Selenium (Se)-enriched plant polypeptide represents a premium selenium source possessing numerous physiological functions. Benzo(a)pyrene (BaP) is a carcinogenic food processing contaminant with hepatotoxic properties.The present study aimed to elucidate the mechanism underlying protective effects of selenium-enriched black soybean polypeptide (SeBSPP) against BaP-induced liver injury by integrating liver transcriptome, metabolomics, and gut microbiome. Our study revealed that SeBSPP effectively mitigated BaP-induced liver damage. SeBSPP suppressed the toxicity of BaP on the liver via inhibiting the formation of the carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-DNA (BPDE-DNA), reducing Aryl hydrocarbon receptor (AhR) enzyme activity and BaP related metabolic enzymes Cytochrome P450 Family (CYP450). Moreover, SeBSPP effectively inhibited liver lipid accumulation and reduced the risk of liver cancer by activating the major urinary proteins (Mups), regulating intestinal flora, and increasing the level of short chain fatty acids. Selenium-enriched yeast tablets also exerted a liver protection effect, albeit weaker compared to SeBSPP. This study provides a new direction for preventing hepatotoxicity of BaP and improves Se resource deficiency.

High-fat diet (HFD) promotes the imbalance of gut microbiota, contributing to the development of metabolic disorders. Pomegranate juice (PJ) and inulin, as dietary polyphenol and dietary fiber respectively, have been reported to ameliorate diet-induced gut microbiota dysbiosis and metabolic disorders. However, the combined effect of PJ and inulin on HFD-induced metabolic disorders has not been elucidated. In current study, we found that the combination of PJ and inulin prevent HFD-induced obesity, dyslipidemia, and gut microbiota dysbiosis. Moreover, the fecal levels of short-chain fatty acids (SCFAs) produced by inulin were increased after inulin combined with PJ. The levels of pomegranate polyphenol metabolites produced by PJ were also increased after PJ combined with inulin, especially pharmacokinetic analysis showed that the presence of inulin enhance the absorption level of urolithin A. Fecal metabolomic analysis found that PJ combined with inulin alter the metabolic status compared with PJ. It was also showed that the levels of SCFAs and pomegranate polyphenol metabolites among groups were correlated with gut microbiota and metabolic disorders indicators. Our results suggested that PJ combined with inulin prevent HFD-induced metabolic disorders, which may be attributed to the promotion of mutual metabolic transformation and absorption of PJ and inulin by gut microbiota.

Anthocyanins are a plant active ingredient in black rice. Here, we used black rice anthocyanin extract (BRAE) as the object of study and explored its protective mechanism against age-related cognitive decline. Briefly, C57BL/6J mice were fed a purified diet containing BRAE and injected with D-galactose (120 mg kg⁻¹) for 24 weeks. The results indicated that BRAE retarded cognitive decline, mitigated the degree of morphological lesions in the hippocampus, restored the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters, enhanced the antioxidant capacity of brain tissue, reduced the contents of proinflammatory factors, inhibited dysbacteriosis. Spearman’s rank correlation analysis indicated a positive correlation between alterations in gut microbiota and the antioxidant capacity of brain tissue, as well as a negative correlation between changes in gut microbiota and the severity of inflammation in brain tissue. Importantly, the hyperphosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and ERK1/2 mitogen-activated protein kinase (ERK1/2 MAPK) was weakened by BRAE in the brain. Meanwhile, BRAE inhibited the protein degradation of IkBα and the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) along with its downstream genes, upregulated the expression of nuclear factor E2-related factor 2 (Nrf2) and its downstream genes. Furthermore, molecular docking showed that differential metabolites of brain could bind to the IkBα/NF-kB complex, suppressing the dissociation of the IkBα/NF-kB complex, which is composed of p65, p50, and IkBα. Therefore, these results suggest that BRAE may exert anti-inflammatory and antioxidant effects on aging brain via the MAPK/NF-kB/Nrf2 pathways, as well as through the inhibition of dysbiosis.

Gut microbiota regulate the activation of adipose browning, which promote energy dissipation and combat diet-induced obesity. Pomegranate peel polyphenols (PPPs) have been shown to reduce obesity, regulate lipid metabolism in adipose tissue, and modulate the composition of gut microbiota in animal fed high-fat diet (HFD). However, the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated. In current study, we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs. The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning, and change the fecal metabolomic profiles in respond to PPPs. Moreover, the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites, such as urolithin A, short-chain fatty acids (SCFAs), and bile acids (BAs), which were associated with activating adipose browning. Therefore, our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity. The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.

This study developed a cell model of oxidative damage by treating PC12 cells for 24 h with 200 µmol/L H₂O₂ and determined the degree of oxidative stress by assaying the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) and the level of malondialdehyde (MDA). Moreover, cell apoptosis and reactive oxygen species (ROS) levels were evaluated. Western blot and real-time polymerase chain reaction (PCR) were used to detect the protein and mRNA expression levels of B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), caspase-3, nuclear factor E2 related factor 2 (Nrf2), kelch-like ECH-associated protein 1 (Keap1), and heme oxygenase-1 (HO-1). The results showed that after being treated with 200 µmol/L H₂O₂ for 24 h, the survival rate of PC12 cells was 60.12%. Cytotoxicity experiments showed that nervonic acid could significantly reduce the contents of LDH and MDA, inhibit excessive production of ROS, and enhance the activities of SOD and GSH-Px in H₂O₂-injuried cells. In addition, it significantly upregulated the expression of Bcl-2, Nrf2 and HO-1, and downregulated the expression of caspase-3, Bax, and Keap1. In summary, nervonic acid has a protective effect on H₂O₂-induced oxidative damage in PC12 cells by a mechanism associated with the activation of the Nrf2/HO-1 signaling pathway.

The high incidence of postpartum hypogalactia hinders the healthy development of postpartum women and the next generation. Lacquer seed oil (LSO), extracted from the seeds of the lacquer tree, has been traditionally used as a dietary supplement for promoting postpartum lactation and recovery in some districts of China. However, its physiological effects have not been verified, and the mechanism and active components of LSO have not been analyzed. Thus, we applied LSO to bromocriptine-induced postpartum hypogalactia rats. The results showed that LSO supplement effectively improves bromocriptine-induced postpartum hypogalactia. LSO also increased prolactin levels reduced by bromocriptine, promoted JAK2/STAT5 and PI3K/AKT pathways and several gene expression levels of milk synthesis in mammary gland. Moreover, metabolomic and network pharmacological analysis further revealed that JAK2/STAT5, PI3K/AKT, and estrogen signaling pathway are the potential main regulatory sites for the beneficial effects of LSO on postpartum hypogalactia, and that quercetin, kaempferol, arachidonic acid, epicatechin, and β-sitosterol are the top 5 main active ingredients of LSO. Our results suggested that LSO has great potential in the application of the improvement of postpartum hypogalactia.

Insulin resistance (IR) has been considered to be an important causative factor of metabolic syndrome (MetS). The present study investigated whether pomegranate peel polyphenols (PPPs) could prevent the development of MetS by improving IR in rats. Male Sprague-Dawley (SD) rats were fed high fat diet (HFD) to induce MetS and supplemented with different dosages of PPPs for 12 weeks. The results showed that HFD-induced insulin resistant rats had disordered metabolism of blood glucose, blood lipid, and terrible muscle fiber morphology when compared with normal diet-fed rats, but PPPs treatment at a dosage of 300 mg/kg·day significantly reversed these negative effects. Moreover, in skeletal muscle tissue of insulin resistant rats, PPPs treatments significantly increased the protein expressions of insulin receptor (InsR) and phosphorylated insulin receptor substrate 1 (IRS-1), stimulated peroxisome proliferator activated receptor gamma (PPARγ) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway, and aggrandized the protein levels of phosphorylated glycogen synthase kinase-3β (GSK-3β) and glucose transporter 4 (GLUT4). Our results suggest that PPPs possess of the beneficial effects on alleviating IR by enhancing insulin sensitivity and regulating glucose metabolism.