Lipase Inhibitor Research Articles

Effect of Protein, Carbohydrate, and Oil on Phytochemical Bioaccessibility and Bioactivities of the Ginkgo biloba L. Leaf Formulations After In Vitro Digestion

The present work evaluates the effect of casein, glucose, and olive oil on phytochemical bioaccessibility, antioxidant potential (DPPH and FRAP), antidiabetic potential (inhibition of amylase, α-glucosidase, and BSA glycation), and antihyperlipidemic potential (inhibition of lipase) of gingko standardized leaf extract in the form of tablets after in vitro digestion. Gingko extract formulations with protein, carbohydrates, and oil had high (>70%) in vitro bioaccessibility of quercetin, kaempferol, and isorhamnetin after each phases of digestion in comparison to moderate (35–70%) in vitro bioaccessibility from gingko water extract. Formulation with the highest in vitro bioaccessibility of the majority of the tested polyphenolic groups and terpene lactones after oral and intestinal phases was ginkgo with olive oil. High (>70%) antioxidant (DPPH and FRAP), antidiabetic (α-glucosidase and BSA glycation), and antihyperlipidemic potential were detected in almost all ginkgo formulations. Based on the results, we conclude that the in vitro bioaccessibility of individual compounds or groups of compounds depends on whether the tablets are taken with water or with foods (protein, carbohydrates, and oil).

In silico prediction of the pharmacological potential of new 7-alkyl-8-hydrazine derivatives of 1,3-dimethylxanthine

The development of new drug-like molecules based on 7-R-8-hydrazine derivatives of 1,3-dimethylxanthine is promising in view of the known pharmacological effect of theophylline and functional hydrazine derivatives. In silico methods make it possible to rationalize the synthesis and reduce the number of chemical compounds at the stage of virtual screening by eliminating potentially ineffective molecules. The aim of the work was to carry out а virtual design and predictive evaluation of pharmacological activity of new 7-alkyl-8-hydrazine derivatives of 1,3-dimethylxanthine by in silico methods. Materials and methods. To perform in silico prediction of the pharmacological potential of several new 7-alkyl-8-hydrazine derivatives of 1,3-dimethylxanthine, we used the online services. As 12 model compounds, we chose 12 derivatives of 5-(2-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-yl)hydrazine)-5-phenylpentanoic acid with linear and branched alkyl substituents at the 7th position of the basic heterocycle: methyl-, ethyl-, n-propyl-, n-butyl, i-butyl, n-amyl, i-amyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl. The use of the freely available web tool SwissADME made it possible to calculate physicochemical parameters and to determine the drug-likeness properties of molecules. And other Internet platforms allowed to predict the spectrum of biological activity of the target compounds. Results. In silico analysis of the pharmacological potential of model compounds was performed. Three biological actions (peripheral vasodilator, kidney function stimulant, lipoprotein lipase inhibitor) with high Pa values are predicted for all derivatives of the series. The ADME parameters of the molecules were evaluated and their potential drug-like properties were determined. Conclusions. It was established that the extension of the alkyl substituent at the 7th position of the basic heterocycle should lead to a deterioration of the ADME parameters of the molecules, potentially reduce their oral bioavailability, but should not radically affect their biological activity profile. Compounds 1–3 and 5 are predicted to be orally bioavailable. They should be characterized by a wide spectrum of biological activity with the highest probability of vasodilator effect on peripheral vessels. In the future, it is advisable to carry out targeted synthesis of hit compounds and thorough in vitro, in vivo studies, and for compounds with violated physicochemical criteria – structural optimization of molecules in order to find a lead compound.

Prospective observational study and mechanistic evidence showing lipolysis of circulating triglycerides worsens hypertriglyceridemic acute pancreatitis.

While most hypertriglyceridemia is asymptomatic, hypertriglyceridemia-associated acute pancreatitis (HTG-AP) can be more severe than other AP etiologies. The reasons underlying this are unclear. We thus studied whether lipolytic generation of non-esterified fatty acids (NEFA) from circulating triglycerides (TGs) could worsen clinical outcomes. Admission serum TGs, NEFA compositions and concentrations were analyzed prospectively in 269 patients with AP. These and demographics, clinical outcomes were compared between HTGAP (TGs >500mg/dL; American Heart Association 2018 guidelines) and other AP etiologies. Serum NEFAs were correlated with the serum triglyceride fatty acids (TGFAs) alone, and with the product of TGFA x serum lipase (NEFA-TGFA x lipase). Studies in mice, rats were done to understand the role of HTG lipolysis in organ failure and to interpret the NEFA-TGFA correlations. HTG-AP patients had higher serum NEFAs and TGs and more severe AP (19% vs. 7% p<0.03) than other etiologies. Correlations of long-chain unsaturated NEFA with corresponding TGFAs increased with TG concentrations up to 500mg/dL and declined thereafter. However, NEFA-TGFA x lipase correlations got stronger with TGs >500mg/dL. AP, and intravenous lipase infusion in rodents caused lipolysis of circulating TGs to NEFA. This led to multi-system organ failure, which was prevented by pancreatic triglyceride lipase deletion, or lipase inhibition. HTG-AP is made severe by the NEFAs generated form intravascular lipolysis of circulating TGs. Strategies that prevent TG lipolysis may be effective in improving clinical outcomes of HTG-AP. Not applicable. This project was supported by Grant numbers RO1DK092460, R01DK119646 from the NIDDK, PR191945 under W81XWH-20-1-0400 from the DOD (VPS), and R01AA031257 from the NIAAA (VPS).

Characterization of 'borde': A traditional ethiopian cereal-based fermented beverage - Microbial analysis, rheological profiling, and functional attributes

The study focused on the characterization of an Ethiopian traditional beverage, borde, produced by lactic acid bacteria (LAB) and yeast through natural fermentation. Samples were collected from three distinct locations in Ethiopia and subjected to analyses encompassing microbiological, antioxidant, enzyme inhibition, rheological and physicochemical aspects. The early stages of fermentation exhibited prevalence of Enterobacteriaceae and aerobic mesophilic bacteria. Towards the end of fermentation, yeast (6.07–6.72) and LAB (6.52–7.12) (log CFU mL−1) dominated the microbiological profile of all borde samples. Significant difference (P < 0.05) in the number of microorganisms were noted between the samples. Antioxidant activities, assessed through DPPH and ABTS values, ranged between 51.5 and 64.6 % and 47.4–62.9.1 %, respectively. The average value of α-glucosidase and pancreatic lipase inhibition for borde samples were ranged from 36.56 to 43.23 % and 31.08–40.19 %, respectively. Rheological investigations indicated pseudoplastic fluid behavior, as evidenced by the decreasing apparent viscosity values with shear rate. Moreover, the samples displayed solid-like structures, with lower loss modulus (G″) values compared to storage modulus (G′). The shared physicochemical characteristics and the dominance of specific microbial groups suggest the potential for developing a direct fermentation system for this traditional cereal-based beverage. Overall, these findings contribute valuable insights into the multifaceted nature of borde, paving the way for further advancements in its production and quality control.

Phytochemical composition, antioxidant activities and anti‐obesity potential of selected vegetables as affected by drying methods

AbstractObesity has reached epidemic statistics worldwide and there is an urgent need to explore more available options in addressing the condition. The potential of vegetables as natural sources of enzyme inhibitors that can regulate the progression of obesity is of great interest particularly due to possible synergistic antioxidant activities. In this study, we evaluated the phytochemical composition, antioxidant activities, and in vitro enzyme inhibition properties of selected vegetables as influenced by sun and cabinet drying methods. While a significant increase was observed in the phytochemical composition of most of the vegetables, the two drying methods had varying effects on all parameters. Cabinet drying yielded higher saponin (2.86–4.67 mg/100 g), phenolics (19.30–57.02 mg/100 g), and alkaloids (31.58–37.61 mg/100 g) contents while sun drying gave better results for flavonoids (88.13–234.15 mg/100 g). The DPPH (11.45%–29.61%) and ABTS (22.70%–35.48%) antioxidant activities varied significantly. Cabinet‐dried cabbage and sun dried carrot flours displayed the highest inhibition against alpha amylase and pancreatic lipase, respectively. A strong positive correlation was observed between phenolics and amylase inhibition and also between saponin and pancreatic lipase inhibition. Consequently, vegetable flours could serve as versatile products for the therapeutic management of obesity and related diseases.

Anti-Obesity Potential of Secamone afzelii K. Leaf and Vine Ethanol Extract: Insights into Lipase Inhibition and Secondary Metabolites

Anti-Obesity Potential of Secamone afzelii K. Leaf and Vine Ethanol Extract: Insights into Lipase Inhibition and Secondary Metabolites

Structural characterization of noni (Morinda citrifolia L.) pectin and its inhibitory activity on pancreatic lipase

This study aimed to investigate the physicochemical properties and biological activities of noni pectin (NP) extracted using various solvents, three fractions of noni pectin were obtained using traditional chemical and deep eutectic solvents. NPs are composed of various ratios of galacturonic acid, arabinose, rhamnose, xylose, glucose, and galactose with different yields, molecular weights, esterification degrees (DE), and microstructures. Among the fractions, noni pectin extracted with Betaine-citric acid (BNP) exhibited higher molecular weight, degree for esterification and pancreatic lipase (PL) inhibitory activity than the other fractions. Enzyme kinetic analysis indicated that BNP inhibited PL via a noncompetitive mechanism. BNP significantly altered the secondary structure of PL and quenched PL fluorescence, suggesting a static quenching mechanism. Isothermal titration calorimetry (ITC) further demonstrated that the binding of BNP to PL was spontaneous and driven by enthalpy, primarily mediated by hydrogen bonding and van der Waals forces. Molecular docking simulations also confirmed strong noncovalent interactions (hydrogen bonding and van der Waals forces) between BNP and PL. This study validated the high efficiency of the deep eutectic solvent-extracted noni pectin fraction in pancreatic lipase inhibition.

Antidiabetic potential of Lavandula stoechas aqueous extract: insights into pancreatic lipase inhibition, antioxidant activity, antiglycation at multiple stages and anti-inflammatory effects

BackgroundWith the increasing global prevalence of type 2 diabetes (T2D) and obesity, there is a pressing need for novel therapeutic interventions. Lavandula stoechas, a medicinal plant traditionally used for various ailments, holds promise as a potential agent for T2D management, particularly in Morocco, where it is commonly used to treat diabetes. This study aims to evaluate the pharmacological potential of L. stoechas aqueous extract (AqLs) by assessing its lipase inhibition antioxidant and anti-inflammatory activities, identifying phenolic compounds, and examining its efficacy in reducing diabetic complications.MethodsThe pharmacological potential of L. stoechas aqueous extract was investigated using in vitro assays. The inhibitory effect on pancreatic lipase, antioxidant power (FRAP), and anti-inflammatory activity (albumin denaturation method) was assessed. High-performance liquid chromatography (HPLC) analysis identified phenolic compounds. Additionally, albumin glycation was evaluated by estimating fructosamine, carbonyl groups, and amyloid β-structures to assess efficacy in mitigating diabetic complications.ResultsThe extract demonstrated concentration-dependent inhibition of pancreatic lipase (IC50 = 0.132 ± 0.006 mg/mL), potent antioxidant activity (IC50 = 604.99 ± 1.01 μg/mL), and dose-dependent anti-inflammatory effects (IC50 = 207.01 ± 34.94 mg/mL). HPLC analysis revealed phenolic compounds: naringin (38.28%), syringic acid (25.72%), and cinnamic acid (15.88%) were the most abundant, with 4-hydroxybenzoic acid, hydrated catechin, and catechin ranging from 9.60% to 5.24%, and p-coumaric acid (1.73%). Furthermore, the extract inhibited albumin glycation and fructosamine production, suggesting efficacy in mitigating diabetic complications.ConclusionThese findings highlight the multifaceted pharmacological potential of L. stoechas aqueous extract in T2D management, suggesting that this plant can be highly beneficial for diabetic individuals.

Angioprotein-like 3 and atheroma progression in statin-treated type 2 diabetic patients with coronary artery disease: the pre-specified analysis from the OPTIMAL randomized controlled trial

Abstract Introduction Despite guideline-recommended control of LDL-C with a statin, type 2 diabetic patients more likely cause cardiovascular events. This indicates the need to identify additional therapeutic targets in those patients. Angioprotein-like 3 (ANGPTL3) is an inhibitor of lipoprotein and endothelial lipase, which increases the levels of LDL-C and other atherogenic lipoproteins. These properties suggest ANGPTL3 as a potential driver associated with diabetic atherosclerosis. The OPTIMAL randomized controlled trial (jRCT1052180152) compared the efficacy of continuous glucose monitoring-guided versus HbA1c-guided glycemic control on coronary atherosclerosis in statin-treated type 2 diabetic patients by using serial intravascular ultrasound (IVUS) imaging. This pre-specified analysis of the OPTIMAL study was designed to evaluate whether ANGPTL3 affects progression of coronary atheroma in statin-treated type 2 diabetic patients. Purpose To elucidate the association of serial change in ANGPTL3 with the degree of atheroma progression in statin-treated type 2 diabetic patients. Methods 59 patients (59 lesions) with serial ANGPTL3 levels at baseline and week 48 were included into the current analysis. Clinical demographics and IVUS-derived measure were compared in patients with and without any increase in ANGPTL3. Results All of study subjects received a statin, and over 60% of them were treated with high-intensity statin. Under these lipid-lowering therapies, any increase in ANGPTL3 levels at week 48 was observed in 52.5% of study participants. Patients with any increase in ANGPTL3 were more likely to have a history of hypertension (90.0% vs. 64.3%, p=0.02), whereas there was no significant difference in on-treatment LDL-C levels between the two groups (1.8 ± 0.4 vs. 1.6 ± 0.6 mmol/L, p=0.25) (Table). On IVUS imaging analysis, baseline percent atheroma volume (PAV) did not differ in those with and without any increase in ANGPTL3. However, patients with any increase in ANGPTL3 presented a greater progression of PAV (0.08 ± 0.28 vs. -0.74 ± 0.29, p=0.04). There was a trend toward a lower frequency of PAV regression in those exhibiting any increase in ANGPTL3 (48.4% vs. 57.1%), but this comparison did not meet statistical significance (p=0.50) (Figure). Multivariate analysis adjusting clinical characteristics demonstrated that any increase in ANGPTL3 level was not independently associated with PAV progression (β=0.16, 95%CI=-0.01 – 0.18, p=0.27). Conclusion Over 50% of statin-treated type 2 diabetic patients with coronary atherosclerosis showed any increase in ANGPTL3 levels at week 48. Serial IVUS imaging revealed that patients with any increase in ANGPTL3 more likely presented a greater atheroma progression. However, this relationship did not exist after adjusting clinical characteristics. Our findings suggest that ANGPTL3 may not be a pivotal driver associated with atheroma progression in statin-treated type 2 diabetic patients.

Reduction of triglyceride-rich lipoproteins with retatrutide in type 2 diabetes may be explained by concurrent reduction in ANGPTL3/8 levels

Abstract Background/Introduction In the recent phase 2 study (NCT04867785) in patients with type 2 diabetes (T2D), retatrutide, an agonist of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), and glucagon receptors, reduced triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) up to 35.0% and 20.7%, respectively. The angiopoietin-like 3/8 complex (ANGPTL3/8) is the most potent circulating inhibitor of lipoprotein lipase (LPL), and its serum levels have been shown to be directly correlated with TG and low-density lipoprotein cholesterol (LDL-C). Purpose In the aforementioned phase 2 study, we examined the effects of retatrutide on circulating ANGPTL3/8 complex concentrations to help understand the mechanism by which retatrutide reduced TG and non-HDL-C. Methods Patients with T2D were randomly assigned to receive once-weekly injections of placebo, 1.5 mg dulaglutide, or retatrutide doses of 0.5 mg, 4 mg, 8 mg, or 12 mg. Fasting serum samples were collected at baseline, week 2, week 4, week 8, week 12, week 16, and week 24, and ANGPTL3/8 levels were measured at all time points using a sensitive and selective immunoassay. Plasma PCSK9 levels were also measured at baseline and 24 weeks. Data were analyzed using a mixed model for repeated measures with log-transformation. Results Baseline ANGPTL3/8 levels (mean 26.3 ng/mL, IQR 17.4-33.0 ng/mL) were not different among all study groups. Mean percent changes of ANGPTL3/8 from baseline at week 24 were -1.3%, -12.0%, -48.7% and -51.0% in 0.5 mg, 4 mg, 8 mg and 12 mg retatrutide groups, respectively (Figure). Percent changes of ANGPTL3/8 in 8 mg and 12 mg retatrutide groups were significantly different from placebo group (p &amp;lt; 0.0001). Mean percent changes of PCSK9 levels from baseline to 24 weeks were not different from placebo for any treatment arm (+6.2%, -3.9%, -3.8% and -9.6% for retatrutide 0.5 mg, 4 mg, 8 mg and 12 mg groups, respectively, and -1.5% for dulaglutide and -6.5% for placebo). Conclusions In patients with T2D, retatrutide dose-dependently decreased serum concentrations of ANGPTL3/8, the most potent circulating LPL inhibitor. These data suggest that retatrutide may reduce TG-rich lipoproteins by decreasing ANGPTL3/8 levels.

Alpha Hydroxyl Acids from Mume Fructus and Schisandrae Chinensis Fructus Prevent Obesity by Inhibiting Intestinal Lipase in Diet-Induced Obese Mice.

Restriction of lipid uptake and absorption from the diet is regarded as an efficient strategy for the management of obesity, while lipase inhibition could successfully block the digestion of dietary lipids. Mume Fructus (MF) and Schisandrae Chinensis Fructus (SCF) were used as fruits, the biological effect of which on obesity desired more attention. Herein, the extracts of MF and SCF displayed significant efficacy in managing obesity in mice fed with a high-fat diet, via the inhibition of hydrolase activity of lipase in the digestive tract. Using the bioactivity guidance strategy, citric acid and malic acid were identified as the major lipase inhibitors from MF and SCF, respectively, which could prevent body weight gain, along with adipose tissue formation, and alleviate hyperlipidemia and hepatic steatosis in obese mice. Above all, MF and SCF could be used for the management of obesity via the lipase inhibition by citric acid and malic acid, displaying potential applications in healthy foods, nutritional supplements, and pharmaceutical materials.

Exploring flavonoid derivatives as potential pancreatic lipase inhibitors for obesity management: An in silico and in vitro study.

Obesity is widely recognized as a major public health issue and is one of the leading causes of death worldwide. Overweight and obesity are prominent lifestyle ailments that not only give rise to additional health issues but also play a role in the development of other chronic diseases, such as cancer, diabetes, metabolic syndrome, and cardiovascular diseases. Orlistat is now the only pharmaceutical drug for the management of obesity. However, prolonged use of orlistat has been associated with detrimental consequences, hence necessitating the development of a new drug with reduced or no adverse reactions. Pancreatic Lipase is a critical enzyme in lipid metabolism. Using naturally occurring compounds as PL inhibitors has garnered significant attention because of their diverse structure and low toxicity. The present work investigates the inhibitory action of flavonoids on PL using in silico and in vitro methods. Thirteen flavonoid derivatives and orlistat were docked with PL. The ADME properties of the flavonoid derivatives were studied, and most of the compounds are in admire range. The stability of the best-docked complexes was checked by REMD. The in silico study demonstrated favorable inhibitory activity of flavonoids compared to orlistat. Consequently, an enzyme inhibitory experiment was conducted to authenticate the in silico results. The lipase inhibitory activity was assessed by using p-nitrophenyl butyrate as the substrate. Kaempferol exhibited significant inhibitory activity against PL, as shown by its IC50 value of 72.7 ± 3µM. This study proposed a natural drug candidate with promising inhibitory efficacy against PL for obesity.

Stevia By-product Fraction has Antioxidant Capacity and has been Evaluated for its Antihyperglycemic and Antilipid Potential

Introduction/Objective: The ethanolic pretreatment of stevia leaves is considered ecologically favorable and increases its yield, purity level, and sensory profile of sweeteners. We investigated the by-product generated so that we can provide a viable and applicable destination to effectively contribute to the production and industrial chain of stevia sweeteners. Recently, an antioxidant and antidiabetic fraction was obtained through stevia methanolic extraction. However, this process is costly, has a low yield, and is non-green. In this study, we got an antioxidant fraction of stevia from its pretreatment by-product, the ethanolic extract, characterized its bioactive compounds – mainly phenolic acids and flavonoids – and evaluated its antidiabetic and antilipid capacity. Methods: The ethanolic extract was fractionated, then the ethyl acetate fraction was microencapsulated. Physicochemical, Mass Spectrometry (UHPLC/MS-MS), scanning electron microscopy, microencapsulation efficiency, and antioxidant capacity analyses were carried out. The antioxidant capacity was evaluated. Antihyperglycemic capacity was assessed by inhibition of α-glucosidase and α-amylase. For antilipid potential, inhibition of pancreatic lipase was measured. Results: Antioxidant potential was observed mainly in the fraction. Microencapsulation improved the stability of the fraction. Mass spectrometry allowed comparison with phenolic and flavonoid compounds from the methanolic and ethanolic fractions of the by-product. Many compounds were coincident, which may explain the similar antioxidant capacity found. The samples showed more than 90% inhibition of alpha-glucosidase, which may indicate potential antidiabetic activity. All samples showed inhibition of the pancreatic lipase enzyme higher than 80%, reaching 91.05% for the free fraction. Conclusion: This study represented the recovery of a by-product and showed that this antioxidant fraction deserves further investigation for its bioactive potential, especially antioxidant, antidiabetic, and anti-lipid.

Effects of acid, alkaline and enzymatic extraction methods on functional, structural and antioxidant properties of dietary fiber fractions from quince (Cydonia oblonga Miller)

In this study, quince soluble dietary fiber (SDF) and insoluble dietary fiber (IDF) were obtained by acid extraction, enzyme extraction and alkaline extraction methods. The acid extracted DF displayed higher results compared to enzyme and alkaline extraction methods in terms of water holding capacity (15.97 g/g SDF), oil holding capacity (1.05 g/g SDF) and nitrite ion adsorption capacity (92.83 mg/g SDF). The antioxidant activity and phenolic content of acid extracted IDF were significantly higher than the other quince DFs. In addition, quince DFs exhibited in vitro hypoglycaemic activity, exhibiting high glucose adsorption capacity (237 mg/g) and α-amylase inhibition activity (82 %). Similarly, acid extracted SDF of quince showed in vitro hypolipidemic activity, with cholesterol adsorption capacity of 155 mg/g and lipase inhibition activity of 36 %. The structures and thermal properties of quince DFs were characterized by FT-IR and TGA. Quince DFs with high functional properties might be suitable agents for functional food formulations, such as meat products, low-calorie fruit bars, flour mixtures, etc.

Modulation of chemotherapy-induced peripheral neuropathy by JZL195 through glia and the endocannabinoid system

Chemotherapy-induced peripheral neuropathy (CIPN) used to treat cancer, is a significant side effect with a complex pathophysiology, and its mechanisms remain unclear. Recent research highlights neuroinflammation, which is modulated by the endocannabinoid system (ECS) and associated with glial activation, and the role of toll-like receptor 4 (TLR4) in CIPN. This study aimed to investigate the effects of JZL195, an inhibitor of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), and explore the connection between cannabinoid receptors and TLR4 in glial cells. A CIPN animal model was developed using cisplatin-injected male C57BL/6 mice. Mechanical and cold allodynia were assessed through von Frey and acetone tests. Western blot analysis was used to examine the expression of catabolic enzymes, cannabinoid receptors, glial cells, and neuroinflammatory factors in the dorsal root ganglia (DRGs) and spinal cord. Immunohistochemistry was used to investigate the colocalization of cannabinoid receptors and TLR4 in glial cells. JZL195 alleviated pain by inhibiting FAAH/MAGL, modulating the ECS and neuroinflammatory factors, and suppressing glial cell activity. Additionally, cannabinoid receptors and TLR4 colocalized with astrocytes and microglia in the spinal cord. This study highlights the therapeutic potential of JZL195 in modulating the ECS and suggests a correlation between cannabinoid receptors and TLR4 in spinal glial cells, providing insight into alleviating pain and neuroinflammation in CIPN.

Metabolic Profiling, Antioxidant, and Anti-lipase Activity from Combined Leaves Extracts of Tamarindus indica and Murraya paniculata: A Simplex Lattice Design Approach

Tamarindus indica leaves are recognized for their potent antioxidant and hypolipidemic properties, whereas Murraya paniculata leaves are known for their abilities to lower lipids and glucose levels. This study aimed to assess the combined extract of both leaves against pancreatic lipase inhibition and analyze their metabolomic profiles as an initial step toward developing a polyherbal treatment for hypertriglyceridemia. The extracts were subjected to Liquid Chromatography-High Resolution Mass Spectrometer (LC-HRMS) untargeted system coupled with Compounds Discoverer software to reveal their metabolomic profile. Subsequently, both individual extracts and their combination were evaluated for anti-lipase activity using pancreatic lipase enzyme with p-nitrophenyl butyrate as the substrate. The combination of the two extracts (0-300 μg/mL, 300 μg/mL in total) was prepared following the Simplex Lattice Experimental Design with 5 different composition variations. Results: The findings indicated that Tamarindus indica leaf extract (TIE) predominantly exhibited lipase inhibitory activity. Interestingly, the addition of Murraya paniculata extract (MPE) diminished this enzyme inhibitory effect. TIE was found to be rich in polyhydroxy flavonoids followed by fatty amides, whereas MPE contained mainly polymethoxy flavonoids, fatty amides, and coumarins. The presence of fatty amides in both extracts was identified as a potential cause for this incompatibility. In summary, Tamarindus indica leaf extract demonstrated strong lipase inhibition; however, its effectiveness was reduced when combined with Murraya paniculata extract, possibly due to primary fatty amides. Further research is necessary to explore strategies for eliminating these compounds and confirming their impact in vivo.

Anti-seizure effects of norepinephrine-induced free fatty acid release.

The brain's ability to rapidly transition between sleep, quiet wakefulness, and states of high vigilance is remarkable. Cerebral norepinephrine (NE) plays a key role in promoting wakefulness, but how does the brain avoid neuronal hyperexcitability upon arousal? Here, we show that NE exposure results in the generation of free fatty acids (FFAs) within the plasma membrane from both astrocytes and neurons. In turn, FFAs dampen excitability by differentially modulating the activity of astrocytic and neuronal Na+, K+, ATPase. Direct application of FFA to the occipital cortex in awake, behaving mice dampened visual-evoked potential (VEP). Conversely, blocking FFA production via local application of a lipase inhibitor heightened VEP and triggered seizure-like activity. These results suggest that FFA release is a crucial step in NE signaling that safeguards against hyperexcitability. Targeting lipid-signaling pathways may offer a novel therapeutic approach for seizure prevention.

Preferential inhibition of α-amylase by cinnamaldehyde-based hydrazones: A comparative study

The escalating issue of obesity and related health conditions, including diabetes mellitus and coronary heart disease, necessitates the development of digestive enzyme inhibitors. Targeting pancreatic lipase to inhibit fatty acid generation to attain reduced lipid absorption is a promising approach for identifying effective agents. Orlistat, the only clinically approved pancreatic lipase inhibitor, is associated with gastrointestinal side effects like oily stools, spotting, and flatulence. Concurrently, α-amylase inhibitors can mitigate rapid spikes in blood sugar levels. With the growing significance of natural products in pharmaceutical research, cinnamaldehyde has been recognized as a potential enzyme inhibitor. This study explores the effects of cinnamaldehyde-derived hydrazone Schiff bases on lipase and α-amylase through in vitro experiments. The synthesized compounds exhibited IC50 value for lipase in the same range ((0.41–12.58) × 10−8 M) as exhibited by the commercial drug orlistat (5.76 × 10−8 M). However, for α-amylase inhibition, the compounds (IC50 value = 0.37–9.54 × 10−9 M) were found effective inhibitors of acarbose (IC50 value = 6.76 × 10−6 M) and curcumin (IC50 value = 467 × 10−9 M). In silico DFT studies, molecular docking, drug likeliness, bioactivity score, ADME, and toxicity are also investigated for these compounds.

Lignan-rich extract from Cinnamomum camphora leaf attenuates metabolic syndrome by modulating glycolipid metabolism and gut microbiota in T2DM mice

BackgroundType 2 diabetes mellitus (T2DM) is a serious metabolic syndrome with high mortality and disability rates globally, which usually caused by unhealthy dietary patterns. Cinnamomum camphora leaf is a traditional Chinese medicinal herb used for attenuating hyperglycemia and digestive disorder, and high level of lignans has been found in C. camphora leaf. PurposeThis study aimed to examine the chemical composition of lignans extracted from C. camphora leaf (LCCL), and illustrate its therapeutic effect and mechanism on T2DM and its concomitant glycolipid metabolic disorder. MethodsThe components of LCCL were separated and purified by silica gel and macroporous adsorption resin, and were distinguished through LC/MS and NMR. The antioxidant activity of LCCL was determined by free radical scavenging assay in vitro; the hypoglycemic and hypolipidemic abilities were evaluated by α-glucosidase, α-amylase and pancreatic lipase inhibition trials, respectively. T2DM model mice were established by high-sugar and high-fat (HSHF) feed together with streptozotocin (STZ) infection, and then grouped to assess the effect of LCCL treatment. Hematoxylin-eosin (H&E), Periodic Acid-Schiff (PAS) and oil red O staining were employed to analyze the histopathology. qRT-PCR assay, 16S rRNA analysis, and western blot were conducted to illuminate the anti-diabetic mechanism of LCCL. Results6 sesamin lignans were identifed from LCCL. The in vitro assays showed strong inhibitive abilities of LCCL with low IC50 on DPPH (33.68 ± 0.54 μg/ml),O2− (39.25 ± 0.61 μg/ml), OH• (45.72 ± 0.72 μg/ml), α-glucosidase (0.82 ± 0.14 mg/ml), α-amylase (0.86 ± 0.11 mg/ml) and pancreatic lipase (0.91 ± 0.12 mg/ml). LCCL treatment (100, 200 and 400 g kg-1mg kg-1) gradually decreased the fasting blood glucose (FBG) and fasting insulin (FINS), improved the glucose and insulin tolerance, down-regulated the homeostasis model assessment insulin resistance (HOMA-IR) indexes, alleviated the hepatic inflammatory response and oxidative stress, promoted the glycogen storage and depleted the fat accumulation in the liver. Besides, LCCL administration alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner, that significantly increased biodiversity, altered the composition of gut microbiota and increased the proportion of Lactobacillus. ConclusionThe lignan-rich extract of C. camphor leaf (LCCL), containing at least 6 lignans compounds, displayed promising antioxidant, hypoglycemic and hypolipidemic activities. The treatment of LCCL alleviated the glycolipid metabolism disorder in T2DM mice with a gut microbiota dependent manner. These finding suggested that LCCL should be further investigated to develop its complementary therapeutic effect on T2DM.

A comparative analysis on impact of drying methods on antioxidants, antidiabetes and antiobesity activities in green algae Caulerpa lentillifera: In vitro study

Marine algae, particularly Caulerpa lentillifera (C. lentillifera), have gained attention as potent sources of bioactive compounds with diverse health benefits. Despite its promising bioactivity, the influence of drying methods on its health-promoting properties remains underexplored. This study investigates the impact of different drying methods on the antioxidant, antidiabetic, and antiobesity activities of C. lentillifera. Fresh samples (GACL-FS) and those dried using air-fryer (GACL-AFD) and microwave (GACL-MD) methods were evaluated for carrageenan content, protein composition, and bioactive potentials. GACL-MD preserved the highest levels of protein, while fresh samples retained the highest carrageenan content. Antioxidant assays revealed superior performance in GACL-MD samples, showing significant DPPH and ABTS inhibition compared to Trolox standards. Similarly, antidiabetic assays demonstrated comparable α-glucosidase inhibition across all drying methods, suggesting robust retention of antidiabetic properties. Antiobesity activity, evaluated through lipase inhibition assays, highlighted GACL-MD's efficacy at lower concentrations, akin to Orlistat, while fresh and air-fryer dried samples showed varied results. In conclusion, C. lentillifera exhibits substantial potential as a functional food ingredient, with the drying method significantly influencing its bioactive profile. Microwave drying emerged as optimal for preserving antioxidant and antiobesity activities, emphasizing the need for tailored drying strategies to enhance nutritional benefits. Future research should focus on optimizing processing techniques and elucidating underlying mechanisms to fully harness C. lentillifera's health-promoting properties in functional food development and public health interventions.