Anti-Obesity and Gut Microbiota Modulation Effect of Secoiridoid-Enriched Extract from Fraxinus mandshurica Seeds on High-Fat Diet-Fed Mice

Abstract

Previously we conducted a phytochemical study on the seeds of <i>Fraxinus excelsior</i> and isolated nine secoiridoid compounds with adipocyte differentiation inhibitory activity and peroxisome proliferator activated receptor alpha (PPARα) activation effects. However, the bioactive constituents and functions of <i>Fraxinus mandshurica</i> seeds have not been studied. In the present study, we investigated the secoiridoid compounds in <i>F. mandshurica</i> seed extract (<b>FM</b>) using column chromatography, ¹H-NMR, ¹³C-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 of <b>FM</b> on high-fat diet-induced obesity in C57BL/6 mice were also studied in vivo. The results showed that 19 secoiridoids were isolated from <b>FM</b> and identified. The total content of secoiridoids in <b>FM</b> reached 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 μM. After obese mice were administrated with <b>FM</b> at 400 mg/kg.bw for 8 weeks, body weight was decreased by 15.81%. Moreover, <b>FM</b> could 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. <b>FM</b> could also modulate the structural alteration of gut microbiota in obese mice, increasing the proportion of anti-obesity gut microbiota (<i>Bacteroidetes</i>, <i>Bacteroidia</i>, <i>S24-7</i> and <i>Allobaculum</i>), and reducing the proportion of obesogenic gut microbiota (<i>Firmicutes</i> and <i>Dorea</i>). This study suggests that <i>F. mandshurica</i> seeds or their secoiridoids may have potential for use as a dietary supplement for obesity management.