stigmasterol and Acute-Disease

Stigmasterol is a common sterol found in plants, but the anti-nociceptive effect of this compound and its mechanism of action are not fully explored. Thus, in the present study, the anti-nociceptive effect of stigmasterol was investigated in acute and chronic models of pain and its mechanism of action. We used adult male albino Swiss mice (25-35 g) to observe the anti-nociceptive effect of stigmasterol in acetic-acid writhing test or in complete Freund's adjuvant injection, surgical incision in hind paw, or partial sciatic nerve ligation. Moreover, we investigate the involvement of opioid receptors (naloxone, 2 mg/kg, intraperitoneally) in stigmasterol anti-nociceptive effect and stigmasterol action on acetylcholinesterase activity. Some possible adverse effects caused by stigmasterol were also investigated. Stigmasterol (0.3-3 mg/kg, orally) exhibited an anti-nociceptive effect on acetic-acid-induced writhing test. Furthermore, it markedly attenuated the mechanical allodynia caused by surgical incision (after acute treatment with stigmasterol, preventive and curative effects were observed) and partial sciatic nerve ligation (after acute treatment with stigmasterol) and complete Freund's adjuvant (after acute or repeated treatment with stigmasterol). The anti-nociceptive effect of stigmasterol was not reversed by naloxone. Moreover, stigmasterol did not alter in vitro acetylcholinesterase activity in spinal cord or brain samples. Also, stigmasterol did not cause gastric ulcers or alter the gastrointestinal transit of mice. Taken together, these results support the potential anti-nociceptive effect of stigmasterol in different models of pain.

Topics: Acetic Acid; Acetylcholinesterase; Acute Disease; Analgesics; Animals; Brain; Chronic Disease; Freund's Adjuvant; Gastrointestinal Transit; Hyperalgesia; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Sciatic Nerve; Spinal Cord; Stigmasterol; Stomach

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

Fecal bile acid and neutral sterol patterns of five healthy adult male volunteers, who were challenged by a virulent Shigella flexneri 2a (M42-43) strain and developed dysentery were studied. It was observed that cholic acid was increased from 1.9 +/- 0.4% of total bile acid in the feces before infection to 14.5 +/- 2.1% during diarrhea (P less than 0.001). Chenodeoxycholic acid also was increased from 3.2 +/- 0.7 to 8.7 +/- 3.2% in diarrhea but the difference was not significant statistically. Deoxycholic and lithocholic acids constituted 34.1 +/- 4.1 and 40.5 +/- 2.8%, respectively, of total bile acid in the normal controls as compared to 13.9 +/- 2.5 and 24.8 +/- 2.5% for the same subjects during diarrhea (P less than 0.005). Total excretion of bile acids, expressed as mg/kg of body weight per day, were higher in diarrhea (5.4 +/- 1.0) than that in controls (4,2 +/- 1.0) but the difference was not statistically significant. In the neutral sterol fraction, unmodified cholesterol was increased during diarrhea (86.2 +/- 8.7 versus 25.0 +/- 4.8% of total cholesterol metabolites in controls, P less than 0.001). Coprostanol was decreased in shigellosis (12.2 +/- 8.2 versus 65.8 +/- 4.7% in controls, P less than 0.001). Epicoprostanol, coprostanone, and unidentified cholesterol metabolites also were reduced in shigellosis. The effect of diarrhea on the plant sterols was not as consistent. However, unidentified plant sterols were reduced significantly in shigellosis stools. Total excretion of cholesterol metabolites and plant sterols, when expressed as mg/kg of body weight per day, were 6.8 +/- 1.7 and 0.6 +/- 0.2), respectively, in Shigellosis. These values were not significantly different from the corresponding values for controls (10.3 +/- 3.0 and 0.8 +/- 0.2). One subject's stool samples were studied during infection for the sequence of bile acid alteration. A progressive reduction of bacterial activity upon fecal steroids was evident following the initial diarrheal episode. The production of coprostanol was correlated with 7 alpha-dehydroxylation of cholic acid (r = 0.937, P less than 0.001) and chenodeoxycholic acid (r = 0.755, P less than 0.01).

Topics: Acute Disease; Adult; Bile Acids and Salts; Chenodeoxycholic Acid; Cholesterol; Cholic Acids; Deoxycholic Acid; Dysentery, Bacillary; Feces; Humans; Lithocholic Acid; Male; Phytosterols; Shigella flexneri; Sitosterols; Sterols; Stigmasterol