ObjectiveTo investigate the effects of Maimendong Yinzi （MMDYZ） on cough with Yin deficiency and lung heat syndrome and explore its potential mechanism of action. MethodsForty-eight Institute of Cancer Research （ICR） mice were randomly divided into a control group， a model group， a Baihe Gujin Tablet （BHGJP） group （1.36 g·kg^-1）， and low-dose， medium-dose， and high-dose MMDYZ groups （5， 10， 20 g·kg^-1·d^-1， based on the weight of crude drug）， with eight mice in each group. The mouse model of cough with Yin deficiency and lung heat syndrome was prepared by a combination of smoke exposure， nasal drip of lipopolysaccharide （LPS）， intragastric gavage with thyroxine， and capsaicin atomization. After successful modeling， drug interventions were administered for seven days. During modeling， the mice were observed for changes in general status， anal temperature， fecal water content， and water intake. After medication， the above indicators were evaluated again， along with assessments of spontaneous activity， cough sensitivity， lung function， lung index， and tracheal phenol red secretion. Bronchoalveolar lavage fluid （BALF） was analyzed for cell differential counts， and the level of cyclic adenosine monophosphate （cAMP）， cyclic guanosine monophosphate （cGMP）， tumor necrosis factor-α （TNF-α）， and interleukin-6 （IL-6） in serum was measured via enzyme linked immunosorbent assay （ELISA）. Lung injury was assessed via hematoxylin-eosin （HE） staining. Network pharmacology was employed to predict the potential mechanism of MMDYZ in alleviation cough with Yin deficiency and lung heat syndrome. Western blot （WB） was used to measure protease-activated receptor1 （PAR1） and GTPhase α_i subunit （Gα_i） protein expressions in lung tissue. ELISA was used to determine lung cAMP content， and immunohistochemistry （IHC） was employed to evaluate transient receptor potential vanilloid subtype 1 （TRPV1） expression. ResultsCompared with the control group， the model group exhibited significantly increased water intake and anal temperature and significantly decreased fecal water content （P<0.05）. The total distance traveled in 5 min and the central zone duration were reduced， while standing frequency significantly increased （P<0.05）. Cough sensitivity and enhanced pause （PenH） were elevated. Peak expiratory flow （PEF） significantly declined （P<0.05）. BALF neutrophil （NEU） and white blood cell （WBC） counts rose. Serum cAMP and cAMP/cGMP ratio significantly increased， and cGMP significantly decreased （P<0.05）. Serum TNF-α and IL-6 levels were significantly elevated （P<0.05）. The lung injury was obvious， and the lung index was significantly elevated （P<0.05）. Compared with the model group， the medium-dose and high-dose MMDYZ groups and the BHGJP group showed significantly improved indicators mentioned above. Additionally， network pharmacology suggested that MMDYZ might alleviate cough with Yin deficiency and lung heat syndrome via cAMP， hypoxia inducible factor-1 （HIF-1）， and TNF signaling pathways. WB， ELISA， and IHC revealed that， compared with the control group， the model group exhibited significantly upregulated PAR1， Gα_i， and TRPV1 expressions and significantly downregulated cAMP in lung tissue （P<0.05）. Compared with the model group， MMDYZ reduced PAR1 （P<0.01）， Gα_i （P<0.05）， and TRPV1 （P<0.01） while increasing cAMP level （P<0.01）. ConclusionMMDYZ may alleviate cough with Yin deficiency and lung heat syndrome by modulating the PAR1/Gα_i/cAMP pathway and TRPV1 expression.

To investigate the effect of Xuebijing injection (XBJ) on cGAS/STING pathway in alleviating sepsis-induced acute lung injury (ALI), the mouse sepsis-induced ALI model was established by cecal ligation and puncture (CLP), and the cell inflammation model was constructed by LPS stimulating RAW264.7 cells. The effects of XBJ on lung tissue injury and cGAS/STING pathway-related protein expression in septic mice were investigated by HE staining, ELISA, and Western blot. The results showed that XBJ intervention could alleviate lung tissue injury, reduce serum IL-6, TNF-α, IFN-β, IL-1-β levels, and the expression of cGAS, STING, p-TBK1, and p-IRF3 proteins in lung tissue in vivo, and reduce the mRNA level of related inflammatory factors in RAW264.7 cells and the expression of cGAS/STING pathway proteins in vitro. The results showed that XBJ could play a role in the prevention and treatment of sepsis-induced ALI by inhibiting the inflammatory response via inhibition of the activation of cGAS/STING pathway. This study provides a new molecular mechanism for the clinical prevention and treatment of sepsis-induced acute lung injury with XBJ.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease with high global prevalence and long course, which affects more than 30% of the population and seriously endangers human health. Lipid metabolism plays an important role in the occurrence and development of MASLD. An increasing number of studies have shown that active ingredients in traditional Chinese medicine can regulate lipid metabolism to improve MASLD. Due to the obvious advantages of multi-target regulation and fewer side effects, the active ingredients have shown great potential and value for application. However, the pathological mechanism of MASLD is intricate and the active ingredients of traditional Chinese medicine can improve MASLD from multiple aspects, there is currently a lack of systematic discussion on lipid metabolism. Therefore, this review focuses on lipid metabolism and reviews the latest research progress of active ingredients from traditional Chinese medicine in ameliorating MASLD from the aspects of lipid uptake, lipid synthesis, lipid oxidation, lipid secretion, etc., in order to provide more theoretical references for active ingredients of traditional Chinese medicine in regulating lipid metabolism to improve MASLD.

ObjectiveTo investigate the effect of Niuhuang Qingxinwan （NHQXW） in improving intracerebral hemorrhage （ICH） with Tanre Fushi （phlegm-heat and fu-organ excess） syndrome by maintaining blood-brain barrier （BBB） integrity， and to explore its potential mechanism. MethodsMale mice were administered with 15% autologous feces for 3 consecutive days to simulate spontaneous Tanre Fushi syndrome， followed by surgical induction of collagenase-induced ICH on the fourth day. Mice were randomly assigned to seven groups： Sham， Sham+NHQXW-H， collagenase， collagenase+feces， and NHQXW intervention groups at low （NHQXW-L， 0.225 g·kg^-1）， medium （NHQXW-M， 0.45 g·kg^-1）， and high （NHQXW-H， 0.9 g·kg^-1） doses. Treatments were administered for 3 days after surgery. NHQXW effects on Tanre Fushi syndrome were assessed via fecal water content and small intestinal carbon propulsion rate. Protective effects of NHQXW against ICH with Tanre Fushi syndrome were evaluated by measuring hematoma volume， neurological deficits， and brain water content. BBB integrity was further assessed using Evans blue staining， hematoxylin-eosin （HE） staining， immunofluorescence， and Western blot for Claudin-5， plasmalemma vesicle-associated protein （PLVAP）， matrix metalloproteinase （MMP）-2， and MMP-9. The potential mechanism of NHQXW was investigated by detecting protein expression of protein kinase B （Akt）， extracellular signal-regulated kinase 1/2 （ERK1/2）， signal transducer and activator of transcription 3 （STAT3）， Yes-associated protein （YAP）， and their phosphorylated forms. ResultsCompared with the collagenase+feces group， NHQXW-M and NHQXW-H significantly reduced fecal water content （P<0.05， P<0.01） and intestinal propulsion rate （P<0.01）， alleviated neurological deficits （P<0.01）， decreased hematoma volume （P<0.01） and Evans blue extravasation （P<0.01）， increased Claudin-5 protein expression （P<0.05， P<0.01） and fluorescence intensity （P<0.01）， and decreased PLVAP protein expression （P<0.01） and fluorescence intensity （P<0.05， P<0.01）， as well as MMP-2 （P<0.05， P<0.01） and MMP-9 （P<0.01） expression. NHQXW-H downregulated p-Akt （P<0.05）， p-ERK1/2 （P<0.05）， p-STAT3 （P<0.01）， and p-YAP （P<0.05）， with the most significant effect observed on STAT3 phosphorylation. ConclusionNHQXW effectively alleviates neurological deficits and BBB injury in ICH mice with Tanre Fushi syndrome， primarily by inhibiting STAT3 activation.

Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals ; Drugs, Chinese Herbal/pharmacology* ; Myocytes, Cardiac/metabolism* ; Mice ; Rats ; Male ; Mitochondrial Dynamics/drug effects* ; Ventricular Remodeling/drug effects* ; Astragalus Plant/chemistry* ; Mice, Inbred C57BL ; Rhizome/chemistry* ; Panax notoginseng/chemistry* ; Rats, Sprague-Dawley ; Natriuretic Peptide, Brain/genetics* ; Humans ; Angiotensin II ; Astragalus propinquus

Stroke is a neurological disease characterized by cerebral ischemia or hemorrhagic injury， leading to death and disability worldwide. At present， there is still a lack of neuroprotective drugs for the treatment of stroke. Niuhuang Qingxin pills are Chinese patent medicine recommended by guidelines and expert consensus for preventing and treating stroke. Studies have shown that Niuhuang Qingxin pills have sedative， anticonvulsant， antipyretic， and other pharmacological effects. Moreover， the main components， such as flavonoids， phenolic acids， and saponins， also exhibit strong pharmacological activities which can improve stroke-induced nerve damage. Studies have confirmed that representative ingredients such as baicalin and ginsenosides can interfere with multiple pathological events， including blood-brain barrier destruction， oxidative stress， inflammatory response， apoptosis， and autophagy， and the mechanisms of the essential ingredients are related to the action on important targets such as Kelch-like ECH-associated protein 1 （Keap1）， matrix metalloproteinase-9 （MMP-9）， and high-mobility group box 1 （HMGB1）， and involvement in the regulation of Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB）， nuclear factor E₂-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）， and phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathways. This article summarized the research status of Niuhuang Qingxin pills and the experimental pharmacological progress of common ingredients in the prevention and treatment of stroke to provide clues for further research into Niuhuang Qingxin pills and the development of active ingredients of traditional Chinese medicines.

As an active hydroxyanthraquinone ingredient, emodin is abundant in Chinese medicine herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum.Modern pharmacological studies have shown that emodin has a variety of pharmacological activities including anti-tumor, anti-inflammatory and immunoregulatory, antibacterial and anti-viral effects, myocardial protection, neuroprotection, renal protection, bone protection, antifibrosis and so on, which indicate its high medicinal value and broad application prospects.This article aims to summarize the progress in the pharmacological activity and mechanism of action of emodin published in domestic and international journals over the last 5 years and highlight the potential targets and molecular signaling pathways linked with emodin, so as to provide some clues and references for further development and clinical application of emodin.

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

Objective: To investigate the association between body mass index ( BMI ) and mortality risk among older Chinese based on the China Health and Retirement Longitudinal Study ( CHARLS ). Methods: The demographic features, BMI, prevalence of chronic diseases and mortality among the elderly at ages of 60 years and greater were captured from the CHARLS database from 2011 to 2018. A multivariable Cox proportional hazards regression model was used to examine the association between BMI and the risk of death. Results: Totally 6 023 subjects were enrolled, including 3 006 men ( 50.09% ) and 3 017 women ( 49.91% ), and 68.69% of the participants ( 4 137 subjects ) were at ages of 60 to 69 years. There were 637 subjects ( 10.58% ) with underweight, 1 544 ( 25.63% ) with overweight, and 557 ( 9.25% ) with obesity. During the follow-up period ( 35 091 person-years ), 1 035 subjects died. Multivariable Cox proportional hazards regression analysis revealed an increased risk of mortality among the underweight elderly ( HR=1.496, 95%CI: 1.261-1.775 ) and a reduced risk of mortality among the obese elderly ( HR=0.671, 95%CI: 0.511-0.881 ) relative to the elderly with normal weight, after adjustment for age, gender, smoking, household registration, administration of anti-diabetic drugs, administration of anti-dyslipidemia drugs, and administration of anti-hypertensive drugs. Conclusion It is found that the risk of mortality among the Chinese elderly correlatives with BMI through the analysis of CHARLS data.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].