The specific mechanisms of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) pathogenesis remain unknown. In the present study we investigated the differences between NAFL and NASH in terms of liver lipid metabolites and serum lipoprotein. In all, 104 Japanese subjects (50 men and 54 postmenopausal women) with histologically verified NAFL disease (NAFLD) (51 with NAFL, 53 with NASH) were evaluated; all diagnoses were based on liver biopsy findings and the proposed diagnostic criteria. To investigate the differences between NAFL and NASH in humans, we carefully examined (1)

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A new type of binaphthyl-based chiral iodide functionalized at positions 8 and 8' of the naphthalene rings has been found as a promising structural motif for the asymmetric hypervalent iodine(III) oxidations, specifically, for the dearomatizing spirocyclization of naphthol carboxylic acids showing expectedly better enantioselectivities versus other atropisomeric biaryls, i.e., a conventionally used binaphthalene having the diiodides in the minor groove.

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A new quassinoid, designated 2′-(R)-O-acetylglaucarubinone (1), and seven known quassinoids (2-8) were isolated, using bioactivity-guided separation, from the bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre (Simaroubaceae)]. The structure of 1 was determined by spectroscopic analysis, and by semi-synthesis from glaucarubolone. Complete 1 H and 13 C NMR assignments of compounds 1-8 were also established from detailed analysis of twodimensional NMR spectra, and the reported configurations in odyendene (7) and odyendane (8) were corrected. Compound 1 showed potent cytotoxicity against multiple cancer cell lines. Further investigation using various types of breast and ovarian cancer cell lines suggested that 1 does not target the estrogen receptor (ER) or progesterone receptor (PR). When tested against mammary epithelial proliferation in vivo using a Brca1/p53-deficient mice model, 1 also caused significant reduction in mammary duct branching.* To whom correspondence should be addressed. . khlee@unc.edu. + Equal Contribution.Supporting Information Available. HPLC analysis of 1 (synthetic and natural), 2, and 4, and NMR spectra of compound 1. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public AccessAuthor Manuscript J Nat Prod. Author manuscript; available in PMC 2011 September 24. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptQuassinoids are known as the bitter principles of Simaroubacaeous plants.1 -3 They are highly oxygenated triterpenes and possess a wide spectrum of in vitro and in vivo biological activities, including antitumor, antimalarial, antiviral, anti-inflammatory, antifeedant, insecticidal, amoebicidal, anti-ulcer, and herbicidal.1 In particular, the quassinoid bruceantin was brought to a phase II clinical trial as an anticancer drug candidate;4 however, lack of significant efficacy in treating human cancer led to termination of its clinical development in the early 1980's.5 From the initial studies on various quassinoids, the mechanism of action was attributed to the inhibition of site-specific protein synthesis by prevention of ribosomal peptidyl transferase activity leading to termination of chain elongation.6 However, other postulated mechanisms for inhibition of cancer cell growth include, but are not limited to, inhibition of plasma membrane NADH oxidase activity,7 down-regulation of c-myc oncogene,8 and mitochondrial membrane depolarization with caspase-3 activation.9The stem bark of Odyendyea gabonensis (Pierre) Engler [syn. Quassia gabonensis Pierre (Simaroubacae)] is a source of quassinoids, and seven quassinoids, 2′-(S)-Oacetylglaucarubinone (2), glaucarubinone (3), ailanthinone (4), 2′-(R)-O-acetylglaucarubin (5), excelsin (6), odyendene (7), and odyendane (8), were previously isolated.10 -12 We have re-investigated the stem bark of this plant, due to its potent selective cytotoxicity against breast cancer cell lines in our prior studies aimed at discovering antitumor agents from high...