Phytosterol supplementation in capsules or tablets as adjunctive treatment for hypercholesterolemia: A systematic review of randomized controlled trials.

BACKGROUND: The exploration of lipid-lowering resources, such as phytosterols, for the complementary nutritional treatment of hypercholesterolemia is relevant to reduce cardiovascular risk. The use of phytosterols in capsules or tablets can bring advantages in the context of diet therapy, but such format is still less studied when compared to fortified foods. OBJECTIVE: Systematically review randomized clinical trials on the effects of phytosterol supplementation, in capsules or tablets, on the lipid profile and its use in the treatment of hypercholesterolemia in adults. DESIGN: A systematic review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis, with a PROSPERO protocol registered under number CRD42021249539. The process was conducted by two independent reviewers. Only randomized clinical trials with phytosterol supplementation in adult individuals with hypercholesterolemia were included. The terms were searched in the databases: PubMed/MEDLINE, Cochrane Library/CENTRAL, Embase, LILACS and Web of Science, without restriction of time and language. The manual search was also performed through the list of references of articles included in this review. RESULTS: The searches resulted in 977 articles. 22 articles were selected, whose full text was read, and according to the eligibility criteria 10 were incorporated into the review. The studies were separated into groups according to the association of the intervention with changes in lifestyle and the characteristics extracted from the studies were summarized and displayed in tables. Most studies have revealed a positive association between phytosterol supplementation and cholesterol reduction, despite the short duration of interventions. CONCLUSION: The analyzed studies showed that phytosterol supplements can be useful to modulate the lipid profile, helping to reduce the plasma concentration of LDL cholesterol. However, more research with the aforementioned supplementation in such pharmaceutical formats should be encouraged.

Supplements for Lipid Lowering: What Does the Evidence Show?

PURPOSE: In this review, the regulation, proposed hypolipidemic mechanism, and efficacy of common dietary supplements (DSs) marketed for cardiovascular health are discussed. RECENT FINDINGS: Data demonstrate modest but inconsistent lipid-lowering effects with common DSs such as probiotics, soluble fibers, plant sterols, green tea, berberine, guggul, niacin, and garlic. Furthermore, data is limited regarding turmeric, hawthorn, and cinnamon. Red yeast rice has shown to be a beneficial DS, but its safety and efficacy are dependent upon its production quality and monacolin K content, respectively. Finally, soy proteins and omega-3 fatty acid-rich foods can have significant health benefits if used to displace other animal products as part of a healthier diet. Despite the rising use of DSs, data demonstrate unpredictable results. Patients should be educated on the difference between these DSs and evidence-based lipid-lowering medications proven to improve cardiovascular outcomes.

Khasianine ameliorates psoriasis-like skin inflammation and represses TNF-α/NF-κB axis mediated transactivation of IL-17A and IL-33 in keratinocytes.

ETHNO-PHARMACOLOGICAL RELEVANCE: Khasianine is recently identified as a bioactive compound from Solanum nigrum L. (SNL) which is a traditional Chinese herb (named LongKui in China) and has been clinically applied for treating psoriasis in China but with limited knowledge about the active ingredients. AIM OF THE STUDY: This study tried to explore the bioactivity of Khasianine and showed that Khasianine possessed highly anti-inflammatory bioactivity which rapidly alleviated psoriasis-like mice skin inflammation. MATERIALS AND METHODS: Imiquimod induced psoriasis-like mouse model, and human keratinocytes were employed in this study. In vivo, immunohistochemistry and immunofluorescence were performed to evaluate the pathological improvement in psoriatic lesions after Khasianine treatment. In vitro, tumor necrosis factor α (TNF-α) treated HaCaT cells with or without Khasianine, were used to analyze the expression and cellular location of NF-κB p65, the expression of IL-17A and IL-33, and the binding intensity of NF-κB p65 on the promoter of IL-17A and IL-33 to understand the molecular mechanism of Khasianine mediated anti-inflammatory effect. RESULTS: Khasianine reduced infiltration of CD4+ T helper cells (Th cells) and macrophages in mice psoriatic lesions. Immunohistochemistry analysis revealed that Khasianine reduced TNF-α levels in lesions and suppressed NF-κB p65 activation as well as expression of IL-17A and IL-33 in mice epidermal keratinocytes. Further studies in human keratinocytes demonstrated that Khasianine inhibited TNF-α-induced transcriptional activation (transactivation) of NF-κB p65 such as evicting NF-κB p65 binding from the promoter regions of IL-17A and IL-33 and preventing NF-κB nuclear translocation. CONCLUSIONS: Our results suggested that Khasianine is a potent anti-inflammatory compound with the bioactivity of NF-κB inhibition and is a promising candidate for psoriasis topical therapy.

Phytosterols: Potential Metabolic Modulators in Neurodegenerative Diseases.

Phytosterols constitute a class of natural products that are an important component of diet and have vast applications in foods, cosmetics, and herbal medicines. With many and diverse isolated structures in nature, they exhibit a broad range of biological and pharmacological activities. Among over 200 types of phytosterols, stigmasterol and ß-sitosterol were ubiquitous in many plant species, exhibiting important aspects of activities related to neurodegenerative diseases. Hence, this mini-review presented an overview of the reported studies on selected phytosterols related to neurodegenerative diseases. It covered the major phytosterols based on biosynthetic considerations, including other phytosterols with significant in vitro and in vivo biological activities.

Effect of phytosterols on reducing low-density lipoprotein cholesterol in dogs.

Hyperlipidemia is described as an increase in serum and/or plasma levels of triglycerides, cholesterol, or both. This disturbance can be primary in some cases, or combined with other comorbidities such as endocrinopathies, liver diseases, or specific drug use. Among the various ways to control dyslipidemia are specific diets, omega-3 fatty acid supplementation, or hypolipemiant treatment. Herbal medicine has been used in the human clinical routine to reduce cholesterol circulation. With an aim to expand its application in veterinary medicine, we analyzed the use of phytosterols in dogs as a potential alternative to control hypercholesterolemia. We performed lipidogram analysis in healthy dogs to examine the possible adverse effects during the treatment. Eight Beagle dogs received orally two 650 mg capsules of phytosterols (Collestra, Aché), for 15 consecutive d, along with the 2 usual meals. All animals remained clinically stable during the trial. There were significant alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels during the trial. LDL was reduced (86.8 ± 29.89 mg/dL [D0], 74.45 ± 31.58 mg/dL [D8], and 58.91 ± 18.65 mg/dL [D15]; P = 0.0442) and HDL was elevated (83.40 ± 12.05 mg/dL [D0], 86.46 ± 13.05 mg/dL [D8], and 101.5 ± 10.52 [D15]; P = 0.0141), while total cholesterol and triglyceride concentrations remained constant and within the normal range for canine species. Thus, a 1300 mg dose of phytosterols, administrated orally and fractionated along with the 2 usual meals, was capable of reducing LDL and increasing HDL concentration in healthy nondyslipidemic dogs, which makes them candidates to be included on the list of hypolipemiant drugs for clinical use in dogs with hypercholesterolemia.

Almond as a nutraceutical and therapeutic agent in Persian medicine and modern phytotherapy: A narrative review.

Sweet almond (Prunus dulcis (Mill.) D.A.Webb) is a known nut, which has long been used in several ethnomedical systems, especially in Persian medicine (PM) for its nutritional and therapeutic activities. In this study, we aimed to provide a summary on traditional uses, phytochemistry, and pharmacological activities of sweet almond. Thus, we reviewed textbooks of PM and electronic literature on traditional medicine. Moreover, the available data on the usage of sweet almond were searched in electronic databases to find articles on its pharmacological properties and phytochemistry. According to phytochemical investigations, this plant contains macronutrients, micronutrients, essential oils, various phenolic compounds, and phytosterols. Current pharmacological studies represent that Prunus dulcis has several biological activities including prebiotic, antimicrobial, antioxidant, antiinflammatory, anticancer, hepatoprotective, cardiometabolic protection, nootropic, anxiolytic, sedative-hypnotic, and nervous-improving effects. Further clinical trials and meta-analysis are required to draw a definitive conclusion on the efficacy and therapeutic activities of almond.

Sex hormone-like Effects of Icariin on T-cells immune modulation in spontaneously hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim as a Chinese herb, is recommended for the treatment of menopausal women with hypertension for 50 years. Icariin, as the main hydrophilic ingredient of Epimedium brevicornu Maxim, has been proven to be a plant sex hormone and lower blood pressure down. Here, we hypothesized that Icariin can regulate T cells differentiation which leads to the blood pressure decrease in castrated SHR rats. AIM OF THE STUDY: The present study aimed to investigate the effects of the exogenous estrogen, androgen and Icariin on T-cell modulation in hypertension. MATERIALS AND METHODS: Two weeks after castration, both male and female SHR rats were given estradiol, testosterone, and Icariin intervention respectively. Body weight, blood pressure, and heart rate were tested weekly. After six weeks, proportion of T helper cells (Th), cytotoxic T cells (Tc), and regulatory T cells (Tregs) in both peripheral blood mononuclear cells (PBMCs) and splenocytes were tested by flowcytometry. Serum levels of estrogen, testosterone, AngII, TNF-α, IL-17 were tested by Elisa. Aortic arches were isolated for HE and Masson staining. The expressions of ERß and AR in aorta were tested by Western-blot. RESULTS: In both male and female SHR rats, we found that Icariin and estradiol lower blood pressure, but testosterone elevates blood pressure. Similar as testosterone, Icariin can attenuate Tc and Th proportions and elevate Tregs proportion in both peripheral blood and splenocyte in male SHR, which can be blunt by flutamide. Besides, Icariin performs similar function as estradiol that attenuates Tc proportions and elevates Tregs proportion in both peripheral blood and splenocytes in female SHR, which leads to the lower blood pressure and can be partly blunt by fulvestrant. Testosterone increases AngII and TNF-α levels in serum, leading to the higher blood pressure in both male and female SHR rats. CONCLUSION: These results verified that Icariin, as a plant sex hormone, can regulate T cells differentiation related to blood pressure decrease in SHR rats.

A double blind, placebo-controlled randomized comparative study on the efficacy of phytosterol-enriched and conventional saw palmetto oil in mitigating benign prostate hyperplasia and androgen deficiency.

BACKGROUND: The present clinical trial was conducted to evaluate the efficacy and tolerability of a standardized saw palmetto oil containing 3% ß-sitosterol in the treatment of benign prostate hyperplasia (BPH) and androgen deficiency. METHODS: Subjects aged 40-65 years with symptomatic BPH were randomized to 12-week double-blind treatment with 500 mg doses of ß-sitosterol enriched saw palmetto oil, conventional saw palmetto oil and placebo orally in the form of capsules (n = 33 in each group). BPH severity was determined using the International Prostate Symptom Score (IPSS), uroflowmetry, serum measurement of prostate specific antigen (PSA), testosterone and 5α-reductase. During the trial, the androgen deficiency was evaluated using Aging Male Symptoms (AMS) scale, the Androgen Deficiency in the Aging Male (ADAM) questionnaire, serum levels of free testosterone. RESULTS: Subjects treated with ß-sitosterol enriched saw palmetto oil showed significant decrease in IPSS, AMS and ADAM scores along with reduced postvoiding residual volume (p < 0.001), PSA (p < 0.01) and 5α-reductase from baseline to end of 12-week treatment as compared to placebo. There was also a significant increment in the maximum and average urine flow rate (p < 0.001), and serum free testosterone level of subjects treated with enriched saw palmetto oil as compared to placebo. CONCLUSION: This study demonstrates the efficacy of ß-sitosterol enriched saw palmetto oil superior to conventional oil thus extending the scope of effective BPH and androgen deficiency treatment with improved quality of life through the intake of functional ingredients. TRIAL REGISTRATION: CTRI/2018/12/016724 dated 19/12/2018 prospectively registered. URL: http://ctri.nic.in/Clinicaltrials/advsearch.php.

Inhibitory effect of ergosterol on bladder carcinogenesis is due to androgen signaling inhibition by brassicasterol, a metabolite of ergosterol.

We previously revealed that Choreito, a traditional Kampo medicine, strongly inhibits bladder carcinogenesis promotion. We have also shown that Polyporus sclerotium, which is one of the crude drugs in Choreito, has the strongest bladder carcinogenesis inhibitory effect and that the ergosterol contained in Polyporus sclerotium is the main active component. In this study, we analyzed the mechanism by which ergosterol inhibits bladder carcinogenesis. Rats were given an N-butyl-N-(4-hydroxybutyl) nitrosamine (BHBN) solution ad libitum, and then a promoter [saccharin sodium (SS), DL-tryptophan, or BHBN] was administered together with ergosterol or its metabolite, brassicasterol. The bladders were removed from rats, and the inhibitory effect on carcinogenesis promotion was evaluated by an agglutination assay with concanavalin A (Con A). Although the oral administration of ergosterol inhibited the promotion of bladder carcinogenesis with SS, the intraperitoneal administration of brassicasterol showed a stronger effect. The effect of brassicasterol on carcinogenesis promotion was observed regardless of the type of promoter. Administration of testosterone to castrated rats increased the number of cell aggregates caused by Con A. In contrast, intraperitoneal administration of brassicasterol to castrated rats treated with testosterone significantly decreased the number of cell aggregates, confirming the inhibition of bladder carcinogenesis promotion. The inhibitory effect of ergosterol on bladder carcinogenesis is due to brassicasterol, a metabolite of ergosterol. The action of brassicasterol via androgen signaling may play a role in the inhibitory effect on bladder carcinogenesis promotion.

Impact of phytosterol supplementation on plasma lipoprotein(a) and free fatty acid (FFA) concentrations: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Although some earlier studies have indicated the effect of phytosterol (PS) supplementation on serum lipoprotein(a) (Lp(a)) and free fatty acid (FFA) concentration, findings are still conflicting. We aimed to assess the impact of PS supplementation on serum Lp(a) and FFA concentration through a systematic review and meta-analysis of available RCTs. METHODS AND RESULTS: We performed a systematic search of all available RCTs conducted up to 21 February 2019 in the following databases: PubMed, Scopus, and Cochrane. The choice of fixed- or random-effect model for analysis was determined according to the I2 statistic. Effect sizes were expressed as weighted mean difference (WMD) and 95% confidence interval (CI). Pooling of 12 effect sizes from seven articles revealed a significant reduction of Lp(a) levels following PS supplementation (MD: -0.025 mg/dl, 95% CI: -0.045, -0.004, p = 0.017) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.599). Also, PS supplementation significantly lowered FFA (MD: -0.138 mg/dl, 95% CI: -0.195, -0.081, p = 0.000) without significant heterogeneity among the studies (I2 = 0.0%, p = 0.911). The results for meta-regression and sensitivity analysis were not significant. CONCLUSION: The meta-analysis suggests that oral PS supplementation could cause a significant reduction in serum Lp(a) and FFA.

Alpha-tocopherol in intravenous lipid emulsions imparts hepatic protection in a murine model of hepatosteatosis induced by the enteral administration of a parenteral nutrition solution.

Intestinal failure-associated liver disease (IFALD) is a risk of parenteral nutrition (PN)-dependence. Intravenous soybean oil-based parenteral fat can exacerbate the risk of IFALD while intravenous fish oil can minimize its progression, yet the mechanisms by which soybean oil harms and fish oil protects the liver are uncertain. Properties that differentiate soybean and fish oils include α-tocopherol and phytosterol content. Soybean oil is rich in phytosterols and contains little α-tocopherol. Fish oil contains abundant α-tocopherol and little phytosterols. This study tested whether α-tocopherol confers hepatoprotective properties while phytosterols confer hepatotoxicity to intravenous fat emulsions. Utilizing emulsions formulated in the laboratory, a soybean oil emulsion (SO) failed to protect from hepatosteatosis in mice administered a PN solution enterally. An emulsion of soybean oil containing α-tocopherol (SO+AT) preserved normal hepatic architecture. A fish oil emulsion (FO) and an emulsion of fish oil containing phytosterols (FO+P) protected from steatosis in this model. Expression of hepatic acetyl CoA carboxylase (ACC) and peroxisome proliferator-activated receptor gamma (PPARγ), was increased in animals administered SO. ACC and PPARγ levels were comparable to chow-fed controls in animals receiving SO+AT, FO, and FO+P. This study suggests a hepatoprotective role for α-tocopherol in liver injury induced by the enteral administration of a parenteral nutrition solution. Phytosterols do not appear to compromise the hepatoprotective effects of fish oil.

Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor.

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial.

BACKGROUND: Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR. METHODS: A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals. RESULTS: Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6. CONCLUSIONS: In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.

Role of Functional Fortified Dairy Products in Cardiometabolic Health: A Systematic Review and Meta-analyses of Randomized Clinical Trials.

There is insufficient evidence on the role of functional fortified dairy products in improving health and in preventing risk factors associated with noncommunicable chronic diseases. This systematic review was conducted to summarize effects of the consumption of fortified dairy products on biomarkers of cardiometabolic risk. MEDLINE and SCOPUS databases were used to perform searches to include studies published up to 30 April 2018. Randomized clinical trials with human subjects consuming dairy products fortified with phytosterols, FAs, vitamins or minerals and relating this consumption with cardiometabolic health were included in this review. Risk of bias assessment according to Cochrane guidelines was performed to determine the quality of the trials. Forty-one studies were finally selected for this synthesis; the selected studies tested dairy products fortified with the following nutrients and bioactive components: phytosterols (n = 31), FAs (n = 8), and vitamin D (n = 2). We found that the consumption of phytosterol-fortified dairy, led to an overall LDL cholesterol reduction of -0.36 (-0.41, -0.31) mmol/L, P < 0.001; this decrease was mainly related to the dosage. Likewise, consumption of ω-3 FA-fortified dairy products resulted in a plasma LDL cholesterol reduction of -0.18 (-0.27, -0.09) mmol/L as well as a decrease of -0.18 (-0.32, -0.05) mmol/L in triacylglycerols (TG). Performing meta-analyses of the consumption of dairy products fortified with vitamin D or FAs other than ω-3 FAs and biomarkers of cardiometabolic risk was not possible because of the few available publications. Our results indicate that consumption of dairy products fortified with phytosterols and ω-3 FAs can lead to a reduction of LDL cholesterol and consumption of fortified dairy products fortified with ω-3 FAs can reduce TG concentration. However, more studies with homogeneous designs are needed to determine the advantages of using dairy products as fortification vehicles to prevent cardiometabolic risk.

Safety of Symptomatic Slow-Acting Drugs for Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

BACKGROUND: Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are an important drug class in the treatment armamentarium for osteoarthritis (OA). OBJECTIVE: We aimed to re-assess the safety of various SYSADOAs in a comprehensive meta-analysis of randomized placebo-controlled trials, using, as much as possible, data from full safety reports. METHODS: We performed a systematic review and random-effects meta-analyses of randomized, double-blind, placebo-controlled trials that assessed adverse events (AEs) with various SYSADOAs in patients with OA. The databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus were searched. The primary outcomes were overall severe and serious AEs, as well as AEs involving the following Medical Dictionary for Regulatory Activities (MedDRA) system organ classes (SOCs): gastrointestinal, cardiac, vascular, nervous system, skin and subcutaneous tissue, musculoskeletal and connective tissue, renal and urinary system. RESULTS: Database searches initially identified 3815 records. After exclusions according to the selection criteria, 25 studies on various SYSADOAs were included in the qualitative synthesis, and 13 studies with adequate data were included in the meta-analyses. Next, from the studies previously excluded according to the protocol, 37 with mainly oral nonsteroidal anti-inflammatory drugs (NSAIDs) permitted as concomitant medication were included in a parallel qualitative synthesis, from which 18 studies on various SYSADOAs were included in parallel meta-analyses. This post hoc parallel inclusion was conducted because of the high number of studies allowing concomitant anti-OA medications. Indeed, primarily excluding studies with concomitant anti-OA medications was crucial for a meta-analysis on safety. The decision for parallel inclusion was made for the purpose of comparative analyses. Glucosamine sulfate (GS), chondroitin sulfate (CS) and avocado soybean unsaponifiables (ASU; Piascledine®) were not associated with increased odds for any type of AEs compared with placebo. Overall, with/without concomitant OA medication, diacerein was associated with significantly increased odds of total AEs (odds ratio [OR] 2.22; 95% confidence interval [CI] 1.58-3.13; I2 = 52.8%), gastrointestinal disorders (OR 2.85; 95% CI 2.02-4.04; I2 = 62.8%) and renal and urinary disorders (OR 3.42; 95% CI 2.36-4.96; I2 = 17.0%) compared with placebo. In studies that allowed concomitant OA medications, diacerein was associated with significantly more dermatological disorders (OR 2.47; 95% CI 1.42-4.31; I2 = 0%) and more dropouts due to AEs (OR 3.18; 95% CI 1.85-5.47; I2 = 13.4%) than was placebo. No significant increase in serious or severe AEs was found with diacerein versus placebo. CONCLUSIONS: GS and CS can be considered safe treatments for patients with OA. All eligible studies on ASU included in our analysis used the proprietary product Piascledine® and allowed other anti-OA medications; thus, the safety of ASU must be confirmed in future studies without concomitant anti-OA medications. Given the safety concerns with diacerein, its usefulness in patients with OA should be assessed, taking into account individual patient characteristics.

BW18, a C-21 steroidal glycoside, exerts an excellent anti-leukemia activity through inducing S phase cell cycle arrest and apoptosis via MAPK pathway in K562 cells.

C-21 steroids displayed the activities of immunosuppressive, anti-inflammatory and anti-virus effects by the reports. However, its antitumor effects and molecular mechanism remain unclear. We previously isolated and identified a C-21 steroidal glycoside (BW18) from the root of Cynanchum atratum Bunge. This study was aimed to assess anti-leukemia activity and its underlying mechanism in K562 cells. MTT assay results showed that BW18 inhibited cell viability and proliferation of K562 cells. We also found that BW18 could induce S phase cell cycle arrest and apoptosis. Furthermore, our results demonstrated that BW18 regulated the expression of apoptosis and cell cycle related proteins. Mechanism investigation revealed that the anti-leukemia activity of BW18 may be mediated through MAPK pathway. These findings indicate that BW18 possesses an excellent anti-leukemia activity via regulating MAPK pathway leading to S phase cell cycle arrest and apoptosis, which suggested BW18 could be as a potential alternative therapeutic agent for CML patients.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma.

BACKGROUND: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Use of Plant Sterol and Stanol Fortified Foods in Clinical Practice.

Plant sterols and stanols (PS) are natural, non-nutritive molecules that play a structural role in plant membranes similar to that of cholesterol in animal membranes and abound in seeds and derived oils. PS exert their physical effect of interference with micellar solubilization of cholesterol within the intestinal lumen and are marginally absorbed by enterocytes, with negiglible increases in circulating levels. The physiological role of PS in plants and their natural origin and non-systemic action, together with their cholesterol-lowering effect, make them an attractive option as non-pharmacological agents for the management of hypercholesterolemia. Recent meta-analyses have summarized the results of >100 controlled clinical trials and have firmly established that the consumption of PS-supplemented foods in different formats at doses of 2-3 g per day results in LDL-cholesterol reductions of 9-12%. PS are both effective and safe cholesterol-lowering agents and have many clinical applications: adjuncts to a healthy diet, treatment of common hypercholesterolemia, combination therapy with statins and other lipid-lowering drugs, and treatment of metabolic syndrome and diabetes. The cholesterol-lowering efficacy is similar in all clinical situations. PS are also useful agents for treatment of hypercholesterolemic children who are not yet candidates to statins or receive low-doses of these agents. In the setting of statin treatment, the average LDL-cholesterol reduction obtained with PS is equivalent to up- titrating twice the statin dose. However, information is still scarce on the efficacy of PS as an add-on therapy to ezetimibe, fibrates, omega- 3 fatty acids, or bile acid binding resins. The consistent scientific evidence on the cholesterollowering efficacy and safety of functional foods supplemented with PS has led several national and international scientific societies to endorse their use for the non-pharmacologic treatment of hypercholesterolemia as adjuncts to a healthy diet. There is, however, a lack of clinical trials of PS with outcomes on cardiovascular events.