Depression is not just a general mental health problem but a serious medical illness that can worsen without treatment. The gut microbiome plays a major role in the two-way communication system between the intestines and brain. The current study examined the effects of flavonoids on depression by observing the changes in the gut microbiome and depressive symptoms of young participants consuming flavonoid-rich orange juice. The depressive symptom was assessed using the Center for Epidemiological Studies Depression Scale (CES-D), a psychiatric screening tool used to detect preexisting mental disorders. The study population was randomly divided into two groups: the flavonoid-rich orange juice (FR) and an equicaloric flavonoid-low orange cordial (FL) group. For 8 weeks, participants consumed FR (serving a daily 380 mL, 600 ± 5.4 mg flavonoids) or FL (serving a daily 380 mL, 108 ± 2.6 mg flavonoids). In total, 80 fecal samples from 40 participants (mean age, 21.83 years) were sequenced. Regarding depression, we observed positive correlations between brain-derived neurotrophic factor (BDNF) and the Lachnospiraceae family (Lachnospiraceae_uc and Murimonas) before flavonoid orange juice treatment. Most notably, the abundance of the Lachnospiraceae family (Lachnospiraceae_uc, Eubacterium_g4, Roseburia_uc, Coprococcus_g2_uc, Agathobacter_uc) increased after FR treatment compared to that after FL treatment. We also validated the presence of unclassified Lachnospiraceae through sensitive real-time quantitative polymerase chain reaction using stool samples from participants before and after flavonoid treatment. Our results provide novel interventional evidence that alteration in the microbiome due to flavonoid treatment is related to a potential improvement in depression in young adults.

Honeyberry (Lonicera caerulea) has been used for medicinal purposes for thousands of years. Its predominant anthocyanin, cyanidin-3-O-glucoside (C3G), possesses antioxidant and many other potent biological activities. We aimed to investigate the effects of honeyberry extract (HBE) supplementation on HepG2 cellular steatosis induced by free fatty acids (FFA) and in diet-induced obese mice. HepG2 cells were incubated with 1 mM FFA to induce lipid accumulation with or without HBE. Obesity in mice was induced by a 45% high fat diet (HFD) for 6 weeks and subsequent supplementation of 0.5% HBE (LH) and 1% HBE (MH) for 6 weeks. HBE suppressed fatty acid synthesis and ameliorated lipid accumulation in HepG2 cells induced by FFA. Moreover, HBE also decreased lipid accumulation in the liver in the supplemented HBE group (LH, 0.5% or MH, 1%) compared with the control group. The expressions of adipogenic genes involved in hepatic lipid metabolism of sterol regulatory element-binding protein-1 (SREBP-1c), CCAAT/enhancer-binding protein alpha (C/EBPα), peroxisome proliferator-activated receptor gamma (PPARγ), and fatty acid synthase (FAS) were decreased both in the HepG2 cells and in the livers of HBE-supplemented mice. In addition, HBE increased mRNA and protein levels of carnitine palmitoyltransferase (CPT-1) and peroxisome proliferator-activated receptor α (PPARα), which are involved in fatty acid oxidation. Furthermore, HBE treatment increased the phosphorylation of AMP-activated protein kinase (AMPK) and Acetyl-CoA Carboxylase (ACC). Honeyberry effectively reduced triglyceride accumulation through down-regulation of hepatic lipid metabolic gene expression and up-regulation of the activation of AMPK and ACC signaling in both the HepG2 cells as well as in livers of diet-induced obese mice. These results suggest that HBE may actively ameliorate non-alcoholic fatty liver disease.

Delphinidin-3-O-β-glucoside (D3G) is a health-promoting anthocyanin whose anti-obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on adipogenesis and lipogenesis in 3T3-L1 adipocytes and primary white adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 adipocytes, D3G downregulated the expression of key adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in adipocytes. Our data indicate that D3G attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of obesity.

In this study, we investigated the effects of black ginseng (BG) and ginsenoside Rb1, which induced browning effects in 3T3-L1 and primary white adipocytes (PWATs) isolated from C57BL/6 mice. BG and Rb1 suppressed the expressions of CCAAT/enhancer-binding protein alpha (C/EBPα) and sterol regulatory element-binding transcription factor-1c (SREBP-1c), whereas the expression level of peroxisome proliferator-activated receptor gamma (PPARγ) was increased. Furthermore, BG and Rb1 enhanced the protein expressions of the brown-adipocyte-specific markers PR domain containing 16 (PRDM16), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and uncoupling protein 1 (UCP1). These results were further supported by immunofluorescence images of mitochondrial biogenesis. In addition, BG and Rb1 induced expressions of brown-adipocyte-specific marker proteins by AMP-activated protein kinase (AMPK) activation. BG and Rb1 exert antiobesity effects by inducing browning in 3T3-L1 cells and PWATs through AMPK-mediated pathway activation. We suggest that BG and Rb1 act as potential functional antiobesity food agents.

Neferine, an alkaloid component extracted from lotus seed embryos, is known for its anti-inflammatory, anticancer, and antioxidant properties. However, the anti-adipogenic activity of neferine has not been thoroughly investigated. In this study, neferine was found to inhibit lipid accumulation in a dose-dependent manner during the differentiation of 3T3-L1 cells without inducing cytotoxicity. Real-time polymerase chain reaction and immunoblot analysis revealed the downregulation in the expression of peroxisome proliferator activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) and the upregulation in carnitine palmitoyltransferase-1 (CPT-1) and sirtuin 1 (SIRT1) levels following neferine treatment. Furthermore, neferine increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which is an important regulator of fatty acid oxidation. Our result indicates that neferine attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling. Therefore, neferine may serve as a therapeutic candidate for obesity treatment.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of β-amyloid plaques and hyperphosphorylated tau proteins in the brain. Cell signaling pathways such as PI3K/Akt are known to play an essential role in regulating cell survival, motility, transcription, metabolism, and progression of the cell cycle. Recent studies demonstrated that the disruption of these signaling pathways in neurodegenerative disorders leads to oxidative stress and cell death. Targeting these altered signaling pathways could be considered as the therapeutic approach for neurodegenerative disorders. Ginsenoside Rh1 is known to provide beneficial effects in various diseases such as cancer, diabetes, and inflammation. In this study, human neuroblastoma SH-SY5Y cells were treated with the β-amyloid oligomers alone or in combination with ginsenoside Rh1. We observed that ginsenoside Rh1 was able to attenuate β-amyloid induced oxidative stress and cell death by activating the PI3K/Akt signaling pathway. Based on these findings, we suggest that ginsenoside Rh1 might be an efficacious therapeutic agent for AD.