Chemical Constituents from Mycelia and Spores of Fungus Cordyceps cicadae

Objective To isolate and identify the chemical constituents from mycelia and spores of the fungus Cordyceps cicadae,respectively.Methods The chemical constituents were isolated and purified by repeated silica gel,Sephadex LH-20,and reversed phase HPLC.The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis,including 1 D and 2D NMR.Results Nine known sterols such as ergosterol(1),ergosterol peroxide(2),9,11-dehydroergosterol peroxide(3),3β,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one(4),3β,5α,9α,14α-tetrahydroxy-(22E,24R)-ergosta-7,22-dien-6-one(5),5x,6x-epoxy-(22E,24R)-ergosta-8(l 4),22-diene-3β,7α-diol(6),3β,5α,6β-(22E,24R)-ergosta-7,22-dien-3,5,6-triol(7),3|3,5x,6x-6-methoxyergosta-(22E,24R)-7,22-diene-3,5-diol(8),4-hydroxy-17R-methylincisterol(9),together with a resorcinol derivative,5-n-nonadecylresorcinol(10),a cyclodesipeptide,beauvericin(11),and a nucleoside,N~6-(2-hydroxyethyl)adenosine(12)were successively isolated from the cultivated C.cicadae mycelia and spores.Conclusion Compounds 3-10 are reported for the first time from the title sample,beauvericin exhibits significant cytotoxicity against human leukemia cell line and human lung cancer cell line.     

Effects of Dietary Plant Sterols and Stanol Esters with Low- and High-Fat Diets in Chronic and Acute Models for Experimental Colitis

In this study, we evaluated the effects of dietary plant sterols and stanols as their fatty acid esters on the development of experimental colitis. The effects were studied both in high- and low-fat diet conditions in two models, one acute and another chronic model of experimental colitis that resembles gene expression in human inflammatory bowel disease (IBD). In the first experiments in the high fat diet (HFD), we did not observe a beneficial effect of the addition of plant sterols and stanols on the development of acute dextran sulphate sodium (DSS) colitis. In the chronic CD4CD45RB T cell transfer colitis model, we mainly observed an effect of the presence of high fat on the development of colitis. In this HFD condition, the presence of plant sterol or stanol did not result in any additional effect. In the second experiments with low fat, we could clearly observe a beneficial effect of the addition of plant sterols on colitis parameters in the T cell transfer model, but not in the DSS model. This positive effect was related to the gender of the mice and on Treg presence in the colon. This suggests that especially dietary plant sterol esters may improve intestinal inflammation in a T cell dependent manner.     

牛白藤的化学成分及其免疫抑制活性研究

研究茜草科耳草属植物牛白藤Hedyotis hedyotidea(DC.) Merr.干燥藤茎的化学成分及免疫抑制活性,为进一步开发利用牛白藤提供依据.以硅胶、凝胶柱色谱、制备高效液相色谱进行分离纯化,并应用MS和NMR技术分析鉴定化合物结构,分离得到11个化合物吐叶醇(6S,9S-vomifoliol,1),桦木酮酸(betulonic acid,2),白桦脂酸(betulinic acid,3),白桦醇(betulin,4),表白桦脂酸(3-epi-betulinic acid,5),乌苏酸(ursolic acid,6),β-谷甾醇(β-sitosterol,7),stigmast-4-en-3-one (8),7β-hydroxysitosterol(9),(3β,7β)-7-methoxystigmast-5-en-3-ol(10)和巴戟醚萜(morindacin,11).化合物1,2,4,8～ 11均首次从该植物中分得,化合物1,2,8 ～ 11均首次从耳草属植物中分得,化合物9,10均首次从茜草科植物中分得.通过体外淋巴细胞转化实验测试化学成分的免疫抑制活性,化合物4,6,9均有较强的免疫抑制活性.     

Apoptotic effect of a phytosterol-ingredient and its main phytosterol (β-sitosterol) in human cancer cell lines

Dietary interventions may effectively control cancer development, with phytosterols (PS) being a class of cancer chemopreventive dietary phytochemicals. The present study, for the first time, evaluates the antiproliferative effects of a PS-ingredient used for the enrichment of several foods and its main PS, β-sitosterol, at physiological serum levels, in the most prevalent cancer cells in women (breast (MCF-7), colon (HCT116) and cervical (HeLa)). In all three cell lines, these compounds induced significant cell viability reduction without a clear time- and dose-dependent response. Moreover, all treatments produced apoptotic cell death with the induction of DNA fragmentation through the appearance of a sub-G1 cell population. Thus, the use of PS as functional ingredients in the development of PS-enriched foods could exert a potential preventive effect against human breast, colon and cervical cancer, although further in vivo studies are required to confirm our preclinical findings.     

Cholesterol metabolism and non-cholesterol sterols in patients with ileal pouch anastomosis

Background: Previous studies suggest only minor changes in bile acid metabolism after panproctocolectomy with ileal pouch construction.Aims/Methods: To investigate these changes further, we studied cholesterol absorption and serum, biliary and fecal non-cholesterol sterols and lipids in 12 ileal pouch patients and 10 controls.Results: In patients, cholesterol absorption was markedly reduced and was associated with low serum total and LDL cholesterol and LDL triglyceride levels, but surprisingly, cholesterol synthesis, as indicated by sterol-balance data or serum cholesterol precursor levels, was within low normal limits. The high proportions of serum plant sterol to cholesterol, particularly that of campesterol, were not related to cholesterol absorption, but were attributable to a markedly reduced biliary cholesterol secretion. Interestingly, in these patients the fractional absorption of campesterol was normal, whereas that of sitosterol, like cholesterol, was reduced and was positively related to the intestinal influx of cholesterol. The patients' serum cholestanol proportion was normal, but the proportion of the cholestanol formed during intestinal passage was significantly reduced (17.9% vs 65.2% in controls).Conclusions: Thus ileal pouch patients are characterized by sterol malabsorption, lowered serum total and LDL-cholesterol levels, but unexpectedly without any increase in cholesterol synthesis. The lack of high serum cholestanol, shown earlier frequently in unoperated patients with ulcerative colitis, may indicate reversible cholestasis, a finding deserving further exploration.     

植物固醇在脂质体中的应用研究进展

脂质体作为药物载体,由于其具有靶向性、可降低药物毒性等优点而备受关注。本文在阐述固醇分子在脂质体中的作用、脂质体液态有序相的特征、脂筏定义的基础上综述了植物细胞中脂筏的发现及植物固醇代替胆固醇作为脂质体膜材的必要性和可行性等相关问题的研究进展。     

Effect of dalcetrapib, a CETP modulator, on non-cholesterol sterol markers of cholesterol homeostasis in healthy subjects

Objective

Subjects with high HDL-C show elevated plasma markers of cholesterol absorption and reduced markers of cholesterol synthesis. We evaluated the effect of dalcetrapib, a cholesteryl ester transfer protein modulator, on markers of cholesterol homeostasis in healthy subjects.

Methods

Dalcetrapib was administered daily with or without ezetimibe in a randomized, open-label, crossover study in 22 healthy subjects over three 7-day periods: dalcetrapib 900 mg, ezetimibe 10 mg, dalcetrapib 900 mg plus ezetimibe 10 mg. Plasma non-cholesterol sterols lathosterol and desmosterol (cholesterol synthesis markers) and campesterol, β-sitosterol and cholestanol (intestinal cholesterol absorption markers) were measured. A hamster model was used to compare the effect of dalcetrapib and torcetrapib with or without ezetimibe on these markers and determine the effect of dalcetrapib on cholesterol absorption.

Results

Dalcetrapib increased campesterol, β-sitosterol, and cholestanol by 27% (p = 0.001), 32% (p < 0.001), and 12% (p = 0.03), respectively, in man (non-cholesterol sterol/cholesterol ratio). Dalcetrapib + ezetimibe reduced campesterol by 11% (p = 0.02); β-sitosterol and cholestanol were unaffected. Lathosterol and desmosterol were unchanged with dalcetrapib, but both increased with ezetimibe alone (56–148%, p < 0.001) and with dalcetrapib + ezetimibe (32–38%, p < 0.001). In hamsters, dalcetrapib and torcetrapib increased HDL-C by 49% (p = 0.04) and 72% (p = 0.003), respectively. Unlike torcetrapib, dalcetrapib altered cholesterol homeostasis towards increased markers of cholesterol absorption; cholesterol synthesis markers were unaffected by either treatment. Dalcetrapib did not change plasma ³H-cholesterol level but increased ³H-cholesterol in plasma HDL vs non-HDL, after oral dosing of labeled cholesterol.

Conclusion

Dalcetrapib specifically increased markers of cholesterol absorption, most likely reflecting nascent HDL lipidation by intestinal ABCA1, without affecting markers of synthesis.