ABSTRACT
Fu Brick tea belongs to fermented dark tea, which is one of the six categories of tea. Fu Brick tea has been reported to reduce adiposity and has beneficial effects in the treatment of hypercholesterolemia and cardiovascular disease. Theabrownin (TB) is one of the pigments with the most abundant content in Fu Brick tea. TB has also been reported to have lipid-lowering effects, but its mechanism remains unclear. We found that TB could effectively reduce the insulin resistance and fat deposition induced by a high fat diet (HFD), decrease inflammation in the liver, improve intestinal integrity, and reduce endotoxins in circulation. Further studies showed that TB increased the abundance of Verrucomicrobiota and reduced the abundance of Firmicutes and Desulfobacterota in the intestinal tract of obese mice. The alteration of gut microbiota is closely linked to the metabolic phenotype after TB treatment through correlation analysis. Moreover, TB changed the gut microbial metabolites including L-ornithine, α-ketoglutarate, and glutamine, which have also been found to be upregulated in the liver after TB intervention. In vitro, L-ornithine, α-ketoglutarate, or glutamine significantly reduced lipopolysaccharide (LPS)-induced inflammation in macrophages. Therefore, our results suggest that TB can reduce adiposity, systemic insulin resistance, and liver inflammation induced by a HFD through altering gut microbiota and improving the intestinal tight junction integrity. The metabolites of gut microbiota might also play a role in ameliorating the HFD-induced phenotype by TB.
Subject(s)
Fatty Liver , Gastrointestinal Microbiome , Inflammation , Insulin Resistance , Mice, Inbred C57BL , Tea , Animals , Male , Mice , Catechin/pharmacology , Diet, High-Fat/adverse effects , Fatty Liver/drug therapy , Fatty Liver/metabolism , Gastrointestinal Microbiome/drug effects , Inflammation/drug therapy , Inflammation/metabolism , Liver/metabolism , Liver/drug effects , Tea/chemistryABSTRACT
Saussurea costus, a perennial herb belonging to the Asteraceae family, is a vital ingredient in traditional Chinese medicine. Increased demands for the herb have led to its widespread cultivation in China, but the corresponding increase in pesticide use has raised concerns about pesticide residues. Such residues would affect the safety and global market potential of Saussurea costus. Thus, a simple method is crucial to detect pesticide residues. The QuEChERS technique, in combination with gas chromatography-tandem mass spectrometry (GC-MS/MS), is commonly used for residue detection. However, traditional adsorbents may be unable to purify complex herbal mixtures well, affecting accuracy and instrument performance. Choosing suitable purification materials for Saussurea costus samples with complex matrices is of significant importance. This study focused on the detection of 35 prohibited pesticides in Saussurea costus. A rapid detection method was established by combining the QuEChERS technique with GC-MS/MS and utilizing a combination of multiwalled carbon nanotubes (MWCNTs), octadecylsilane-bonded silica gel (C18), and anhydrous magnesium sulfate (MgSO4) as the purification adsorbent. The samples were extracted with acetonitrile, purified by an improved QuEChERS process, subjected to GC-MS/MS analysis in multiple reaction monitoring (MRM) mode, and quantified using the internal standard method. The purification effects of four materials (C18, MWCNTs, N-propyl ethylenediamine (PSA), and graphitized carbon black (GCB)) and their optimal dosages were investigated by considering the matrix characteristics of the samples. An orthogonal experimental design was employed to optimize the ratio of adsorbent combinations, and the optimal adsorbent combination was determined to be 450 mg of MgSO4, 400 mg of C18, and 50 mg of MWCNTs. Matrix effect (ME) evaluation of the S. costus matrix showed that 31 target compounds strongly exhibited matrix-enhancement effects. Thus, matrix-matched calibration was employed in this study. Methodological investigation revealed that the standard curves for the 35 pesticides exhibited good linearity, with correlation coefficients (r2) greater than 0.9970. The average recoveries at three spiked levels ranged from 69.6% to 126.9%, and the relative standard deviations (RSDs) for parallel groups were all less than 10%. The limits of detection (LODs) and quantification (LOQs) ranged from 0.2 to 5.4 µg/kg and from 0.6 to 18.1 µg/kg, respectively. The developed method was used to screen and detect 35 pesticide residues in 20 batches of S. costus samples, and the target compounds were detected in six batches. The proposed method is simple, sensitive, and accurate. Thus, it is suitable for the rapid screening and detection of the 35 pesticide residues in S. costus and provides technical support for the cultivation, production, and quality control of the herb.
Subject(s)
Nanotubes, Carbon , Pesticide Residues , Saussurea , Tandem Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/methods , Nanotubes, Carbon/analysis , Nanotubes, Carbon/chemistry , Pesticide Residues/analysisABSTRACT
The excellent comprehensive properties of microfiber synthetic leathers have led to their wide application in various aspects of our lives. However, the issue of flammability remains a significant challenge that needs to be addressed. Nowadays, the bio-based chemicals used in the flame-retardant materials have extremely grabbed our eyes. Herein, we developed an ecologically friendly flame-retardant microfiber synthetic leather using phosphorus-free layer-by-layer assembly technology (LBL) based on natural polysaccharide alginate (SA) coupled with polyethyleneimine (PEI) and 3-aminopropyltriethoxysilane (APTES). The effect of different LBL coating systems on the flame retardancy of microfiber synthetic leather was investigated. The results demonstrated that the introduction of APTES can completely inhibit the melt-dripping by enhancing char formation through silica elements. Furthermore, the trinary coating system consisting of SA/APTES/PEI exhibited excellent flame retardancy by combining gas-phase action from PEI and condensed-phase function from APTES. This modified microfiber synthetic leather showed a significantly higher limiting oxygen index (LOI) value of 33.0 % with no molten droplet. Additionally, the SA-based coating slightly suppressed the heat release, resulting in a 20 % reduction in total heat release during the combustion test. Overall, this work presents a facile and environmentally-friendly approach for achieving flame-retardant and anti-dripping microfiber synthetic leather.
Subject(s)
Alginates , Flame Retardants , Propylamines , Silanes , Epidermis , Eye , Phosphorus , PolyethyleneimineABSTRACT
To better elucidate the chemical constituents and evaluate the quality consistency of Chuanxiong dispensing granules (CDG), qualitative and quantitative analyses were performed in this study. Firstly, a high-performance liquid chromatography-diode array detector (HPLC-DAD) based fingerprint was constructed by 12 batches of CDGs from different manufacturers, in which 16 common peaks were assigned. Then, two of them were directionally isolated for structural elucidation. According to the nuclear magnetic resonance (NMR) and mass spectrometry (MS) spectra, 5,6-dihydrophthalic acid was identified as novel compound, and 8-O-4/8-O-4-dehydrotriferulic acid was firstly discovered in plant belonging to the genus Ligusticum. Secondly, a total of 46 components were detected in CDG using high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (HPLC-Q-TOF-MS), and 14 of them were unambiguously identified by comparing with reference standards. Additionally, a HPLC-DAD method was firstly established to quantify 10 characteristic peaks specified in the China National Standard of CDG, and the results revealed that ferulic acid (1.71 mg/g), chlorogenic acid (1.14 mg/g), 5,6-dihydrophthalic acid (1.13 mg/g), and senkyunolide I (1.13 mg/g) are the major components in CDGs. Chemometrics analyses suggested that phenolic acids are more important than phthalides in discrimination of CDGs from different manufacturers.
Subject(s)
Chemometrics , Drugs, Chinese Herbal , Mass Spectrometry , Drugs, Chinese Herbal/chemistry , Chromatography, High Pressure Liquid/methods , Reference StandardsABSTRACT
Electroacupuncture (EA) has been shown to enhance the recovery of symptoms in rheumatoid arthritis (RA); however, the underlying mechanism remains unclear. Both the pathogenesis of RA and the therapeutic effects of EA are closely associated with the metabolic activity of the brain. In this study, we investigated the effect of EA at the "Zusanli" acupoint (ST36) on a rat model of collagen-induced rheumatoid arthritis (CIA). The results demonstrated that EA effectively alleviated joint swelling, synovial hyperplasia, cartilage erosion, and bone destruction in CIA rats. Additionally, the metabolic kinetics study revealed a significant increase in the 13C enrichment of GABA2 and Glu4 in the midbrain of CIA rats treated with EA. Correlation network analysis showed that changes in Gln4 levels in the hippocampus were strongly associated with the severity of rheumatoid arthritis. Immunofluorescence staining of c-Fos in the midbrain's periaqueductal gray matter (PAG) and hippocampus demonstrated increased c-Fos expression in these regions following EA treatment. These findings suggest that GABAergic and glutamatergic neurons in the midbrain, along with astrocytes in the hippocampus, may play vital roles in the beneficial effects of EA on RA. Furthermore, the PAG and hippocampus brain regions hold potential as critical targets for future RA treatments. Overall, this study provides valuable insights into the specific mechanism of EA in treating RA by elucidating the perspective of cerebral metabolism.
Subject(s)
Arthritis, Rheumatoid , Electroacupuncture , Rats , Animals , Rats, Sprague-Dawley , Kinetics , Arthritis, Rheumatoid/therapy , Arthritis, Rheumatoid/chemically induced , Periaqueductal GrayABSTRACT
Carotenoids are powerful antioxidants that mediate transfer of electrons, directly affect abiotic stress responses in plants through regulating activity of antioxidant enzymes. ζ-Carotene desaturase (ZDS) is a key enzyme in carotenoid biosynthesis pathway, which can catalyze ζ-carotene to form lycopene to regulate carotenoid biosynthesis and accumulation. However, the mechanism of its regulation of saline-alkali stress remains unclear. In this research, based on transcriptomic analysis of Malus halliana with a apple rootstock, we screened out ZDS gene (LOC103451012), with significantly high expression by saline-alkali stress, whose expression in the leaves was 10.8-fold than that of the control (0 h) under 48 h of stress. Subsequently, the MhZDS gene was isolated from M. halliana, and transgenic Arabidopsis thaliana, tobacco, and apple calli were successfully obtained through agrobacterium-mediated genetic transformation. We found that overexpression of MhZDS enhanced the tolerance of A. thaliana, tobacco and apple calli under saline-alkali stress and caused a variety of physiological and biochemical changes: compared with wild-type, transgenic plants grew better under saline stress and MhZDS-OE lines showed higher chlorophyll content, POD, SOD, CAT activities and proline content, lower electrical conductivity and MDA content. These results indicate that MhZDS plays an important role in plant resistance to saline-alkali stress, providing excellent resistance genes for the regulatory network of salinity stress response in apples and provide a theoretical basis for the breeding of apple varieties with strong saline-alkali resistance. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01333-5.
ABSTRACT
Sympathetic neurons activate thermogenic adipocytes through release of catecholamine; however, the regulation of sympathetic innervation by thermogenic adipocytes is unclear. Here, we identify primary zinc ion (Zn) as a thermogenic adipocyte-secreted factor that promotes sympathetic innervation and thermogenesis in brown adipose tissue and subcutaneous white adipose tissue in male mice. Depleting thermogenic adipocytes or antagonizing ß3-adrenergic receptor on adipocytes impairs sympathetic innervation. In obesity, inflammation-induced upregulation of Zn chaperone protein metallothionein-2 decreases Zn secretion from thermogenic adipocytes and leads to decreased energy expenditure. Furthermore, Zn supplementation ameliorates obesity by promoting sympathetic neuron-induced thermogenesis, while sympathetic denervation abrogates this antiobesity effect. Thus, we have identified a positive feedback mechanism for the reciprocal regulation of thermogenic adipocytes and sympathetic neurons. This mechanism is important for adaptive thermogenesis and could serve as a potential target for the treatment of obesity.
Subject(s)
Adipocytes , Zinc , Male , Mice , Animals , Zinc/metabolism , Zinc/pharmacology , Adipocytes/metabolism , Adipose Tissue, Brown/metabolism , Thermogenesis , Obesity/metabolismABSTRACT
Strategies to increase carbon (C) sequestration in tea plantation soils are pertinent to mitigating global climate change, but little is known about the variation in C sequestration in soils planted with different tea varieties. In the current study, we collected 0-20 and 20-40 cm layer soil samples from a tea plantation planted with four tea varieties (Chuancha No.3 (CC3), Chuanmu No. 217 (CM217), Chuannong Huangyazao (CN), and C. sinensis 'Fuding Dabaicha' (FD)). Soil organic carbon (SOC) stock and composition in the bulk soil and aggregate fractions, as well as the SOC stability index (SI), were investigated. Both SOC stock and composition in the bulk soil or aggregate fractions were variable among the soils after planting different tea varieties. Overall, the highest SOC stock (0-40 cm) was observed in FD soil, followed by CN, CC3, and CM217 soil. This difference was dominated by the SOC stock associated with macroaggregates, and the highest macroaggregate-associated SOC stock was detected in FD soil in both soil layers. Moreover, FD soil showed the highest proportion of macroaggregates in both soil layers, accumulated the greatest recalcitrant organic carbon (ROC) and further contributed to the highest SI values of SOC associated with most aggregate fractions. In contrast, CN topsoil (0-20 cm) accumulated the greatest labile organic carbon (LOC) in most aggregate fractions, which had a positive correlation with the amount of C return by pruning litter. Ultimately, long-term planting of FD promoted macroaggregate formation, and ROC accumulation in aggregates greatly contributed to maintaining high C sequestration in the tea plantation soils and showed a high potential for future C budgets; in contrast, the tea plantation soil planted with CN could be a potential C source because of high C return.
Subject(s)
Carbon Sequestration , Soil , Carbon/analysis , Tea , ChinaABSTRACT
Background: Patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis are associated with poor clinical outcomes. N-acetylcysteine (NAC) is a widely used therapeutic option for such patients; however, the clinical efficacy of NAC has not been conclusively determined. We hypothesized that high-dose oral NAC can improve the clinical outcomes for patients with concurrent chronic bronchitis and COPD. Objective and Methods. This was a randomized, double-blind, placebo-controlled trial evaluating the efficacy of high-dose NAC for COPD patients with concurrent chronic bronchitis. Study participants were randomized into two groups and administered with NAC (900 mg) twice daily or matching placebo for 3 months. Then, respiratory health status was evaluated using the St. George's Respiratory Questionnaire (SGQR), which was set as the primary end point. Results: A total of 143 COPD patients with chronic bronchitis were screened, and as a result, only 100 patients were enrolled in this study (50 participants were randomized to receive placebo, and others were randomized to receive NAC). After treatment, differences in SGQR scores between the placebo and NAC groups were not significant. Moreover, differences in secondary end points between the two groups after treatment were insignificant. Discussion. High-dose NAC has no marked clinical benefits for COPD patients with concurrent chronic bronchitis.
Subject(s)
Bronchitis, Chronic , Pulmonary Disease, Chronic Obstructive , Acetylcysteine/adverse effects , Bronchitis, Chronic/chemically induced , Bronchitis, Chronic/drug therapy , Double-Blind Method , Humans , Surveys and QuestionnairesABSTRACT
Piptanthus nepalensis (Hooker) Sweet is a semi deciduous or deciduous shrub belonging to the genus Piptanthus, Leguminosae. P. nepalensis has been used as a folk medicinal herb in Nepal and was cultivated all over the world as an ornamental plant. In the present study, we sequenced the entire genome of the chloroplast of P. nepalensis. The total length of the chloroplast genome in P. nepalensis is 152,195 bp, including a large single-copy region of 82,048 bp, a small single-copy region of 17,675 bp, and a pair of inverted repeats regions of 26,236 bp. The overall guanine-cytosine (GC) content of the genome was 36.7%. There are 131 genes in the chloroplast genome of P. nepalensis, including 85 protein-coding genes, 8 rRNA genes and 38 tRNA genes. Phylogenetic analysis showed that P. nepalensis is closely related to Maackia floribunda.
ABSTRACT
Performance and molecular changes of an aerobic denitrifying phosphorus accumulating bacteria Pseudomonas psychrophila HA-2 have been investigated under different temperatures and ZnO nanoparticles (NPs) exposures. Strain HA-2 removed 95.7% of total nitrogen (TN) and 24.6% of phosphorus at 10 °C, which was attributed to the joint up-regulation of intracellular energy metabolism and ribosome. Moreover, with the increase of ZnO NPs from 0 to 100 mg/L, TN and phosphurs removal efficiencies decreased from 95.7% to 44.5% and 24.6% to 6.8% at 10 °C, respectively, whereas phosphorus removal rate increased from 10.5% to 24.5% at 20 °C. Further transcriptomics and proteomics revealed that significant down-regulation of purine and amino acid metabolisms was the main reason for the inhibitory effect at 10 °C, while the up-regulation of antioxidant pathways and functional genes expressions was responsible for the promoted phosphorus accumulation at 20 °C. This study provides a potential solution for improving biological nutrients removal processes in winter months.
Subject(s)
Nanoparticles , Zinc Oxide , Bacteria, Aerobic/metabolism , Bioreactors/microbiology , Denitrification , Nitrogen/metabolism , Phosphorus/metabolism , Pseudomonas/metabolism , Temperature , Zinc Oxide/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: As a typical heat-clearing prescription, Shaoyao decoction (SYD) has a robust function of clearing viscera heat for the treatment of several intestinal discomfort symptoms. Clinical evidence indicated that it had the potential to cure radiation enteritis. However, its underlying mechanisms remain unclear. AIM OF THE STUDY: The present study was designed to probe the protective effects and the involved mechanisms of SYD on X-ray radiation-induced enteritis of C57BL/6 mice. MATERIALS AND METHODS: X-ray irradiation were used to establish the radiation enteritis model. Forty-eight male C57BL/6 mice (20 ± 2 g) were randomly divided into six groups: the control group, model group, dexamethasone group (DEX, 0.12 mg/kg) and SYD groups (0.12, 0.24 and 0.36 g/mL), respectively. All mice (except the control group) were intragastrically administrated for a continuous 7 days. H&E and Masson staining were employed to evaluate the morphological and collagen fibers changes of the colon. ELISA was performed to assess the levels of MDA, SOD, COX, LPS, IL-6, IL-1ß and TNF-α in serum. Moreover, TUNEL fluorescence, western blot and qRT-PCR were used to detect the levels of apoptosis-related proteins and genes of Dclk-1, ATM, MRE-11, Bcl-2, Bax, Caspase-3, and Cyto-c. Furthermore, immunofluorescent staining was applied to detect the protein levels of p53 and Claudin-1 in colon. RESULTS: Treatment with SYD decreased the exfoliated and necrotic epithelial cells and prevent the proliferate from damaged fibrous tissue in the crypt layer of mucos. The levels of serum peroxidation and pro-inflammatory cytokines (MDA, COX, LPS, IL-6, IL-1ß and TNF-α) were obviously inhibited, while SOD sharply increased in serum after administration. Moreover, SYD can significantly ameliorate the apoptosis of colon cells, evidenced by the reduced positive expression of TUNEL staining. Meanwhile, the results of qRT-PCR and western blot demonstrated that SYD can dramatically stimulate the expression of genes and proteins Dclk-1, ATM and MRE-11, thus promoting the expression of mitochondrial pro-apoptotic proteins Bax, Caspase-3 and Cyto-c, while increasing the level of anti-apoptotic protein Bcl-2. Furthermore, immunofluorescence revealed that SYD can notably decreased the protein level of p53 while reverse the reduction of Claudin-1. CONCLUSIONS: These results indicated that radiation enteritis in C57BL/6 mice can be ameliorated by treatment with SYD. The potential protection mechanisms may be involved in ameliorating tissue fibrosis by decreasing inflammatory and apoptotic events.
Subject(s)
Enteritis , Tumor Necrosis Factor-alpha , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Apoptosis , Caspase 3 , Claudin-1 , Enteritis/drug therapy , Enteritis/etiology , Enteritis/prevention & control , Interleukin-6 , Lipopolysaccharides/pharmacology , Male , Mice , Mice, Inbred C57BL , Superoxide Dismutase , Tumor Necrosis Factor-alpha/pharmacology , Tumor Suppressor Protein p53 , X-Rays , bcl-2-Associated X ProteinABSTRACT
OBJECTIVE: To investigate the effect of seabuckthorn berries extract (SBE) on pulmonary vascular hyperpermeability in the mice model of acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Sixty Kunming mice were allocated into 6 groups by a random number table, including control, LPS, dexamethasone (Dex, 1 mg/kg), and 120, 240 and 480 mg/kg SBE groups, 10 mice in each group. Except the control group, mice were pre-treated with Dex and SBE, respectively, for 7 days before LPS was intraperitoneally injected to induce ALI. Pulmonary vascular hyperpermeability was evaluated by histopathologic observation and transvascular leakage determination. Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) levels in serum were measured using enzyme-linked immunosorbent assay. The expression of nuclear factor-kappa B (NF-κB) p65 in lung cells was determined by immunofluorescence analysis. The contents of cytoplasmic inhibitor of nuclear factor-κB kinase (IKK) and nuclear p65, as well as downstream proteins of E-selectin (CD62E) and intercellular adhesion molecule-1 (ICAM-1), were determined using Western blot analysis. RESULTS: Histopathological observation confirmed SBE treatment alleviated morphological lesion induced by LPS. Compared with the LPS group, 480 mg/kg SBE significantly decreased the water content of lung, Evans blue accumulation in lung tissue, and protein concentration and neutrophils count in bronchoalveolar lavage fluid (P<0.01); moreover, 480 mg/kg SBE significantly suppressed release of TNF-α and IL-6, and down-regulated expressions of IKK, nuclear p65, ICAM-1 and CD62E (P<0.01). CONCLUSION: SBE maintained alveolar-capillary barrier integrity under endotoxin challenge in mice by suppressing the key factors in the pathogenesis of ALI.
Subject(s)
Acute Lung Injury , Hippophae , Plant Extracts , Animals , Mice , Acute Lung Injury/chemically induced , Acute Lung Injury/drug therapy , Fruit/chemistry , Hippophae/chemistry , Intercellular Adhesion Molecule-1/metabolism , Interleukin-6/metabolism , Lipopolysaccharides , Lung/pathology , NF-kappa B/metabolism , Tumor Necrosis Factor-alpha/metabolism , Plant Extracts/therapeutic useABSTRACT
Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3ß as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3ß signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 µM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3ß. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3ß signaling pathway and restoring podocyte autophagy.
Subject(s)
Autophagy/drug effects , Diabetic Nephropathies/metabolism , Drug Delivery Systems/methods , Glycogen Synthase Kinase 3 beta/metabolism , Podocytes/drug effects , Spirostans/administration & dosage , Animals , Autophagy/physiology , Diabetic Nephropathies/drug therapy , Drugs, Chinese Herbal/administration & dosage , Male , Podocytes/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/physiologyABSTRACT
Silent information regulator 1 (Sirt1) is a deacetylase, which plays an important role in the occurrence and development of diabetic nephropathy (DN). Our previous study shows that Yin yang 1 (YY1), a widely expressed zinc finger DNA/RNA-binding transcription factor, is a novel regulator of renal fibrosis in diabetic nephropathy. Since the activity of YY1 is regulated via acetylation and deacetylation modification, this study aimed to explore whether Sirt1-induced deacetylation of YY1 mediated high glucose (HG)-induced renal tubular epithelial-mesenchymal transition (EMT) and renal fibrosis in vivo and in vitro. We first confirmed that Sirt1 expression level was significantly decreased in the kidney of db/db mice and in HG-treated HK-2 cells. Diabetes-induced Sirt1 reduction enhanced the level of YY1 acetylation and renal tubular EMT. Then, we manipulated Sirt1 expression in vivo and in vitro by injecting resveratrol (50 mg·kg-1·d-1. ip) to db/db mice for 2 weeks or application of SRT1720 (2.5 µM) in HG-treated HK-2 cells, we found that activation of Sirt1 reversed the renal tubular EMT and YY1 acetylation induced by HG condition. On the contrary, Sirt1 was knocked down in db/m mice or EX527 (1 µM) was added in HK-2 cells, we found that inhibition of Sirt1 exacerbated renal fibrosis in diabetic mice and enhanced level of YY1 acetylation in HK-2 cells. Furthermore, knockdown of YY1 inhibited the ameliorating effect of resveratrol on renal tubular EMT and renal fibrosis in db/db mice. In conclusion, this study demonstrates that Sirt1 plays an important role in renal tubular EMT of DN through mediating deacetylation of YY1.
Subject(s)
Diabetes Mellitus, Experimental/complications , Diabetic Nephropathies/physiopathology , Sirtuin 1/genetics , YY1 Transcription Factor/metabolism , Animals , Cell Line , Diabetes Mellitus, Experimental/genetics , Diabetic Nephropathies/genetics , Epithelial-Mesenchymal Transition/genetics , Fibrosis , Gene Knockdown Techniques , Glucose/metabolism , Heterocyclic Compounds, 4 or More Rings/pharmacology , Humans , Male , Mice , Resveratrol/pharmacology , YY1 Transcription Factor/geneticsABSTRACT
The intestinal microenvironment, a potential factor that contributes to the development of non-alcoholic fatty liver disease (NALFD) and type 2 diabetes (T2DM), has a close relationship with intestinal tight junctions (TJs). Here, we show that the disruption of intestinal TJs in the intestines of 16-week-old db/db mice and in high glucose (HG)-cultured Caco-2 cells can both be improved by sodium butyrate (NaB) in a dose-dependent manner in vitro and in vivo. Accompanying the improved intestinal TJs, NaB not only relieved intestine inflammation of db/db mice and HG and LPS co-cultured Caco-2 cells but also restored intestinal Takeda G-protein-coupled (TGR5) expression, resulting in up-regulated serum GLP-1 levels. Subsequently, the GLP-1 analogue Exendin-4 was used to examine the improvement of lipid accumulation in HG and free fatty acid (FFA) co-cultured HepG2 cells. Finally, we used 16-week-old db/db mice to examine the hepatoprotective effects of NaB and its producing strain Clostridium butyricum. Our data showed that NaB and Clostridium butyricum treatment significantly reduced the levels of blood glucose and serum transaminase and markedly reduced T2DM-induced histological alterations of the liver, together with improved liver inflammation and lipid accumulation. These findings suggest that NaB and Clostridium butyricum are a potential adjuvant treatment strategy for T2DM-induced NAFLD; their hepatoprotective effect was linked to the modulation of intestinal TJs, causing the restoration of glucose and lipid metabolism and the improvement of inflammation in hepatocytes.
Subject(s)
Butyric Acid/pharmacology , Intestines/drug effects , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Tight Junctions/drug effects , Animals , Blood Glucose/metabolism , Caco-2 Cells , Cholesterol , Clostridium butyricum , Colon/pathology , Cytokines/blood , Diabetes Mellitus, Type 2/metabolism , Exenatide , Glucagon-Like Peptide 1/genetics , Glucagon-Like Peptide 1/metabolism , Hep G2 Cells , Humans , Hypoglycemic Agents/pharmacology , Inflammation/metabolism , Lipid Metabolism , Liver/injuries , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Receptors, G-Protein-Coupled/genetics , Receptors, G-Protein-Coupled/metabolism , TriglyceridesABSTRACT
Understanding the response mechanism of soil aggregate-associated organic carbon (OC) and nutrients to tea cultivation age can lay a theoretical foundation for improving soil fertility, ensuring soil health, and promoting sustainable utilization of soil resources in the tea plantations. In this study, concentrations of soil OC and nutrient were analyzed in >2, 2-1, 1-0.25, and <0.25 mm fractions (split by a dry-sieving procedure) at the 0-20 cm soil layer in four tea plantations with Baimao tea of different ages (8, 17, 25, and 43 a) in southern Guangxi, China. The distribution of soil aggregates showed that the dominant aggregates were >2 mm fractions with a mean value of 63.8%, followed by <0.25 mm fractions, while 2-1 and 1-0.25 mm fractions with mean values of 9.9% and 7.8%, respectively. As an indicator of soil aggregate stability, the mean weight diameter (MWD) in the tea plantations showed an order of 17 a >8 a >25 a >43 a. Regardless of tea cultivation age, soil aggregate-associated OC and total nitrogen (TN) concentrations increased with increasing aggregate size. Soil OC and TN concentrations in >2 and 2-1 mm fractions were significantly higher than those in other fractions. The mean values of soil OC and TN concentrations were 18.76 and 0.84 g·kg-1 in the >2 mm fractions, and were 18.65 and 0.80 g·kg-1 in the 2-1 mm fraction. Soil aggregate-associated available nitrogen (AN), available phosphorus (AP), and availa-ble potassium (AK) concentrations were highest in the <0.25 mm fractions with mean values of 50.43, 23.06, and 68.04 mg·kg-1, respectively. Long-term tea cultivation was favorable to the accumulation of soil OC, TN, AN, and AP, whereas the accumulation rates of these element stocks in the whole soil decreased with increasing tea cultivation age. In contrast, soil AK was susceptible to leaching in tea cultivation, with the loss rate of this element stock in the middle stage (from 17 to 25 a) being higher than those in the other stages. To ensure soil quality and promote the sustainable utilization of soil resources, more attention should be paid to the problems such as the decrease of soil aggregate stability and the aggravation of AK loss after 17 a of tea cultivation.
Subject(s)
Carbon , Soil , China , Nitrogen , Nutrients , TeaABSTRACT
Ba-Wei-Long-Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti-arthritic mechanisms of BWLZ against collagen-induced arthritis (CIA) by using 1 H-NMR-based metabolomics, molecular docking and network pharmacology methods. After 30â days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti-arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti-arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti-arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.
Subject(s)
Antirheumatic Agents/chemistry , Drugs, Chinese Herbal/chemistry , Metabolomics , Animals , Antirheumatic Agents/metabolism , Antirheumatic Agents/pharmacology , Arthritis, Experimental/chemically induced , Arthritis, Experimental/drug therapy , Binding Sites , Biomarkers/blood , Biomarkers/metabolism , Cytochrome P-450 CYP1A2/chemistry , Cytochrome P-450 CYP1A2/metabolism , Discriminant Analysis , Drugs, Chinese Herbal/metabolism , Drugs, Chinese Herbal/therapeutic use , Hesperidin/chemistry , Hesperidin/metabolism , Hesperidin/therapeutic use , Isoquinolines/chemistry , Isoquinolines/metabolism , Isoquinolines/therapeutic use , Magnetic Resonance Spectroscopy , Male , Medicine, Chinese Traditional , Molecular Docking Simulation , Principal Component Analysis , Protein Structure, Tertiary , Rats , Rats, WistarABSTRACT
High-fat and high-sucrose diet (HFHSD)-induced obesity leads to oxidative stress and chronic inflammatory status. However, little is known about the beneficial effects of total lipids extracted from Spirulina. Hence, in the present study, Spirulina lipids were extracted with chloroform/methanol (SLC) or ethanol (SLE) and then their effects on oxidative stress and inflammation in the mice fed a HFHSD were investigated. The results show that the major lipid classes and fatty acid profiles of SLC and SLE were almost similar, but the gamma-linolenic acid (GLA) and carotenoid contents in SLE was a little higher than that in SLC. Dietary 4% SLC or SLE for 12 weeks effectively decreased the hepatic lipid hydroperoxide levels as well as increased the activities and mRNA levels of antioxidant enzymes in the mice fed a HFHSD. In addition, supplementation with SLC and SLE also markedly decreased the levels of serum pro-inflammatory cytokines and the mRNA expression of pro-inflammatory cytokines in the liver and epididymal white adipose tissue of mice fed a HFHSD, and the effects of SLC and SLE were comparable. These findings confirm for the first time that dietary Spirulina lipids could alleviate HFHSD-induced oxidative stress and inflammation.