tacca leontopetaloides (T. leontopetaloides) contain a number of active compounds such as flavonoids, tannins, phenolics, steroids, and alkaloids. The active compounds from plants have been shown to reduce the risk of cardiovascular disease by lowering cholesterol levels by inhibiting the enzyme 3-hydroxy-3-methylglutaryl-coenzym A (HMG-CoA) reductase activity. This study aims to investigate the potential active compounds in the ethanolic extract of Tacca tubers (T. leontopetaloides) from the Banyak Islands, Aceh Singkil Regency, Aceh Province both in vitro and in silico. Tacca tubers contain secondary metabolites including flavonoids, phenolics, tannins, steroids and saponins, according to phytochemical screening. In vitro investigation of ethanolic extract of Tacca tuber revealed inhibitory activity of HMG Co-A reductase with an IC50 value of 4.92 ppm. Based on the in silico study, active compound from the extract, namely Stigmasterol with the highest binding affinities with HMG Co-A reductase (-7.2 kcal/mol). As a comparison, the inhibition of HMG Co-A reductase activity by simvastatin with an IC50 4.62 ppm and binding affinity -8.0 Kcal/mol. Our findings suggest that the ethanolic extract of Tacca tuber (T. leontopetaloides) from Banyak Islands, Aceh Province has the potential to inhibit the activity of HMG Co-A reductase.

Abstract 11397: Circulating Human Metabolites Resulting From TOTUM-070 Absorption (a Plant-Based, Polyphenol-Rich Hypocholesterolemic Ingredient) Improve Lipid Metabolism in Human Hepatocytes: Lessons From an Original ex vivo Clinical Trial

Introduction: TOTUM-070 is a patented polyphenol-rich compound which has shown hypocholesterolemic properties in preclinical studies. However, clinically validated approaches and further investigations on the mode of action at cellular level especially in humans are required for optimized care management. In this study, we designed an ex-vivo clinical innovative approach considering the metabolites produced by the digestive tract following the ingestion of TOTUM-070 in humans. Methods: Human serum was collected in healthy subjects before and following acute intake of 5g of TOTUM-070. Availability of circulating metabolites was confirmed and characterized by UPLC-MS. Human serum enriched with metabolites deriving from TOTUM-070 absorption was further incubated with human hepatocytes, pretreated or not with palmitate (250 μM). In such lipotoxic environment, hepatocyte behavior was monitored to determine whether and how TOTUM-070 metabolites may improve cholesterol metabolism in human. Results: In the presence of the human metabolites from TOTUM-070, human hepatocytes were protected from an induced lipotoxic stress. No effect on cell toxicity was detected in the presence of enriched sera. Hepatocyte protection was characterized by (1) the inhibition of both triglycerides (-41%, p<0.001) and cholesterol (-50%, p<0.001) storage, (2) a reduced de novo cholesterol synthesis (HMG-CoA reductase activity reduced by 44%, p<0.001), (3) a lowered fatty acid synthase expression (p<0.001), (4) the stimulation of the Lecithin Cholesterol Acyl Transferase (LCAT) activity (p<0.05) and finally (5) a higher CYP7A1 expression (p<0.05). All together, these data provide new biochemical insights into the mechanisms underlying, in humans, the beneficial impact of TOTUM-070 on lipid metabolism in liver cells. Conclusion: Using a pioneering clinical ex vivo approach considering the digestive processes of nutrients, we give clues on the role of circulating metabolites produced following TOTUM-070 intake in humans in hepatocyte protection.

Chemical characterization of Passiflora edulis extracts and their in vitro antioxidant, anti-inflammatory, anti-lipid activities, and ex-vivo vasodilation effect

Passion fruit is a dietary plant with the protective proterties against many diseases such as cardiovascular diseases. The aim of this study was to explore the biological properties (anti-oxidant, anti-inflammatory, anti-lipid, and vascular relaxation) of the P. edulis extracts obtained from seed (PSEE) and fruit (PFWE). Thin-layer chromatography (TLC) and HPLC were used to analyze the phytochemical constituents in the extracts. Antioxidant and enzyme inhibition properties were examined. Anti-inflammatory activities of PFWE and PSEE were evaluated in lipopolysaccharide (LPS)-induced macrophages and ex-vivo vascular relaxation were also determined. A high contents of piceatannol and polyphenolic stilbene were found in PSEE extracts. On the other hand, beta-carotene and gamma-tocopherol were predominant in PFWE. PFWE exhibited stronger anti-oxidant activity than PSEE. Both PSEE and PFWE showed significant inhibition of lipase and cholesterol esterase activities. However, only PFWE showed minimal inhibitory effect against HMG-CoA reductase. PSEE and PFWE caused a significant reduction of nitric oxide level in LPS-induced inflammation in RAW264.7 cells. Both extracts also showed ex-vivo vasorelaxation of rat aortic rings. It has been demonstrated that PFWE and PSEE possesses anti-oxidant activity, anti-inflammatory activity, pancreatic lipase and cholesterol esterase, and ex-vivo vasorelaxation of rat aortic rings, however, the activity of HMG-CoA reductase was inhibited by only PFWE. These findings suggest the beneficial effect of PSEE and PFWE against hyperlipidemia thus preventing the development of hypertension. However, further investigations in animal are needed to elucidate.

Anti-inflammatory, cytotoxicity and antilipidemic properties: novel bioactivities of true cinnamon (Cinnamomum zeylanicum Blume) leaf

BackgroundThe leaf of Ceylon cinnamon (true cinnamon) is traditionally claimed for a variety of health benefits. However, reported scientific information is scanty and needs urgent attention for value addition.MethodsEthanolic (95%) and Dichloromethane:Methanol (DM, 1:1 v/v) leaf extracts of Ceylon cinnamon were evaluated for a range of medically important bioactivities namely anti-inflammatory [nitric oxide scavenging activity (NOSA), superoxide scavenging activity (SCA), COX1 and COX2 inhibition], growth inhibition & cytotoxicity against MCF7, HePG2 and AN3CA carcinoma cell lines, glutathionase-S-transferase (GST) inhibition and antilipidemic (anti-HMG-CoA reductase, anti-lipase, anti-cholesterol esterase, and cholesterol micellization inhibition) properties in vitro (n = 3). Further, a range of bioactive compounds in both leaf extracts was also quantified (n = 3).ResultsBoth leaf extracts had all the investigated bioactive compounds and possessed moderately potent bioactivities compared to the reference drugs used in the study. Ethanolic leaf extract (ELE) exhibited the highest activities (IC50: μg/mL) for NOSA (40.26 ± 0.52), SCA (696.24 ± 40.02), cholesterol esterase inhibition (110.19 ± 1.55), cholesterol micellization inhibition (616.69 ± 7.09), GST inhibition (403.78 ± 2.70) and growth inhibition (GI50: 144.84 ± 1.59-269.00 ± 0.51) & cytotoxicity (LC50: 355.44 ± 9.38-717.71 ± 23.69) against studied cancer cell lines. In contrast, COX1 & COX2 (IC50: 6.62 ± 0.85 and 44.91 ± 3.06 μg/mL) and HMG-CoA reductase & lipase inhibitory activities (36.72 ± 4.74 and 19.71 ± 0.97% inhibition at 200 and 600 μg/mL) were highest in DM extract. ELE also showed the highest quantities (0.81 ± 0.06-104.38 ± 1.79) of tested compounds (mg/g extract) where eugenol was the highest and gallic acid was the lowest among quantified.ConclusionBoth leaf extracts of Ceylon cinnamon had all the tested bioactive compounds and possess all the investigated bioactivities. This is the 1st study to report all the investigated bioactivities of the leaf of Ceylon Cinnamon.

Krill Oil Inhibits Cholesterol Synthesis and Stimulated Cholesterol Excretion in Hypercholesterolemic Rats.

The present study aimed to investigate the antihypercholesterolemic effects of krill oil supplementation in high-cholesterol diet-induced hypercholesterolemic rats, and the mechanisms underlying these effects. Rats were divided into five groups: normal control, control (high-cholesterol diet), krill oil 100 mg/kg b.w. (high-cholesterol diet with Krill oil 100 mg/kg b.w.), and krill oil 200 mg/kg b.w. (high-cholesterol diet with Krill oil 200 mg/kg b.w.). After 12 weeks, the rats were sacrificed to observe the effects of krill oil on cholesterol synthesis and excretion. We found that krill oil supplementation suppressed total triglycerides, total cholesterol, and LDL-cholesterol levels, as well as HMG-CoA reductase activity. It stimulated AMPK phosphorylation, LDL receptor and ACAT2 expression in the liver, and the fecal output of cholesterol. Furthermore, it decreased the levels of P-selectin, sVCAM-1, and NO, as well as aortic wall thickness, demonstrating its role in the prevention of atherosclerosis. Thus, we suggest that krill oil supplementation can reduce LDL-cholesterol levels in the blood during hypercholesterolemia by stimulating the uptake of LDL-cholesterol into tissue and cholesterol excretion, as well as inhibition of cholesterol synthesis.

Anti-HMG-CoA reductase, antioxidant, anti-urease potentials, and anti-leukemia properties of 4-Butylresorcinol as a potential treatment for hypercholesterolemia

ABSTRACT Leukemia is a type of dangerous cancer in humans. Many efforts have been done to find effective drugs to treat leukemia. One of the suitable options is the antioxidant molecules. Thus, the discovery of novel metabolites against cancer cells is of interest in current biomedicine. HMG-CoA Reductase activity was determined according to the method described by Takahashi S. et al. The MTT protocol was applied to determine the anti-leukemia potentials of 4-Butylresorcinol. Because of the 4-Butylresorcinol study, IC50 of HMG-CoA reductase enzyme: 182.04 micromolar was obtained, for urease IC50 was 91.44 micromolar. Molecular docking calculations were made to learn the theoretical activities of the 4-Butylresorcinol against the 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase reductase (PDB ID: 4I6A) and urease enzyme (PDB ID: 4H9M). Afterward, ADME/T calculations were made so that the molecule could be used as a drug. Additionally, the anticancer effects of molecule samples against the leukemia cells (KASUMI-1, HL-60, THP-1‎, K-562‎, RS4;11‎, and MOLT-4‎) were investigated. The aim of this study is to find a candidate compound for drug design that we recorded 4-Butylresorcinol as a good inhibitor and as an anticancer potential.

In vitro Inhibitory HMG-CoA Reductase Activity of Purified Polyphenol Compounds from Water Lettuce (Pistia Stratiotes) Leaf Extract

In vitro Inhibitory HMG-CoA Reductase Activity of Purified Polyphenol Compounds from Water Lettuce (Pistia Stratiotes) Leaf Extract

Anti-atherosclerotic Effects of Myrtenal in High-Fat Diet-Induced Atherosclerosis in Rats

The major cause of death worldwide is atherosclerosis-related cardiovascular disease (ACD). Myrtenal was studied to determine control rats were given standard diets and a high-fat diet was given to AS model groups. Atherosclerosis-related cardiovascular disease (ACD) is globally attributed to being a predominant cause of mortality. While the beneficial effects of Myrtenal, the monoterpene from natural compounds, are increasingly being acknowledged, its anti-atherosclerotic activity has not been demonstrated clearly. The present study is proposed to determine the anti-atherosclerotic activity of Myrtenal in high-fat diet-induced atherosclerosis (AS) rat models. Control groups were maintained with standard diets, the AS model rats were provided a high-fat diet, two of the experimental groups fed with a high-fat diet were treated with Myrtenal (50mg/kg and 100mg/kg), and one experimental group on high-fat diet was treated with simvastatin (10mg/kg) for 30days. The levels of inflammatory cytokines were analyzed using kits. The lipoproteins and the lipid profile were estimated using an auto-analyzer. The atherogenic index and marker enzyme activities were also determined. Serum concentrations of 6-keto-prostaglandin F1α (6-keto-PGF1α), thromboxaneB2 (TXB2), endothelin (ET), and nitric oxide (NO) were measured. The AS model groups indicated altered lipid profile, lipoprotein content, atherogenic index, calcium levels, HMG-CoA reductase activity, collagen level, and mild mineralization indicating atherosclerosis, while the AS-induced Myrtenal-treated groups demonstrated anti-atherogenic activity. The Myrtenal-treated groups exhibited a decreased TC, TG, and LDLc levels; increased HDLc levels; and a decline in the inflammatory cytokines such as CRP, IL-1β, IL-8, and IL-18 when compared to the untreated AS rats. Furthermore, Myrtenal decreased ET, TXB2, and 6-keto-PGF1α levels indicating its anti-atherosclerotic activity. The study results thus indicate that Myrtenal modulates the lipid metabolic pathway to exert its anti-atherosclerotic activity.

Modulation of obesity associated metabolic dysfunction by novel lipophilic fraction obtained from Agaricus bisporus

AimThe present study aimed to prepare a novel lipophilic fraction rich in fat soluble bioactive from Agaricus bisporus and investigated its impact through in vitro and in vivo assessments since the prospective biological activities of fat soluble components from mushrooms are limited. MethodsErgosterol concentrate fraction (ECF) preparation followed by subsequent characterization of the extract using various analytical techniques (HPLC-UV, Mass spectroscopy, NMR). Furthermore, the fraction has been evaluated for antioxidant activity, DNA protection ability, hypolipidemic properties by in vitro specific enzyme inhibition and in vivo animal model (C57BL/6). Key findingsThe fraction majorly contains ergosterol (504 mg/100 g dw) and linoleic acid (71.92 %). In vitro studies showed that the fraction limited free radicals induced DNA damage, exhibited significant free radical scavenging activities (IC50 of DPPH 15.64; ABTS 8.28 mg/ml), and inhibited HMG-CoA reductase activity (IC50 5.03 mg/ml). Further, in vivo study showed that ECF treatment significantly (p < 0.05) improved insulin sensitivity (reduced plasma glucose & insulin, increased adiponectin) and reduced inflammatory markers (CRP & TNF-α) in comparison to high fat fed mice. Furthermore, ECF has significantly reduced plasma lipid profile and accumulation of lipids in liver. This could be due to down regulation of mRNA expression of lipogenic transcription factors such as SREBP-1c and SREBP-2, and key lipogenic enzyme ACC. Moreover, ECF treatment has suppressed protein expression of FAS, induced cholesterol clearance by enhancing LDL-R protein expression. SignificanceThe present work for the first time evaluated the synergistic potential of ergosterol and linoleic acid to improve antioxidant defense system and ameliorate obesity associated metabolic dysfunction.

Activity of Phenolic Compounds in Figs (Ficus carica L.) as Antihyperlipidemic through in Silico Study

&lt;p&gt;Figs (Ficus carica L.) belongs to family Moraceae which contains a lot of phenolic compounds that have an antihyperlipidemic effect. However, the phenolic compounds of figs have not been intensively studied. The purpose of this study was to determine the activity of phenolic compounds in figs as antihyperlipidemic in inhibiting the work of the HMG-CoA reductase enzyme. This research uses an experimental technique with the in silico method. The in-silico method was performed to predict the physicochemical, pharmacokinetic, toxicity, and molecular docking properties by comparing the phenolic compounds in figs and Pravastatin with the HMG-CoA reductase receptor. Rutaretin, Pimpinellin dan Seselin has the highest affinity values, met the physicochemical, pharmacokinetic, and toxicity parameters compared to Psoralen, 8-Methoxypsoralen, Angelicin, Bergapten and Pravastatin control compounds. The presence of this binding enzyme was able to inhibit the work activity of HMG-CoA reductase with amino acid residues Cys526, Gln814, Ile536, Leu811, Ile762, Pro813, Ala763, Ala556, Val538, Pro535, Tyr533, Met534, Gly765, Tyr517, Val522, Cys527. These results suggest that phenolic compounds Rutaretin, Pimpinellin, and Seselin in figs could be an antihyperlipidemic on inhibiting the action of HMG-CoA reductase enzyme.&lt;/p&gt;

Comprehensive study of chemical composition and biological activity of Thymus pubescens Boiss. et Kotschy ex Čelak.

The use of Thymus species amongst the public and their importance in the scientific world is increasing day by day. In addition to being consumed as tea and spice, Thymus species are used as folk medicine for respiratory, digestive, skin, circulatory, genital, nervous, visual and urinary diseases. In this study, it was aimed to examine the essential oil and ethanol extract of the root and aerial parts of Thymus pubescens Boiss. et Kotschy ex Celak in the terms of their biological activity and chemical content. The phenolic content of the species was determined by LC-MS/MS, while triterpenoid content, the chemical composition of the essential oil as well as flavour was determined by GC–MS. In addition, their antioxidant and cytotoxic activities, as well as acetyl- (AChE) and butyrylcholinesterase (BChE), urease, tyrosinase, elastase, collagenase, HMG-CoA reductase and angiotensin-converting enzyme (ACE) inhibitory activities were studied. Thymol (53.33%) was determined as the major component in the essential oil, while β-fenchyl alcohol (43.87%) was determined as the major component of the flavour. According to the LC-MS/MS and GC–MS results, it was found that especially the aerial parts of the species have a high amount of rosmarinic acid (3875.76 µg analyte/g extract), quinic acid (2392.55), naringenin (970.39), oleanolic (92785.96) and ursolic (63373.32) acids. The essential oil of T. pubescens species was observed to show high activity in four antioxidant assays, e.g. inhibition of lipid peroxidation, DPPH and ABTS radical scavenging activity as well as CUPRAC, while the ethanol extracts showed moderate antioxidant activity. In enzyme inhibition assays, the aerial parts exerted marked BChE, elastase, and collagenase inhibitory activities (92.43±1.28%, 42.59±0.56, and 48.61±0.39 at 100 µg/mL, respectively). On the other hand, AChE, urease, tyrosinase, HMG-CoA reductase and ACE inhibitory activities of all extracts were from low to moderate levels. In particular, the aerial parts of the species displayed a high cytotoxic effect (vitality%: 6.82±0.01 at 200 µg/mL) in breast cancer (MCF-7) cell line. Due to its remarkable antioxidant capacity, high content of rosmarinic, oleanolic, and ursolic acids and especially BChE, elastase, and collagenase inhibitory activity, T. pubescens has the potential for using in food supplements, food preservatives, cosmetics, and pharmaceutical industries.

A mechanistic review on immunomodulatory effects of selective type two cannabinoid receptor β-caryophyllene.

β-Caryophyllene (BCP) is a plant-derived compound and occurs naturally in various foods and spices, including cinnamon, citrus, fruits, clove, curry, and pepper. BCP showed different pharmacological effects, such as antioxidant and antimicrobial properties. This article tried to gather updated knowledge of the anti-inflammatory, antioxidant, and immunomodulatory effects of BCP and searched using various databases and appropriate keywords until April 2022. Several studies showed that the anti-inflammatory effects of BCP are mainly provided through cannabinoid receptor 2 (CB2 ) receptor activation and the peroxisome proliferator-activated receptor (PPAR) γ pathway. It has also been demonstrated that BCP suppresses both protein and mRNA expression levels of interleukin (IL)-6 and reduces relevant proinflammatory cytokines but increases the anti-inflammatory cytokine IL-13. Previous results indicated that the antioxidant effects of β-caryophyllene were suggested through different pathways, including activation of nuclear factor erythroid 2-related factor-2 (Nrf2)/heme oxygenase-1 (HO-1)/antioxidant axis and inhibition of the HMG-CoA reductase activity, and oxidative stress biomarkers levels. Furthermore, various results showed immunomodulatory effects of BCP through inhibiting microglial cells, CD4+ and CD8+ T lymphocytes, modulated Th1 /Treg immune balance through the activation of the CB2 receptor, and reducing mitogen-activated protein kinases (p38MAPK) and NF-kB activation and increased ionized calcium-binding adaptor molecule-1 (Iba-1) and IL-1β.

Roles for inter‐organelle contacts in organizing metabolism

When faced with nutrient shortage, cells adapt by remodeling their metabolic pathways and organelles. I will discuss our work using budding yeast to dissect how nutrient shortage impacts the spatial organization of metabolism and lipid droplets. We find that in response to glucose restriction, yeast remodel their mevalonate pathway by spatially compartmentalizing its rate‐limiting enzyme, HMG‐CoA Reductase (HMGCR). HMGCR spatial compartmentalization occurs at a unique inter‐organelle contact site called the nucleus‐vacuole junction (NVJ). This spatial partitioning enhances HMGCR activity, driving mevalonate synthesis to enable cellular adaptation. Our work suggests a new use for an inter‐organelle contact site in the fine‐tuning of mevalonate metabolism during nutrient stress.Remarkably, we also find that glucose restriction drives the phase transition of lipids within lipid droplets (LDs), causing them to convert from a disordered to liquid‐crystalline phase. Mechanistically, we find that these liquid crystalline lattices (LCLs) within LDs require triglyceride lipolysis. We also find that LCL‐LDs exhibit changes to the LD surface proteome. Several known LD proteins redistribute from LDs to the ER network, whereas others remain on LCL‐LDs, suggesting phase transitions of LD lipids influences LD protein targeting. Global proteomics also reveals that triglycerides harvested from LDs fuel cellular energetics at peroxisomes and mitochondria. This indicates that glucose starvation induces inter‐organelle lipid flux while promoting lipid phase transitions within LDs.

Subchronic Exposure to Benzene Induced Lipotoxic and Non-Lipotoxic Perturbations of Lipid Metabolic Dynamics in Male Wistar Rats

Benzene is a ubiquitous environmental pollutant. In this study, the effect of benzene exposure on lipid metabolism was investigated. Male albino rats were exposed to 100, 200, and 300 mg/kg body weight benzene through oral gavage for 12 weeks. At the end of the exposure, changes in lipid dynamics in the plasma, lipoprotein fractions, liver, and brain were investigated spectrophotometrically. One-way analysis of variance, followed by Tukey’s test was used to analyze the results with p &lt; 0.05 considered significant. Exposure to benzene for 12 weeks significantly (p &lt; 0.05) increased the concentration of plasma free fatty acids and reduced the plasma concentration of cholesterol and triacylglycerol. Benzene exposure also increased the triacylglycerol concentration in the plasma and lipoprotein fractions of the exposed animals. Furthermore, the exposure significantly (p &lt; 0.05) reduced the phospholipid concentrations in the plasma and lipoprotein fractions of the benzene-exposed animals. Benzene exposure significantly (p &lt; 0.05) reduced HDL cholesterol concentration. The exposure also resulted in a significant (p &lt; 0.05) elevation of cholesterol and phospholipids in the liver and brain of the exposed animals. The activity of HMG CoA reductase in the liver and brain of benzene-exposed animals was also enhanced significantly. Findings from the present study indicated that exposure to benzene perturbs lipid metabolic homeostasis through the induction of lipotoxic and non-lipotoxic dyslipidemia. Exposure to benzene may therefore represent an important risk factor in the pathogenesis of cardiovascular diseases.

Sesamum indicum diet prevents hyperlipidemia in experimental rats

Cardiovascular diseases and metabolic complications caused by hyperlipidemia are the leading cause of death globally. In this study, the hypolipidemic potency of Sesamum indicum (SI) seeds was investigated. Of the thirty-five (35) male rats used in the study, five (5) were randomly selected for baseline measurements and thirty (30) were fed high fat diet (HFD) for four (4) weeks before random assignment into three (3) groups. The experimental group was treated with 50% SI seed, the positive control group was given a hypolipidemic drug, atorvastatin (5 mg/kg/day) while the untreated group served as the negative control. With SI administration, the dyslipidemia induced by the HFD consumption in the plasma and the investigated body organs was reversed to a comparable degree with that of atorvastatin treatment. Taken together, this study demonstrates the hypolipidemic potency of SI in ameliorating hyperlipidemia and its associated complications, facilitated by the inhibition of HMG-CoA reductase activity.

Metformin enhances LDL-cholesterol uptake by suppressing the expression of the pro-protein convertase subtilisin/kexin type 9 (PCSK9) in liver cells.

Metformin (MF) intake associates with reduced levels of circulating low-density lipoprotein-cholesterol (LDL-C). This has been attributed to the activation of AMPK, which differentially regulates the expression of multiple genes involved in cholesterol synthesis and trafficking. However, the exact mechanism underlying the LDL-C lowering effect of MF remains ambiguous. MF-treated Hep-G2 and HuH7 cells were evaluated for cell viability and the expression status of key lipid metabolism-related genes along with LDL-C uptake efficiency. MF treatment resulted in decreased expression and secretion of PCSK9, increased expression of LDLR and enhanced LDL-C uptake in hepatocytes. It also resulted in increased expression of activated AMPK (p-AMPK) and decreased expression of SREBP2 and HNF-1α proteins. Transcriptomic analysis of MF-treated Hep-G2 cells confirmed these findings and showed that other key lipid metabolism-related genes including those that encode apolipoproteins (APOB, APOC2, APOC3 and APOE), MTTP and LIPC are downregulated. Lastly, MF treatment associated with reduced HMG-CoA reductase expression and activity. These findings suggest that MF treatment reduces circulating LDL-C levels by suppressing PCSK9 expression and enhancing LDLR expression; hence the potential therapeutic utility of MF in hypercholesterolemia.

Therapeutic properties of isoliquiritigenin with molecular modeling studies: investigation of anti-pancreatic acinar cell tumor and HMG-CoA reductase inhibitor activity for treatment of hypercholesterolemia.

Isoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have 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. HMG-CoA reductase activity was determined according to the method described by Takahashi et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with the X-ray diffraction method (PDB ID: 1HWK) was obtained from the PDB database. In our study, the inhibitory activity of isoliquiritigenin towards HMG-CoA reductase showed a lower value of IC50 = 193.77 ±14.85 μg/ml. For a better understanding of biological activities and interactions, the molecular docking study was performed. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the activity of isoliquiritigenin against common human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47, was evaluated. The cells treated with isoliquiritigenin were assessed by MTT assay for 48 h as regards the cytotoxicity and anti-human pancreatic acinar cell tumor properties in normal (HUVEC) and human pancreatic acinar cell tumor cell lines, i.e. 266-6, TGP49, and TGP47. The IC50 values of isoliquiritigenin were 262, 389, and 211 μg/ml against 266-6, TGP49, and TGP47 cell lines, respectively. The viability of the human pancreatic acinar cell tumor cell line decreased dose-dependently in the presence of isoliquiritigenin. After clinical study, isoliquiritigenin can be utilized as an efficient drug in the treatment of human pancreatic acinar cell tumor in humans.

Hydroethanolic Extracts of Senna alata Leaves Possess Antimalarial Effects and Reverses Haematological and Biochemical Pertubation in Plasmodium berghei-infected Mice.

The current work investigated the chemical profile, antimalarial potential and capacity of hydroethanolic Senna alata extract (SAE) to reverse hematological and biochemical pertubation in Plasmodium berghei infected mice. Results of the phytochemical analysis revealed the presence of alkaloids, flavonoids, phenolics, tannins, terpenoids, saponins, steroids and cardiac glycosides. Total phenolic and flavonoid content was estimated to be 45.29 ± 2.34 mg GAE/g and 25.22 ± 2.26 mg QE/g respectively. In vitro analysis of the extract also confirmed its antioxidant property. Results of the test for prophylaxis of P. berghei indicated that SAE suppressed parasitemia significantly in treated groups in a dose dependent manner when compared with negative control group. Similarly, SAE improved the mean survival time (MST) and packed cell volume (PCV) of infected mice. The test for curative effect showed that SAE significantly suppressed parasitemia to 4.50 ± 1.05% compared to untreated group 29.83 ± 3.49%. Results of liver and kidney functions indices of treated animals indicated that whereas infection with P. berghei caused increase in the levels of AST, ALT, ALP, urea and creatinine, treatment with SAE significantly reversed the perturbation. Similarly, infected mice were dyslipidemic with concomitant increased activity of HMG CoA reductase and decreased activity of antioxidant enzymes with increase in lipid peroxides levels. However, these alterations were significantly reversed by administration of SAE. Results of this study shows that Senna alata possess antimalarial activity and therefore justify the traditional use of plant for the treatment of malaria.

Effects of octacosanol on HMG-CoA reductase and cyclooxygenase-2 activities in the HT-29 human colorectal cancer cell line

Effects of octacosanol on HMG-CoA reductase and cyclooxygenase-2 activities in the HT-29 human colorectal cancer cell line

HMG-COA REDUCTASE INHIBITORY ACTIVITY OF EXTRACT AND CATECHIN ISOLATE FROM UNCARIA GAMBIR AS A TREATMENT FOR HYPERCHOLESTEROLEMIA

The article describes a new idea of plant-based hypercholesterolemia treatment. Statins are commonly used for hypercholesterolemia treatment. Due to the side effects of statins, natural HMG-CoA reductase inhibitors plant-based are needed. Based on the affordability and less toxicity, the plant has increasing acceptability for treating ailments. The 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase is the key enzyme of the mevalonate pathway producing cholesterol. Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in a liver. As an Indonesian plant containing catechin, Uncaria gambir can reduce cholesterol in the blood through HMG-CoA reductase inhibitory activity. This study aims to investigate the potential antihypercholesterolemic of the extract and catechin isolate of Uncaria gambir. Gambier leaves were extracted in water. The catechin from gambier extract was isolated with ethyl acetate-hexane using column chromatography. Phytochemical analysis of extract and catechin isolate were conducted by high-performance liquid chromatography (HPLC). Antioxidant activity was tested using a 2.2-diphenyl-1-picrylhydrazyl (DPPH) assay with vitamin C as a positive control. The inhibitory activity of HMG-CoA enzymes was carried out enzymatically using an HMG-CoA reductase assay kit by spectrophotometric and simvastatin as a standard. The results showed that the catechin in the extract was 68.32% while in isolate - 96.74%. The extract's scavenging activity (IC50) was 6.2 μg/mL, catechin isolate was 2.4 μg/mL, and vitamin C was 4.1 μg/mL. The in-vitro assessment of HMG-CoA reductase activity indicated 73.12%; 97.46%; 85.74% inhibition by the extract, catechin isolate, and simvastatin, respectively. Catechin isolate from Uncaria gambir showed strong HMG-CoA reductase inhibitory activity offers a high potential for hypercholesterolemia treatment.