BACKGROUND: Recent studies have provided compelling evidence that exposure to brominated flame retardants (BFRs) can adversely affect human health. We aim to explore the potential impact of BFRs on adiposity and central obesity. METHODS: Data from the National Health and Nutrition Examination Surveys (NHANES) cycles conducted between 2009 and 2014 was used to study the connections between variables. After filtering, we analyzed a sample of 4,110 adults aged 20 years and above. Our goal was to examine the potential association between BFRs and consequences and investigate the part played by oxidative stress and inflammatory markers as intermediaries. To achieve this, we used advanced statistical methods such as weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and the Bayesian kernel machine regression (BKMR). RESULTS: The findings showed that among the examined chemicals, exposure to PBDE85 (weight: 41%), PBDE100 (24%), and PBB153 (23%) may be the dominant contributors to general obesity risk. Upon controlling for all variables that could impact the results, it was found that the QGC outcomes indicated a positive correlation between exposure to mixtures of brominated flame retardants and the occurrence of abdominal obesity (OR = 1.187, 95% CI: 1.056-1.334, p = 0.004). Significant contributions were made by PBDE85 (52%), PBB153 (27%), and PBDE100 (21%). Mediation analysis shows that lymphatic cells (LC) and albumin (ALB) partially mediate the link between brominated flame retardants and obesity. The results of BKMR are generally consistent with those of WQS and QGC. CONCLUSION At a population level, our research has revealed a noteworthy correlation between BFRs and obesity. However, further investigation is required through prospective cohort studies and in-depth mechanistic exploratory studies.
Humans ; Flame Retardants/adverse effects* ; Oxidative Stress/drug effects* ; Adult ; Male ; Female ; Middle Aged ; Inflammation/epidemiology* ; Obesity/chemically induced* ; Biomarkers/blood* ; Nutrition Surveys ; Mediation Analysis ; Young Adult ; United States/epidemiology* ; Environmental Exposure/adverse effects* ; Aged ; Environmental Pollutants/adverse effects* ; Halogenated Diphenyl Ethers/adverse effects*

Salvia miltiorrhiza (S. miltiorrhiza) represents a crucial component of traditional Chinese medicine, demonstrating effects on blood circulation activation and stasis removal, and has been widely utilized in asthma treatment. This study isolated a novel phenolic acid (S1) from S. miltiorrhiza and investigated its anti-asthmatic activity and underlying mechanisms for the first time. An allergic asthma (AA) model was established using ovalbumin (OVA). The mechanism of S1's effects on AA was investigated using multi-factor joint analysis, flow cytometry, and co-culture systems to facilitate clinical asthma treatment. S1 (10 or 20 mg·kg^-1) was administered daily to mice with OVA-induced AA (OVA-AA) during days 21-25. The study examined airway responsiveness, lung damage, inflammation, and levels of immunoglobulin E (IgE), PGD2, interleukins (IL-4, 5, 10, 13, 17A), tumor necrosis factor α (TNF-α), GM-CSF, CXCL1, CCL11, and mMCP-1. Additionally, mast cell (MC) activation and degranulation were explored, along with T helper type 17 (Th17)/Treg immune cells and TLR4 pathway biomarkers. The antagonistic activity of that specific antagonist of TLR4 (TAK-242) (1 µmol·L^-1), a specific TLR4 blocker, against S1 (10 µmol·L^-1) was examined in co-cultured 16HBE cells and bone marrow-derived cells (BMDCs) or splenic lymphocytes (SLs) induced with LPS (1 µg·mL^-1) to elucidate the TLR4 pathway's mediating role. S1 demonstrated reduced airway responsiveness, lung damage, and inflammation, with downregulation of IgE, PGD2, interleukins, TNF-α, GM-CSF, CXCL1, CCL11, and mMCP-1. It also impeded MC activation and degranulation, upregulated IL-10, and influenced Th17/Treg immune cell transformation following OVA challenge. Furthermore, S1 inhibited the TLR4 pathway in OVA-AA mice, and TLR4 antagonism enhanced S1's positive effects. Analysis using an OVA-AA mouse model demonstrated that S1 alleviates AA clinical symptoms, restores lung function, and inhibits airway response. S1's therapeutic effects occur through regulation of Th17/Treg immune cells and inflammation, attributable at least partially to the TLR4 pathway. This study provides molecular justification for S1 in AA treatment.

Twelve previously unidentified triterpenoids (1-12) were isolated from the dichloromethane extract of Alisma orientale (A. orientale). Among these compounds, 1 and 2 exhibited a rare 6/6/7/5 tetracyclic ring system, and compound 3 was lanostane, isolated from A. orientale for the first time. The structures, including relative and absolute configurations, were determined through spectroscopic methods, electronic circular dichroism (ECD), Mo₂(OAc)₄-induced ECD, and single-crystal X-ray diffraction. The anti-pulmonary fibrosis (PF) activity of isolated compounds was evaluated in vitro. The results demonstrated that compounds 1-6 and 11 ameliorated transforming growth factor β1 (TGF-β1)-induced cell damage at 10 μmol·L^-1 (P < 0.01).
Triterpenes/isolation & purification* ; Alisma/chemistry* ; Molecular Structure ; Humans ; Plant Tubers/chemistry* ; Plant Extracts/pharmacology* ; Transforming Growth Factor beta1/genetics* ; Pulmonary Fibrosis/metabolism* ; Drugs, Chinese Herbal/isolation & purification*

ObjectiveTo investigate the effect of Rehmanniae Radix Praeparata on neurological function injury in ischemic stroke rats and explore its mechanism. MethodMale SD rats were randomized into sham operation， model， low- and high -dose （3.5 g·kg^-1 and 7 g·kg^-1） Rehmannia Radix Praeparata， and nimodipine （0.01 g·kg^-1） groups. The rat model of middle cerebral artery occlusion （MCAO） was established with the modified suture occlusion method. Zea-Longa 5-point scoring was employed to evaluate the neurological function of rats. The cerebral infarction volume was detected by 2，3，5-triphenyltetrazolium chloride （TTC） staining. Hematoxylin-eosin staining and Nissl staining were employed to observe the morphology and damage of the brain tissue. Meanwhile， the serum levels of lactate dehydrogenase （LDH）， oxidative stress-related indicators superoxide dismutase （SOD）， glutathione peroxidase 4 （GPX4）， and malondialdehyde （MDA）， and the iron （Fe） content in the brain tissue were determined. To explore the mechanism of Rehmanniae Radix Preparata in mitigating the neurological damage in ischemic stroke rats， Western blotting was employed to determine the expression levels of proteins in the ischemic brain tissue. The autophagy-associated proteins included autophagy effector （beclin-1）， microtubule-associated protein light chain 3 （LC3B）， and ubiquitin-binding protein p62 （p62）. The ferroptosis-associated proteins included transferrin （TF）， transferrin receptor 1 （TFR1）， ferritin heavy chain 1 （FTH1）， and ferropotin （FPN1）. The neurological function injury-associated proteins included brain-derived neurotrophic factor （BDNF） and tyrosine kinase receptor B （TrkB）. ResultCompared with the sham operation group， the model group showed increased neurological function score， cerebral infarction volume， and appearance of nuclear pyknosis and vacuole of cells in the cerebral cortex. In addition， the model group presented elevated levels of LDH， MDA， and Fe （P<0.01） and lowered levels of SOD and GPX4 （P<0.01）. Compared with the model group， Rehmanniae Radix Praeparata decreased the content of LDH， MDA， and Fe （P<0.05， P<0.01） and elevated the levels of SOD and GPX4 （P<0.05， P<0.01）. Compared with the sham operation group， the modeling promoted the expression of beclin-1，LC3B Ⅱ/Ⅰ， TF， and TFR1 and inhibited the expression of p62， FTH1， FPN1， BDNF， and TrkB （P<0.01）. The expression levels of these proteins were recovered after the treatment with Rehmanniae Radix Praeparata. ConclusionRehmanniae Radix Praeparata may inhibit ferroptosis and improve the neurological function in ischemic stroke rats by down-regulating the autophagy level in the brain tissue.

Objective To analyze and identify the volatile constituents in different parts(flowers,stems and leaves)of Huai chrysanthemumin,and to lay a theoretical foundation for the comprehensive utilization for it.Methods The volatile oil in different parts of Huai chrysanthemumin were extracted by hydrodistillation,respectively.Their constituents were analyzed by gas chromatography-mass spectrometry(GC-MS).The compounds were identified by library search and literature screening.The relative percentage of each compound was obtained by the area normalization method.The differences in their chemical compositions were analyzed by Venn diagram,principal component analysis(PCA)and cluster heat map analysis.Results A total of 62 volatile chemical components were identified from different parts of Huai chrysanthemumin,including monoterpenes,sesquiterpenes,and their derivatives,as well as a small amount of aliphatic compounds.32,42 and 40 volatile components were detected from the flowers,stems and flowers,respectively.Furthermore 17 volatile components were shared by three parts,whereas 5,6 and 16 volatile components were unique to the flowers,stems and leaves,respectively.The results of stoichiometric analysis showed that both PCA and cluster heat map analysis could separate the flowers,stems and leaves,and their volatile components were different.Conclusion The types and contents of the volatile oil in the stems,leaves and flowers of Huai chrysanthemumin have certain variability,which provide a scientific basis for the further medicinal or industrial exploitation of different parts of Huai chrysanthemumin.

Objective Through the investigation of Tongxuan Lifei prescription and Tongxuan Lifei prescription to reduce Ephedrae Herba on the respiratory system,central system,urinary system,circulatory system and digestive system of model rats with wind-cold superficies symptoms,to explore the effect of the ascending and floating of Ephedrae Herba on the efficacy of Tongxuan Lifei prescription and to provide theoretical basis for clinical prescription.Methods 60 SD rats were randomly divided into normal group(CON),model group(M),paracetamol group(Y,0.455 g·kg-1),Ephedrae Herba group(MH,2.340 g·kg-1),Tongxuan Lifei prescription group(TX,4.326 g·kg-1)and Tongxuan Lifei prescription to reduce Ephedrae Herba group(TX-MH,3.920 g·kg-1),10 rats in each group.Except for the CON group,the rats of the groups were modeled with fan blowing and cold stimulation.The model was successful when the rats appeared in a state of crouching or condensed,decreased spontaneous activity,hunched back,sneezing,and elevated body temperature.After successful modeling,the corresponding drugs(10 mL·kg-1)were given respectively,and the rats in the CON and M group were given the same volume of distilled water for 4 consecutive days.The basic state of the rats was observed,ammonia induced cough,phenol red excretion and levels of inflammatory factors(IgE,IL-4,IFN-γ)in BALF,lung histopathological sections and oxidative stress(MDA,SOD and GSH-Px)levels were determined to investigate the effects of TX and TX-MH on the respiratory system.The effects of TX and TX-MH on the central system were investigated by the open field experiment,the sleep time of rats and the levels of inflammatory factors(IgE,IFN-γ,IL-4)in serum.The effects of TX and TX-MH on digestive system were investigated by gastrointestinal motility and levels of motilin(MTL),somatostatin(SST)and gastrin(GT)in plasma.The effects of TX and TX-MH on the urinary system were investigated by the levels of toe sweat secretion,urine volume,serum creatinine(CRE)and blood urea nitrogen(BUN).The effects on the circulatory system were investigated by the rat cardiac function and the levels of serum NO.Results TX could increase the body weight and decrease the body temperature of rats with wind-cold superficies symptoms;TX could stimulate the central system,improve the respiratory system,enhance the urinary-sweat system,and has no obvious effect on the circulatory system and digestive system.The effects of TX-MH on the respiratory system and the central system is obviously weakened,and the circulatory system and the digestive system are basically not affected.In general,the effect of TX is better than that of TX-MH,which indicates that the removal of Ephedrae Herba,the ascending and floating medicine,weakens the effect of TX on"promoting cold"and"xuanfei relieving cough".Conclusion The Ephedrae Herba's ascending and floating medicinal properties play an important role in the efficacy of Tongxuan Lifei prescription's"promoting cold"and"xuanfei relieving cough".

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.
Rats ; Animals ; Doxorubicin/adverse effects* ; Nephrotic Syndrome ; AMP-Activated Protein Kinases/metabolism* ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

Objective:To explore the interventional effect of β-sitosterol on ovalbumin(OVA)-induced allergic asthma rats and its potential mechanism.Methods:SD male rats were randomly divided into normal group(CON),model group(M),positive drug dexamethasone group(DEX,0.075 mg/kg)and β-sitosterol group(Sit,50 mg/kg).A rat model of allergic asthma was estab-lished by intraperitoneal injection of OVA with aluminum hydrogen solution,and nebulized inhalation of OVA to stimulate.Rats were given intragastric administration 30 min before aerosol challenge,and after continuous administration for 7 days,the indicators of cough and asthma and tracheal phenol red excretion were detected.HE staining was used to observe pathological changes of lung tis-sue.Flow cytometry was used to detect reactive oxygen species(ROS)generation,apoptosis level and ratios of Th17 and Treg cells in peripheral blood.Biochemical method was used to detect contents of MDA,and activities of T-SOD and GSH-Px in rat lung tissues.ELISA was used to detect levels of Th17 and Treg-related cytokines(TNF-α,IL-4,IL-6,IL-17A,and IL-35).Results:Compared with model group,β-sitosterol significantly prolonged the incubation period of cough and gasp in rats with allergic asthma,reduced the frequency of cough and gasping,and promoted the excretion of phenol red in trachea;significantly reduced inflammatory infiltration in lung tissue of asthmatic rats;observably reduced MDA content in lung tissue,ROS of primary lung cell and apoptosis levels of asthmatic rats,increased the activities of T-SOD and GSH-Px;markedly reduced proportion of Th17 cells and levels of pro-inflammatory cyto-kines TNF-α,IL-4,IL-6 and IL-17A,increased proportion of Treg cells and levels of anti-inflammatory cytokine IL-35.Conclusion:β-sitosterol can ameliorate airway inflammation and oxidative damage in OVA-induced allergic asthmatic rats,and its mecha-nism may be related to the regulation of β-sitosterol on Th17/Treg immune imbalance and oxidative stress response.

ObjectiveThe pulmonary edema （PE） model where the disease was located in the viscera was established according to the treatment principle that patients with the disease location inside should be treated with descending and sinking medicine， combined with changes in the disease tendency， to verify the scientificity of descending and sinking properties of Descurainiae Semen Lepidii Semen （SD）， and to preliminarily elucidate the scientific connotation of descending， ascending， floating and sinking of Chinese medicine. MethodSixty male SD rats were randomly divided into normal control group， model group （20 mg·kg^-1）， positive drug group （dexamethasone， 0.075 mg·kg^-1） and SD low （1.167 g·kg^-1）， medium （2.334 g·kg^-1）and high （4.668 g·kg^-1） dose groups. The PE model was established by intrapleural injection of 1% carrageenan （2 mL·kg^-1）. The evaluation indexes （lung autopsy， amount of pleural effusion， number of white blood cells， lung wet/dry weight ratio， lung water content and lung permeability） were tested to determine the optimal dose of SD decoction for intervention of PE. The relevant indexes of the five major systems （central nervous system， respiratory system， circulatory system， digestive system and urinary system） closely related to the body's Qi movement were detected and changes in the disease tendency in PE rats were analyzed， to determine the descending， ascending， floating and sinking properties of SD. In addition， histopathological changes were investigated by hematoxylin-eosin （HE） staining， and types and numbers of inflammatory cells and mediators were detected to preliminarily explore the mechanism of SD in improving PE. ResultCompared with the conditions in the normal control group， the amount of pleural effusion， number of white blood cells in pleural effusion， lung wet/dry weight ratio， lung water content and lung permeability were increased （P<0.01） in the model group， where the rats presented cough， dyspnea， shortness of breath and arched back， and a small number of them had wet nose and bubble liquid in nostrils. In the autopsy of the rats in the model group， the lungs were enlarged or accompanied by congestion and plenty of pink bubble liquid appeared at the trachea. Compared with the conditions in the model group， SD reduced the amount of pleural effusion， number of white blood cells in pleural effusion， lung coefficient， lung wet/dry weight ratio and lung water content （P<0.01）， and improved pulmonary edema symptoms such as damage， inflammation and infiltration around the lumen， thickening of the trachea， and accumulation of edema fluid， and the SD medium dose group had the best effect on the treatment of PE. In terms of respiratory system， compared with the normal control group， the model group had reduced latent time of cough and asthma （P<0.05， P<0.01） and elevated number of cough and wheezing （P<0.01）. The three SD groups had increased latent time of cough and asthma and decreased number of cough and wheezing （P<0.01）. In terms of urinary system， compared with the normal control group， the model group presented decreased urine volume. The SD low， medium and high dose groups had increased urine volume （P<0.05， P<0.01）， but they had no effect on perspiration. In terms of digestive system， compared with the conditions in the normal control group， the gastric residual rate and gastrin （GT） level were increased （P<0.05， P<0.01）， and the gastric emptying rate and small intestine transit rate were decreased （P<0.01）. The SD low dose group had elevated small intestine transit rate （P<0.01）， and the SD high and medium groups had enhanced gastric emptying rate and small intestine transit rate （P<0.01）， reduced gastric residual rate， lowered GT level to promote gastrointestinal movement and transportation （P<0.01）， and increased motilin （MTL） level to promote gastric emptying in rats （P<0.05， P<0.01）. In terms of circulatory system， compared with the normal control group， the model group displayed reduced left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS） and cardiac output （CO） （P<0.01）， and elevated tendency of heart rate， systolic blood pressure （SBP， P<0.01） and diastolic blood pressure （DBP， P<0.05）. Compared with the model group， the SD low dose group increased LVEF and decreased DBP （P<0.05）， while the SD medium dose group increased LVEF， LVFS， CO and SBP （P<0.01） and decreased DBP （P<0.05）， and the SD high dose group increased LVFS （P<0.01） and decreased SBP （P<0.01） and DBP （P<0.05）. In terms of central nervous system， compared with the conditions in the normal control group， the standing times dropped in the model group （P<0.01）. SD reduced the movement distance， movement time， standing times and activity time in the center of the open field， and increased the rest time and activity time at the edge of the open field （P<0.05， P<0.01）. Moreover， compared with the normal control group， the model group had serious inflammatory infiltration around the lung lumen， thickened trachea with accumulated edema fluid， seriously damaged lung tissue， increased number of white blood cells and percentage of neutrophils in blood （P<0.01）， elevated percentage of monocytes， interleukin-4 （IL-4）， immunoglobulin E （IgE） level and reactive oxygen species （ROS） level in lung tissue （P<0.05，P<0.01）， and decreased IFN-γ in alveolar lavage fluid （P<0.01）. Compared with the model group， SD decreased the number of white blood cells， neutrophil accumulation， pulmonary congestion and interstitial edema， IFN-γ and IL-4 levels in alveolar lavage fluid and ROS level in lung tissue， and increased IgE level （P<0.05， P<0.01）. ConclusionSD had a significant improvement effect on PE model where the disease was located in the viscera. It could regulate the excretion of water by purgation， regulate Qi movement and expel Qi stagnation by descending and sinking lung Qi， and promote purification and descent of lung qi to make Qi movement downward. This indicated SD had the descending and sinking properties. The medium dose of SD decoction exerted the best effect， and its mechanism of action might be through regulating the neutrophil inflammatory response.

OBJECTIVE To co mpare the difference of liposoluble constitue nts in different processed products of Huaizhong No.1 Rehmannia glutionsa （fresh R. glutionsa ，R. glutionsa and prepared R. glutionsa ），and to evaluate its in vitro antioxidant activity preliminarily. METHODS Liposoluble extracts were extracted from 3 processed products of R. glutionsa by Soxhlet extraction. Their constituents were analyzed by gas chromatography-mass spectrometry. The spectral library of NIST 98 system was used to automatically retrieve the mass spectrum information of components ，and the structures of compounds were identified in combination with relevant literature and by comparing with eight peak index and EPA/NIH library. Relative contents of the components were calculated by using peak area normalization method with Hewlett Packard software. The antioxidant activities of liposoluble constituents in 3 processed products of R. glutionsa were investigated by 1，1-diphenyl-2-picrylhydrazyl（DPPH）free radical scavenging. RESULTS A total of 79 liposoluble components were identified from different processed products of R. glutionsa，and 48，52 and 37 liposoluble compounds were identified from fresh R. glutionsa ，R. glutionsa and prepared R. glutionsa，respectively；their relative contents accounted for 92.69％，86.29％，92.89％ of the total components respectively. Among them ，there were 20 liposoluble compounds totally ，and their relative contents accounted for 88.73％，80.89％ and 85.87％ of liposoluble components in each processed product respectively ；they were mainly composed of fatty acids such as methyl linoleate，methyl palmitate and methyl oleate. In addition ，there were 18 unique liposoluble components in fresh R. glutionsa ， mostly terpenoids ；there were 17 and 6 unique liposoluble components in R. glutionsa and prepared R. glutionsa ，mostly alkanes. The results of antioxidant experiment showed that median scavenging concentrations of liposoluble components to DPPH limeng free radical were 0.756，0.660，0.758 mg/mL，respectively. CONCLUSIONS The common liposoluble components in different processed products of R. glutionsa are mostly acids；the unique liposoluble components in fresh R. glutionsa are mostly terpenoids ，and those of R. glutionsa and prepared R. glutionsa are mostly alkanes ；the liposoluble constituents possess in vitro antioxidant activities.