Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract fromFraxinus mandshuricaSeeds on High-Fat Diet-Fed Mice

Previously we conducted a phytochemical study on the seeds ofFraxinus excelsiorand isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPAR alpha) activation effects. However, the bioactive constituents and functions ofFraxinus mandshuricaseeds have not been studied. In the present study, we investigated the secoiridoid compounds inF. mandshuricaseed extract (FM) using column chromatography,H-1-NMR,C-13-NMR and HPLC-DAD methods. The pancreatic lipase inhibitory activities of isolated compounds were evaluated in vitro. Additionally, the anti-obesity and gut microbiota modulation effect ofFMon high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated fromFMand identified. The total content of secoiridoids inFMreached 181.35 mg/g and the highest content was nuzhenide (88.21 mg/g). All these secoiridoid compounds exhibited good pancreatic lipase inhibitory activity with inhibition rate ranged from 33.77% to 70.25% at the concentration of 100 mu M. After obese mice were administrated withFMat 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover,FMcould attenuate the lipid accumulation in serum and liver, relieve the damage in liver and kidney, and extenuate oxidative stress injury and inflammation caused by obesity in mice.FMcould also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (Bacteroidetes,Bacteroidia,S24-7andAllobaculum), and reducing the proportion of obesogenic gut microbiota (FirmicutesandDorea). This study suggests thatF. mandshuricaseeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.