Citrus peel extracts attenuated obesity and modulated gut microbiota in mice with high-fat diet-induced obesity.

Polymethoxyflavones (PMFs) and hydroxyl PMFs (HOPMFs) are mainly found in citrus peel and have shown anti-obesity potential in in vitro and in vivo studies. Herein, we have investigated the anti-obesity effects of two citrus peel extracts obtained via supercritical fluid extraction: PMF A, with a lower content of PMFs and HOPMFs, and PMF B, with a higher content of PMFs and HOPMFs. PMF A and PMF B were administered orally for 16 weeks to mice with high fat diet (HFD)-induced obesity. The results showed that PMF B decreased the lipid content more statistically significantly (p < 0.05) than PMF A in 3T3-L1 preadipocytes, reduced the adipocyte size, decreased the adipose tissue weight and alleviated the total body weight in the HFD mice. Both PMF A and PMF B reduced the adipocyte size in the perigonadal fat by markedly decreasing the levels of lipid droplets (LD) and perilipin 1 protein and Sterol regulatory element binding protein 1 (SREBP-1) expression. Compared to the case of the HFD group, PMF B altered the gut microbiota by increasing Prevotella and decreasing rc4-4 bacteria. The change in the composition of gut microbiota, the community of symbiotic and pathogenic microorganisms, may determine the metabolic health and be responsible for the anti-obesity mechanism. Our results indicate that the citrus peel extracts decrease lipid accumulation both in vivo and in vitro and should be considered for the management of overweight and obesity conditions.

Liposomal-formulated curcumin [Lipocurc™] targeting HDAC (histone deacetylase) prevents apoptosis and improves motor deficits in Park 7 (DJ-1)-knockout rat model of Parkinson's disease: implications for epigenetics-based nanotechnology-driven drug platform.

BACKGROUND: Converging evidence suggests dysregulation of epigenetics in terms of histone-mediated acetylation/deacetylation imbalance in Parkinson's disease (PD). Targeting histone deacetylase (HDAC) in neuronal survival and neuroprotection may be beneficial in the treatment and prevention of neurodegenerative disorders. Few pharmacological studies use the transgenic model of PD to characterize the neuroprotection actions of a lead compound known to target HDAC in the brain. METHODS: In our study, we investigated neuroprotective effects of liposomal-formulated curcumin: Lipocurc™ targeting HDAC inhibitor in the DJ-1(Park 7)-gene knockout rat model of PD. Group I (DJ-1-KO-Lipocurc™) received Lipocurc™ 20 mg/kg iv 3× weekly for 8 weeks; Group II: DJ-1 KO controls (DJ-1 KO-PBS) received i.v. phosphate-buffered saline (PBS). Group III: DJ-1-Wild Type (DJ-1 WT-PBS) received PBS. We monitored various components of motor behavior, rotarod, dyskinesia, and open-field behaviors, both at baseline and at regular intervals. Toward the end of the 8 weeks, we measured neuronal apoptosis and dopamine (DA) neuron-specific tyrosine hydroxylase levels by immunohistochemistry methods at post-mortem. RESULTS: We found that DJ-KO Group I and Group II, as compared with DJ-1 WT group, exhibited moderate degree of motor impairment on the rotarod test. Lipocurc™ treatment improved the motor behavior motor impairment to a greater extent than the PBS treatment. There was marked apoptosis in the DJ-1 WT group. Lipocurc™ significantly blocked neuronal apoptosis: the apoptotic index of DJ-1-KO-Lipocurc™ group was markedly reduced compared with the DJ-KO-PBS group (3.3 vs 25.0, p<0.001). We found preliminary evidence Lipocurc™ stimulated DA neurons in the substantia nigra. The ratio of immature to mature DA neurons in substantia nigra was statistically higher in the DJ-1-KO-Lipocurc™ group (p<0.025). CONCLUSIONS: We demonstrated for the first time Lipocurc™'s anti-apoptotic and neurotrophic effects in theDJ-1-KO rat model of PD. Our promising findings warrant randomized controlled trial of Lipocurc™ in translating the novel nanotechnology-based epigenetics-driven drug discovery platform toward efficacious therapeutics in PD.