(4α)-Kaura-2,16-dien-18-ol benzoate

Two novel acylated steroidal sapogenins, 3β-acetoxy-1α, 2α, 4β, 5α, 7α-pentahydroxy-spirost-25(27)-en-6-one (1) and (25S)-3α-acetoxy-1α, 2β, 4α, 5α, 7α-pentahydroxyspirostan-6-one (2), together with two known steroidal sapogenins (3 and 4), were isolated from Rohdea chinensis rhizomes. Their structures were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. In addition, the antifungal activities of the isolated compounds against Penicillium digitatum and Rhizopus stolonifera were evaluated. Compound 2 significantly inhibited R. stolonifera growth, which was comparable to the positive control (sodium benzoate and carbendazim). Compound 4 showed the highest potency to inhibit P. digitatum growth compared to other compounds.

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of lipid and glucose metabolism. MS-275, as a class I-specific histone deacetylase (HDAC) inhibitor, has also been reported to affect energy metabolism. In this current study, we investigated the effects of MS-275 on hepatic FGF21 expression in vitro and in vivo and explored whether cAMP-responsive element-binding protein H (CREBH) was involved in the action of MS-275. Our results showed that MS-275 stimulated hepatic FGF21 mRNA and protein expressions in a dose- and time-dependent manner, as well as FGF21 secretion in primary mouse hepatocytes. Serum concentration and hepatic expression of FGF21 were elevated after injection of MS-275, along with increased expressions of genes involved in fatty acid oxidation and ketogenic production (peroxisome proliferator-activated receptor gammacoactivator1α, PGC-1α; carnitine palmitoyl-transferase 1a, CPT1a; 3-hydroxy-3-methylglutaryl-CoA synthase 2, Hmgcs2) as well as improved blood lipid profile. As a proved transcription factor of FGF21, the expression of CREBH was initiated by MS-275, with increased histone H3 lysine 18 acetylation (H3K18ac) signals and hepatocyte nuclear factor 4 alpha (HNF-4α) recruitment in CREBH promoter. Adenovirus-mediated knockdown of CREBH abolished MS-275-induced hepatic FGF21 and lipid metabolism-related gene expressions. These results suggest that MS-275 induces hepatic FGF21 by H3K18ac-mediated CREBH expression.

Averrhoa carambola L. (Oxalidaceae) was widely cultivated for fruits (star fruit), whereas the value of leaves remains to be discovered. Our study on the leaves yielded five flavan-3-ols (1-5) and two 2-diglycosyloxybenzoates. Their structures were determined by spectroscopic and chemical methods. Epicatechin-(5,6-bc)-4β-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (1) and benzyl 2-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyloxybenzoate (6) were new structures. 6-(S-2-Pyrrolidinone-5-yl)epicatechin (4) and 6-(R-2-pyrrolidinone-5-yl)epicatechin (5) were obtained as monomeric diastereomer for the first time and their absolute configurations were determined by electronic circular dichroism (ECD) computation. Epicatechin-(7,8-bc)-4α-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (2), epicatechin-(7,8-bc)-4β-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (3), and methyl 2-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosyloxybenzoate (7) were not previously reported from the genus Averrhoa. Compounds 1-5 showed more potent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities and ferric reducing antioxidant power (FRAP) than l-ascorbic acid. Meanwhile 1 and 3 exhibited lipase and α-glucosidase inhibitory activities, respectively. The results clarified the structures of flavan-3-ols and 2-diglycosyloxybenzoates in the leaves and their antioxidant, lipase, and α-glucosidase inhibitory activities.