Apocynum venetum is a traditional medicine that is rich in polyphenols. Apocynum venetum polyphenol extract (AVP) contains the active substances neochlorogenic acid, chlorogenic acid, rutin, isoquercitrin, astragaloside and rosmarinic acid. In the present study, the preventive effect of AVP against D-galactose-induced oxidative stress was studied in a mouse model. The sera, skin, livers and spleens of mice were examined using hematoxylin and eosin staining, reverse transcription-quantitative PCR and western blot analysis. The biochemical results showed that AVP improved the thymus, brain, heart, liver, spleen and kidney indices in a mouse model of oxidative stress. AVP was also able to reverse the reduction in levels of superoxide dismutase (SOD), glutathione peroxidase and glutathione, and increased the levels of nitric oxide and malondialdehyde identified in the serum, liver, spleen and brain of mice exposed to oxidative stress. Pathological observations confirmed that AVP could inhibit oxidative damage to the skin, liver and spleen of mice caused by D-galactose. Further molecular biological experiments also demonstrated that AVP increased the expression of neuronal nitric oxide synthase, endothelial nitric oxide synthase, Cu/Zn-SOD, Mn-SOD, catalase, heme oxygenase-1, nuclear factor-erythroid 2-related factor 2, γ-glutamylcysteine synthetase and NAD(P)H quinone dehydrogenase 1 and reduced the expression of inducible nitric oxide synthase in the liver and spleen of treated mice compared to controls. Notably, the preventive effect of AVP against D-galactose-induced oxidative damage in mice was better than that of the confirmed antioxidant vitamin C. In conclusion, AVP exhibited an antioxidant effect and the AVP-rich Apocynum venetum may be considered a plant resource with potential antioxidative benefits.

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Vascular cognitive impairment (VCI) has emerged as the second major disease responsible for dementia, and there is still a lack of effective treatment methods for this disorder to date. Clinical medications have found that Yisui Fuyongtang (YSFYT) Decoction is effective in improving neurological signs and learning-memory functions in patients who develop white matter lesions and whole brain atrophy. To clarify the effect and molecular regulation mechanism of YSFYT Decoction on model rats, this research analyzed the influence of YSFYT Decoction on the learning-memory ability and lipid metabolism of rats based on behavioral and biochemical analysis. Further pathology and protein detection methods were adopted to investigate the action of YSFYT Decoction on the neurons in the hippocampus of model rats and the regulation of the brain derived neurotrophic factor (BDNF)-tyrosine protein kinase receptor B (TrkB) signaling pathway. Compared with the VCI group, after YSFYT Decoction administration, the ratio of swimming time in the platform, number of crossing the platform, number of active avoidance, and proportion of active avoidance of the rats were markedly increased, whereas the response latency was substantially reduced ( p < 0.05 ). Biochemical tests indicated that contents of lipoprotein lipase (LPL), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) of the model rats in YSFYT Decoction treatment group were greatly reduced, whereas those of total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-PX), catalase (CAT), malondialdehyde (MDA), and superoxide dismutase (SOD) were elevated ( p < 0.05 ). Additionally, Bcl-2 expression in YSFYT Decoction treatment group was significantly increased, but neuron apoptosis of the hippocampus tissue was reduced. Meanwhile, neuron number was apparently higher than that in VCI model group. Following Yisui Decoction treatment, expressions of growth-associated protein 43 (GAP43), synaptophysin (SYP), postsynaptic density 95 (PSD95), NMDAR subunit 2B (NR2B), BDNF, TrkB, phospho-mitogen-activated protein kinase (p-MAPK), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3-kinase (PI3K), and phospho-protein kinase B (p-AKT) were markedly elevated. Taken together, YSFYT Decoction could activate the BDNF-TrkB signaling pathway, elevate Bcl-2 expression, and minimize neuronal apoptosis in hippocampus, thereby improving the behavioral characteristics and biochemical indicators of the VCI rat model.

Depression, a sort of common psychological disorder, is a serious hazard to people’s health and social progress. Conventional clinical means for this disorder nowadays are mostly chemical medicine treatments accompanied by psychological counseling. Chinese application of using TCM to treat mental diseases like depression could be traced from hundreds of years ago, in comparison to the long-term depression course and the chemical medicine administration demerits like side effects and resistance, traditional Chinese medicines are milder, more lasting, stable and are the optimal choice for perennial depression treatment. This study was committed to making a comprehensive investigation of Changyu Daotan Decoction’s efficacy in the depression mice model, and it turned out that the Changyu Daotan Decoction was capable of restoring the hippocampus of the depression mice and altering the expressions of neurotrophic factors (the expressions of β-Catenin, cyclin D1 and in GSK-3β BDNF, GFAP, NGF, and Wnt signaling pathways). Results of metabonomics analysis showed that the contents of GABA, His, Tyr, Trp, PA, and 5-HIAA in the mice of the Changyu Daotan Decoction group were restored after administration and showed a conspicuous relevance with the metabolic.

This study clarified the regulatory effect of Yisui multipurpose Soup towards D-galactose-induced cognitive impairment cell model on the molecular level. We first constructed and cultured the cell model of cognitive impairment induced by D-galactose in neurons in vitro and then cultured the cells in the medium supplemented with different doses of drug-containing serum of Yisui multipurpose soup. Expressions of inflammatory cytokine tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), nitric oxide (NO), and interleukin-1β (IL-1β) were assessed by the ELISA and western blot, and cell apoptosis was determined by flow cytometry and TUNEL. The expression changes of apoptosis-related proteins Bcl-2 and Bax were estimated by immunofluorescence, qPCR, and western blot. Finally, we analyzed and made the network interaction diagram of Yisui multipurpose soup-components-targets through the network pharmacology method, from which we could learn that there were 1104 gene targets related to vascular cognitive impairment (VCI) and 1071 component targets of Yisui multipurpose soup. And there were 251 overlapping genes, mainly gathering in protein binding, protein modification, MAPK signaling pathway, and calcium signaling pathway. The expressions of TNF-α, iNOS, NO, and IL-1β were significantly decreased after the culture medium was replaced by medium containing drug serum. We also found that the effect of high-dose drug-containing serum on the expression of inflammatory factors was better than that of low dose. The Yisui multipurpose soup drug serum in the medium not only significantly increased Bcl-2 expression and effectively reduced Bax expression, but also inhibited the apoptosis of neurons induced by D-galactose. In conclusion, Yisui multipurpose soup could effectively protect D-galactose-induced neuronal cell cognitive impairment by orchestrating expressions of the inflammatory factors TNF-α, iNOS, NO, and IL-1β and the apoptosis-related proteins Bcl-2 and Bax.