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).

Research Progress in Heterologous Crocin Production.

Crocin is one of the most valuable components of the Chinese medicinal plant Crocus sativus and is widely used in the food, cosmetics, and pharmaceutical industries. Traditional planting of C. sativus is unable to fulfill the increasing demand for crocin in the global market, however, such that researchers have turned their attention to the heterologous production of crocin in a variety of hosts. At present, there are reports of successful heterologous production of crocin in Escherichia coli, Saccharomyces cerevisiae, microalgae, and plants that do not naturally produce crocin. Of these, the microalga Dunaliella salina, which produces high levels of ß-carotene, the substrate for crocin biosynthesis, is worthy of attention. This article describes the biosynthesis of crocin, compares the features of each heterologous host, and clarifies the requirements for efficient production of crocin in microalgae.

CsAAP7.2 is involved in the uptake of amino acids from soil and the long-distance transport of theanine in tea plants (Camellia sinensis L.).

Tea plant roots can uptake both inorganic nitrogen (NH4+ and NO3-) and organic nitrogen (amino acids) from the soil. These amino acids are subsequently assimilated into theanine and transported to young shoots through the xylem. Our previous study showed that CsLHT1 and CsLHT6 transporters take up amino acids from the soil, and CsAAPs participate in the transport of theanine. However, whether other amino acid transporters are involved in this process remains unknown. In this study, we identified two new CsAAPs homologous to CsAAP7, named CsAAP7.1 and CsAAP7.2. Heterologous expression of CsAAP7.1 and CsAAP7.2 in the yeast mutant 22Δ10α showed that CsAAP7.2 had the capacity to transport theanine and other amino acids, whereas CsAAP7.1 had no transport activity. Transient expression of the CsAAP7.2-GFP fusion protein in tobacco leaf epidermal cells confirmed its localization to the endoplasmic reticulum. Tissue-specific analysis showed that CsAAP7.2 was highly expressed in roots and stems. In addition, CsAAP7.2 overexpression lines were more sensitive to high concentrations of theanine due to the high accumulation of theanine in seedlings. Taken together, these findings suggested that CsAAP7.2 plays an important role in the uptake of amino acids from soil and the long-distance transport of theanine. These results provide valuable tools for nitrogen nutrition studies and enrich our understanding of theanine transport in tea plants.

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.

Transcutaneous Electrical Acupoint Stimulation Ameliorates Cognitive Function through PINK1/Parkin Mediated Mitophagy in VD Rats.

In this study, we investigated whether transcutaneous electrical acupoint stimulation (TEAS) could improve cognitive function in VD rats by regulating PINK1/Parkin-mediated mitophagy. VD rat model was prepared by modified 2-vessel occlusion (2-VO) and randomly divided into four groups: Sham group (Sham), Model group (Model), TEAS group (TEAS), and TEAS + 3-MA group (T +3 -MA). In the T +3 -MA group, autophagy inhibitor (3-MA) was injected into the lateral ventricle. After modeling, Y maze (YM), new object recognition test (NORT), Morris water maze (MWM), immunofluorescence, and Western blot were used to observe the effects of TEAS on VD rats. Behavioral experiments revealed that TEAS effectively improved the learning and memory ability of VD rats. Immunofluorescence results showed that TEAS could upregulate LC3 expression. Western blot results showed that TEAS upregulated the expression of PINK1, Parkin, and LC3-II, and downregulated the expression of LC3-I and p62 in VD rats. T +3 -MA group shows the opposite trend to TEAS group. This study demonstrates that TEAS ameliorates cognitive function through PINK1/Parkin-mediated mitophagy in VD rats.

Danggui Buxue decoction ameliorates lipid metabolic defects involved in the initiation of diabetic atherosclerosis; identification of active compounds.

OBJECTIVE: To determine the constituent compounds of Danggui buxue decoction (DBD) involved and the potential mechanisms mediating its effects, with specific reference to lipids playing a role in the initiation of diabetic atherosclerosis. METHODS: Liquid chromatography-tandem mass spectrometry was used to identify and quantify the absorbed bioactive compounds (ABCs) present in DBD. Goto-Kakizaki (GK) rats were randomly allocated to a diabetes atherosclerosis (DA) group, a DBD group, and an ABC group (10 per group), which were all high-fat diet-fed. The treated rats were administered DBD (4 g/kg) or ABCs (in amounts equal to those present in DBD) once daily for 28 d, and a control group of Wistar rats were administered vehicle. Body mass gain, fasting blood glucose, and homeostasis assessment of insulin resistance (HOMA- IR) were measured. Serum triglyceride (TG), cholesterol (CHOL), high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL- C) and tumor necrosis factor-α (TNF-α) concentrations were determined. Hematoxylin and eosin staining and microscopy were used to characterize the abdominal aorta and the expression of lipogenic genes was quantified in this vessel. RESULTS: Seven ABCs were identified in rat serum: ferulic acid, formononetin, calycosin, astragaloside, caffeic acid, ligustilide, and butyphthalide. DBD significantly reduced HOMA-IR, the serum concentrations of TG, CHOL, and LDL-C, and the expression of the lipogenic genes monocyte chemotactic protein 1, Fas, intercellular adhesion molecule 1, and Cd36 in aorta; and significantly increased the mRNA expression of Scd1 in aorta. CONCLUSION: DBD affects lipid metabolism in the early stage of atherosclerosis in diabetic GK rats, with the mechanism likely involving the regulation of lipid metabolic genes in vessels. The contribution of ABCs to the effect of DBD on lipid metabolism was 24%-101%.

[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.

Nutrient retention by different substrates from an improved low impact development system.

The reuse of water in agriculture has become more common in water management worldwide. However, there is very limited information about nutrient retention in water reclamation management. In this study, an improved low impact development (LID) practice was constructed to investigate the synergistic effects of three substrates amendment on nitrogen (N) and phosphorus (P) retention under two irrigation modules: spray and drip irrigation. The orthogonal combination of the three substrates was controlled during four leaching events, with polyacrylamide (PAM), peat soil, and straw biochar application rates of 1, 2, and 4 g kg-1; 5, 10, and 20 g kg-1; and 10, 20, and 40 g kg-1, respectively. Results showed that the optimum treatments for N and P were 2 g kg-1 of PAM; 2 g kg-1 of PAM, 10 g kg-1 of peat soil, and 40 g kg-1 of straw biochar, respectively. The highest amounts of N and P retention under spray and drip irrigation were 83.12 mg N kg-1 and 50.09 mg N·kg-1, and 11.88 mg P·kg-1 and 7.47 mg P·kg-1, respectively. The analysis of variance indicated that PAM, biochar, and peat soil affected the retention of leachate, N, and P differently. PAM application could not only improve the water, N, P retention capacity of soil, but also significantly increase the content of ＞2 mm water-stable soil aggregate (WSA) (p＜0.05), and there is an advisable linear relation between N, P retention and the content of ＞2 mm WSA (R2 = 0.79, 0.67, respectively). Overall, this study concludes that a combined application of PAM and biochar could reduce P loss and increase the ＞2 mm WSA under leaching condition.

OsTSD2-mediated cell wall modification affects ion homeostasis and salt tolerance.

Salt stress is a major environmental threat to meeting the food demands of an increasing global population. The identification and exploitation of salt adaption mechanisms in plants are therefore vital for crop breeding. We here define the rice mutant (sstm1) whose salt sensitivity was unambiguously assigned to a single T-DNA insertion through segregational analysis following backcrossing to the wild type line. Insertion was within OsTSD2, which encoded a pectin methyltransferase. The sstm1 and allelic mutants, collectively known as tsd2, displayed higher content of Na+ and lower level of K+ in the shoot, which is likely to lead to reduced salt tolerance. Molecular analysis revealed reduced expression of the genes maintaining K+ /Na+ homeostasis in tsd2, including OsHKT1;5, OsSOS1, and OsKAT1. Furthermore, OsTSD2 influenced ion distribution between the hull and the rice seed, which could improve food safety with heavy metal pollution. Amino acid levels tended to be increased in tsd2 mutants, implicating a role of pectin in the regulation of metabolism. Taken together, we have demonstrated an important facet of salt tolerance, which implicated OsTSD2-mediated cell wall pectin modification as a key component that could be widely applied in crop science.

Effects of Angelicae Pubescentis and Loranthi Decotion on repairing knee joint cartilages in rats.

BACKGROUND: Knee osteoarthritis (KOA) is a common orthopedics disease and its pathological changes at early stage are the damage and loss of articular cartilage. Traditional Chinese medicine (TCM) prescription contains multiple components and has the unique advantages of the diversity of targets.We compared the traditional Chinese medical formulae (Angelicae Pubescentis and Loranthi decotion, APLD, or Duhuo Jisheng) with a western medicine (glucosamine sulfate, GS) to treat the rat arthritis models, and tracked the outcomes. METHODS: Thirty-two Wistar rats (weight 180 ± 10 g, 6-week-old) were randomly divided into four groups (eight for each): group A as normal control group (no surgery and no drug treatment), group B as SIA (surgery-induced arthritis) model control without drug treatment, group C as SIA model + APLD, and group D as SIA model + GS. Anterior cruciate ligament in the knee joint of both hind legs from each rat in groups B, C, and D was shown and cut off to establish the SIA model. After 6 weeks of the surgery, rats in group C or D were treated with APLD or GS, respectively, for 8 weeks. Bone X-ray examination, histological images, and determination of genes of collagen II and aggrecan were performed. At week 14, both knee joint gap and bone structure disappeared in rats of group B, but they were visible in rats of groups A, C, and D. RESULTS: Histological images revealed that the structure and composition of the knee joint cartilage were significantly degenerated in group B and improved in group C. Genes of collagen II and aggrecan were significantly increased in both group C and D. CONCLUSION: APLD or GS gavage treatment for knee osteoarthritis (KOA) rat models was effective on the proliferation of cartilage chondrocytes and the damaged knee joint tissue repairing, and the APLD showed slightly superior in general.

Antifungal curcumin promotes chitin accumulation associated with decreased virulence of Sporothrix schenckii.

Curcumin, a yellow polyphenol compound, is known to possess antifungal activity for a range of pathogenic fungi. However, the fungicidal mechanism of curcumin (CUR) has not been identified. We have occasionally found that chitin redistributes to the cell wall outer layer of Sporothrix schenckii (S. schenckii) upon sublethal CUR treatment. Whether CUR can affect chitin synthesis via the protein kinase C (PKC) signaling pathway has not been investigated. This study describes a direct fungicidal activity of CUR against S. schenckii demonstrated by the results of a checkerboard microdilution assay and, for the first time, a synergistic effect of CUR with terbinafine (TRB). Furthermore, the results of real-time PCR showed that sublethal CUR upregulated the transcription of PKC, chitin synthase1 (CHS1), and chitin synthase3 (CHS3) in S. schenckii. The fluorescence staining results using wheat germ agglutinin-fluorescein isothiocyanate (WGA-FITC) and calcofluor white (CFW) consistently showed that chitin exposure and total chitin content were increased on the conidial cell wall of S. schenckii by sublethal CUR treatment. A histopathological analysis of mice infected with CUR-treated conidia showed dampened inflammation in the local lesion and a reduced fungal burden. The ELISA results showed proinflammatory cytokine secretion at an early stage from macrophages stimulated by the CUR-treated conidia. The present data led to the conclusion that CUR is a potential antifungal agent and that its fungicidal mechanism may involve chitin accumulation on the cell wall of S. schenckii, which is associated with decreased virulence in infected mice.