6-O-Alkyl 4-methylumbelliferyl-ß-D-glucosides as selective substrates for GBA1 in the discovery of glycosylated sterols.

Gaucher disease (GD) is a lysosomal storage disorder (LSD) resulting from inherited glucocerebrosidase (GBA1) deficiency. GD diagnosis relies on GBA1 activity assays, typically employing 4-methylumbelliferyl-ß-D-glucopyranoside (4MU-ß-Glc) as fluorogenic substrate. However, these assays suffer from background 4MU release by the non-lysosomal GBA2 and cytosolic GBA3 enzymes. Here we developed GBA1-selective fluorogenic substrates by synthesizing a series of 6-O-acyl-4MU-ß-Glc substrates with diverse fatty acid tails. Because of chemical and enzymatic instability of the ester bonds, analogues of 6-O-palmitoyl-4MU-ß-Glc (3) with different chemical linkages were synthesized. 6-O-alkyl-4MU-ß-Glc 9, featuring an ether linkage, emerged as the most optimal GBA1 substrate, exhibiting both a low Km and compared to substrate 3 a high Vmax. Importantly, substrate 9 is not hydrolyzed by GBA2 and GBA3, and therefore acts as superior substrate for GD diagnosis. Plants contain glycosyl phytosterols (campesterol, ß-sitosterol and sigmasterol) that may also be acylated at C-6. LC-MS/MS analysis revealed that 6-O-acylated and regular glycosylcholesterol (HexChol) tend to be increased in GD patient spleens. Moreover, significant increases in 6-O-acyl-glycosyl-phytosterols were detected in GD spleens. Our findings suggest uptake of (6-O-acyl)-glycosyl-phytosterols from plant food and subsequent lysosomal processing by GBA1, and comprise the first example of accumulation of an exogenous class of glycolipids in GD. Excessive exposure of rodents to glycosylated phytosterols has been reported to induce manifestations of Parkinson's disease (PD). Further investigation is warranted to determine whether (6-O-acyl)-glycosyl-phytosterols could contribute to the enigmatic link between inherited defects in GBA1 and the risk for PD.

Brazil Nut Semi-Defatted Flour Oil: Impact of Extraction Using Pressurized Solvents on Lipid Profile, Bioactive Compounds Composition, and Oxidative Stability.

Brazilian nuts are native to the Amazon rainforest and are considered a non-timber forest-product of extreme economic importance to local populations. This study evaluated the lipid profile, bioactive compounds, and oxidative stability of semi-defatted Brazilian nut flour oil (BNSDFO) obtained using pressurized fluids (n-propane at 40 °C and 2, 4, and 8 MPa or a CO2/n-propane mixture at 40 °C and 12 MPa). A Brazilian nut kernel oil (BNKO) processed by conventional cold pressing was also obtained. The BNKO showed a higher concentration of total phenolic compounds and saturated fatty acids, higher antioxidant activity, and the presence of gallic acid derivatives. The oils extracted using pressurized fluids showed a higher concentration of linoleic acid, ß-sitosterol, and polyunsaturated fatty acids. The utilization of pressurized n-propane resulted in higher yields (13.7 wt%), and at intermediate pressures (4 MPa), the product showed myricetin 3-O-rhamnoside and higher oxidative stability (OSI, 12 h) than at lower pressures (2 MPa). The CO2/n-propane mixture of pressurized solvents resulted in higher concentrations of squalene (4.5 times), the presence of different phenolic compounds, and a high OSI (12 h) but lower yield (2.2 wt%). In conclusion, oils with better fatty acid profiles (oleic e linoleic acids), phytosterol composition, and suitable radical scavenging activity may be obtained using pressurized fluids and Brazilian nut flour, a byproduct of oil extraction. The mixture of solvents may improve the concentration of squalene, whereas using only n-propane may increase oil yield.

Plant Sterol-Enriched Palm Oil Intervention to Improve Lipid Profile and Inflammation Status in Hyperlipidemic Individuals.

Background: Cardiovascular diseases, including coronary heart disease (CHD), are currently positioned among the leading causes of mortality globally. Risk factors of CHD include, among others, hypercholesterolemia and elevations in systemic inflammation. Functional foods enriched with compounds showing cholesterol-lowering effects are considered one among various dietary and lifestyle intervention strategies to tackle this problem. A CHD-preventive effect of dietary plant sterols has been broadly discussed, not only due to their ability to reduce blood cholesterol level, but also to their proven anti-inflammatory potential. Palm oil is one of the most widely consumed edible oils in the world. Despite its widespread use, especially in Asian countries, no study has been conducted using palm oil as a vehicle for plant sterols. Methods: The aim of the placebo-controlled double-blinded trial presented here was, therefore, to evaluate the effect of palm oil enriched with plant sterols, used as a cooking oil, on lipid profile and systemic inflammation marker in 100 adult hyperlipidemic residents of Bogor, Indonesia. Results: The study has shown a significant reduction in total cholesterol and LDL cholesterol level in study subjects consuming plant sterol-enriched palm oil as a replacement for usual palm oil for cooking, with no similar effect on CRP levels. Conclusions: The study suggests that, along with a healthy diet and lifestyle promotion, incorporating plant sterols in palm oil used for cooking may be an effective strategy to reduce cardiovascular risks in hyperlipidemic individuals.

Lygodium microphyllum Inhibits de Novo Lipogenesis Activity in the Hepatocytes of High-Fat High-Fructose-Induced Rats by Increasing the Levels of SIRT1 and AMPK.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is currently of great concern due to its risk of developing T2DM and cardiovascular disease. The development of NAFLD may be initiated by de novo lipogenesis in the hepatocytes. Sirtuin1 (SIRT1) and adenosine monophosphate-activated protein kinase (AMPK), are responsible for the lipogenesis mechanism. Interestingly, plant sterols, such as beta-sitosterol and stigmasterol, have the potential to lower the LDL-cholesterol in dyslipidemic patients. Beta-sitosterol was present in the ethanol extract of Lygodium microphyllum herbs at a concentration of 283.55 µg/g extract. This sterol interacted with the active allosteric-binding site of SIRT1 and AMPK similarly to the proteins' activators. Purpose: To investigate the anti-lipogenesis activity of the ethanol extract of L. microphyllum (ELM) in the liver tissue of rats through the SIRT1 and AMPK levels. Methods: Forty male Wistar rats were used in this study: (1) normal control group; (2) high-fat high-fructose diet (HFHFD) rats; (3) HFHFD rats treated with metformin; (4) HFHFD rats treated with resveratrol; (5) HFHFD rats treated with beta-sitosterol; (6-8) HFHFD rats treated with ELM doses of 200, 400, and 600 mg/kg BW. Rats in the normal control group were fed regular chow, while other groups of rats were given HFHFD for 35 days. All drugs were given orally on D15 till D35. On D35, the rats were sacrificed, and the liver organs were examined for the liver index, morphology, NAFLD activity score (NAS), and levels of SIRT1 and AMPK. Results: ELM improves the morphology, the liver index, the steatosis condition, and the NAS of HFHFD-induced NAFLD rats. ELM increases the levels of SIRT1 and AMPK in the liver tissue of HFHFD-induced NAFLD rats. Conclusion: ELM may have the potential to inhibit de novo lipogenesis by increasing the levels of SIRT1 and AMPK.

Identifying Potential Human Monoacylglycerol Lipase Inhibitors from the Phytoconstituents of Morinda Citrifolia L. Fruits by in silico Pharmacology and in vitro Study.

Background: Human monoacylglycerol lipase (MGL) is accountable for the hydrolysis of 2-arachidonoylglycerol (2-AG), thus contributing pivotally to neuroprotection because 2-AG is the main source of arachidonic acid, the precursor of prostaglandins production. Inhibiting MGL reduces inflammatory damage in the ischemic brain and enhances cerebral blood flow. Plants have been reported for their neuroprotective effect, such as Morinda citrifolia on pentylenetetrazol (PTZ)-induced kindling seizures in mice, by reducing the seizures and restoring behavioral and biochemical changes, although the mechanism is not described. Purpose: To evaluate the binding affinity and stability of phytoconstituents in M. citrifolia fruits toward human MGL (PDB ID 3PE6), compared to the known MGL inhibitors (JZL195 and ZYH). The in silico pharmacology study was validated by an in vitro study of the phytosterols and the ethanol extract of M. citrifolia fruits (EEMC) towards MGL. Methods: Initially, nine phytoconstituents of M. citrifolia fruits were docked to the catalytic pocket of human MGL (PDB ID: 3PE6), and compounds with the best affinity were subjected to a molecular dynamic (MD) simulation. The in vitro study was performed using the MGL inhibitor screening assay kit. Results: The best binding affinity and stability toward human MGL were shown by stigmasterol and beta-sitosterol, and the MM-PBSA total binding energy of stigmasterol and beta-sitosterol to MGL is stronger than that of JZL195 and ZYH. Moreover, beta-sitosterol and EEMC inhibit MGL with an IC50 value of, respectively, 8.10 µg/mL and 196.20 µg/mL, while JZL195 shows an IC50 of 0.028 µg/mL. Conclusion: Beta-sitosterol of Morinda citrifolia fruits may have the potential to protect human neurons by occupying the catalytic site of human MGL, thus competitively inhibiting the substrate of the enzyme. However, the inhibitory activity towards human MGL is lower than JZL195.

Selective Agonism of Liver and Gut FXR Prevents Cholestasis and Intestinal Atrophy in Parenterally Fed Neonatal Pigs.

BACKGROUND & AIMS: We aimed to investigate the relative efficacy of feeding different bile acids in preventing PNALD in neonatal pigs. METHODS: Newborn pigs given total parenteral nutrition (TPN) combined with minimal enteral feeding of chenodeoxycholic acid (CDCA), or increasing doses of obeticholic acid (OCA) for 19 days. RESULTS: Enteral OCA (5 and 15 mg/kg), but not CDCA (30 mg/kg) reduced blood cholestasis markers compared to TPN controls and increased bile acids in the gallbladder and intestine. Major bile acids in the liver and distal intestine were CDCA, HCA, HDCA and OCA, and their relative proportions were increased by the type of bile acid (CDCA or OCA) given enterally. High doses of OCA increased the total NR1H4-agonistic bile acid profile in the liver and intestine above 50% total bile acids. Both CDCA and OCA treatments suppressed hepatic cyp7a1 expression, but only OCA increased hepatobiliary transporters, ABCB11, ABCC$ and ABCB1. Plasma phytosterol levels were reduced and biliary levels were increased by CDCA and OCA and hepatic sterol transporters, abcg5/8, expression were increased by OCA. Both CDCA and OCA increased plasma FGF19 and OCA increased intestinal FGF19, FABP6, and SLC51A. Both CDCA and OCA increased intestinal mucosal growth, whereas CDCA increased the plasma GLP-2, GLP-1 and GIP. CONCLUSIONS: Enteral OCA prevented cholestasis and phytosterolemia by increased hepatic bile acid and sterol transport via induction of hepatobiliary transporter FXR target genes and not by suppression of bile acid synthesis genes. We also showed an intestinal trophic action of OCA that demonstrates a dual clinical benefit of FXR agonism in the prevention of PNALD in piglets.

Evaluation of plasma phytosterols in sitosterolemia, their kindreds and hyperlipidemia subjects.

BACKGROUND: Patients suffering from sitosterolemia with ABCG5/8 mutation typically present with early-onset or rapidly progressive atherosclerosis. Their kindreds with partial genetic deficiencies of ABCG5/8 are often considered healthy. However, discerning sitosterolemia from its familial kindreds and hyperlipidemia subjects has remained challenging. METHODS: Here we retrospectively recruited seven families including 8 individuals diagnosed with sitosterolemia subjects, and 14 kindreds carrying single gene mutations. Additionally, 17 individuals with hyperlipidemia and 130 healthy controls served as positive and negative controls, respectively. A total of 6 phytosterols combined with cholesterol absorption indices (including sitosterol, campesterol, stigmasterol, and cholestanol) and cholesterol synthesis markers (desmosterol and 7-dehydrocholesterol), was compared across the aforementioned four groups. RESULTS: As expected, the sitosterolemia subjects with double mutations demonstrated significantly elevated levels of sitosterol and other cholesterol absorption indices. Meanwhile, sitosterolemia kindreds with single gene mutation showed a similar pattern of activated cholesterol-absorption ability to the hyperlipidemia group, but not as high as the double mutation group. Notably, the cholesterol-synthesis enzyme 7-dehydrocholesterol reductase displayed an increase in the hyperlipidemia group but a decrease in the sitosterolemia kindred group, suggesting a potential discriminative role of 7-dehydrocholesterol in distinguishing between these two groups. The combination of phytosterols was more valuable than clinical lipid index for sitosterolemia diagnosis. CONCLUSION: Our study revealed mild disruptions of cholesterol absorption capacities in sitosterolemia kindreds with single mutations. Furthermore, the combination of 6 phytosterols proved effective in distinguishing between sitosterolemia, its single mutation carriers, and hyperlipidemia patients.

Unveiling the oxidative stability, phytochemical richness, and nutritional integrity of cold-pressed Linum usitatissimum oil under UV exposure.

This study examines the effect of UV irradiation on the oxidation stability of Linum usitatissimum oil, presenting possible changes in the phytochemical profile due to photo-oxidation. GC-MS analysis of the oils identified 11 fatty acid compounds with a high percentage of unsaturated fatty acids, the most important of which is α-linolenic acid (ALA), known as omega-3 (48.88 %), also significant profiles of phytosterol and tcocopherol isomers rich in ß-Sitosterol and γ-tocopherols respectively. As well as physicochemical properties such as free fatty acids (FFA %), peroxide value (PV) and iodine value (IV), and nutritional indexes that determine the significant changes observed during the oxidation process, the most important of which is the progressive increase in acidity, peroxide, conjugated dienes and trienes and degrees of unsaturation over 8 h of UV exposure. High levels of carotenoids and phenolic compounds (TPC) protect and enhance oil quality in the face of irradiation, so a significantly small difference is observed between irradiated and non-irradiated oil during photo-oxidation.

Aspects of ß-sitosterol's Pharmacology, Nutrition and Analysis.

Phytosterols are bioactive substances found naturally in the cell membranes of plants and have an arrangement of molecules similar to that of fat, which is produced by mammalian cells. They are widely distributed as dietary sources of lipids in plants, such as nuts, seeds, olive oil, and legumes. This review provides a summary of the efficacy of BS in treating lifestyle problems, as well as an appraisal of previous research. Data was collected from PubMed, ScienceDirect, Scopus, and Google scholar (1968 -2024) using standard keywords "ß-sitosterol," "Classification," "Biosynthesis," "Pharmacokinetics," "Herbal nutraceutical," "Analytical," "Structure," "Pharmacological effect." A total of 222 studies were included in this review. Numerous in vitro and in vivo investigations have shown that BSs exhibit several biological properties such as calming and anxiolytic effects; narcotic and immune-stimulating effects; antibacterial, antineoplastic, inflammation-causing, lipid-lowering, and hepatoprotective effects; and antioxidant, anti-diabetic, and wound-healing effects in contrast to respiratory and non-alcoholic fatty liver disease illnesses. ß-sitosterol is a promising natural substance for the management of cholesterol and inflammation. However, further studies are needed to understand its pharmacological consequences and determine its best use in clinical applications. ß-Sitosterol, also known as "plant sterol ester," is often present in plants and has several applications, notably in medicine and the food industry. Experimental research on ß-sitosterol provides unequivocal evidence that phytosterol can be supplemented with other methods to combat serious illnesses. Such a high potential identifies this substance as a noteworthy medication for the future based on its composition. Although ß-sitosterol has anticancer and anti-inflammatory properties and is useful in human clinical trials for enlarged prostates, its mechanism of action remains unclear.

Phytosterols in mountain cultivated ginseng, as master healthy ageing dietary supplement, activates steroid signaling in ageing Drosophila melanogaster.

Mountain cultivated ginseng (MCG) is planted in mountain forests to simulate traditional wild ginseng; therefore, it has a greater pharmacological effect than cultivated ginseng (CG) in the garden; however, insufficient evidence confirms this theory. In light of the health-promoting and life-extending properties of ginseng, we analyzed the efficacy of MCG and CG. Initial observations revealed that the phytosterols content of MCG was higher than that of CG, with a positive correlation to the duration of growth. The distinction between phytosterols in MCG and in CG is predominately determined by the stigmasterol content using High-Performance Liquid Chromatography (HPLC). The lifespan of Drosophila melanogaster (fruit flies) that aged naturally was prolonged by phytosterols in MCG and CG and stigmasterols. Further, they prolonged healthy ageing as measured by progeny numbers, length of sleep, climbing distance, and survival following oxidative damage. The findings of behavioral observations revealed that phytosterols in MCG were more efficacious than in CG in promoting health maintenance and life extension; moreover, stigmasterol indicated that these effects were dose-dependent. Stigmasterols, phytosterols in MCG and CG have restored age-associated decreases in steroid hormone levels. Notably, molecular docking was predicted to promote stigmasterol's binding to the steroid hormone receptor ECR due to its similarity to steroid hormones. In addition, stigmasterols triggered the steroid hormone signaling pathway by increasing the activity of key genes Eip75B and Br in 20E signaling and Jhamt, HmGR, Met, and Kr-h1 in JH signaling. Phytosterols, as a natural product, regulated health and longevity as a dietary supplement similar to that of steroids, which supported the social requirements of healthy ageing.

Endophytic fungi from Cissus quadrangularis plant a promising source of bioactive compounds.

Cissus quadrangularis is a succulent, perennial plant belonging to the family Vitaceae typically found in Asia and Africa's tropical and subtropical forest zones. It is an ancient medicinal plant, containing phytosterols, polyphenols, flavonoids, carbohydrates, and ascorbic acid. Due to the presence of phytosterols it plays a crucial role in bone fracture healing. However, due to the limited resources of these medicinal plants there is a need to search for a reservoir of biologically active metabolites. This medicinal property of the plants therefore may be attributed to the endophytic fungi within the plant. This study includes isolation of endophytic fungi from C. quadrangularis and the characterization of fungal extracts. Three endophytes were isolated namely Colletotrichum gloeosporioides, Colletotrichum siamense and Phoma sp. The qualitative analysis of targeted metabolites from Cissus quadrangularis stem and fungal extracts of all the three endophytes showed the presence of phytosterols. Methanol extracts of endophytes and C. quadrangularis plant exhibit significant antioxidant and the radical scavenging activity because of the presence of ß-carotene. The Ic50 value for stem and isolated endophytes was 5.748, 19.937, 7.00, and 6.493 respectively. This study will give further scope for studying the bone healing ability of phytosterol from the endophytic isolates of C. quadrangularis plant.

The benefits and challenges of treating skin with natural oils.

The term natural oil refers to a fixed (non-volatile) oil of animal or plant origin. These types of oils - in contrast to essential (volatile) oils, which are obtained by steam distillation methods of plant matter - are typically obtained from plant seeds and nuts by a mechanical pressing technique or solvent extraction. The natural movement in cosmetics of the 21st century has led to renewed interest in formulating skin care products with botanical ingredients. In this article, we discuss the benefits and caveats of natural oil treatments as moisturizing agents (as occlusives and emollients) as well as their utility in wound healing and treatment of skin diseases. We also address the paradoxical behaviour of natural oils in relation to barrier function and highlight the current state of our knowledge with respect to the use of natural oils in neonatal skin care. Finally, we provide a comparison of natural oils to conventional petroleum-based oils.

Le terme huile naturelle fait référence à une huile fixe (non volatile) d'origine animale ou végétale. Ces types d'huiles, contrairement aux huiles essentielles (volatiles) qui sont obtenues par des méthodes de distillation à la vapeur de matières végétales, sont généralement obtenues à partir de graines et de noix de plantes par une technique de pressage mécanique ou d'extraction par solvant. Le mouvement naturel des cosmétiques du XXI siècle a suscité un regain d'intérêt pour la formulation de produits de soins pour la peau à base d'ingrédients botaniques. Dans cet article, nous examinons les avantages et les mises en garde des traitements à base d'huiles naturelles en tant qu'agents hydratants (comme occlusifs et émollients), ainsi que leur utilité dans la cicatrisation des plaies et le traitement des maladies de la peau. Nous abordons également le comportement paradoxal des huiles naturelles par rapport à la fonction barrière et mettons en évidence l'état actuel de nos connaissances en ce qui concerne l'utilisation des huiles naturelles dans les soins de la peau néonatale. Enfin, nous comparons les huiles naturelles aux huiles conventionnelles à base de pétrole.

The Effect of High-Temperature Heating on Amounts of Bioactive Compounds and Antiradical Properties of Refined Rapeseed Oil Blended with Rapeseed, Coriander and Apricot Cold-Pressed Oils.

Cold-pressed oils are rich sources of bioactive substances, which may protect triacylglycerols from degradation during frying. Nevertheless, these substances may decompose under high temperature. This work considers the content of bioactive substances in blends and their changes during high-temperature heating. Blends of refined rapeseed oil with 5% or 25% in one of three cold-pressed oils (rapeseed, coriander and apricot) were heated at 170 or 200 °C in a thin layer on a pan. All non-heated blends and cold-pressed oils were tested for fatty acid profile, content and composition of phytosterols, tocochromanols, chlorophyll and radical scavenging activity (RSA) analyzed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Moreover, the stability of phytosterols, tocochromanols, DPPH and ABTS values was determined in heated blends. All tocochromanols were lost during the heating process, in particular, at 200 °C. However, there were some differences between homologues. α-Tocopherol and δ-tocopherol were the most thermolabile and the most stable, respectively. Phytosterols were characterized by very high stability at both temperatures. We observed relationships between ABTS and DPPH values and contents of total tocochromanols and α-tocopherol. The obtained results may be useful in designing a new type of fried food with improved health properties and it may be the basis for further research on this topic.

Nutriomic Effects of Precision Lipids on Murine Hepatic Triacylglycerol Alterations Induced by High-Fat Diets.

INTRODUCTION: This study aims to investigate if a mixture of functional lipids (FLs), containing conjugated linoleic acid (CLA), tocopherols (TPs), and phytosterols (PSs), prevents some lipid alterations induced by high-fat (HF) diets, without adverse effects. METHODS: Male CF1 mice (n = 6/group) were fed (4 weeks) with control (C), HF, or HF + FL diets. RESULTS: FL prevented the overweight induced by the HF diet and reduced the adipose tissue (AT) weight, associated with lower energy efficiency. After the intervention period, the serum triacylglycerol (TAG) levels in both HF diets underwent a decrease associated with an enhanced LPL activity (mainly in muscle). The beneficial effect of the FL mixture on body weight gain and AT weight might be attributed to the decreased lipogenesis, denoted by the lower mRNA levels of SREBP1-c and ACC in AT, as well as by an exacerbated lipid catabolism, reflected by increased mRNA levels of PPARα, ATGL, HSL, and UCP2 in AT. Liver TAG levels were reduced in the HF + FL group due to an elevated lipid oxidation associated with a higher CPT-1 activity and mRNA levels of PPARα and CPT-1a. Moreover, genes linked to fatty acid biosynthesis (SREBP1-c and ACC) showed decreased mRNA levels in both HF diets, this finding being more pronounced in the HF + FL group. CONCLUSION: The administration of an FL mixture (CLA + TP + PS) prevented some lipid alterations induced by a HF diet, avoiding frequent deleterious effects of CLA in mice through the modulation of gene expression related to the regulation of lipid metabolism.

Human Oral Phase Coupled with In Vitro Dynamic Gastrointestinal Digestion for Assessment of Plant Sterol Bioaccessibility from Wholemeal Rye Bread.

A dynamic gastrointestinal digestion system (simgi) after a human oral phase was used, for the first time, to assess the bioaccessibility of plant sterols (PS) from wholemeal rye bread (74.8 ± 2.2 mg of PS/100 g d.m.) and PS-enriched wholemeal rye bread (PS-WRB) (1.6 ± 0.04 g of PS/100 g of fresh bread). The use of these solid food matrices requires a novel adaptation of the gastric phase of the system. The PS identified in the breads are campesterol, campestanol, stigmasterol, ß-sitosterol, sitostanol, Δ5-avenasterol, Δ5,24-stigmastadienol, Δ7-stigmastenol, and Δ7-avenasterol. The bioaccessibility of the total PS, only quantifiable in PS-WRB, is 19.9%, with Δ7-avenasterol being the most bioaccessible and Δ5-avenasterol being the least (p < 0.05). As shown in this study, PS-WRB can be considered to be a good choice to include in the daily diet. Furthermore, although the use of dynamic digestion methods for evaluating bioaccessibility implies high costs and technical complexity, their application means a closer approximation to in vivo scenarios.

Nuclear receptors behind the therapeutic effects of plant sterols on metabolism: A review.

Plant sterols are known for their hypocholesterolemic action, and the molecular mechanisms behind this within the gut have been extensively discussed and demonstrated to the point that there is a degree of consensus. However, recent studies show that these molecules exert an additional umbrella of therapeutic effects in other tissues, which are related to immune function, lipid metabolism, and glucose metabolism. A strong hypothesis to explain these effects is the structural relationship between plant sterols and the ligands of a group of nuclear receptors. This review delves into the molecular aspects of therapeutic effects related with lipid and energy metabolism that have been observed and demonstrated for plant sterols, and turns the perspective to explore the involvement of nuclear receptors as part of these mechanisms.

Biosynthesis of the triterpenoid withanolides in Withaniasomnifera.

Ashwagandha (Withania somnifera L. Dunal) is a versatile medicinal plant of Solanaceae family, renowned for its potent therapeutic properties, due to which it is extensively used in Indian traditional systems of medicine such as Ayurveda. The medicinal properties are attributed to specialized metabolites known as withanolides, which are chemically triterpenoid steroidal lactones. Despite their significance, the biosynthetic pathway of withanolides remains poorly understood. It is hypothesized that withanolides are synthesized through the universal sterol pathway, wherein sterol precursors undergo various biochemical modifications such as hydroxylation, oxidation, cyclization, and glycosylation, yielding a diverse array of downstream withanolides and withanosides. Consequently, comprehending the biosynthetic pathway of withanolides is crucial to facilitate advancements in withanolides productivity through metabolic engineering or synthetic biology approaches. This article aims to provide an update on the efforts made toward understanding withanolides formation and regulation and highlights gaps and approaches to elucidate the withanolides biosynthesis in W. somnifera.

Anti-Inflammatory Activity and Acute Toxicity Of Pereskia aculeata, In Zophobas morio Larvae.

Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as ß-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200 µg/mL; STIG and ß-SIT showed toxicity up to 25 µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6 mg/kg for PHEX, 101.5 mg/kg for STIG, and 103.8 mg/kg for ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.

Hypoglycemic and hypolipidemic effects of unsaponifiable matter from okra seed in diabetic rats.

BACKGROUND/OBJECTIVES: Okra seed is a rich source of various nutritional and bioactive constituents, but its mechanism of action is still unclear. The aim of this study was to evaluated the effects on glucose uptake and serum lipid profiles of unsaponifiable matter (USM) from okra seed in adipocytes and diabetic animal models. MATERIALS/METHODS: USM was prepared from okra seed powder by saponification. The contents of phytosterols and vitamin E in USM were measured. 3T3-L1 preadipocytes were cultured for 6 days with different concentrations of USM (0-200 µg/mL). The diabetic rats were administered with or without USM for 5 wk. RESULTS: In the USM, the contents of phytosterols and vitamin E were 394.13 mg/g USM and 31.16 mg/g USM, respectively. USM showed no cytotoxicity and led to an approximately 1.4-fold increase in glucose uptake in 3T3-L1 adipocytes. The treatment of USM also increased the expressions of peroxisome proliferator-activated receptor-γ and glucose transporter-4 in a dose-dependent manner in adipocytes. The body weight change was not significantly different in all diabetic rats. However, blood glucose and the weights of liver and adipose tissues were significantly reduced compared to those in the control diabetic rats. Treatment with USM decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the control group. The USM group also showed significantly decreased atherogenic indices and cardiac risk factors. CONCLUSION: These results suggest that USM from okra seed improves the hypoglycemic and hypolipidemic effects in diabetic rats, and provides valuable information for improving the functional properties of okra seed.

Phytosterols: Physiological Functions and Potential Application.

Dietary intake of natural substances to regulate physiological functions is currently regarded as a potential way of promoting health. As one of the recommended dietary ingredients, phytosterols that are natural bioactive compounds distributed in plants have received increasing attention for their health effects. Phytosterols have attracted great attention from scientists because of many physiological functions, for example, cholesterol-lowering, anticancer, anti-inflammatory, and immunomodulatory effects. In addition, the physiological functions of phytosterols, the purification, structure analysis, synthesis, and food application of phytosterols have been widely studied. Nowadays, many bioactivities of phytosterols have been assessed in vivo and in vitro. However, the mechanisms of their pharmacological activities are not yet fully understood, and in-depth investigation of the relationship between structure and function is crucial. Therefore, a contemporaneous overview of the extraction, beneficial properties, and the mechanisms, as well as the current states of phytosterol application, in the food field of phytosterols is provided in this review.