Inhibition Of Reductase Activity Research Articles

Synthesis, α-Glucosidase, α-Amylase, and Aldol Reductase Inhibitory Activity with Molecular Docking Study of Novel Imidazo[1,2-a]pyridine Derivatives.

Inhibition ofaldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) are some of the essential targets in diabetes mellitus (DM). Here, a series of imidazo[1,2-a]pyridine-based 1,3,4-thiadiazole derivatives (8a-k) were successfully synthesized and characterized using 1H NMR, 13C NMR, and HRMS spectroscopic techniques. The inhibition effects of the synthesized derivatives against AR, α-GLY, and α-AMY were evaluated using both in vitro and in silico methods. In vitro studies revealed that the derivatives (8a-k) showed significant inhibition activity. The results showed that the novel derivatives (8a-k) demonstrated potential inhibitory activity, with K I values covering the following ranges: 23.47 ± 2.40 to 139.60 ± 13.33 nM for AR and 6.09 ± 0.37 to 119.80 ± 12.31 μM for α-GLY, with IC50 values 81.14 to 153.51 μM for α-AMY. Furthermore, many of these compounds exhibited high inhibition activity, while some of them showed higher potency than the reference compounds. Molecular docking of the target compounds was carried out in the active sites of AR (PDB ID: 4JIR) and α-GLY (PDB ID: 5NN8).

GC-MS Analysis of Chemical Constituents in Water and Methanol Crude Extracts of Red Sea Soft Coral Xenia macrospiculata Gohar, 1940

Soft corals are marine invertebrates known to be a prolific source of marine natural products. The genus Xenia is a rich source of bioactive compounds including terpenoids, steroids, saturated, unsaturated and poly unsaturated fatty acids. The water and methanol solvent extracts of soft coral Xenia macrospiculata Gohar, 1940 (X. macrospiculata) were screened for the novel chemical constituents using gas chromatography–mass spectroscopy (GC-MS). In the water extracts, seventeen compounds were identified including monounsaturated fatty acids (35.29%), saturated fatty acids (23.52%) followed by unsaturated fatty acids (5.88%), poly unsaturated fatty acid (5.88%), sesquiterpenoids (5.88%), aromatic compounds (5.88%), Alcohols (5.88%), thio compounds (5.88%) and pleuromutilin derivatives (5.88%). In methanol extract thirty compounds were identified, among which 30% are the poly unsaturated fatty acids (PUFA) followed by monounsaturated fatty acids (13.33%), unsaturated fatty acids (13.33%), saturated fatty acids (13.3%), sesquiterpenoids (10%), alcohols (6.66%), oxygenated heterocyclic compounds (3.33%), steroid (3.33%), organo-fluro compounds (3.33%) and aldehyde derivatives (3.33%). The GC-MS screening of water and methanol extracts of X. macrospiculata revealed the presence of several novel bioactive compounds. Fatty acids are potential nutraceutical compounds playing vital role in preventing the risk of cardiovascular disorders and fatty liver. In addition, these compounds also showed potential antioxidant activity, antimicrobial, antineoplastic, ichthyotoxic, cytotoxic, HIV-inhibitory, anti-inflammatory activity and 5α reductase inhibitory activity.

Drug-drug interactions between pemafibrate and statins on pharmacokinetics in healthy male volunteers: Open-label, randomized, 6-sequence, 3-period crossover studies.

Elevated triglyceride levels are associated with an increased risk of cardiovascular events despite guideline-based statin treatment of low-density lipoprotein cholesterol. Peroxisome proliferator-activated receptor α (PPARα) agonists exert a significant triglyceride-lowering effect. However, combination therapy of PPARα agonists with statins poses an increased risk of rhabdomyolysis, which is rare but a major concern of the combination therapy. Pharmacokinetic interaction is suspected to be a contributing factor to the risk. To examine the potential for combination therapy with the selective PPARα modulator (SPPARMα) pemafibrate and statins, drug-drug interaction studies were conducted with open-label, randomized, 6-sequence, 3-period crossover designs for the combination of pemafibrate 0.2 mg twice daily and each of 6 statins once daily: pitavastatin 4 mg/day (n = 18), atorvastatin 20 mg/day (n = 18), rosuvastatin 20 mg/day (n = 29), pravastatin 20 mg/day (n = 18), simvastatin 20 mg/day (n = 20), and fluvastatin 60 mg/day (n = 19), involving healthy male volunteers. The pharmacokinetic parameters of pemafibrate and each of the statins were similar regardless of coadministration. There was neither an effect on the systemic exposure of pemafibrate nor a clinically important increase in the systemic exposure of any of the statins on the coadministration although the systemic exposure of simvastatin was reduced by about 15% and its open acid form by about 60%. The HMG-CoA reductase inhibitory activity in plasma samples from the simvastatin and pemafibrate combination group was about 70% of that in the simvastatin alone group. In conclusion, pemafibrate did not increase the systemic exposure of statins, and vice versa, in healthy male volunteers.

Molecular Docking Studies and ADME-Tox Prediction of Phytocompounds from Punica granatum Peel as a Potential Anti-Alopecia Treatment

Background: Alopecia is a condition in which some or all of the hair from the scalp is lost. One recent preventative measure is the inhibition of the enzyme 5-α-reductase. Inhibition of the enzyme 5-α-reductase converts circulating testosterone to its more potent metabolite, dihydrotestosterone. Pomegranate (Punica granatum L.) peels are widely employed in industry and to treat a variety of illnesses. However, accurate identification is necessary to improve efficacy, repeatability, and quality. Pomegranate, or Punica granatum L., is a member of the Punicaceae family. It is known as "anar" or "dadima" on the Indian subcontinent. For hundreds of years, P. granatum has been used to treat conditions like peptic ulcer, dental disorders, diabetes, hypertension, hyperlipidemia, and numerous types of cancer. Method: Further scientific validation of the current investigation was done by computational based molecular docking study of lead molecules of P.granatum Peel against 5α-reducatase(SRD5As) enzyme. The binding was determined by the Auto Dock software utilizing a grid-based docking method. Compounds' 2D structures were constructed using the chem sketch, converted to 3D, and then energetically reduced up to an arms gradient of 0.01. (MMFF). Result: Punica found to be effective anti-alopecic agent and their lead molecules effectively binds to be target protein 5α-reducatase (SRD5As) with binding energy -7.15, -7.66 & -7.07 kcalmol-1 for Apigenin, luteolin and taxifolin respectively. Conclusion: The results demonstrated that every lead compound that was chosen for further study exhibited strong 5'-reductase (SRD5 As) inhibitory activity, hence eliciting the anti-alopecic potential.

Antidiabetic and aldose reductase inhibitory activity and LC-MS/MS compositional polyphenol determination of aqueous extract of Ammodaucus leucotrichus fruits

This study's objective was to examine the antidiabetic effect of the aqueous extract of Ammodaucus leucotrichus Coss. (AEAL) in diabetic rats, its aldose reductase inhibitory activity, as well as identify its major phytochemical components using LC-MS. Rats were divided into five groups: normal and diabetic control groups, three diabetic groups received 150 and 300 mg/kg of AEAL and metformin (150 mg/kg) per day for 4 weeks. Blood glucose, body weight, urinary volume, daily food consumption, water intake, hepatic glycogen, catalase, malondialdehyde. After the experimental period, the rats were sacrificed to collect blood for biochemical analysis (level of creatinine, uric acid, alanine aminotransferase, aspartate aminotransferase, triglycerides, and cholesterol). Moreover, AEAL was tested against aldose reductase, in vitro. Phytochemical analysis of the AEAL revealed a rich composition and especially high amounts of phenolic acid. The administration of the AEAL significantly reduced glycemia, triglycerides, alanine aminotransferase, aspartate aminotransferase, creatinine, uric acid, and increased the amount of hepatic glycogen. In addition, AEAL decreased urinary volume per day, induced body weight gain in diabetic rats, and inhibited aldose reductase activity.

In vitro and in silico studies of the potential cytotoxic, antioxidant, and HMG CoA reductase inhibitory effects of chitin from Indonesia mangrove crab (Scylla serrata) shells

This study aimed to characterize chitin extracted from Indonesia mangrove crab (Scylla serrata) shells, as well as to assess its in vitro cytotoxic, antioxidant, and HMG CoA reductase inhibitory potentials. In silico molecular docking, molecular dynamic, and ADMET prediction analyses were also carried out. Chitin was extracted from mangrove crab shells using deproteination and demineralization processes, Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) characterization are then performed. The MTT method was further tested in a study of cell viability, while in vitro method was used to assess HMG CoA reductase inhibitory and antioxidant activities. The extracted chitin was found to have a moderate level of cytotoxic and antioxidant activities. In vitro studies showed that it has an IC50 of 36,65 ± 0,082 μg/mL as an HMG CoA reductase inhibitor, and decreased enzyme activity by 68.733 % at 100 μg/mL as a concentration. Furthermore, in the in silico study, chitin showed a strong affinity to several targets, including HMG CoA reductase, HMG synthase, LDL receptor, PPAR-alfa, and HCAR-2 with binding energies of −5.7; −5.8; −3.6; −5.6; −4.6 kcal/mol, respectively. Based on the ADMET properties, it had non-toxic molecules, which were absorbed and distributed across the blood-brain barrier. The molecular dynamics (MD) simulation also showed that it remained stable in the active sites of HMG CoA reductase receptor for 100 ns. These results indicated that chitin from Indonesian mangrove crab shells can be used to develop more potent HMG CoA reductase inhibitor with antioxidant and cytotoxic activities for effective dyslipidemia therapy.

Lactic acid bacteria-malted vinegar: fermentation characteristics and anti-hyperlipidemic effect.

In this study, the fermentation characteristics and functional properties of lactic acid bacteria-malted vinegar (LAB-MV) were investigated during the fermentation period. Changes in the components (organic acids, free sugars, free amino acids, β-glucan, and gamma-aminobutyric acid (GABA)) of MV (BWAF0d, BWAF10d, BWAF20d) and LAB-MV (LBWAF0d, LBWAF10d, LBWAF20d) were analyzed according to the fermentation time. The amounts of β-glucan and GABA in LBWAF20d were greater than those in BWAF20d (122.00μg/mL, 83.06μg/mL and 531.00μg/mL, 181.31μg/mL, respectively). The ACE1 and HMG-CoA reductase inhibitory activities of LBWAF20d were 98.16% (1/20 dilution factor, DF) and 91.01% (1/25 DF), respectively. The lipid accumulation ratio and total cholesterol levels in HepG2 cells treated with LBWAF20d (1/200 DF) were reduced by 45.85% and 54.48%, respectively, compared to those in the untreated group. These results suggest that LAB-MV, which comprises barley wine manufactured from LAB and yeast, may improve hepatic lipid metabolism.

Angular dihydropyranocoumarins from the flowers of Peucedanum japonicum and their aldo-keto reductase inhibitory activities

Twenty-one angular dihydropyranocoumarins and a linear furanocoumarin, including four previously undescribed compounds (1–4), were isolated from the flowers of Peucedanum japonicum (Umbelliferae). The structures of 1–4, along with their absolute stereochemistry, were determined to be (3′S,4′S)-3′-O-propanoyl-4′-O-(3‴-methyl-2‴-butenoyl)khellactone (1), (3′S,4′S)-3′-O-propanoyl-4′-O-(2‴-methyl-2‴Z-butenoyl)khellactone (2), (3′S,4′S)-3′-O-propanoyl-4′-O-(2‴-methylbutanoyl)khellactone (3), and (3′S,4′S)-3′-O-(2″-methylpropanoyl)-4′-O-(3‴-methyl-2‴-butenoyl)khellactone (4) using one- and two-dimensional nuclear magnetic resonance, high-resolution electrospray ionization mass spectroscopy, and electronic circular dichroism spectroscopy. In addition, the absolute configuration of the three angular dihydropyranocoumarins (5–7) was determined for the first time in this study. Among the previously reported compounds isolated in this study, 8 and 9 were isolated for the first time from the genus Peucedanum, whereas 10 and 11 were previously unreported and had not been isolated from P. japonicum to date. Furthermore, all isolated compounds were evaluated for their aldo–keto reductase 1C1 inhibitory activities on A549 human non-small-cell lung cancer cells. Compounds 10 and 12 exhibited substantial AKR1C1 inhibitory activities with IC50 values of 35.8 ± 0.9 and 44.2 ± 1.5 μM, respectively.

Cholesterol-lowering Effect of Protein Hydrolysates from Lemongrass (Cymbopogon citratus Stapf.)

Lemongrass (Cymbopogon citratus Stapf.) has been used in the Philippines for cooking and as an herb to treat a variety of ailments including hypertension and related cardiovascular diseases (CVDs). This study determined the potential of peptides obtained from the hydrolysis of lemongrass proteins to lower cholesterol in vitro and in an animal model. Proteins were extracted and digested in vitro simulating gastrointestinal conditions. Protein hydrolysates were collected and fractionated using RP-SPE column, and assayed for HMG-CoA reductase inhibitory activity against pravastatin as a control drug. Tannin-free protein extract (TFPE) and total protein hydrolysates (TPC) were administered to Sprague-Dawley rats maintained on a high-fat high-cholesterol diet for two weeks. TFPE yield was 0.03%. Simulated gastrointestinal digestion of the TFPE resulted in 74% yield of protein hydrolysates. Three fractions were obtained from RP-SPE elution of the protein hydrolysates, each with potent HMG-CoA inhibitory activity. The F3 fraction had the highest inhibition of HMG-CoA reductase (IC50 = 0.76 ppm, comparable to pravastatin (IC50 = 0.25 ppm). The inhibitory activity of the fractions was further confirmed through significant serum cholesterol reduction (p < 0.05) in Sprague-Dawley rats. Thus, protein hydrolysates from lemongrass have potential cholesterol-lowering effects in vitro through HMG-CoA reductase inhibition and in vivo through significant reduction of cholesterol levels in an animal model. Protein hydrolysates from lemongrass dietary proteins may serve as promising functional foods for the prevention of CVD risk.

Aldose Reductase and Protein Glycation Inhibitory Activity of Dark Chocolate-Assisted Zinc Oxide Nanoparticles.

Introduction One of the most common health issues that the global population is dealing with is the associated complications of diabetes, which encompasses cataracts, peripheral neuropathy, vascular damage, impaired wound healing, retinal issues, and arterial wall stiffening. The present study is aimed to evaluate the effect of dark chocolate and its assisted zinc oxide nanoparticles against diabetes-associated complications. Materials and methods Zinc oxide nanoparticles were synthesized using commercially dark chocolate (DC-ZnO NP). The synthesized DC-ZnO NPs were evaluated against recombinant aldose reductase (AR) activity and the formation of advanced glycation end products (AGEs). Aminoguanidine and gallic acid were used as reference standards for AGE assay and sorbitol accumulation inhibition, respectively. Results The results of the present study showed that green synthesized DC-ZnO NP had a significant dose-dependent inhibitory activity on both AR and AGEs. The inhibitory activity was compared to that of quercetin and aminoguanidine, respectively. Conclusion Targeting the endogenous antioxidant systems like AGEs and AR enzymes seems to provide a promising therapeutic approach, thus concluding that ZnO-NP could be a promising agent for treating diabetes-related complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy that provide grounds for further clinical investigations and trials.

In silico exploration and in vitro validation of the filarial thioredoxin reductase inhibitory activity of Scytonemin and its derivatives

Lymphatic filariasis (LF) caused by the vector borne parasitic nematode Wuchereria bancrofti is of major concern of the World Health Organization (WHO). Lack of potential drug candidates worsens the situation. Presently available drugs are promising in killing the microfilaria (mf) but are not effective as adulticidal therapeutics. Previous studies have revealed that routine administration of the available drugs (albendazole, ivermectin and albendazole) sometime is associated with severe adverse effects (SAEs) in co-infection state. Therefore, potential and safe therapeutics are still required. Earlier studies on filarial thioredoxin reductase (TrxR) have shown that successful inhibition of it can lead to apoptotic death of the parasites. TrxR in filarial parasites plays a significant role in disease progression and pathogenesis, hence efficient non-reversible inhibition of TrxR can be a good strategy to treat LF. In this research, inhibitory potential of Scytonemin, a cyanobacterial metabolite on filarial TrxR was evaluated via different in silico methods and validated through in vitro experiments. Parasite death upon exposure to Scytonemin can be correlated with the TrxR inhibiting capacity of the compound. Therefore, this cyanobacterial-derived compound may possibly be used further as novel and safe therapeutic candidate against filarial infection. Communicated by Ramaswamy H. Sarma

Quinoline-2-one derivatives as promising antibacterial agents against multidrug-resistant Gram-positive bacterial strains.

This study describes the discovery of a variety of quinoline2-one derivatives with significant antibacterial action vs a spectrum of multidrug-resistant Gram-positive bacterial strains, especially methicillin-resistant Staphylococcus aureus (MRSA). Compounds 6c, 6l, and 6o exhibited significant antibacterial activity versus the Gram-positive bacterial pathogens evaluated. In comparison to the reference daptomycin, compound 6c demonstrated the most effective activity among the assessed derivatives, with MIC concentrations of 0.75 μg/mL versus MRSA and VRE and 2.50 μg/mL against MRSE. We also reported on these compounds' biofilm and dihydrofolate reductase inhibitory activities. Compound 6c showed the greatest antibiofilm action in a dose-dependent way and a substantial decrease of biofilm development in the MRSA ACL51 strain at concentrations of 0.5, 0.25, and 0.12 MIC, with reductions of 79%, 55%, and 38%, consecutively, whereas the corresponding values for vancomycin were 20%, 12%, and 9%. These findings imply that these quinoline compounds could be used to develop a new category of antibiotic representatives to prevent Gram-positive drug-resistant bacterial strains.

Synthesis and dihydrofolate reductase inhibitory activity of 2-amino-6-(arylaminomethyl) thieno[2,3-d]pyrimidin-4(3H)-ones

Synthesis and dihydrofolate reductase inhibitory activity of 2-amino-6-(arylaminomethyl) thieno[2,3-d]pyrimidin-4(3H)-ones

Effect of Various Solvents Extraction on the Antioxidant and Aldose Reductase Inhibition Activities of the Tamarind Leaves (Tamarindus indica L.)

Diabetes and its complications are major causes of illness and death all over the world. Present study aimed to evaluate the effect of varying polarity solvents on the extraction of tamarind leaves antioxidant polyphenols and in vitro aldose reductase inhibition. In all the extracts, total phenol, total flavonoids, antioxidant activities, and in vitro aldose reductase inhibition activity were measured. Distilled water extract had the highest phenolic content, flavonoid content, DPPH-RSA, ABTS-RSA, and aldose reductase inhibition among all the extracts while the aqueous methanol extract showed the highest FRAP value among all the extracts. A positive Pearson’s correlation existed between total polyphenol content and antioxidant activities. Significant Pearson’s correlation was found between aldose reductase and polyphenol compounds. Overall, distilled water was the most effective solvent for polyphenol extraction and had the highest aldose reductase inhibition of all the tamarind leaves solvents. Thus, tamarind leaves can be used as nutraceuticals to show beneficial effects to minimize diabetic secondary complications.

Development of new thiazolidine-2,4-dione hybrids as aldose reductase inhibitors endowed with antihyperglycaemic activity: design, synthesis, biological investigations, and in silico insights

This research study describes the development of new small molecules based on 2,4-thiazolidinedione (2,4-TZD) and their aldose reductase (AR) inhibitory activities. The synthesis of 17 new derivatives of 2,4-TZDs hybrids was feasible by incorporating two known bioactive scaffolds, benzothiazole heterocycle, and nitro phenacyl moiety. The most active hybrid (8b) was found to inhibit AR in a non-competitive manner (0.16 µM), as confirmed by kinetic studies and molecular docking simulations. Furthermore, the in vivo experiments demonstrated that compound 8b had a significant hypoglycaemic effect in mice with hyperglycaemia induced by streptozotocin. Fifty milligrams per kilogram dose of 8b produced a marked decrease in blood glucose concentration, and a lower dose of 5 mg/kg demonstrated a noticeable antihyperglycaemic effect. These outcomes suggested that compound 8b may be used as a promising therapeutic agent for the treatment of diabetic complications.

Predictive Modeling of HMG-CoA Reductase Inhibitory Activity and Design of New HMG-CoA Reductase Inhibitors.

As blood cholesterol increases, it accumulates in the intima of blood vessels, elevating the risk of atherosclerosis and coronary artery disease. Drugs that inhibit enzymes essential for cholesterol synthesis are effective in improving blood cholesterol levels. Statins are used to treat hypercholesterolemia as they inhibit 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), the rate-limiting enzyme in cholesterol synthesis. Statins are known to exert their effects by translocating to the liver, where they are taken up by the organic anion transporting polypeptide 1B1 (OATP1B1). Therefore, we hypothesized that a compound with high HMGR inhibitory activity and high affinity for OATP1B1 would be an excellent new therapeutic agent for hypercholesterolemia with increased liver selectivity and fewer side effects. In this study, we developed two models for predicting HMGR inhibitory activity and OATP1B1 affinity to propose the chemical structure of a new therapeutic agent for hypercholesterolemia with both high inhibitory activity and high liver selectivity. HMGR inhibitory activity and OATP1B1 affinity prediction models were constructed with high prediction accuracy for the test data: r2 = 0.772 and 0.768, respectively. New chemical structures were then input into these models to search for candidate compounds. We found compounds with higher HMGR inhibitory activity and OATP1B1 affinity than rosuvastatin, the most recently developed statin drug, and compounds that did not have a common structure of statins with high HMGR inhibitory activity.

Biochemical Analysis and Human Aldose Reductase Inhibition Activity of Selected Medicinal Plants of Nepal

Aldose reductase has received extensive research as a key enzyme in the development of long-term problems linked to diabetes mellitus. Overexpression of this enzyme or with exceeded glucose concentration in the blood increases sorbitol on the retina leading to retinopathy, which is the adverse effect of type II diabetes. Approximately 100 million people are suffering from diabetic retinopathy globally. This research is focused on studying the total phenolic content (TPC), total flavonoid content (TFC), antioxidant potential, and aldose reductase inhibiting properties of selected medicinal plants such as Anacyclus pyrethrum, Bergenia ciliata, Rhododendron arboreum, and Swertia chirayita. In addition, ADMET analysis and molecular docking of seven previously identified compounds from the chosen medicinal plants were carried out against human aldose reductase (PDB ID: 4JIR). The ethanol extract of S. chirayita exhibited the highest TPC (4.63 ± 0.16 mg GAE/g) and TFC (0.90 ± 0.06 mg QE/g). Analysis of 2,2-diphenyl-1-picrylhydrazyl (DPPH)-based antioxidant assay showed that IC50 of the ethanolic extract of B. cilata and R. arboreum showed a significant antioxidant activity with IC50 value of 0.05 mg/mL. The percentage inhibition of AR by extract of B. ciliata (94.74 ± 0.01%) was higher than other plant extracts. A molecular docking study showed that morin isolated from B. ciliata showed a good binding interaction with AR. This study showed that the extracts of A. pyrethrum, B. ciliata, and R. arboreum could be potential sources of inhibitors against AR to treat retinopathy.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitory activity of Indonesian Cajanus cajan leaves and Zingiber officinale extracts

One indicator of antihypercholesterolemic candidates is their inhibitory activity on 3hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase enzyme. This study aimed to analyze the HMG-CoA reductase inhibitory activities of Cajanus cajan leaves, Zingiber officinale var Amarum and Zingiber officinale var Rubrum. C. cajan leaves and two types of Z. officinale were extracted using the maceration method with three solvents: distilled water, 70% ethanol and 96% ethanol. All nine types of resulted extracts were then analyzed for bioactive compounds and tested for the HMG-CoA reductase inhibitory activity using the HMG-CoA reductase analysis kit (BioVision’s K588-100). It was carried out in vitro using a colorimetric microplate reader with a wavelength of 340 nm at 37°C. The results showed that the extracts contained flavonoids, tannins, saponins and steroids. The nine extracts showed inhibitory activities on the HMG-CoA reductase enzyme. The three extracts showed the highest inhibitory activity; 70% ethanolic Z. officinale var Amarum extract (47.87%), aqueous Z. officinale var Rubrum extract (40.62%) and 70% ethanolic C. cajan leaves extract (39.38%). These results indicate that the three extracts have a medium inhibitory level of HMG-CoA reductase. The study suggested that the three types of extracts could be used as antihypercholesterolemic candidates such as antihypercholesterolemic functional food.

Anti-Hypercholesterolemia Effects of Edible Seaweed Extracts and Metabolomic Changes in Hep-G2 and Caco-2 Cell Lines.

Hypercholesterolemia is a major risk for the development of cardiovascular diseases (CVDs), the main cause of mortality worldwide, and it is characterized by high levels of circulating cholesterol. The drugs currently available for hypercholesterolemia control have several side effects, so it is necessary to develop new effective and safer therapies. Seaweeds serve as sources of several bioactive compounds with claimed beneficial effects. Eisenia bicyclis (Aramé) and Porphyra tenera (Nori) are edible seaweeds that were previously recognized as rich in bioactive compounds. In the present study, we aim to evaluate the anti-hypercholesterolemia effect of these two seaweed extracts and their health potential. Both extracts, but more efficiently Aramé extract, have liver 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitory activity as well as the capability to reduce approximately 30% of cholesterol permeation through human Caco-2 cells by simulating the intestinal lining, which is a target for hypercholesterolemia treatments. An untargeted metabolomic assay on human intestinal Caco-2 and liver Hep-G2 cell lines exposed to Aramé and Nori extracts revealed changes in the cells' metabolism, indicating the extracts' health beneficial effects. The metabolic pathways affected by exposure to both extracts were associated with lipid metabolism, such as phospholipids, and fatty acid metabolism, amino acid pathways, cofactors, vitamins, and cellular respiration metabolism. The effects were more profound in Aramé-treated cells, but they were also observed in Nori-exposed cells. The metabolite modifications were associated with the protection against CVDs and other diseases and to the improvement of the cells' oxidative stress tolerance. The results obtained for the anti-hypercholesterolemia properties, in addition to the revelation of the positive impact on cell metabolism, offer an important contribution for further evaluation of these seaweed extracts as functional foods or for CVD prevention.

High‐performance thin layer chromatography method development, validation, and assessment of enzymatic inhibition potential of Potentilla fulgens hydroalcoholic roots extract

AbstractPotentilla fulgens is known as Himalayan Cinquefoil and Lyngniangbru, rich in polyphenolic constituents and used as folk medicine by inhabitants of northeast India. This study intended to develop and validate a high‐performance thin‐layer chromatography method for the quantification of catechin in the Potentilla fulgens roots extract and explore its antioxidant potential, acetylcholinesterase, and hydroxymethylglutaryl‐coenzyme A reductase inhibition activity. The separation was achieved using the mobile phase of toluene: ethyl acetate: acetone: formic acid (6:6:6:1, v/v) in which the Potentilla fulgens roots extract delivered a condensed peak at RF 0.58 equivalent to catechin as a phytomarker. The amount of catechin in the Potentilla fulgens roots extract was found to be 2.01% w/w. Potentilla fulgens roots extract showed abundant 1,1‐diphenyl‐2‐picrylhydrazyl scavenging potential with half‐maximal inhibitory concentration values of 43.39 ± 1.43 μg/ml and inhibited acetylcholinesterase and hydroxymethylglutaryl‐coenzyme A reductase in a concentration‐dependent manner against (half‐maximal inhibitory concentration 74.78 ± 1.2 and 64.02 ± 1.7 μg/ml, respectively). The developed and validated high‐performance thin‐layer chromatography method is easy, accurate, and appropriate. These results support the use of Potentilla fulgens as folk medicine and suggest that Potentilla fulgens might be utilized as a rich source of natural antioxidants as well as acetylcholinesterase and hydroxymethylglutaryl‐coenzyme A reductase enzyme inhibitory agents.