Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment.

Pesticides are the most effective way to control diseases, insects, weeds, and fungi. The central nervous system (CNS) is damaged by pesticide residues in various ways. By consulting relevant databases, the systemic relationships between the possible mechanisms of pesticides damage to the CNS causing cognitive impairment and related learning and memory pathways networks, as well as the structure-activity relationships between some natural substances (such as polyphenols and vitamins) and the improvement were summarized in this article. The mechanisms of cognitive impairment caused by pesticides are closely related. For example, oxidative stress, mitochondrial dysfunction, and neuroinflammation can constitute three feedback loops that interact and restrict each other. The mechanisms of neurotransmitter abnormalities and intestinal dysfunction also play an important role. The connection between pathways is complex. NMDAR, PI3K/Akt, MAPK, Keap1/Nrf2/ARE, and NF-κB pathways can be connected into a pathway network by targets such as Ras, Akt, and IKK. The reasons for the improvement of natural substances are related to their specific structure, such as polyphenols with different hydroxyl groups. This review's purpose is to lay a foundation for exploring and developing more natural substances that can effectively improve the cognitive impairment caused by pesticides.

Malvidin and its derivatives exhibit antioxidant properties by inhibiting MAPK signaling pathways to reduce endoplasmic reticulum stress in ARPE-19 cells.

Malvidin (MV) and its derivatives, such as malvidin-3-O-guaiacol (Mv3C) and malvidin-3-O-6-(acrylic acid-(2-hydroxy,4-carboxy-cyclohexanol)ester)-guaiacol (Mv3ACEC), are natural compounds with antioxidant properties. However, the basic mechanisms underlying their functional activities are unclear. In this study, we show that MV, Mv3C, and Mv3ACEC inhibit reactive oxygen species production and malondialdehyde content, promote glutathione peroxidase activity, and increase superoxide dismutase levels in ARPE-19 cells treated with H2O2. Western blotting and immunofluorescence analysis revealed that MV, Mv3C, and Mv3ACEC regulate mitogen-activated protein kinase signal transduction pathways related to endoplasmic reticulum stress. Interestingly, Mv3C and Mv3ACEC showed greater beneficial properties than MV. Our results show that MV and its derivatives have potential as therapeutic compounds for ocular diseases associated with oxidative stress, such as age-related macular degeneration.

Cordycepin alleviates hepatic lipid accumulation by inducing protective autophagy via PKA/mTOR pathway.

As the major active ingredient of Cordyceps militaris, cordycepin (3'-deoxyadenosine) has been well documented to possess lipid-lowering and anti-oxidative activities, making it a promising candidate for treatment of NAFLD. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, this study aims to elucidate the mechanism of cordycepin regulating autophagy and lipid metabolism. Here, we found that cordycepin decreased palmitate-induced lipid accumulation by Oil Red O staining, Nile Red staining assays, triglyceride and total cholesterol measurements. Based on Western blot assay and immunocytochemistry, we found that cordycepin induced autophagy in PA-induced steatotic HepG2 cells. Whereas pretreatment with CQ, an autophagy inhibitor, substantially deteriorated the mitigative effects of cordycepin on PA-induced hepatic lipid accumulation. These data taken together indicate that cordycepin protects against PA-induced hepatic lipid accumulation via autophagy induction. Further, cordycepin remarkably increased the expression of P-PKA and decreased P-mTOR, whereas pretreatment with H89, a PKA inhibitor, abolished the ability of cordycepin to activate autophagy via mTOR activation. These data suggested that cordycepin protects against PA-induced hepatic lipid accumulation through the promotion of autophagy. The underlying mechanism might be associated with the PKA/mTOR pathway.

Biotransformation of anthocyanins from Vitis amurensis Rupr of "Beibinghong" extract by human intestinal microbiota.

1. Anthocyanins (ACNs) are a subclass of polyphenolic pigments belonging to the flavonoids and constitute an important group of human diets. There is accumulated evidence that consumption of ACN-rich diets such as Vitis amurensis Rupr of "Beibinghong" exerts protective activities against some human diseases. These beneficial properties may be due to the biotransformation by intestinal microbiota and its related bacterial dependent metabolism of ACNs. However, despite the compositional characterization of ACNs in extracts from V. amurensis Rupr, the biotransformation pathways of these compounds in the human intestinal tract have not been investigated so far. 2. In this study, the biotransformation of ACNs by the human intestinal microbiota and the derived metabolites were analyzed and characterized by RRLC-Q-TOF-MS and MS/MS methods. Eight kinds of ACNs were identified and could be bio-transformed under the action of human intestinal microbiota. The biotransformation pathway analysis showed that the microbiota acted by removing all glucosides to produce the corresponding aglycones, which were subsequently converted to phenolic acid and aldehydes. 3. These findings shed light on the mechanisms of ACNs degradation by the human intestinal microbiota and will lay a foundation for the industrial and pharmacological applications of the ACNs.