gamma-sitosterol and Chronic-Disease

The physiological roles of phytosterols in chronic inflammation, which are believed to be involved in the underlying mechanisms for metabolic diseases, have yet to be elucidated. Therefore, in the present study, we aimed to elucidate the physiological roles of phytosterols in both clinical studies and animal experiments. We observed the existence of rather specific negative correlations between the serum sitosterol level and the serum IL-6 and the TNF-α levels in both diabetic subjects (n=46) and non-diabetic subjects (n=178). Multiple regression analyses also revealed that the serum IL-6 and TNF-α levels exhibited strong negative correlations with the serum sitosterol levels. When ABCG5/8 KO mice with markedly elevated plasma sitosterol levels and ABCG5/8 hetero mice were fed a high-fat diet, we observed that the increase in body weight, the fatty liver changes, and the expansion of perigonadal adipose tissues were suppressed in ABCG5/8 KO mice without any modulation of food intake. We also observed that the plasma IL-6 and TNF-α levels, the expressions of TNF-α and PAI-1 in the liver and the expressions of the IL-6, TNF-α, and MCP-1 levels in the adipose tissue were lower in ABCG5/8 KO mice. These results suggest that sitosterol might suppress obesity-related chronic inflammation and might be applicable to the treatment of metabolic diseases.

Topics: Animals; ATP Binding Cassette Transporter, Subfamily G, Member 5; Chronic Disease; Female; Humans; Inflammation; Interleukin-6; Lipoproteins; Male; Mice; Mice, Knockout; Middle Aged; Obesity; Sitosterols; Tumor Necrosis Factor-alpha

We have produced a chloroform extract from Achillea which includes stigmasterol and sitosterol. By comparing it with the pure compounds an anti-inflammatory effect (with mouse ears) is assumed. The topical anti-inflammatory effect of the chloroform extract from Achillea ageratum (Asteraceae) and of stigmasterol and beta-sitosterol, isolated of this extract has been evaluated, against to 12-0-tetradecanoylphorbol acetate (TPA)-induced mouse ear edema, using simple (acute model) and multiple applications (chronic model) of the phlogistic agent. Myeloperoxydase activity also was studied in the inflamed ears. In the acute model the extract exerted a dose-dependent effect. All the doses assayed (1, 3 and 5 mg/ear) significantly reduced the edema (50%, 66% and 82%, respectively). The isolated sterols stigmasterol and beta-sitosterol (with doses of 0.5 mg/ear) had similar effect as the extract with doses of 1 and 3 mg (59% and 65% respectively). In the chronic model the anti-inflammatory effect generally was a more moderate one. The highest dose of the extract decreased the edema reduction to 26% with the highest dose of the extract applied. With the compounds the effect decreased to 36% with stigmasterol, and 40.6% with beta-sitosterol. Myeloperoxydase activity (MPO) was reduced by the extract and the compounds in the acute model, however, in the chronic edema, the enzyme inhibition was very weak with all treatments even with the standard substance. These results indicate that the chloroform extract of Achillea ageratum and some of the its components stigmasterol and beta-sitosterol are more effective as topical anti-inflammatory agents in acute than in the chronic process and their action is markedly influenced by the inhibition of neutrophil migration into inflamed tissue.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Chloroform; Chronic Disease; Dexamethasone; Disease Models, Animal; Ear; Edema; Indomethacin; Mice; Peroxidase; Plant Extracts; Plants, Medicinal; Sitosterols; Stigmasterol; Tetradecanoylphorbol Acetate

Many types of chronic blepharitis have been believed to be primarily microbial in origin; however, it was proposed that differences and changes in lipid composition of meibomian secretion may be the initiating factor in some of these. It was recently reported that there are two subgroups of normals, those whose meibomian secretions contain high levels of cholesterol esters and those whose secretions contain very low levels of these esters. Thus, these subgroups of normals were defined on the basis of detailed lipid analyses of meibomian secretions from individuals showing no clinical signs of chronic blepharitis. All secretions from patients in the various disease groups contain high levels of these esters. Based on previous observations that in some chronic blepharitis disease groups certain Staphylococcus species were capable of hydrolyzing cholesterol esters, the authors tested the hypothesis that the resulting cholesterol might affect growth of Staphylococcus aureus.. Staphylococcus aureus growth stimulation in Mueller-Hinton broth by cholesterol was determined by colony forming units. Growth stimulation by cholesterol and other additives was also determined by the optical density 650 nm method. Statistical analyses included analysis of variance and the Student's t test.. Cholesterol stimulated Staphylococcus aureus growth was significant during the first 24 hr period (20% increase at 25 microM cholesterol, P < 0.02), and for the total 48 hr period (40% increase at 400 microM cholesterol, P < 0.005) when compared to the respective control. Growth stimulation, determined by OD at 650 nm, in the presence of cholesterol was significantly greater (P < 0.02) than that in the presence of either sitosterol or cholestanol when the sterol concentration was 190 microM.. These results suggest that the presence and hydrolysis of cholesterol esters of meibomian secretions may contribute to the proliferation of Staphylococcus spp, especially Staphylococcus aureus, observed in some chronic blepharitis disease groups.

Topics: Blepharitis; Cholestanol; Cholesterol; Chronic Disease; Colony Count, Microbial; Eye Infections, Bacterial; Fatty Acids; Humans; Hydrolysis; Sitosterols; Staphylococcal Infections; Staphylococcus aureus

The circumference of both Achilles tendons had gradually increased over the years in a now 32-year-old man (diameter of the left tendon 4.5 cm, of the right one 3.5 cm). This finally led to exercise-related pain in both tendons. Biopsy revealed benign deposition of xanthomata. Serum total cholesterol concentration was 261 mg/dl. Determination of various sitosterol fragments in serum gave a beta-sitosterol level of 43 mg/dl (normal range 0.3-1.7 mg/dl), characteristic of sitosterolaemia, which is an autosomal recessive disease causing intestinal hyperabsorption of a range of plant steroids closely related to cholesterol. On a diet low in plant steroids and treatment with cholestyramine (up to 32 g daily) the beta-sitosterol concentration fell, but only to 35 mg/dl, because of poor patient compliance. The patient died suddenly from coronary artery stenosis seven months after the diagnosis of sitosterolaemia.

Topics: Achilles Tendon; Adult; Biopsy; Chronic Disease; Combined Modality Therapy; Diagnosis, Differential; Humans; Male; Muscular Diseases; Sitosterols; Xanthomatosis

The measurement of prostaglandin E2 (PGE2) concentrations in the serum and prostatic fluid of healthy men, patients with prostatic hyperplasia and of patients with prostatitis was attempted and correlated to the state of disease, respectively. PGE2-concentrations with prostatic fluid of healthy men were found to be significantly lower than in patients with prostatitis. Corresponding to the course of treatment concentrations normalized, being favorably influenced by sitosterin as an adjuvant medication. Compared to healthy men, PGF2 concentrations in the prostatic fluid of patients with hyperplasia of the prostate incline to lower levels.

Topics: Adult; Chronic Disease; Dinoprostone; Follow-Up Studies; Humans; Male; Middle Aged; Prostaglandins E; Prostate; Prostatic Hyperplasia; Prostatitis; Radioimmunoassay; Sitosterols