Anti-Obesity Effect of Fermented Panax notoginseng Is Mediated Via Modulation of Appetite and Gut Microbial Population.

Panax notoginseng (PN) is a traditional herbal medicine containing several active compounds such as saponins and ginsenosides with many therapeutic applications including anti-obesity activity. Fermentation by lactic acid bacteria has the potential to metabolize ginsenosides to more active forms. This study examined whether fermentation has any benefits on the protective effects of a PN extract against obesity using a high-fat diet (HFD)-fed mouse model. PN was fermented with Lactobacillus plantarum which exhibited high ß-glucosidase activity. Upon fermentation, the PN extract exhibited an altered ginsenoside profile, a dramatic increase in the lactate level. Treatment of the HFD group with fermented PN (FPN), but not PN, decreased both the food and calorie intake significantly, which was consistent with the more potent suppressing effects of FPN than PN on the signaling pathways involved in appetite and energy intake. The PN treatment also modulated the gut microbial composition. The PN and FPN treatment groups showed clear differences in the population of gut microbiota. The relative abundance of Bacteroidetes, Erysipelotrichaceae, Coprococus, and Dehalobacterium were significantly higher in the FPN group then the normal, HFD, and XEN groups. Furthermore, the relative abundances of Akkermansia, Dehalobacterium, Erysipeliotrichaceae and parpabacteroides were significantly higher in the FPN group than the PN group, but the relative abundances of Allobaculum, Erysipelotrichi and Erysipelotrichale were significantly lower. The relative abundance of Bacteroides and Lactococcus was significantly higher and lower, respectively in the PN and FPN groups than the HFD group. In conclusion, the altered ginsenoside and organic acid's profile, and altered gut microbial composition are believed to be the major factors contributing to the anti-obesity properties of FPN.

Lactate-Fortified Puerariae Radix Fermented by Bifidobacterium breve Improved Diet-Induced Metabolic Dysregulation via Alteration of Gut Microbial Communities.

BACKGROUND: Puerariae Radix (PR), the dried root of Pueraria lobata, is reported to possess therapeutic efficacies against various diseases including obesity, diabetes, and hypertension. Fermentation-driven bioactivation of herbal medicines can result in improved therapeutic potencies and efficacies. METHODS: C57BL/6J mice were fed a high-fat diet and fructose in water with PR (400 mg/kg) or PR fermented by Bifidobacterium breve (400 mg/kg) for 10 weeks. Histological staining, qPCR, Western blot, and 16s rRNA sequencing were used to determine the protective effects of PR and fermented PR (fPR) against metabolic dysfunction. RESULTS: Treatment with both PR and fPR for 10 weeks resulted in a reduction in body weight gain with a more significant reduction in the latter group. Lactate, important for energy metabolism and homeostasis, was increased during fermentation. Both PR and fPR caused significant down-regulation of the intestinal expression of the MCP-1, IL-6, and TNF-α genes. However, for the IL-6 and TNF-α gene expressions, the inhibitory effect of fPR was more pronounced (p < 0.01) than that of PR (p < 0.05). Oral glucose tolerance test results showed that both PR and fPR treatments improved glucose homeostasis. In addition, there was a significant reduction in the expression of hepatic gene PPARγ, a key regulator of lipid and glucose metabolism, following fPR but not PR treatment. Activation of hepatic AMPK phosphorylation was significantly enhanced by both PR and fPR treatment. In addition, both PR and fPR reduced adipocyte size in highly significant manners (p < 0.001). Treatment by fPR but not PR significantly reduced the expression of PPARγ and low-density lipoproteins in adipose tissue. CONCLUSION: Treatment with fPR appears to be more potent than that of PR in improving the pathways related to glucose and lipid metabolism in high-fat diet (HFD)+fructose-fed animals. The results revealed that the process of fermentation of PR enhanced lactate and facilitated the enrichment of certain microbial communities that contribute to anti-obesity and anti-inflammatory activities.

Structural and rheological properties of pectic polysaccharide extracted from Ulmus davidiana esterified by succinic acid.

The present study was carried out to investigate the physicochemical and structural properties of pectic polysaccharide extracted from Ulmus davidiana (UDP) and to determine the physicochemical, structural, and rheological properties of esterified UDP with succinic acid (ES-UDP). The results indicated that UDP had high amounts of galacturonic acids and various neutral sugars, such as galactose, rhamnose, and glucose. UDP was identified as a low methoxyl pectin, consisting of 1,4-linked α-d-GalpA (the main backbone chain), supported by the results of Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction, and 1D Nuclear magnetic resonance (NMR) spectroscopy. In the FT-IR and XRD, no difference was detected between UPD and ES-UDPs. However, 1H and 13C NMR spectra revealed that the new ester bonds were formed between a hydroxyl group of UDP and a carboxyl group of succinic acid during esterification. In the steady shear rheological analysis, the consistency index (K) of ES-UDP was significantly higher than that of UDP and increased significantly with increasing concentration of succinic acid. In the dynamic rheological analysis, the tan δ values of all ES-UDP solutions were significantly lower than those of the UDP solution.

The characterization, selenylation and anti-inflammatory activity of pectic polysaccharides extracted from Ulmus pumila L.

The specific objective of this study was to investigate characterization, selenylation, and anti-inflammatory activities of pectic polysaccharides extracted from Ulmus pumila L. (PPU). Four different monosaccharides were found in PPU, including galacturonic acid, galactose, rhamnose, and glucose. FT-IR spectra indicated that pectic polysaccharides were successfully extracted from Ulmus pumila L., and were probably low methoxyl pectin. GC-MS and NMR analysis of PPU suggested the major monosaccharide of PPU was α-1,4-linked galacturonic acid with α-1,2-linked rhamnose as the backbone and glucose or galactose residues as branches at C-3 and C-4 positions of rhamnose. Selenylation of PPU was synthesized by 0.2 and 0.4% of sodium selenites. Selenized-PPU (Se-PPU) inhibited LPS-induced nitric oxide production in RAW 264.7 cells, and increasing selenium content enhanced anti-inflammatory properties of PPU. Therefore, Se-PPU can be used as a potential source of bioactive compounds for nutraceuticals and pharmaceutical applications.

Erythro-austrobailignan-6 down-regulates HER2/EGFR/integrinß3 expression via p38 activation in breast cancer.

BACKGROUND: Despite the benefits from different options of therapy for breast cancer, resistance of the disease to these therapies is rising and a novel agent is needed. Erythro-austrobailignan-6 (EA6) exhibits anti-cancer activity. However, the detailed anti-tumor mechanisms by which EA6 inhibits 4T-1 and MCF-7 cell growth have not been well studied. PURPOSE: In this study, we investigated the anti-proliferative and anti-tumor properties of EA6 on breast carcinoma and its accompanying mechanisms. METHODS: The cytotoxic and apoptotic effect of EA6 were measured in breast cancer cell lines of 4T-1 and MCF-7. The role of EA6 on cell proliferation and migration was examined by immunoblotting. The anti-tumor activity of EA6 was assessed in mice inoculated with 4T-1 breast cancer cells. RESULTS: EA6 increased the number of Annexin V-positive apoptotic bodies and cleaved form of caspase-3 in a dose-dependent manner and phosphorylated JNK and p38 in both cells. Moreover, EA6 down-regulated cell cycle dependent proteins of CDK-4 and cyclin D1, and increased G0/G1 population in both cells. EA6-induced apoptosis is mediated by p38 MAPK and caspase-3 activation in both cells. EA6 significantly reduced HER2/EGFR/integrin ß3 expression and Src phosphorylation, which was dependent on p38 MAPK activation in 4T-1 and MCF-7 cells. Furthermore, we confirmed the down-regulation of topoisomerases by EA6 treatment, but the overall effects of EA6 on topoisomerase isotype were cell type specific. Finally, EA6 (20mg/kg/day) significantly reduced mammary tumor volume in 4T-1 bearing mice by down-regulating HER2/EGFR/integrin ß3 expression in tumor tissues. CONCLUSIONS: Our results offer a novel insight into the mechanism of EA6-induced apoptosis in breast cancer cells. We propose that EA6 treatment resulted in the activation of p38 MAPK and caspase-3, which eventually participated in regulating apoptosis in 4T-1 and MCF-7 cells.