Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract. AIM OF THE STUDY: The pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice. MATERIALS AND METHODS: To determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE-/- mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis. RESULTS: The main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium_IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria. CONCLUSION: BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels).

Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson's Disease Models of Caenorhabditis elegans.

Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson's disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of PIII-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a-6j). The antioxidant potential of the compounds was evaluated both by ABTS and ORAC methods. Among these newly synthesized melatonin derivatives, 6a showed significantly higher activity than MT at 10-5 M. In the transgenic Caenorhabditis elegans model of PD, 6a significantly reduces alpha-synuclein aggregation and dopaminergic neuronal damage in nematodes while reducing intracellular ROS levels and recovers behavioral dysfunction induced by dopaminergic neurodegeneration. Further study of the mechanism of action of this compound can provide new therapeutic ideas and treatment strategies for PD.

[Response of Soil Respiration and Its Components to Nitrogen and Phosphorus Addition in Farming-Withdrawn Grassland in the Semiarid Loess Hilly-Gully Region].

Understanding the soil respiration characteristics in response to nitrogen and phosphorus addition in farming-withdrawn grasslands within semi-arid loess hilly-gully regions is of great importance for providing a theoretical basis for evaluating the effects of artificial regulation approaches on carbon cycling. We report on a field experiment that was undertaken from May to September 2018 in a farming-withdrawn grassland ecosystem in China, which is dominated by Stipa bungeana and Lespedeza davurica. Three different levels of nitrogen and phosphorus additions were used, including three main plots of N[0, 50, and 100 kg·(hm2·a)-1] and three subplots of P (P2O5)[0,40, and 80 kg·(hm2·a)-1]. The soil respiration rate, heterotrophic respiration rate, soil temperature, and soil moisture were measured monthly in each treatment. Results showed that N and P addition had no effect on soil temperature or moisture content (P>0.05). The soil respiration rate showed an obvious monthly variation and peaked in July. In the treatment without fertilizer addition, the monthly mean soil respiration rate, heterotrophic respiration rate, and autotrophic respiration rate were 0.69, 0.39, and 0.29 g·(m2·h)-1, respectively. P addition had no significant effect on the soil respiration rate and its components without N addition (P>0.05). Under conditions of N addition, P addition significantly increased the soil respiration rate and its component (P<0.05). The monthly mean soil respiration rate, heterotrophic respiration rate, and autotrophic respiration rate were 0.93, 0.50, and 0.47 g·(m2·h)-1, respectively. The Q10 (i.e., temperature sensitivity) values for soil respiration, heterotrophic respiration, and autotrophic respiration in unfertilized soil were 1.86, 2.36, and 2.24, respectively. The addition of N and P reduced the Q10 value of soil respiration and its components. Our findings suggest that the response of soil respiration and its two components to N and P addition in studied farming-withdrawn grassland in the semiarid loess hilly-gully region were closely related to their addition amounts.

[Responses of leaf functional traits of dominant plant species in grassland communities to nitrogen and phosphorus addition in loess hilly-gully region.] / é»„åœŸä¸˜é™µåŒºè‰åœ°æ¤è¢«ç¾¤è½ä¼˜åŠ¿ç§å¶ç‰‡åŠŸèƒ½æ€§çŠ¶å¯¹æ°®ç£·æ·»åŠ çš„å“åº”.

To analyze plant functional traits of dominant species to nitrogen and phosphorus addition, three species (Bothriochloa ischaemum, Stipa bungeana, and Lespedeza davurica) were selected in the loess hilly-gully region. A split-plot experiment which included three N treatments (0, 50, and 100 kg N·hm-2·a-1) and three P treatments (0, 40, and 80 kg P2O5·hm-2·a-1) was conducted. At the fast-growing stage, leaf length, leaf width, specific leaf area, leaf dry matter content, leaf N content, leaf P content, and leaf N:P were measured. Results showed that under 50 and 100 kg N·hm-2·a-1 treatments, leaf length and width of B. ischaemum increased significantly by 35.3% and 64.4%, respectively, while only the leaf length of S. bungeana and the leaf width of L. davurica increased significantly by 58.8% and 33.9%, respectively. Leaf dry matter content of the three species decreased significantly by 10.7%, 15.3% and 11.2%, respectively. Leaf N content and N:P of B. ischaemum and S. bungeana increased significantly by 23.0% and 99.2%, 45.8% and 96.9%, respectively, compared with unfertilized treatments. Under 40 and 80 kg P2O5·hm-2·a-1 treatments, leaf length, leaf width and specific leaf area of L. davurica increased significantly by 56.9%, 41.4% and 19.6%, respectively, while leaf dry matter content decreased significantly by 14.9%. Leaf P content of three species increased significantly by 96.7%, 110.9% and 238.4%, while the N:P decreased significantly by 45.8%, 42.8% and 53.7%, respectively, compared with those under unfertilized. Under 50 kg N·hm-2·a-1 treatment, compared with no P application, leaf length and leaf width of L. davurica and leaf P content of the three species significantly increased, and leaf N content of B. ischaemum and S. bungeana decreased significantly at 40 and 80 kg P2O5·hm-2·a-1 treatments. Under 100 kg N·hm-2·a-1 treatment, leaf length of B. ischaemum and S. bungeana, leaf width of L. davurica and leaf P content of three species significantly increased, while leaf N content of B. ischaemum decreased significantly after P application. In summary, functional traits of dominant species showed significant responses to short-term nitrogen and phosphorus addition, with the different responses were mainly related to species traits and fertilization levels. Such difference reflected plant adaptation to habitat changes. The divergent responses of different species to nitrogen and phosphorus addition played an important role in maintaining diversity and stability of grassland communities.

Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE-/- mice via anti-inflammatory and BDNF-TrkB pathway.

The comorbidity of coronary heart disease (CHD) and depression in patients is extremely prevalent, with a rate from 20 to 50%, while depression-like behaviors exist in a larger percentage of patients. Therefore, the study of comorbidities is particularly urgent. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine formula, has been used to treat CHD with depression for hundreds of years. However, the mechanism of its action on comorbidities remains unclear. Here, we focused on the behavioral changes in ApoE-/- mice fed a high-fat diet (HFD) and elucidated the mechanism of CSS and its main absorbed component, meranzin hydrate (MH), as an anti-atherosclerosis and anti-depression agent. In the present study, mice were fed an HFD for 16 weeks and were intragastrically administered high and low doses of CSS and MH. Depressive-like behaviors were evaluated by the sucrose preference test, the open-field test, the light-dark test and the tail-suspension test, after which atherosclerotic plaques, plasma lipids, inflammatory cytokine levels and the expression of BDNF/TrkB were measured. We demonstrated that the atherosclerosis model group exhibited significant depressant behaviors. Moreover, CSS inhibited depressive-like behavioral changes, reduced atherosclerotic plaque areas, plasma total cholesterol, triglycerides, LDL-cholesterol levels and inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in plasma and hippocampi, increased the protein and mRNA expression of BDNF and TrkB in the aorta and the hippocampus. Interestingly, MH, the main component in CSS that is absorbed in the plasma and hippocampus, exerted effects similar to those of CSS. In addition, MH increased the protein and mRNA expression of BDNF and TrkB in human umbilical vein endothelial cells (HUVECs) induced by LPS. Collectively, these results suggest that MH represents the CSS decoction, induces anti-atherosclerosis effects and improves depression-like behaviors in HFD-fed ApoE-/- mice. Moreover, the regulation of proinflammatory factors and BDNF-TrkB signaling are possibly involved in this process. Our findings indicate that MH is a potential phytochemical compound for the prevention of the comorbidity of atherosclerosis and depression.