Pancreatic Lipase Inhibitory Activity Research Articles

Pancreatic lipase inhibitory activity of phlorotannins isolated from Eisenia bicyclis.

Pancreatic lipase is a potential therapeutic target for the treatment of diet-induced obesity in humans. In an ongoing search for new pancreatic lipase inhibitors from natural sources, a methanolic extract of marine brown algae, Eisenia bicyclis, showed a significant inhibitory effect against pancreatic lipase. Bioassay-guided isolation of this methanolic extract using a pancreatic lipase inhibitory assay led to the isolation and identification of six known phlorotannins: eckol (1), fucofuroeckol A (2), 7-phloroeckol (3), dioxindehydroeckol (4), phlorofucofuroeckol A (5), and dieckol (6). The structures were established on the basis of nuclear magnetic resonance and mass spectrometry spectroscopic data interpretation. Among the isolated phloroglucinol polymers, compounds 2 and 3 showed potent inhibitory effects on pancreatic lipase with IC₅₀ values ranging from 37.2 ± 2.3 to 12.7 ± 1.0 μM, respectively.

Testing edible mushrooms to inhibit the pancreatic lipase activity by an in vitro digestion model

SummaryOne of the strategies in prevention or treatment of obesity is altering metabolism of lipids by inhibition of dietary fat absorption. The extracts obtained with methanol, water and methanol:water (1:1) from 21 mushroom species were screened as potential sources of pancreatic lipase (PL) inhibitors using a standardised in vitro test. Lepiota procera methanol:water (1:1) extracts showed the highest inhibition activity closely followed by Grifola frondosa, Pleurotus eryngii and Lyophyllum shimeji. Other mushroom strains such as Morchella conica, Marasmius oreades, Lentinula edodes, Amanita ponderosa and Boletus edulis also showed a certain inhibitory activity. However, when the PL inhibitory activity was evaluated using an in vitro digestion model mimicking gut conditions, none of the selected mushroom extracts were able to inhibit PL activity. On the contrary, stimulation of the lipase activity levels was observed and it was not due to endogenous mushroom lipases activities.

In vitro prevention of chick pancreatic lipase activity by Abroma augusta extract

ObjectiveTo investigate chick pancreatic lipase inhibitory activities of the Abroma augusta (A. augusta). MethodsA. augusta was first extracted with methanol and subjected to phytochemical screenings. Quantitative estimation of flavonoids, phenolics and alkaloids was done. Pancreatic lipase from chick pancreas was isolated and used as substrate for anti-lipase studies. ResultsA. augusta extract effectively inhibited concentration dependent lipase activity, whereby extract at concentration 100 μg/mL inhibited 88.6% enzyme activity. ConclusionsFrom these results, it could be concluded that A. augusta can be used as a potential source anti-lipase agents.

Anti-hyperlipidemic constituents from the bark of Shorea roxburghii

The methanol extract from the bark of Shorea roxburghii (Dipterocarpaceae, "Phayom" in Thai) was found to suppress plasma triglyceride elevation in olive oil-treated mice, and also to inhibit pancreatic lipase activity (IC(50) = 31.6 μg/ml). From the extract, two new 3-acetyl-4-phenyl-3,4-dihydroisocoumarins, phayomphenols A(1) (1) and A(2) (2) were isolated, together with 22 known compounds. The structures of 1 and 2 were elucidated on the basis of chemical and spectroscopic evidence, including X-ray crystallographic analysis. Among the isolates, several oligostilbenoids, including (-)-hopeaphenol (3) and (+)-isohopeaphenol (4), showed inhibitory effects on plasma triglyceride elevation at a dose of 200 mg/kg p.o. and pancreatic lipase inhibitory activity (IC(50) = 32.9 and 26.5 μM, respectively).

Pre–clinical evolutionary study of Clerodendrum phlomidis as an anti–obesity agent against high fat diet induced C57BL/6J mice

ObjectiveAnti–obesity activity of alcoholic and methanolic extracts of roots of Clerodendrum phlomidis was evaluated against high fat diet (HFD) induced obesity in C57BL/6J female mice. MethodsObesity was induced by feeding high fat diet for 13 weeks to C57BL/6J female mice and one group was kept on normal chow diet in order to evaluate the effect of Clerodendrum phlomidis on food intake, body weight changes, digestive enzyme activity, lipid metabolism, theromogenesis, adiposities diameter and histology of fat pad. ResultsAmong these two extracts methanolic extract of Clerodendrum phlomidis (MECP) have shown strong anti–obesity effect compare to alcoholic extract of Clerodendrum phlomidis (AECP). LD50 value was found to be more than 2000 mg/kg. ConclusionsMECP have shown more promising effects than AECP may be because of its multiple mechanisms. Anti–obesity activity produced by MECP is because of inhibition of pancreatic lipase activity which delays the intestinal absorption of dietary fat. Inhibition of pancreatic lipase activity was confirmed by in-vitro studies. MECP also contains β-sitosterol in abundant amount which was confirmed by HPTLC analysis. Moreover flavonoid content in the plant has anorexic property. By this study we concluded that MECP is beneficial for the suppression of obesity and associated complications like T2DM.

Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model

Overweight and obesity are usually related with high fat and calorie intake, and seriously causative of lifestyle-related diseases such as cardiovascular disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel dietary therapy against overweight and obesity using mixtures of protamine and chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in the body. Protamine is a dietary protein originated from salmon reproductive organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS strongly suppressed the activity of pancreatic lipase, which is the primary enzyme for the digestion and absorption of lipids in the intestine. In in vivo animal test, the mixtures of protamine and COS significantly reduced the serum levels of triglyceride (TG), total cholesterol (T-CHO), and low density lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they increased fecal TG and T-CHO contents. From these alterations in lipid metabolism, we verified that protamine and COS mixtures could effectively interrupt the digestion and absorption of dietary lipids in the body by inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures increased the serum level of high density lipoprotein-cholesterol (HDLC), responsible for removing cholesterol from cells and protecting atherosclerosis, and therefore decreased the potential risks of cardiovascular diseases by lowering values of the atherogenic index (AI) and cardiac risk factor (CRF). Taken together, we suggest protamine and COS mixtures as a prominent dietary therapy for the prevention of overweight, obesity, and further cardiovascular diseases related with hyperlipidemia.

Preventive effect of Terminalia bellirica on obesity and metabolic disorders in spontaneously obese type 2 diabetic model mice

Visceral obesity induces insulin resistance and is recognized as an important risk factor for metabolic syndrome (MS). Therefore, inhibition of lipid absorption from the intestine is regarded as an effective way of preventing MS. Terminalia bellirica is extensively used in Ayurvedic medicine in India and neighboring countries, and the fruit of this plant has been reported to have hypoglycemic and hypolipidemic effects. In this study, we investigated the preventive effect of a hot water extract of T. bellirica fruit (TB) on obesity and various metabolic disorders, and explored its molecular mechanisms and active ingredients. TB treatment had a preventive effect on obesity, insulin resistance, and hyperlipidemia in spontaneously obese type 2 diabetic TSOD mice. To clarify the molecular mechanisms of TB in preventing obesity, we investigated the inhibitory effect on lipid absorption. TB suppressed absorption of triacylglycerol in an olive oil loading test (in vivo) and showed a strong inhibitory effect on pancreatic lipase activity (in vitro). Furthermore, a search for the active ingredients in TB revealed that gallic acid is the component primarily responsible for the inhibition of pancreatic lipase activity. Thus, our findings indicate that TB could be useful in preventing MS. The mechanisms probably involve suppression of the absorption of meal-derived lipids mediated by gallic acid.

Polyphenolic Constituents from the Aerial Parts of Thymus quinquecostatus var. japonica Collected on Ulleung Island

Phytochemical investigation on the polar constituents in the aerial parts of Thymus quinquecostatus var. japonica resulted in the isolation of three flavonoids along with four known phenolic components. The isolated compounds were characterized as 2(S)-5,7,3′,5′-tetrahydroxyflavanone (1), (+)-taxifolin (2), (+)-aromadendrin (3), rosmarinic acid (4), caffeic acid (5), protocatechuic acid (6), and protocatechuic aldehyde (7) from comparisons of their physicochemical and spectroscopic data 1H-, 13C-NMR, two-dimentioal NMR, and mass spectrometery) with those of authentic samples and reference data. This is the first report on the isolation of compounds 1–7 from T. quinquecostatus var. japonica. In addition, compounds 2 and 4 exhibited the most potent pancreatic lipase inhibitory activities in a concentration-dependent manner with IC50 values of 15.4±0.8 and 62.8±2.7 μM, respectively.

Wild Mediterranean Dietary Plants as Inhibitors of Pancreatic Lipase

Lipids are essential compounds for all living organisms. Agents that inhibit fat digestion are of theoretical benefit in the treatment of obesity. A total of 18 species (21 hydroalcoholic extracts) of edible plants from Calabria region (Italy) were evaluated for their in vitro pancreatic lipase inhibitory activity. Lipase activity was measured by monitoring the hydrolysis of p-NPC, which releases the yellow chromogen, p-nitrophenol. The aqueous ethanol extracts of Portulaca oleracea (leaves) and Silene vulgaris (leaves) exhibited the strongest inhibitory effect on lipase. The amounts of total phenolics, measured by Folin-Ciocalteu method, varied widely in the different analysed extracts and ranged from 29 to 482 mg/g of extract. In this study, the findings do not show any relationship between lipase inhibitory activity and total phenolic content.

참당귀(Angelica gigas Nakai) 꽃 추출물의 생리활성

본 연구에서는 참당귀(Angelica gigas Nakai) 꽃 부위를 이용하여 항산화 활성, 암세포 억제 효과, 항당뇨 활성, 항비만 활성, 항염 활성 효과를 평가하였다. 항산화 활성 검정을 위해 참당귀 꽃의 물과 에탄올 추출물에 대하여 DPPH radical scavenging을 측정한 결과 IC50 값이 각각 3,535, 105.0 ㎍/㎖로 나타났으며, 대조구로 쓰인 ascorbic acid는 12.7 ㎍/㎖을 나타냈다. 총 폴리페놀 함량은 에탄올 추출물 (48.43±0.18 ㎎/g)이 물 추출물(39.03±0.69 ㎎/g)보다 높았고, 총 플라보노이드 함량도 에탄올 추출물(67.02±4.38 ㎎/g)이 물 추출물(50.32±1.24 ㎎/g)보다 높음을 알 수 있었다. 항당뇨 활성을 위해 α-glucosidase와 α-amylase 저해 활성을 측정한 결과, 참당귀 꽃 에탄올 추출물에서는 acarbose 대비 약 34.45%의 낮은 활성 저해 효과를 나타내었고, α-amylase 활성 저해 효과는 에탄올 추출물이 acarbose 대비 23.62%의 낮은 활성 저해 효과를 나타내었다. Pancreatic lipase에 대한 저해 활성을 측정한 결과 참당귀 꽃 물 추출물은 16.76%의 낮은 저해 활성을 나타내었다. 항암 및 항염활성 측정 결과 모두 활성이 없거나 낮은 수준이었다. 이러한 결과 참당귀 꽃 추출물은 항산화 관련 기능성 소재로의 활용가능성이 높음을 알 수 있었다.

Structural analysis of A-type or B-type highly polymeric proanthocyanidins by thiolytic degradation and the implication in their inhibitory effects on pancreatic lipase

Compared with oligomeric proanthocyanidins, highly polymeric proanthocyanidins have more difficulty to analyze the molecular sizes and the mode of interflavan linkages of flavan-3-ol units through doubly linked A-type bonds and single B-type bonds. Recently, we have shown that seed shells of the Japanese horse chestnut contain highly polymeric proanthocyanidins as dominant polyphenolics that can be separated into two fractions according to the difference in the molecular sizes. Here, we tried to perform the structural characterization of them in terms of the molecular sizes and the proportions of A-type linkages relative to B-type linkages. The results were compared with those of the corresponding preparations with variations in the sizes from fruits of blueberry and cranberry. Gel permeation chromatography revealed that the molecular sizes of them were higher in the order of blueberry > cranberry > seed shells of the Japanese horse chestnut when they are compared between the respective fractions. For the analysis of terminal and extension units of those proanthocyanidins, the isolated fractions were subjected to the thiolytic cleavage of the B-type linkages using 1-dodecanethiol, and the resulting degradation products were identified by ultra-performance liquid chromatography electrospray-ionization mass spectrometry (UPLC-ESI/MS). These analyses provided fast and good resolution of the degradation products and revealed higher proportions of A-type linkages compared with B-type linkages in the both isolated fractions in the order of the seed shells > cranberry > blueberry. Moreover, the isolated fractions with higher molecular sizes and those more abundant in the proportions of A-type linkages were found to be more effective in the inhibition of pancreatic lipase activity. The results suggest that higher molecular sizes and more abundance of A-type bonds in polymeric proanthocyanidins are promising key factors for the attenuation of lipid digestion as dietary supplements.

생강 추출물의 pancreatic lipase 저해 및 항산화 활성

Ginger (Zingiber officinale) is a well-known herb that is widely consumed as spice for the flavoring of foods. As part of our continuing search for bioactive materials, the in vitro pancreatic lipase inhibition and antioxidant properties of an aqueous ethanolic extract of Z. officinale were investigated. The total phenolic content was determined using a spectrophotometric method. The antioxidant efficacies of the extract was studied with radical scavenging assays using DPPH and radicals. Further more, the antiobesity effect of the extract was evaluated by porcine pancreatic lipase assay. In particularly, the pancreatic lipase inhibitory activity of the ethyl acetate (EtOAc)-soluble portion from Z. officinale was significantly higher than that of the other solvent-soluble portions. The results suggest that Z. officinale may have therapeutic potential that may be useful in development of an anti-obesity agent or its precursors.

Influence of Alpinia galanga Rhizomes on Cafeteria Diet Induced Obesity in Rats

The present study was aimed to screen the possible antiobesity effects of ethanol extract of Alpinia galanga rhizomes in cafeteria diet fed obese rats. Obesity was induced in albino rats by feeding cafeteria diet daily for 6 weeks in addition to normal diet. The ethanol extract of rhizomes was administered at a daily dose of 500 mg/kg orally for 6 weeks. Body weight and food intake was measured initially and then every week thereafter. On day 42, serum glucose, lipids and leptin levels were estimated and then the weight of liver and parametrial adipose tissues was determined. The liver triglyceride content was estimated. The in vitro pancreatic lipase inhibitory activity of the extract was also determined. The extract produced inhibition of increase in body weight, energy intake and parametrial adipose tissue weight induced by cafeteria diet. The extract significantly reduced serum lipid and leptin levels, which were elevated by feeding cafeteria diet. In addition, the extract significantly inhibited the increase in liver weight and accumulation of hepatic triglycerides. The extract also produced dose dependent inhibition of in vitro pancreatic lipase activity. The present study concludes that, ethanol extract of Alpinia galanga rhizomes is useful for treatment of cafeteria diet induced obesity in rats.

마디풀 추출물의 Pancreatic Lipase 저해 및 항산화 활성 평가

As part of our continuing search for novel bioactive natural products, antioxidant and pancreatic lipase inhibitory activities of the aqueous ethanolic extract of Polygonum aviculare were investigated. In addition, the total phenolic content was quantified by a spectrophotometric method. The antioxidant properties of the extract were evaluated by radical scavenging assays such as DPPH and radicals. The anti-obesity efficacy of P. aviculare extract was tested by porcine pancreatic lipase assay. All tested samples showed a dose-dependent pancreatic lipase inhibitory and radical scavenging activities. In terms of the value, the ethyl acetate (EtOAc) soluble portion was most potent than other solvent soluble portions. The results suggested that P. aviculare could be considered as a new potential source of natural antioxidant and anti-obesity agent for food, nutraceutical, cosmetics industries.

The 2′,4′,6′-Trihydroxyacetophenone Isolated fromMyrcia multifloraHas Antiobesity and Mixed Hypolipidemic Effects with the Reduction of Lipid Intestinal Absorption

This study evaluated the hypolipidemic and antiobesity effects of phloroacetophenone (2',4',6'-trihydroxyacetophenone, THA) isolated from Myrcia multiflora and their relationship with triglyceride (TG) intestinal absorption and pancreatic lipase activity inhibition. The hypolipidemic effect of THA was evaluated by acute (Triton WR-1339 treatment) and chronic assay (high-fat diet treatment), the antiobesity effect was evaluated by chronic assay (high-fat diet treatment), while the inhibition of enzymatic activity of pancreatic lipase was measured in the intestinal tissue of mice treated with high olive oil concentration. In the acute assay, THA caused greater total cholesterol (37 %) and triglyceride (46 %) serum level reduction than lovastatin (32 and 1 %), a HMG-CoA reductase inhibitor or orlistat (26 and 34 %), a gastrointestinal lipase inhibitor. In addition, in the chronic assay with a high-fat diet, THA reduced cholesterol and triglyceride levels (32 and 61 %, respectively) while lovastatin showed a decrease of 35 and 49 %, respectively. THA also caused a reduction in weight gain very similar to orlistat (40 and 38 %, respectively) when the animals were submitted to a high-fat diet. Moreover, THA showed a stronger and continuous pancreatic lipase inhibitory activity when compared with orlistat, causing inhibition of this enzyme during 6 hours associated to a significant reduction of triglyceride serum levels. The IN VIVO antiobesity and hypolipidemic effects of THA may be partly mediated by delaying the intestinal absorption of dietary fat by inhibiting pancreatic lipase activity.

Natural Inhibitors of Pancreatic Lipase as New Players in Obesity Treatment

Obesity is a multifactorial disease characterized by an excessive weight for height due to an enlarged fat deposition such as adipose tissue, which is attributed to a higher calorie intake than the energy expenditure. The key strategy to combat obesity is to prevent chronic positive impairments in the energy equation. However, it is often difficult to maintain energy balance, because many available foods are high-energy yielding, which is usually accompanied by low levels of physical activity. The pharmaceutical industry has invested many efforts in producing antiobesity drugs; but only a lipid digestion inhibitor obtained from an actinobacterium is currently approved and authorized in Europe for obesity treatment. This compound inhibits the activity of pancreatic lipase, which is one of the enzymes involved in fat digestion. In a similar way, hundreds of extracts are currently being isolated from plants, fungi, algae, or bacteria and screened for their potential inhibition of pancreatic lipase activity. Among them, extracts isolated from common foodstuffs such as tea, soybean, ginseng, yerba mate, peanut, apple, or grapevine have been reported. Some of them are polyphenols and saponins with an inhibitory effect on pancreatic lipase activity, which could be applied in the management of the obesity epidemic.

Antiobesity and lipid lowering effects of Glycyrrhiza chalcones: Experimental and computational studies

Twelve flavonoids (1-12), isolated from Glycyrrhiza glabra roots were evaluated for their pancreatic lipase (PL) inhibitory activity in vitro. The structures of the isolated compounds were elucidated by spectroscopic methods. Amongst all the compounds 7, 8, 10 and 11 showed strong inhibition against PL with IC(50) values of 7.3 μM, 35.5 μM, 14.9 μM and 37.6 μM, respectively. Molecular docking studies on the most active compound 7 revealed that it binds with the key amino acid residues of the PL active site. In silico absorption, distribution, metabolism and excretion (ADME) parameters were also computed on the active compounds to determine their preliminary pharmacokinetic properties. Further, investigations were carried out to determine the antiobesity and lipid lowering effects of 7 and 10 in high fat diet (HFD) fed male SD rats. In the rats supplemented with compound 7 the body weight increase was only 23.2±3.6 g as compared to 64.2±0.5 g in the HFD control group while in the rats treated with compound 10 showed 23.2±3.6 g weight gain only. Compound 7 decreased the levels of plasma total cholesterol (TC) to 84.6±1.4 mg/dl and plasma total triglycerides (TG) to 128.8±6.0 mg/dl. Compound 10 also lowered the plasma TC and TG levels considerably. The results indicate the potential of the chalcone scaffold as a source of PL inhibitors for preventing obesity.

Enhancement of pancreatic lipase inhibitory activity of curcumin by radiolytic transformation

The naturally occurring yellow dietary diarylheptanoid curcumin (1) was converted by γ-ray to two new γ-lactones, curculactones A (2) and B (3), as well as four known transformates, erythro-1-(3-methoxy-4-hydroxy-phenyl)-propan-1,2-diol (4), threo-1-(3-methoxy-4-hydroxy-phenyl)-propan-1,2-diol (5), vanillic acid (6), and vanillin (7). The structures of the two new γ-lactone derivatives were elucidated on the basis of spectroscopic methods. The steroisomeric phenylpropanoids 4 and 5 exhibited significantly enhanced inhibitory activity against pancreatic lipase when compared to parent curcumin.

Effect of Argyreia speciosa root extract on cafeteria diet-induced obesity in rats

Objectives:To evaluate the antiobesity effects of the ethanolic extract of Argyreia speciosa roots in rats fed with a cafeteria diet (CD).Materials and Methods:Obesity was induced in albino rats by feeding them a CD daily for 42 days, in addition to a normal diet. Body weight and food intake was measured initially and then every week thereafter. On day 42, the serum biochemical parameters were estimated and the animals were sacrificed with an overdose of ether. The, liver and parametrial adipose tissues were removed and weighed immediately. The liver triglyceride content was estimated. The influence of the extract on the pancreatic lipase activity was also determined by measuring the rate of release of oleic acid from triolein.Results:The body weight at two-to-six weeks and the final parametrial adipose tissue weights were significantly lowered (P < 0.01 and P < 0.05, respectively) in rats fed with the CD with Argyreia speciosa extract 500 mg/kg/day as compared to the CD alone. The extract also significantly reduced (P < 0.01) the serum contents of leptin, total cholesterol, low density lipoprotein (LDL), and triglycerides, which were elevated in rats fed with CD alone. In addition, the extract inhibited the induction of fatty liver with the accumulation of hepatic triglycerides. The extract also showed inhibition of pancreatic lipase activity by using triolein as a substrate.Conclusions:The ethanolic extract of Argyreia speciosa roots produces inhibitory effects on cafeteria diet-induced obesity in rats.

Anti-obesity (Pancreatic lipase inhibitory) activity of Everniastrum cirrhatum (Fr.) Hale (Parmeliaceae)

Introduction: Obesity has increased at an alarming rate and is now a worldwide health problem. Everniastrum cirrhatum (Fr.) Hale (Parmeliaceae) is a foliose lichen and grow luxuriantly in tropical Himalayas, central India and higher altitudes of southern India. In this study, we report Anti-obesity activity, in terms of pancreatic lipase inhibitory activity, of methanol extract of E. cirrhatum for the first time. Methods: The powdered lichen material was extracted with methanol in soxhlet apparatus. The extract was tested for secondary metabolites by standard phytochemical tests and thin layer chromatography (TLC). Lipase enzyme was obtained from the chicken pancreas. Lipase inhibitory activity of different concentrations of methanol extract was determined in terms of inhibition of lipase activity using olive oil as substrate. Results: The extract was found to inhibit activity of chicken pancreatic lipase and the effect was found to be concentration dependent. Phytochemical analysis revealed the presence of alkaloids, saponins, tannins and terpenoids. TLC revealed Atranorin, Salazinic acid and Protolichesterinic acid. Conclusion: The result of lipase inhibitory activity of the lichen in this study is promising. The inhibitory activity may be attributed to the presence of secondary metabolites. In suitable form, the lichen could find its application as anti-obesity agent. Further studies on isolation of active principles from the extract and their enzyme inhibitory activity are under investigation.