Pericarpium Citri Reticulatae 'Chachiensis' (PCRC), the premium aged pericarps of Pericarpium Citri Reticulatae, is widely used in traditional Chinese medicines with a diversity of promising bioactivity. Herein we report the extraction, characterization and underlying mechanism of anti-metabolic syndrome of an arabinan-rich polysaccharide from PCRC (PCRCP). This polysaccharide was obtained in a 7.0% yield by using ultrasound-assisted extraction under the optimized conditions of 30 mL/g liquid-to-solid ratio, 250 W ultrasound power for 20 min at 90 °C with pH 4.5. The PCRCP with an average molecular weight of 122.0 kDa, is mainly composed of D-galacturonic acid, arabinose and galactose, which may link via 1,4-linked Gal(p)-UA, 1,4-linked Ara(f) and 1,4-linked Gal(p). Supplementation with PCRCP not only effectively alleviated the weight gain, adiposity and hyperglycemia, but also regulated the key metabolic pathways involved in the de novo synthesis and β-oxidation of fatty acid in high-fat diet (HFD)-fed mice. Furthermore, PCRCP treatment caused a significant normalization in the intestinal barrier and composition of gut microbiota in mice fed by HFD. Notably, PCRCP selectively enriched Lactobacillus johnsonii at the family-genus-species levels, a known commensal bacterium, the level of which was decreased in mice fed by HFD. The depletion of microbiome induced by antibiotics, significantly compromised the effects of anti-metabolic syndrome of PCRCP in mice fed by HFD, demonstrating that the protective phenotype of PCRCP against anti-obesity is dependent on gut microbiota. PCRCP is exploitable as a potential prebiotic for the intervention of obesity and its complications.
Doxorubicin is a powerful anticancer agent used to treat a variety of human neoplasms. However, the clinical use of doxorubicin is hampered by cardiotoxicity and effective cardioprotective adjuvants do not exist. Dietary zinc, an essential nutrient, is required to maintain steady-state tissue zinc levels and intestinal homeostasis and may yield therapeutic benefits in diseases associated with zinc dysregulation or gut dysbiosis. Here, we investigated the effects of dietary Zn(II)-curcumin (ZnCM) solid dispersions on gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity in rats. Rats were injected with multiple low doses of doxorubicin and orally administered ZnCM daily over four weeks. Daily administration of ZnCM not only alleviated Dox-induced gut dysbiosis—as indicated by the increased Firmicutes-to-Bacteroidetes ratio and the maintenance of the relative abundances of major beneficial bacteria including Clostridium_XIVa, Clostridium_IV, Roseburia, Butyricicoccus and Akkermansia—but also maintained intestinal barrier integrity and decreased the lipopolysaccharide (LPS) contents of feces and plasma. ZnCM also significantly attenuated doxorubicin-induced zinc dyshomeostasis, which was mirrored by preservation of zinc levels and expression of zinc-related transporters. Furthermore, ZnCM significantly improved heart function and reduced cardiomyocyte apoptosis and myocardial injury in doxorubicin-treated rats. Notably, the regulation of zinc homeostasis and cardioprotective and microbiota-modulating effects of ZnCM were transmissible through horizontal feces transfer from ZnCM-treated rats to normal rats. Thus, ZnCM supplementation has potential as an effective therapeutic strategy to alleviate gut dysbiosis and zinc dyshomeostasis during doxorubicin-induced cardiotoxicity.
Diets(饮食) rich in fat are a major(主要) cause(原因) of metabolic disease(疾病), and nutritional(营养) food has been widely(广泛) used(使用) to counteract the metabolic disorders such(这样) as obesity(肥胖) and fatty(脂肪) liver(肝). The present study investigated the effects of oleuropein-enriched extract(提取物) from Jasminum grandiflorum L. flowers (OLE-JGF) in high-fat diet(饮食) (HFD)-fed mice and oleic acid(酸) (OA)-treated AML-12 cells. Treatment(治疗) of HFD-fed mice with 0.6% OLE-JGF for 8 weeks significantly reduced body and liver(肝) weights, as well as attenuating lipid dysmetabolism and hepatic steatosis. OLE-JGF administration(政府当局) prominently suppressed the mRNA expressions(表达) of monocyte chemoattractant protein(蛋白)-1 (MCP-1) and cluster of differentiation 68 (CD68), and it also downregulated acetyl-CoA carboxylase (ACC) and fatty(脂肪) acid(酸) synthase (FAS) as well as sterol-regulatory-element(元素)-binding protein(蛋白) (SREBP-1c) in the liver(肝). Meanwhile, mitochondrial DNA and uncoupling protein(蛋白) 2 (UCP2) were upregulated along with the increased expression(表达) of mitochondrial biogenic promoters including liver(肝) kinase B1 (LKB1), peroxisome proliferator–activated receptor-γ coactivator-1α (PGC-1α), nuclear(核) factor(因子)-erythroid-derived 2-like 2 (Nrf2), and mitochondrial transcription factor(因子) A (Tfam), but did not change AMP-activated protein(蛋白) kinase (AMPK) in liver(肝). The lipid droplets were decreased significantly after treatment(治疗) with 80 μM oleuropein for 24 h in OA-induced AML-12 cells. Furthermore, oleuropein significantly inhibited ACC mRNA expression(表达) and upregulated LKB1, PGC-1α, and Tfam mRNA levels, as well as increasing the binding level of LKB1 to PGC-1α promoter in OA-induced cells. These findings indicate(表明) that OLE-JGF reduces hepatic lipid deposition in HFD-fed mice, as well as the fact that OA-induced liver(肝) cells may be partly(部分) attributed to upregulation of the LKB1-PGC-1α axis, which mediates hepatic lipogenesis and mitochondrial biogenesis. Our study provides a scientific(科学) basis(基础) for the benefits and potential(潜在) use(使用) of the J. grandiflorum flower as a food supplement(补充) for the prevention(预防) and treatment(治疗) of metabolic disease(疾病).
We reported the first example of quantitative multiplexed Raman imaging with orthogonal gap-enhanced Raman tag flavors for fast detection of microsatellite instability in cancer.