Spexin (SPX) is a novel peptide involved in glucose and lipid metabolism and suppresses hepatic total bile acid levels by inhibiting hepatic cholesterol 7α-hydroxylase 1 expression. As important mediators for glycolysis/gluconeogenesis and lipid metabolism, the effects of bile acids on SPX expression is yet to be understood. By using SMMC7721 and BEL-7402 cell lines, we screened the effects of bile acids and found that chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) can stimulate SPX gene transcription. Both CDCA and DCA were able to stimulate SPX mRNA expression in the liver but not colon and ileum in mice. In SMMC7721 and BEL-7402 cells, CDCA- and DCA-induced SPX promoter activity was mimicked by bile acid receptor FXR and TGR5 activation and suppressed by FXR and TGR5 silencing. Adenylate cyclase (AC)/cyclic adenosine monophosphate (cAMP) activators significantly increased SPX promoter activity whereas the inhibitors for AC/CAMP/protein kinase A (PKA) and mitogen-activated protein kinases (MAPK) pathway attenuated CDCA- and DCA-induced SPX transcription. Thus, CDCA and DCA stimulate SPX expression at the hepatic level through FXR and TGR5 mediated AC/cAMP/PKA and MAPK cascades.

An ethanol extract of the dried aerial of Pedicularis densispica Franch (Scrophulariaceae) afforded a new lignan, densispicoside (1), and two new iridoids, densispicnin C and D (14, 15), together with four lignans, (+)-isolarisiresinol 3a-O-β -D-glucopyranoside (2), (-)-pinoresinol-β - D-glucopyranoside (3), syringaresinol mono-β -D-glucopyranoside (4), longifloroside B (5), eight phenylpropanoids, 4-O-β -D-glucopyranosyl-sinapic acid methyl ester (6), 3-(4-hydroxy-3-methoxyphenyl)- 1,2,3-propantriol (7), citrusin C (8), robustaside B (9), verbascoside (10), martynoside (11), 2ʺ-O-acetylverbascoside (12), cis-martynoside (13), and two iridoid glycosides, shanzhiside methyl ester (16), and 8-epiloganin (17). Their structures were established on the basis of chemical and spectroscopic studies. Bioactivity results indicate that P. densispica shows activity on PAI-1 antithrombus assay in vitro and antifatigue activities in vivo.

Human DNA topoisomerase I (Topo I) is an essential enzyme in regulating DNA supercoiling during transcription and replication, and it is an important therapeutic target for anti-tumor agents. Bidens pilosa L. is a medicinal herb that is used as a folk medicine for cancers in China. A new flavonoid (1) and a new polyacetylene (20), along with eighteen flavonoids (2–19) and nine polyacetylenes (21–29), were isolated and identified from the methanol extract of the whole plant of B. pilosa, and some of the compounds (4, 5, 6 and 7) exhibited potent cytotoxicity against a panel of five human cancer cell lines. The DNA relaxation assay revealed that some flavonoids and polyacetylenes exerted inhibitory activities on human DNA Topo I, among them compounds 1, 2, 5, 6, 7, 8, 15, 19, 20, 22, and 24 were the most active ones, with IC₅₀ values of 393.5, 328.98, 145.57, 239.27, 224.38, 189.84, 89.91, 47.5, 301.32, 178.03, and 218.27 μM, respectively. The structure–activity analysis of flavonoids was performed according to the results from the Topo I inhibition assay. The DNA content analysis revealed that 5, 6, and 7 potently arrested cell cycle at the G₁/S and G₂/M phases in human colon cancer cell DLD-1 depending on the concentration of the inhibitors. The levels of protein expression related to the G₁/S and G₂/M cell cycle checkpoints were in accordance with the results from the DNA content analysis. These findings suggest that flavonoids are one of the key active ingredients accounting for the anti-tumor effect of B. pilosa.