Inhibitory effect of Bofutsushosan (Fangfengtongshengsan) extract on the absorption of fructose in rats and mice.

Bofutsushosan (BTS; fangfengtongshengsan in Chinese) is a formula in traditional Japanese Kampo and Chinese medicine comprising 18 crude drugs and used to treat obesity and metabolic syndrome. In our previous study, BTS boiling water extract inhibited the uptake of fructose absorbed via glucose transporter 5 into cultured cells. In this study, the inhibitory effect of BTS extract on the absorption of fructose from the intestine was investigated in vivo. The extract of BTS was orally administered to rats at doses equivalent to 25-fold of the daily dose for humans. One minute after sample administration, fructose was orally administered and blood samples were collected from the jugular vein 0.5, 1, 1.5, 2, and 4 h after the administration of fructose. The absorption of fructose from the intestine was significantly reduced by treatment with BTS extract, and this in vivo study reproduced previous in vitro results. Subsequently, the blood samples were collected from the portal vein 30 min after the oral administration of fructose in mice. BTS extract significantly reduced fructose absorption in mice, and compared the effect of modified BTS samples by removing one to several crude drugs from BTS. We found that the dried rhizome of Rheum palmatum (RR) significantly contributed to the inhibitory effect of BTS on fructose absorption. We found sennoside A to be the active ingredient of RR for the inhibition of fructose absorption, and that its effect almost saturated at a dose of 3 mg/kg. These results support the action mechanisms of BTS when used for the treatment of obesity in clinics and drug stores.

Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch.

The incidence of sensitive skin with stinging and itch following chemical exposure in products such as cosmetics is increasing, but molecular mechanisms underlying this pathophysiology remain understudied. Here we performed transcriptional analysis of reconstructed human epidermis (RHE) 1, 6, and 24 h following topical lactic acid (LA) application, a known inducer of the sensitive skin reaction. Since little is known about the specific role of keratinocyte transcriptional changes in mediating stinging and itch, we performed pathway analysis using several publically available databases and then focused on significantly changed transcripts involved in stress responses and itch signaling using the Comparative Toxicogenomics Database. LA treatment induced damage-associated genes HSPA1A, DDIT3, IL1A, and HMGB2. Neurotrophic factors including BDNF, ARTN, PGE2, and chemokines were also upregulated. Stimulation of the RHE with 5% LA did not reduce cell viability, but reduced the trans-epidermal electric resistance, suggesting barrier dysfunction. Accordingly, skin barrier formation genes such as filaggrins (FLG, FLG2) and corneodesmosin (CDSN) were downregulated. To our knowledge, this is the first study focusing on transcriptional changes underlying the stinging response of keratinocytes upon LA stimulation. While follow-up research is needed, this study provides new insight into the mechanisms underlying the sensitive skin reaction.