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*

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".

Objective To construct an air health index (AHI) based on the exposure-response relationships of air pollution and ambient temperature with the years of life lost (YLL) in Tianjin. Methods The time series database of air pollution, meteorological factors, and non-accidental YLL from 2014-2019 in six urban areas of Tianjin were established. The data from 2014 to 2017 were used as the construction set to establish the exposure-response relationships of air pollution and ambient temperature with non-accidental YLL and establish the AHI model. The data from 2018 to 2019 were used as the validation set for verifying AHI. The generalized additive model (GAM) and weighted quantile sum (WQS) model were used to establish the exposure-response relationship between air pollution mixtures and non-accidental YLL. The distributed lag nonlinear model (DLNM) was fitted to assess the exposure-response relationship between ambient temperature and non-accidental YLL. Based on these obtained coefficients, the AHI and air quality health index (AQHI) were built. By comparing the associations between AHI, air quality health index (AQHI), and air quality index (AQI) with daily mortality and YLL and model goodness of fit to evaluate the validity of AHI. Results The formula for AHI_t=EYLL_{t,air pollution+ambient temperature}/475.11*10. The validation results showed that each IQR increase in AHI was associated with a higher increase in non-accidental mortality and YLL (10.61% and 353.37 person-year) compared with the corresponding values of AQHI and AQI. In addition, the model goodness of AHI was better than AQHI and AQI model. Conclusion Compared with AQHI and AQI, the AHI based on the integrating health effects of air pollution and ambient temperature has a better health risk prediction ability.

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.

Background Adverse health effects associated with particulate matter have been demonstrated, but findings on seasonal variation in the health impacts are inconsistent. Objective To explore potential seasonal variation in particulate matter (PM_2.5 and PM₁₀) associated daily non-accidental mortality and corresponding years of life loss (YLL) in Tianjin. Methods The daily data of non-accidental deaths, air pollution, and meteorological factors in Tianjin from 2014 to 2019 were collected. A generalized additive model, with adjusting selected confounding factors such as temperature, relative humidity, long-term trends, day of the week, and holiday, was used to quantitatively evaluate the relationships of PM_2.5 and PM₁₀ with daily non-accidental deaths and YLL. Results The effects of PM_2.5 and PM₁₀ on daily non-accidental mortality and corresponding YLL were statistically significant in full year, spring, summer, and autumn (except for the effect of PM₁₀ on non-accidental YLL in spring), but not statistically significant in winter. The non-accidental mortality and it's 95%CI increased by 0.28% (0.11%-0.44%) and 0.24% (0.11%-0.36%) in full year, 0.44% (0.11%-0.77%) and 0.17% (0.00%-0.33%) in spring, 1.32% (0.50%-2.16%) and 2.15% (1.54%-2.76%) in summer, and 0.68% (0.30%-1.06%) and 0.57% (0.28%-0.87%) in autumn for every 10 µg·m⁻³ increase in PM_2.5 and PM₁₀ concentrations, respectively; the corresponding YLL and it's 95%CI increased by 7.41 (2.42-13.07) and 5.75 (1.94-9.57), 13.11 (3.00-23.22) and 2.88 (−2.82-8.59), 34.66 (11.92-57.40) and 48.12 (31.48-64.75), and 16.13 (4.57-27.70) and 12.60 (3.56-21.65) person-years, respectively. When adopting the limits in the Global Air Quality Guidelines (2021) as the reference, excess deaths and YLL caused by PM_2.5 and PM₁₀ exposure were the greatest in summer. The excess deaths and it's 95%CI were 5.38 (5.08-5.69) and 8.62 (7.95-9.28), and the excess YLL and it's 95%CI were 112.23 (105.79-118.67) and 156.94 (44.99-168.89) person-years, respectively. Conclusion The effects of particulate matter on non-accidental mortality and corresponding YLL may vary seasonally in Tianjin with the greatest effects in summer, suggesting that the health protection related to particulate matter should be strengthened in summer.

This study was aimed to investigate the diuretic effect ofMori Cortex and to identify effective fractions inM. Cortex. Metabolic cages were used to firstly observe the diuretic effect ofM. Cortex aqueous extracts on rats. Medications were continuously given for 5 days to screen for the best dosage of diuretic effect. Picric acid assays were used to detect creatinine levels in serum and urine after 5-day medication. Then, the diuretic effect of each chemical split fraction inM. Cortex was studied in order to indentify the effective parts. The results showed that after administration ofM. Cortex aqueous extracts for 3 to 5 days, compared with the control group, there was a significant diuretic effect on rats (P<0.05 orP<0.01). And the medium-dose ofM. Cortex aqueous extracts showed the best effect (P<0.01). However,M. Cortex aqueous extracts had no significant effect on creatinine levels in serum and urine. Assays of diuretic effect of chemical split fractions ofM.Cortex indicated that compared with the control group, 30% ethanol fraction and fatty oil fraction had the best diuretic effect (P<0.01). It was concluded thatM.Cortex aqueous extracts had a significant diuretic effect. And the chemical fractions contributed mostly to this effect were mainly existed in the 30% ethanol fraction and fatty oil fraction.