Apple phenolic extracts ameliorate lead-induced cognitive impairment and depression- and anxiety-like behavior in mice by abating oxidative stress, inflammation and apoptosis via the miR-22-3p/SIRT1 axis.

Lead can lead to neurotoxicity and cognitive impairment. In this study, for the first time, the protective effects and working mechanisms of apple phenolic extracts (APEs) against lead acetate (Pb(Ac)2)-induced cognitive impairment and depression- and anxiety-like behavior were examined in vivo. Forty male mice were administered daily (via gastric gavage; 8 weeks) with 0.9% normal saline (control), Pb(Ac)2 (20 ppm), APE (200 ppm) or Pb(Ac)2 (20 ppm) + APE (200 ppm). The APE contained five major phenolic compounds: chlorogenic acid, proanthocyanidin B2, epicatechin, phloridzin and phloretin. Behavioral tests, histopathological examinations and biochemical analyses revealed that Pb(Ac)2-treated mice exhibited cognitive and behavioral deficits (i.e. a reduced percentage of spontaneous alternation, prolonged duration of immobility and decreased open field test scores compared with the control. Pb(Ac)2 exposure significantly increased cellular oxidative damage and the levels of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6 and tumor necrosis factor-α (TNF-α), ionized calcium binding adaptor molecule 1 (Iba1) and pro-apoptotic proteins (caspase 3, caspase 9 and Bax), while downregulating the expression of Bcl-2 in the brain. APE administration alleviated these Pb(Ac)2-induced changes through regulating oxidative stress, neuroinflammation and apoptosis via the miR-22-3p/Sirtuin 1 (SIRT1) signaling pathway. Taken together, the APE has the potential to treat lead-induced neurotoxicity and neurodegenerative disorders via antioxidant, anti-inflammatory and anti-apoptotic actions.

Lycopene supplementation attenuates western diet-induced body weight gain through increasing the expressions of thermogenic/mitochondrial functional genes and improving insulin resistance in the adipose tissue of obese mice.

This passive overconsumption of western diet has precipitated a steep rise in obesity and its comorbidities, and obesity has become one of the main threats to health worldwide. Thus, deciphering the molecular mechanisms leading to obesity is therefore of utmost importance to guide the search for novel therapeutic and preventive strategies. Lycopene (LYC), a major carotenoid present in tomato, has been regarded as a nutraceutical that has powerful anti-oxidant and anti-obesity bioactivities. Even though substantial progress has been made in deciphering the mechanism of how LYC affects obesity in recent years, whether thermogenic genes, mitochondrial function and insulin resistance are involved in the anti-obesity effect of LYC is yet to be elucidated. In the current study, we demonstrated that LYC remarkably suppressed HFFD-elevated mice body weight gain. LYC blocked lipid accumulation in adipose tissue by decreasing the expressions of lipogenesis genes and increasing the expressions of lipidolysis related genes, including thermogenic and mitochondrial functional genes. Moreover, LYC improved HFFD-induced insulin resistance in WATs via inhibiting the inflammation responses in WATs, decreasing circulating proinflammatory cytokines, suppressing gut leak and intestinal inflammation. Our study indicating that the supplementation of LYC might be a nutritional preventive strategy to combat obesity.

Anti-Fatigue Activity of Aqueous Extracts of Sonchus arvensis L. in Exercise Trained Mice.

Sonchus arvensis L. is a nutritious vegetable and herbal medicine that is consumed worldwide. The aim of this study was to evaluate the anti-fatigue effects and underlying effects of aqueous extract of Sonchus arvensis L. (SA). Male C57BL/6 mice from four groups designated vehicle, exercise, exercise with low dose (250 mg/kg) or high dose of SA (500 mg/kg), were trained by swimming exercise and orally administrated with SA every other day for 28 days. The anti-fatigue activity was determined by exhaustive swimming test, as well as the muscle structure, levels of blood hemoglobin, and metabolites including lactate and urea nitrogen. SA alleviated mice fatigue behaviors by eliminating metabolites, while improving muscle structure and hemoglobin levels. Moreover, SA enhanced glycogen synthesis of liver but not muscle via increasing GCK and PEPCK gene expressions. Importantly, SA improved antioxidant enzymes expression and activities in both liver and muscle, which was possibly related to its primary components polysaccharides and the antioxidant components including chlorogenic acid, luteolin, and chicoric acid. Taken together, the anti-fatigue effects of SA could be partly explained by its antioxidant activity and mediating effects on glycogen synthesis and metabolites elimination. Therefore, SA could be a potential nutraceutical for improving exercise performance and alleviating physical fatigue.

Lycopene ameliorates systemic inflammation-induced synaptic dysfunction via improving insulin resistance and mitochondrial dysfunction in the liver-brain axis.

Systemic inflammation is an important determinant of synaptic dysfunction, but the underlying molecular mechanisms remain elusive. Lycopene (LYC), a major carotenoid present in tomato, is regarded as a nutraceutical that has significant antioxidant and anti-obesity bioactivities. In the current study, we randomly divided 3-month-old C57BL/6J mice into 3 groups: the control, LPS and LPS + LYC groups (LYC, 0.03% w/w, mixed with normal chow) for 5 weeks, and then mice were intraperitoneally injected with LPS (0.25 mg kg-1) for 9 days. Our results demonstrated that LYC supplementation effectively attenuated LPS-elicited neuronal damage and synaptic dysfunction through increasing the expressions of neurotrophic factors and the synaptic proteins SNAP-25 and PSD-95. LYC ameliorated LPS-induced insulin resistance and mitochondrial dysfunction in the mouse brain and liver. LYC alleviated the neuroinflammation and hepatic inflammation. Furthermore, LYC decreased the circulating levels of insulin and proinflammatory mediators LPS, TNF-α, IL-1ß and IL-6. In conclusion, these results indicated that the supplementation of LYC might be a nutritional preventive strategy in systemic inflammation-induced synaptic dysfunction.

Lycopene Supplementation Attenuates Oxidative Stress, Neuroinflammation, and Cognitive Impairment in Aged CD-1 Mice.

The carotenoid pigment lycopene (LYC) possesses several properties, including antioxidative, anti-inflammatory, and neuroprotective properties. This study examined the effects of dietary supplementation with LYC on age-induced cognitive impairment, and the potential underlying mechanisms. Behavioral tests revealed that chronic LYC supplementation alleviated age-associated memory loss and cognitive defects. Histological and immunofluorescence-staining results indicated that LYC treatment reversed age-associated neuronal damage and synaptic dysfunctions in the brain. Additionally, LYC supplementation decreased age-associated oxidative stress via suppression of malondialdehyde levels, which increased glutathione, catalase, and superoxide dismutase activities and the levels of antioxidant-enzyme mRNAs, including those of heme oxygenase 1 and NAD-(P)-H-quinone oxidoreductase-1. Furthermore, LYC supplementation significantly reduced age-associated neuroinflammation by inhibiting microgliosis (Iba-1) and downregulating related inflammatory mediators. Moreover, LYC lowered the accumulation of Aß1-42 in the brains of aged CD-1 mice. Therefore, LYC has the potential for use in the treatment of several age-associated chronic diseases.

Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress.

Neuroinflammation is documented to be the major culprit of Alzheimer's disease. Lycopene (LYC), a fat soluble carotenoid, exhibits neuroprotective function in several neurodegenerative disorders. However, the effects of LYC to countering systemic inflammation-induced amyloidogenesis and memory deficiency remain to be elucidated. In current study, 3-month-old male C57BL/6J mice were treated with 0.03% LYC (w/w, mixed into normal chow) for 5 weeks. The mice were then treated by intraperitoneal injection of LPS (0.25mg/kg) for 9 days. It was found that LYC inhibited LPS-induced memory loss by behavior tests including Y-maze test and Morris water test. Meanwhile, LYC prevented LPS-induced accumulation of Aß, levels of amyloid precursor protein (APP), and suppressed neuronal ß-secretase BACE1 and elevated the expressions of α-secretase ADAM10. Furthermore, LYC down-regulated the expression of IBA-1 (a marker of microglia activation), reduced the levels of inflammatory mediators and inhibited oxidative stress in LPS-treated mice. Moreover, LYC suppressed the phosphorylation of MAPKs, NFκB, and activated Nrf2 signaling pathways in LPS-treated BV2 microglial cells. Therefore, our study indicated that LYC could ameliorate LPS-induced neuroinflammation, oxidative stress, amyloidogenesis and cognitive impairments possibly through mediating MAPKs, NFκB and Nrf2 signaling pathways, indicating that LYC might be a nutritional preventive strategy in neuroinflammation-related diseases such as AD.