Phytosterol and phytostanol-mediated epigenetic changes in cancer and other non-communicable diseases: a systematic review.

Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.

The effect of phytosterol supplementation on lipid profile: A critical umbrella review of interventional meta-analyses.

Despite multiple investigations assessing the impact of phytosterol supplementation on serum lipid levels, there is still a great deal of debate regarding the benefits of this intervention in the management of dyslipidemia. Therefore, we aimed at clarifying this dilemma by conducting the present umbrella review of interventional meta-analyses. Scopus, PubMed, Web of Science, and EMBASE were used to search for pertinent publications on the effect of phytosterol supplementation on the lipid profile in humans up to June 2023. To compute the overall effect size (ES) and confidence intervals (CI), the random-effects model was used. The I2 statistic and Cochrane's Q-test were applied to estimate the heterogeneity among the studies. Seventeen meta-analyses with 23 study arms were included in the umbrella meta-analysis. Data pooled from the 23 eligible arms revealed that phytosterol supplementation reduces low-density lipoprotein cholesterol (LDL-C) (ES = -11.47 mg/dL; 95% CI: -12.76, -10.17, p < 0.001), total cholesterol (TC) (ES = -13.02 mg/dL; 95% CI: -15.68, -10.37, p < 0.001), and triglyceride (TG) (ES = -3.77 mg/dL; 95% CI: -6.04, -1.51, p = 0.001). Subgroup analyses showed that phytosterol administration with dosage ≥2 g/day and duration over 8 weeks and in hypercholesterolemic subjects was more likely to decrease LDL-C, TC, and TG. Phytosterol administration did not significantly modify HDL-C (ES = 0.18 mg/dL; 95% CI: -0.13, -0.51, p = 258) levels when compared to controls. The present umbrella meta-analysis confirms that phytosterol administration significantly reduces LDL-C, TC, and TG, with a greater effect with doses of ≥2 g/day and treatment duration >8 weeks, suggesting its possible application as a complementary therapy for cardiovascular risk reduction. Further studies are needed to determine the efficacy of phytosterols in patients with specific health conditions, as well as to ascertain the adverse effects, the maximum tolerable dose, and the maximum recommended duration of phytosterol administration.

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.

Dietary supplements: clinical cholesterol-lowering efficacy and potential mechanisms of action.

This review aims to analyse the efficacy of dietary supplements in reducing plasma cholesterol levels. Focusing on evidence from meta-analyses of randomised controlled clinical trials, with an emphasis on potential mechanisms of action as supported by human, animal, and cell studies. Certain dietary supplements including phytosterols, berberine, viscous soluble dietary fibres, garlic supplements, soy protein, specific probiotic strains, and certain polyphenol extracts could significantly reduce plasma total and low-density lipoprotein (LDL) cholesterol levels by 3-25% in hypercholesterolemic patients depending on the type of supplement. They tended to be more effective in reducing plasma LDL cholesterol level in hypercholesterolemic individuals than in normocholesterolemic individuals. These supplements worked by various mechanisms, such as enhancing the excretion of bile acids, inhibiting the absorption of cholesterol in the intestines, increasing the expression of hepatic LDL receptors, suppressing the activity of enzymes involved in cholesterol synthesis, and activating the adenosine monophosphate-activated protein kinase signalling pathway.

Progress in the treatment of Osteoarthritis with avocado-soybean unsaponifiable.

Osteoarthritis (OA) is one of the leading causes of joint dysfunction and disability in the elderly, posing serious social problems and a huge socio-economic burden. Existing pharmacological treatments have significant drawbacks, and searching for an effective pharmacological intervention is an urgent priority. Recent studies have demonstrated the chondroprotective, anabolic, and anti-catabolic properties of avocado-soybean unsaponifiable (ASU), a natural plant extract made from avocado and soybean oils, consisting of the remainder of the saponified portion of the product that cannot be made into soap. The main components of ASU are phytosterols, beta-sitosterol, canola stanols, and soya stanols, which are rapidly incorporated into cells. Studies have confirmed the anti-inflammatory, antioxidant, and analgesic properties of phytosterols. ASU slows down the progression of OA primarily by inhibiting pathways involved in the development of OA disease. ASU prevents cartilage degradation by inhibiting the release and activity of matrix metalloproteinases and by increasing the tissue inhibition of these catabolic enzymes; ASU is also involved in the inhibition of the activation of nuclear factor κB (NF-κB) which is a transcriptional inhibitor that regulates the inflammatory response of chondrocytes. NF-κB is a transcription factor that regulates the inflammatory response of chondrocytes, and inhibition of the transfer of the transcription factor NF-κB from the cytoplasm to the nucleus regulates the transcription of many pro-inflammatory factors. By appealing to the mechanism of action and thus achieving anti-inflammatory, anti-catabolic, and pro-synthetic effects on cartilage tissues, AUS is clinically responsive to the reduction of acute pain and OA symptom progression. This paper aims to summarize the studies on the use of avocado-soybean unsaponifiable in the pharmacological treatment of osteoarticular.

Liposomal Phytosterols as LDL-Cholesterol-Lowering Agents in Diet-Induced Hyperlipidemia.

The high blood level of low-density lipoprotein cholesterol (LDL-C) is a primary risk factor for cardiovascular disease. Plant sterols, known as phytosterols (PSs), can reduce LDL-C in a range of 8-14%. The extent of LDL-C reduction depends on its formulation. Encapsulation into liposomes is one formulation strategy to enhance the efficiency of PSs. PSs (campesterol, stigmasterol, and ß-sitosterol) have frequently been assessed alone or in combination for their LDL-C-lowering ability. However, one naturally abundant PS, brassicasterol, has not yet been tested for its efficacy. We have previously developed a novel liposomal formulation containing the PS mixture present naturally in canola that is composed of brassicasterol, campesterol, and ß-sitosterol. In this work, the efficacy of our novel liposomal PS formulation that includes brassicasterol was assessed in a hamster model. Animals were divided into five groups: (i) liposomal PS in orange juice, (ii) liposomal PS in water, (iii) marketed PS in orange juice, (iv) control orange juice, and (v) control water. The animals were fed a high-fat, cholesterol-supplemented (0.5%) diet to induce hypercholesterolemia. The treatment was administered orally once daily for 4 weeks. Fasting blood samples were collected at baseline, week 2, and week 4. The extent of the reduction of total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides was compared among the groups. Liposomal PSs in both orange juice and water significantly reduced LDL-C compared to their controls. Furthermore, the liposomal PS was as effective as a marketed PS-containing product in reducing LDL-C. Liposomal PSs in both orange juice and water showed similar efficacy in LDL-C reduction, highlighting that these vehicles/food matrices do not affect the efficacy of PSs. The liposomal formulation of a natural PS mixture extracted from canola oil, with brassicasterol as a major component, exhibited a significant LDL-C reduction in a hamster model.

Phytosterols as bioactive food components against nonalcoholic fatty liver disease.

Phytosterols are bioactive food components widely present in cell membranes of plants, especially in nuts and oilseeds. In recent years, many studies have shown that phytosterols possess therapeutic potentials for nonalcoholic fatty liver disease (NAFLD). This review summarizes the effects of phytosterols from in vitro and in vivo studies to lower the levels of total cholesterol (TC) and triglycerides (TG), and the evidence supporting the potential of phytosterols against NAFLD. The potential mechanisms by which phytosterols improve NAFLD may include (i) competition with cholesterol; (ii) regulation of key factors involved in cholesterol and TG metabolism; and (iii) inhibition of liver inflammation and (iv) regulation of liver fatty acid composition. In summary, phytosterols are potential natural ingredients with good safety profile against NAFLD, which deserve more future studies.

The critical role of the phytosterols in modulating tumor microenvironment via multiple signaling: A comprehensive molecular approach.

Cancer is the leading cause of mortality and morbidity worldwide, and its cases are rapidly increasing every year. Several factors contribute to the development of tumorigenesis. including radiation, dietary lifestyle, smoking, environmental, and genetic factors. The cell cycle is regulated by a variety of molecular signaling proteins. However, when the proteins involved in the cell cycle regulation are altered, cellular growth and proliferation are significantly affected. Natural products provide an important source of new drug development for a variety of ailments. including cancer. Phytosterols (PSs) are an important class of natural compounds reported for numerous pharmacological activities, including cancer. Various PSs, such as ergosterol, stigmasterol, sitosterol, withaferin A, etc., have been reported for their anti-cancer activities against a variety of cancer by modulating the tumor microenvironment via molecular signaling pathways discussed within the article. These signaling pathways are associated with the production of pro-inflammatory mediators, growth factors, chemokines, and pro-apoptotic and anti-apoptotic genes. These mediators and their upstream signaling are very active within the variety of tumors and by modulating these signalings, thus PS exhibits promising anti-cancer activities. However, further high-quality studies are needed to firmly establish the clinical efficacy as well the safety of the phytosterols.

A Mixture of Dietary Plant Sterols at Nutritional Relevant Serum Concentration Inhibits Extrinsic Pathway of Eryptosis Induced by Cigarette Smoke Extract.

Cell death program of red blood cells (RBCs), called eryptosis, is characterized by activation of caspases and scrambling of membrane phospholipids with externalization of phosphatidylserine (PS). Excessive eryptosis confers a procoagulant phenotype and is implicated in impairment of microcirculation and increased prothrombotic risk. It has recently been reported that cigarette smokers have high levels of circulating eryptotic erythrocytes, and a possible contribution of eryptosis to the vaso-occlusive complications associated to cigarette smoke has been postulated. In this study, we demonstrate how a mixture of plant sterols (MPtS) consisting of ß-sitosterol, campesterol and stigmasterol, at serum concentration reached after ingestion of a drink enriched with plant sterols, inhibits eryptosis induced by cigarette smoke extract (CSE). Isolated RBCs were exposed for 4 h to CSE (10-20% v/v). When RBCs were co-treated with CSE in the presence of 22 µM MPtS, a significant reduction of the measured hallmarks of apoptotic death like assembly of the death-inducing signaling complex (DISC), PS outsourced, ceramide production, cleaved forms of caspase 8/caspase 3, and phosphorylated p38 MAPK, was evident. The new beneficial properties of plant sterols on CSE-induced eryptosis presented in this work open new perspectives to prevent the negative physio-pathological events caused by the eryptotic red blood cells circulating in smokers.

Multiomic Analyses Reveal the Effects of Supplementing Phytosterols on the Metabolic Function of the Rumen Microbiota in Perinatal Cows.

Phytosterols are natural steroids in plants, possessing bioactivities that could modify gut microbes. This experiment aimed to evaluate the effects of feeding phytosterols on the community structures and metabolic functions of the rumen microbiota in perinatal cows. Perinatal cows were supplied with 0 mg (control) or 200 mg (treatment) phytosterols per day. Multiomic analyses were used to analyze the community structures and metabolic functions of rumen microbiota. Results showed that dietary phytosterols increased the copy number of total ruminal bacteria, the concentration of microbial crude protein, and the molar percentage of propionate in the rumen of perinatal cows but had no effects on the alpha diversity of ruminal bacteria. However, they enriched three genera (i.e., Fibrobacter) and seven species (i.e., Fibrobacter succinogenes) within active ruminal bacteria. Metatranscriptomic and metabolomic analyses revealed that dietary phytosterols enhanced the pathway of glycolysis and the family of glycoside hydrolase 13 but depressed the citrate cycle and pyruvate metabolism and several pathways of amino acid biosynthesis. In conclusion, dietary addition of phytosterols improved the growth of ruminal bacteria and changed rumen fermentation by modifying the rumen microbiome and the energy metabolism pathways, which would be beneficial for the energy utilization of perinatal cows. IMPORTANCE Perinatal cows suffer serious physiological stress and energy deficiency. Phytosterols have bioactive functions for gut microbes. However, little knowledge is available on their effects on rumen microbiota and rumen fermentation. Results of the present experiment revealed that dietary supplementation of phytosterols could improve the growth of ruminal bacteria and changed the rumen fermentation to provide more glycogenetic precursors for the perinatal cows by modifying the ruminal bacteria community and altering the energy metabolism pathways of the rumen microbiota. These findings suggest that dietary supplementation of phytosterols would be beneficial for perinatal cows suffering from a negative energy balance.

Association of Dietary Phytosterols Intake and Survival of Esophageal Squamous Cell Carcinoma: A Prospective Cohort Study.

BACKGROUND: The association of dietary phytosterols intake with survival of esophageal squamous cell carcinoma (ESCC) remains unclear. This study was to examine the effect of dietary phytosterols intake on ESCC survival in a Chinese rural population. METHODS: A total of 942 incident ESCC patients diagnosed between 2011 and 2013 in Yanting area were followed up until March 1st, 2020. Dietary intake five years before ESCC diagnosis was collected using a food frequency questionnaire. The outcome of interest was all-cause mortality. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence intervals (CI). RESULTS: When comparing the highest with lowest intake quartiles, intake of five specific and total phytosterols was not significantly associated with risk of death after adjustment for covariates, the adjusted HR (95% CI) for ß-sitosterol, campesterol, stigmasterol, ß-sitostanol, campestanol and total phytosterols was 0.90 (95% CI: 0.70-1.16), 0.92 (95% CI: 0.71-1.19), 0.86 (95% CI: 0.66-1.12), 0.93 (95% CI: 0.73-1.20), 0.94 (95% CI: 0.72-1.21), 0.89 (95% CI: 0.69-1.15), respectively. CONCLUSION: This study does not find any association between pre-diagnostic phytosterols intake and risk of all-cause mortality among ESCC patients. Further research is required to determine the effect of post-diagnostic phytosterols intake on ESCC survival.

Phytosterols and phytostanols and the hallmarks of cancer in model organisms: A systematic review and meta-analysis.

Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2-1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action.

The effects of phytosterol and phytostanol supplementation on the lipid profile in postmenopausal women: A systematic review and meta-analysis of randomized controlled trials.

Various studies have proven that phytosterols and phytostanols (PS) are lipid-lowering agents. These compounds play a role in regulating high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) metabolism. Although various drugs are available and are currently used to treat dyslipidemia, the management of lipid abnormalities during the postmenopausal period remains a challenge. Thus, scientists are trying to develop new strategies to reduce serum lipids concentrations using natural products. However, the impact of PS administration on serum lipids in postmenopausal women remains unclear. Hence, the purpose of this study was to assess the effect of PS supplementation on the lipid profile in postmenopausal women based on a systematic review of the literature and a meta-analysis of randomized controlled trials. PubMed/Medline, Scopus, Embase, and Web of Science were searched to identify suitable papers published until January 18, 2022. We combined the effect sizes with the DerSimonian and Laird method using a random effects model. PS supplementation resulted in a significant decrease in TC (weighted mean difference [WMD]: -16.73 mg/dl) and LDL-C (WMD: -10.06 mg/dl) levels. No effect of PS supplementation on TG (WMD: -1.14 mg/dl) or HDL-C (WMD: -0.29 mg/dl) concentrations was detected. In the stratified analysis, there was a notable reduction in TC and LDL-C levels when the PS dose was ≥2 g/day (TC: -22.22 mg/dl and LDL-C: -10.14 mg/dl) and when PS were administered to participants with a body mass index ≥25 kg/m2 (TC: -20.22 mg/dl and LDL-C: -14.85 mg/dl). PS administration can decrease TC and LDL-C, particularly if the dose of administration is ≥2 g/day and if the participants are overweight or obese. Further high-quality studies are needed to firmly establish the clinical efficacy of PS usage in postmenopausal females.

Biological and pharmacological effects and nutritional impact of phytosterols: A comprehensive review.

Phytosterols (PSs), classified into plant sterols and stanols, are bioactive compounds found in foods of plant origin. PSs have been proposed to exert a wide number of pharmacological properties, including the potential to reduce total and low-density lipoprotein (LDL) cholesterol levels and thereby decreasing the risk of cardiovascular diseases. Other health-promoting effects of PSs include anti-obesity, anti-diabetic, anti-microbial, anti-inflammatory, and immunomodulatory effects. Also, anticancer effects have been strongly suggested, as phytosterol-rich diets may reduce the risk of cancer by 20%. The aim of this review is to provide a general overview of the available evidence regarding the beneficial physiological and pharmacological activities of PSs, with special emphasis on their therapeutic potential for human health and safety. Also, we will explore the factors that influence the physiologic response to PSs.

Pharmacology of α-spinasterol, a phytosterol with nutraceutical values: A review.

α-Spinasterol is a phytosterol found in various edible and non-edible plant sources. The edible plant materials containing α-spinasterol include spinach leaves, cucumber fruits, seeds of pumpkin and watermelon, argan seed oil, cactus pear seed oil and Amaranthus sp. It is a bioavailable nutraceutical, and it can cross the blood-brain barrier. It possesses several important pharmacological properties such as anti-diabetes mellitus, antiinflammation, hypolipidemic, antiulcer, neuroprotection, anti-pain and antitumour activities. For this review, literature search was made focusing on the pharmacological properties of α-spinasterol using PubMed and Google Scholar data bases. Recent studies show the promising antidiabetic properties of α-spinasterol. Its anti-diabetic mechanisms include enhancement of insulin secretion, reduction in insulin resistance, anti-diabetic nephropathy, increase in glucose uptake in muscle cells and inhibition of glucose absorption from intestine. Besides, it is a safe antiinflammatory agent, and its antiinflammatory mechanisms include inhibition of cyclooxygenases, antagonism of TRPV1 receptor and attenuation of proinflammatory cytokines and mediators. It is a promising and safe nutraceutical molecule for human health care. Food supplements, value-added products and nutraceutical formulations can be developed with α-spinasterol for the management of diabetes, chronic inflammatory diseases and improving general health. This review provides all scattered pharmacological studies on α-spinasterol in one place and highlights its immense value for human health care.

The Impacts of Cholesterol, Oxysterols, and Cholesterol Lowering Dietary Compounds on the Immune System.

Cholesterol and its oxidized forms, oxysterols, are ingested from foods and are synthesized de novo. Cholesterol and oxysterols influence molecular and cellular events and subsequent biological responses of immune cells. The amount of dietary cholesterol influence on the levels of LDL cholesterol and blood oxysterols plays a significant role in the induction of pro-inflammatory state in immune cells, leading to inflammatory disorders, including cardiovascular disease. Cholesterol and oxysterols synthesized de novo in immune cells and stroma cells are involved in immune homeostasis, which may also be influenced by an excess intake of dietary cholesterol. Dietary compounds such as ß-glucan, plant sterols/stanols, omega-3 lipids, polyphenols, and soy proteins, could lower blood cholesterol levels by interfering with cholesterol absorption and metabolism. Such dietary compounds also have potential to exert immune modulation through diverse mechanisms. This review addresses current knowledge about the impact of dietary-derived and de novo synthesized cholesterol and oxysterols on the immune system. Possible immunomodulatory mechanisms elicited by cholesterol-lowering dietary compounds are also discussed.

Lipophilic Compounds and Antibacterial Activity of Opuntia ficus-indica Root Extracts from Algeria.

The chemical composition, investigated by gas chromatography-mass spectrometry, and antibacterial activity of lipophilic extractives of three varieties of Opuntia ficus-indica roots from Algeria are reported in this paper for the first time. The results obtained revealed a total of 55 compounds, including fatty acids, sterols, monoglycerides and long chain aliphatic alcohols that were identified and quantified. ß-Sitosterol was found as the major compound of the roots of the three varieties. Furthermore, considerable amounts of essential fatty acids (ω3, ω6, and ω9) such as oleic, linoleic, and linolenic acids were also identified. The green variety was the richest among the three studied varieties. The antibacterial activity, evaluated with disc diffusion method, revealed that lipophilic extracts were effective mainly against Gram-positive Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) (19~23 mm). Gram-negative strains mainly Pseudomonas aeruginosa gave an inhibition zone of 18 mm, which is considered high antibacterial activity. The minimal inhibitory concentrations of the tested bacteria revealed interesting values against the majority of bacteria tested: 75-100 µg mL-1 for Bacillus sp., 250-350 µg/mL for the two Staphylococcus strains, 550-600 µg mL-1 for E. coli, and 750-950 µg mL-1 obtained with Pseudomonas sp. This study allows us to conclude that the lipophilic fractions of cactus roots possess interesting phytochemicals such as steroids, some fatty acids and long chain alcohols that acted as antibiotic-like compounds countering pathogenic strains.

The Bioavailability and Biological Activities of Phytosterols as Modulators of Cholesterol Metabolism.

Phytosterols are natural sterols widely found in plants that have a variety of physiological functions, and their role in reducing cholesterol absorption has garnered much attention. Although the bioavailability of phytosterols is only 0.5-2%, they can still promote cholesterol balance in the body. A mechanism of phytosterols for lowering cholesterol has now been proposed. They not only reduce the uptake of cholesterol in the intestinal lumen and affect its transport, but also regulate the metabolism of cholesterol in the liver. In addition, phytosterols can significantly reduce the plasma concentration of total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), with a dose-response relationship. Ingestion of 3 g of phytosterols per day can reach the platform period, and this dose can reduce LDL-C by about 10.7%. On the other hand, phytosterols can also activate the liver X receptor α-CPY7A1 mediated bile acids excretion pathway and accelerate the transformation and metabolism of cholesterol. This article reviews the research progress of phytosterols as a molecular regulator of cholesterol and the mechanism of action for this pharmacological effect.

Physicochemical, Antioxidant and Anticancer Characteristics of Seed Oil from Three Chenopodium quinoa Genotypes.

Chenopodium quinoa Willd. is recognized to be an excellent nutrient with high nutritional content. However, few genotypes of quinoa were analyzed, so we found a knowledge gap in the comparison of quinoa seeds of different genotypes. This study aims to compare the physicochemical, antioxidant, and anticancer properties of seed oil from three C. quinoa genotypes. Seeds of three genotypes (white, red, and black) were extracted with hexane and compared in this study. The oil yields of these quinoa seeds were 5.68-6.19% which contained predominantly polyunsaturated fatty acids (82.78-85.52%). The total tocopherol content ranged from 117.29 to 156.67 mg/kg and mainly consisted of γ-tocopherol. Total phytosterols in the three oils ranged from 9.4 to 12.2 g/kg. Black quinoa seed oil had the highest phytosterols followed by red and white quinoas. The chemical profile of quinoa seed oils paralleled by their antioxidant and anticancer activities in vitro was positively correlated with the seed coat color. Black quinoa seed oil had the best antioxidant and anti-proliferation effect on HCT 116 cells by the induction of apoptosis in a dose-dependent manner, which may play more significant roles in the chemoprevention of cancer and other diseases related to oxidative stress as a source of functional foods.

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach.

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.