The Polymethoxyflavone Sudachitin Modulates the Circadian Clock and Improves Liver Physiology.

SCOPE: Polymethoxylated flavones (PMFs) are a group of natural compounds known to display a wide array of beneficial effects to promote physiological fitness. Recent studies reveal circadian clocks as an important cellular mechanism mediating preventive efficacy of the major PMF Nobiletin against metabolic disorders. Sudachitin is a PMF enriched in Citrus sudachi, and its functions and mechanism of action are poorly understood. METHODS AND RESULTS: Using circadian reporter cells, it shows that Sudachitin modulates circadian amplitude and period of Bmal1 promoter-driven reporter rhythms, and real-time qPCR analysis shows that Sudachitin alters expression of core clock genes, notably Bmal1, at both transcript and protein levels. Mass-spec analysis reveals systemic exposure in vivo. In mice fed with high-fat diet with or without Sudachitin, it observes increased nighttime activity and daytime sleep, accompanied by significant metabolic improvements in a circadian time-dependent manner, including respiratory quotient, blood lipid and glucose profiles, and liver physiology. Focusing on liver, RNA-sequencing and metabolomic analyses reveal prevalent diurnal alteration in both gene expression and metabolite accumulation. CONCLUSION: This study elucidates Sudachitin as a new clock-modulating PMF with beneficial effects to improve diurnal metabolic homeostasis and liver physiology, suggesting the circadian clock as a fundamental mechanism to safeguard physiological well-being.

Sudachi peel extract powder including the polymethoxylated flavone sudachitin improves visceral fat content in individuals at risk for developing diabetes.

In vitro and animal studies have indicated that extracts from the peel of the Japanese Citrus sudachi, including sudachitin, ameliorate hyperlipidemia and reduce obesity. Sudachitin, a polymethoxylated flavone, has been reported as having favorable effects on lipid and glucose metabolism but results from clinical trials have been inconsistent. The aim of this study was to determine the effect of consuming capsules of sudachi peel extract powder on visceral fat in Japanese men and women in a randomized controlled trial. This was a 12-week randomized, double-blind, placebo-controlled trial involving 41 participants aged 30-65 years with BMI 23-30 kg/m2, randomly allocated to receive either sudachi peel extract powder (sudachitin 4.9 mg/day, n = 21) or placebo (n = 20) of identical appearance. The primary outcome measure was visceral fat mass, assessed during intervention. Thirty-eight of the 41 subjects completed the protocol. Compared with placebo, sudachi peel extract powder significantly reduced the ratio of visceral fat to subcutaneous fat, and moderately reduced waist circumference, a metabolic syndrome marker. Glycemic control and lipid profile were not changed significantly in these subjects. Consumption of capsules of sudachi peel extract powder favorably improves the ratio of visceral fat to subcutaneous fat in individuals at risk for developing diabetes, especially in individuals with large visceral fat area, while not adversely affecting glycemic control.

Prenylated benzophenones and xanthones from Hypericum scabrum.

Two new polyprenylated benzophenones, a new polyprenylated phloroglucinol, and six new xanthone derivatives were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were elucidated on the basis of spectroscopic evidence. The isolated compounds showed moderate cytotoxicity for human tumor cells.

Sesquiterpenes from Ferula penninervis.

The ethyl acetate soluble extract of the dried roots of Ferula penninervis gave 17 new sesquiterpenes [15 of the guaiane-type, ferupennins A-O (1-15), and two of the eudesmane-type, 1alpha-hydroxy-2-oxo-5alpha,7beta,11betaH-eudesm-3-en-6alpha,12-olide (16) and penninervin (17)] and nine known sesquiterpenes. The structures of the new compounds were elucidated on the basis of spectroscopic evidence and X-ray analysis. The absolute configuration of ferupennin A (1) was determined by a modified Mosher method.

Benzoylphloroglucinol derivatives from Hypericum scabrum.

Nine new polyprenylated benzoylphloroglucinol derivatives, hyperibones A-I (1-9), were isolated from the aerial parts of the Uzbekistan medicinal plant Hypericum scabrum. Their structures were determined mainly on the basis of spectroscopic evidence (2D NMR and HRMS). Compounds 1, 2, and 4 showed mild in vitro antibacterial activity against methicillin-resistance Staphylococus aureus (MRSA) and methicillin-sensitive Staphylococus aureus (MSSA).

Coumarins and gamma-pyrone derivatives from Prangos pabularia: antibacterial activity and inhibition of cytokine release.

The n-hexane and ethyl acetate extracts of the stems and the ethyl acetate extracts of roots from Prangos pabularia afforded an gamma-pyrone derivative and furanocoumarin derivatives with three glucose and gamma-pyrone (pabularin A, B and C), along with 26 previously known compounds (18 coumarins, six terpenoids and two glycosides). Their structures were established on the basis of spectroscopic studies. Of these, 16 coumarin derivatives isolated from P. pabularia were tested for antibacterial activity and inhibition of cytokine release.