Chinese Formula Research Articles

Modified Guo-Min decoction ameliorates PM2.5-induced lung injury by inhibition of PI3K-AKT and MAPK signaling pathways

Background/PurposeExposure to particles with an aerodynamic diameter of ≤2.5 μm (PM2.5) increased various lung diseases, which lack effective treatment. Massive evidence links PM2.5 to the development of allergic lung diseases like asthma. Modified Guo-Min Decoction (MGMD) is a traditional Chinese formula for allergic diseases. However, whether MGMD could improve PM2.5-induced lung injury and the underlying mechanism remain unclear and we aimed to explore. Study Design/MethodsMale Wistar rats (200–220 g) were intratracheally instilled of PM2.5 suspension daily for 4 weeks to establish PM2.5-induced lung injury model. MGMD (2.1 g/kg) treatment by gavage was started 1 week before, at the same time or 1 week after the instillation of PM2.5 suspension, namely the pre-, sync- or post-administration groups. HE and Masson staining were used to observe morphological changes. Immunohistochemistry staining was used to detect macrophage and neutrophil infiltration. The levels of inflammatory cytokines in the bronchoalveolar lavage fluid were detected by ELISA. The main components of MGMD were detected by UHPLC-LTQ-Orbitrap MSn. Network pharmacology was used to identify the key targets mediating the effect of MGMD in treating PM2.5-induced lung injury. Changes in the expression of target proteins were examined by western blot. In-vitro experiments were carried out in Beas2b cells to evaluate the protective effect and mechanism of MGMD against PM2.5 induced injury. ResultsExposure to PM2.5 suspension resulted in disarrangement of tracheal epithelium, neutrophil and M1 macrophage infiltration and collagen deposition, and significantly increased IgE, IL-1β and IL-17 secretion and NLRP3 expression, which were inhibited by MDMD treatment and pre-MGMD treatment showed the best effect. By UHPLC-LTQ-Orbitrap MSn, 46 main compounds were identified in MGMD. Using network pharmacology approach, we found MGMD attenuate PM2.5-induced lung damage by targeting 216 genes, and PPI network, GO and KEGG analysis all indicated that PI3K-AKT and MAPK pathways were important. Western blot showed that PM2.5 suspension exposure increased PI3K, AKT, ERK and JNK phosphorylation, which were reversed by MGMD intervention significantly. In vitro, the viability of Beas2b cells was significantly decreased after PM2.5 suspension exposure, and was obviously upregulated after MGMD-containing serum or LY294002 treatment. Conclusion: The present study demonstrated that MGMD could improve PM2.5-induced lung injury through reducing inflammation and pulmonary fibrosis, which was probably mediated by inhibition of the PI3K-AKT and MAPK signaling pathways, and NLRP3 inflammasome. The results of this study support and provide scientific evidence for the clinical application of MGMD on PM2.5-induced lung injury. Pre-treatment, sync-treatment, and post-treatment is the highlight of this study.

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics

BackgroundDiabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PurposeThis study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. MethodsFirstly, the content determination methods of QXLZY were established with calycosin-7-O-β-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. ResultsA method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. ConclusionThis study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.

Xihuang pill facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.

Glioma is the most common malignancy in the central nervous system. This study aims to disclose the impacts of Xihuang pill (XHP), a traditional Chinese formula, on glioma cell pyroptosis and relevant molecular mechanism. U251 and SHG-44 cells were treated with XHP alone or together with oe-POU4F1 and sh-STAT3. CCK8 assay detected the viability, flow cytometry evaluated pyroptosis, and microscopy observed cell morphology. LDH release was determined by the LDH kit and the levels of IL-1β and IL-18 were detected by ELISA. Immunofluorescence showed NLRP3 expression in glioma cells and western blotting measured the levels of POU4F1, STAT3, NLRP3, ASC, cleaved caspase-1, and IL-1β. The binding of POU4F1 to STAT3 was verified. Primary glioma model was established to observe tumor change by in vivo imaging, determine the levels of Ki67 and NLRP3 by immunochemistry, and detect relevant protein levels by western blotting. XHP treatment alone downregulated POU4F1 and STAT3 levels, aroused pyroptotic appearance in glioma cells such as ballooning swelling, reduced cell viability and number of pyroptotic cells, increased LDH release and IL-1β and IL-18 levels, formed NLRP3 sports in cells, and elevated the levels of pyroptosis-related proteins. However, POU4F1 overexpression or STAT3 silencing suppressed XHP-promoted pyroptosis. Mechanistically, POU4F1 acted as a transcription factor of STAT3 and regulated its transcription. In primary glioma models, XHP enhanced glioma cell pyroptosis and blocked glioma growth. XHP facilitates glioma cell pyroptosis via the POU4F1/STAT3 axis.

Efficacy and safety of Duhuo-Jisheng decoction in rheumatoid arthritis: A systematic review and meta-analysis of 42 randomized controlled trials.

Duhuo-Jisheng decoction (DJD) is a Chinese herb formula. Previous studies have reported that the clinical symptoms and laboratory indicators of rheumatoid arthritis (RA) patients could be improved by DJD. However, the existing evidence was not robust enough and controversial. Randomized controlled trials of DJD for RA were retrieved from Chinese and English databases from their inception to April 16, 2023. Meta-analysis was performed by Stata 17 software. We used subgroup analysis, meta-regression, and sensitivity analysis to identify potential sources of heterogeneity. The subgroup analysis and meta-regression were conducted from 6 aspects, including age, course of disease, course of treatment, interventions used in the experimental or control group, and random sequence generation. Galbraith plot was used to find studies with possible heterogeneity. Publication bias was assessed by Egger's test and funnel plots when the number of relevant studies was greater than or equal to 10. Forty-two studies were included, involving 3635 patients and 19 outcome indicators. Meta-analysis showed that, compared with the routine disease-modifying antirheumatic drugs (rDMARDs), DJD could better improve the level of laboratory indicators, main symptoms and signs, and questionnaire scores of RA patients. The laboratory indicators included rheumatoid factor, T lymphocyte subpopulation (including CD4+, CD8+, and CD4+/CD8+), and inflammatory biomarkers (including erythrocyte sedimentation rate, C-reactive protein, tumor necrosis factor-α, interleukin 6, interleukin 1β, and interleukin 1). The main symptoms and signs included the duration of morning stiffness, the number of joint tenderness, the number of swollen joints, and the grip strength of both hands. The questionnaire included visual analogue scale, health assessment questionnaire, and disease activity score in 28 joints. In addition, the adverse events of DJD treatment were significantly lower than those of rDMARDs. However, the results of a few subgroup analyses differed from the overall results. Furthermore, the publication bias assessment showed that, out of 11 evaluated results, 4 had publication bias. DJD could be a satisfactory complementary and alternative therapy for RA. However, due to a small number of subgroup analysis results being different from the overall results, it should be verified by further studies.

Fermentation improves antioxidant capacity and γ-aminobutyric acid content of Ganmai Dazao Decoction by lactic acid bacteria.

Ganmai Dazao Decoction is a traditional Chinese recipe, and is composed of licorice, floating wheat, and jujube. Effects of lactic acid bacteria fermentation on the physicochemical properties, antioxidant activity, and γ-aminobutyric acid of Ganmai Dazao Decoction were studied. The changes of small and medium molecules in Ganmai Dazao Decoction before and after fermentation were determined by LC-MS non-targeted metabolomics. The results showed that the contents of lactic acid, citric acid, acetic acid, and total phenol content increased significantly, DPPH free radical clearance and hydroxyl free radical clearance were significantly increased. γ-aminobutyric acid content was 12.06% higher after fermentation than before fermentation. A total of 553 differential metabolites were detected and identified from the Ganmai Dazao Decoction before and after fermentation by partial least squares discrimination and VIP analysis. Among the top 30 differential metabolites with VIP values, the content of five functional substances increased significantly. Our results showed that lactic acid bacteria fermentation of Ganmai Dazao Decoction improves its antioxidant effects and that fermentation of Ganmai Dazao Decoction with lactic acid bacteria is an innovative approach that improves the health-promoting ingredients of Ganmai Dazao Decoction.

The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. An AP model was established with CBA/J×DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

A comprehensive quality evaluation for Huangqi Guizhi Wuwu decoction by integrating UPLC-DAD/MS chemical profile and pharmacodynamics combined with chemometric analysis

Ethnopharmacological relevanceHuangqi Guizhi Wuwu Decoction (HGWD), a classical Chinese formula originally recorded in Jin Kui Yao Lue, was used for the treatment of human “blood impediment” (a type of “Bi” syndrome). In clinical practice, HGWD has been applied to treat rheumatoid arthritis (RA). Aim of the studyThe characterization of chemical markers reflecting both efficacy and chemical characteristics is of great significance for TCM quality control. With the anti-RA effects of HGWD as an example, the aim of this study was to develop a comprehensive strategy combining the overall chemical profile and biological activity data to identify chemical markers. Materials and methodsFirst, an ultra-performance liquid chromatography-diode array detector (UPLC-DAD) fingerprint was established and validated to evaluate the holistic quality of HGWD of different origins. Characteristic markers associated with HGWD from different geographical origins were screened by a combination of UPLC-DAD fingerprint and chemometrics methods. Second, the chemical profiles of the 15 batches of HGWD samples were characterized by UPLC coupled tohybrid linear ion trap-Orbitrap mass spectrometry (UPLC-HRMS). The in vitro anti-RA activities of the 15 HGWD samples were then evaluated. Third, spectrum-effect relationship analysis was performed to identify bioactive compounds that could potentially be used as quality markers. Finally, a UPLC-triple quadrupole tandem mass spectrometry approach was optimized and established for quantitative analysis of the characteristic and quality markers in 15 batches of HGWD. ResultsIn total, 30 common peaks were assigned in the UPLC-DAD fingerprint. Nine peaks were recognized and considered characteristic markers: protocatechuic acid, coumarin, cinnamic acid, oxypaeoniflorin, paeoniflorin, calycosin, formononetin, catechin, and albiflorin. Furthermore, ninety-five common compounds were identified in the UPLC-HRMS chemical profile. The pharmacological analysis indicated that the anti-RA activities of the 15 HGWD samples were vastly different. The spectrum-effect relationship analysis revealed 30 potential bioactive constituents positively correlated with anti-RA activity. Among them, five compounds with relative amounts >1%, paeoniflorin, astragaloside IV, hexahydrocurcumin, formononetin and calycosin-7-glucoside, were selected as quality markers, and their activity was verified in LPS-induced RAW264.7 macrophages. Finally, the above 12 representative components were simultaneously quantified in the 15 batches of HGWD samples. ConclusionCombining a holistic chemical profile with representative component evaluation, this systematic strategy could be a reliable and effective method to improve quality evaluations of HGWD.

The chemical constituents and metabolite profiles of Huangqin decoction in normal and ulcerative colitis rats by UHPLC-Q-TOF/MS analysis

Ulcerative colitis (UC) is a recurrent and palliative inflammatory bowel disease (IBD) begins in distal colon and spreads proximally to the entire colon, characterized by mucosal inflammation which reduces patients' quality of life and increases the risk of bowel cancer. Huangqin decoction (HQD), a classical Chinese formula recorded in Treatise on Febrile Diseases has been widely used for the treatment of UC. Studies found that HQD has good curative effect on UC. However, the chemical constituents and metabolites of it has not been fully elucidated due to lack of in vitro and in vivo studies, which also limits the pathogenesis study and clinical application of UC. In this study, a rapid and high-throughput UHPLC-Q-TOF/MS method was established and applied to analyse the chemical constituents and metabolites of HQD. Besides, we established an UC rat model and compared the differences of metabolite profiles between normal and UC rats both in plasma and urine. A total of 139 constituents were chemically defined or tentatively identified, including 98 flavonoids, 10 triterpene saponins, 10 monoterpene glycosides, 4 phenols, 5 phenylethanoid glycosides and 12 other types of compounds. A total of 175 and 147 HQD-related xenobiotics were detected in normal and UC rats, respectively. The main metabolic pathways of HQD were methylation, hydrolysis, hydroxylation, glucuronidation and sulfation. The holistic metabolic profiles of HQD revealed that normal and UC rats had certain differences in drug absorption and metabolism. This study can provide references for the follow-up study of HQD, and provide essential data for the further study of the relationships between chemical constituents and pharmacological activities of HQD.

Liuwei Dihuang Decoction Drug-containing Serum Attenuates Transforming Growth Factor-β1-induced Epithelial-Mesenchymal Transition in HK-2 cells by Inhibiting NF-κB/Snail Signaling Pathway.

The nuclear factor-κB (NF-κB) signaling pathway plays an important role in regulating tubular epithelial-mesenchymal transition (EMT), an indispensable cellular programme for driving organ fibrosis and tumor progression. Liuwei Dihuang Decoction (LWD) is an effective Chinese formula for treating chronic renal failure. First, by using morphological examination, immunofluorescence staining assay, RT-qPCR, and Western blot analysis, in vitro experiments were designed to analyze NF-κB and EMT markers (including Snail, α-SMA, and E-cadherin) in transforming growth factor-β1 (TGF-β1) induced renal tubular epithelial cells (HK-2) and to detect the expression levels of LWD-CS co-treatment. Then, the recombinant lentiviral vector was overexpressed and knocked down by NF-κB and transfected into HK-2 cells. Cells were treated with TGF-β1 (10ng/ml) with blank serum or LWD-containing serum, respectively, and the expression of these molecules in the NF-κB/Snail signaling pathway was further evaluated. Our results confirmed that TGF-β1 could induce EMT, nuclear translocation of NF-κB p65, and activate the NF-κB/Snail signaling pathway in HK-2 cells. Furthermore, NF-κB knocked-down dramatically increases the TGF-β1-induced mRNA and protein expression level of E-cadherin and reduces the level of Snail and α-SMA; this is reversed by NF-κB overexpression. LWD can decrease the EMT levels through the NF-κB/Snail signaling activation in TGF-β1-induced EMT of HK-2 cells. The present study provides evidence suggesting a novel mechanism that LWD exerts anti-fibrosis effects through inhibiting activation of the NF-κB/Snail signaling pathway and consequently downregulating the TGF-β1-induced EMT in renal tubular epithelial cell.

Rapid detection of multi-indicator components of classical famous formula Zhuru Decoction concentration process based on fusion CNN-LSTM hybrid model with the near-infrared spectrum

Traditional Chinese Medicine (TCM) is a collective term for the medicines of all ethnic groups in China, including Han Chinese and ethnic minority medicines, reflecting the Chinese people's understanding of life, health and disease, and is a system of medicine with a long historical tradition and unique theories and technical methods. Due to the nonlinearity, large hysteresis, and strong interference in the concentration process used in the production of traditional Chinese medicine, it is challenging to use just one conventional control method to achieve the desired control effect. The majority of traditional quality control methods used in processing the samples will result in the loss of the active ingredient and in the detection of impurities. Monitoring of multiple critical quality attributes (CQAs) is crucial for the overall process of the index ingredient. In this study, based on the above background, fast and nondestructive near-infrared spectroscopy (NIRS) technique incorporating convolutional neural network (CNN) and long-short-term memory network (LSTM) was utilized to construct a quantitative model based on the seven characteristic components, puerarin, 3′-hydroxy puerarin, 3′-methoxy puerarin, puerarin apigenin, daidzin, glycyrrhizin and glycyrrhizic acid, during the concentration process. The results showed that the relative mean error (MAPE) values of the different components ranged from 0.7% to 2.8% and R2 from 0.981 to 0.992 based on the proposed CNN-LSTM model. The results showed that the combined model of near-infrared spectroscopy fused with convolutional neural network (CNN) and long-short-term memory network (LSTM) was feasible for accurate and rapid monitoring of the concentration of the classic famous prescription Zhuru Decoction (ZRD) during the decoction process and that the method could provide a reference value for rapid nondestructive testing of traditional Chinese medicine compound formulas.

Effect and mechanism of Qing Gan Zi Shen decoction on heart damage induced by obesity and hypertension

Ethnopharmacological relevanceQing Gan Zi Shen Decoction (QGZS) is a traditional Chinese formula. It has been extensively used for decades in the treatment of hypertension combined with metabolic diseases, but its cardioprotective effects and underlying mechanisms are poorly understood. Aim of the studyTo explore the cardioprotective effects and potential mechanisms of QGZS in an animal model of obese hypertension. Materials and methodsIn this study, spontaneously hypertensive rats (SHRs) were utilized as an animal model to examine the effects of a high-fat diet and two concentrations of QGZS. Echocardiography, hematoxylin eosin (H&E) staining, and wheat germ agglutinin (WGA) staining were employed to assess the cardiac structure and function of the SHRs throughout a 16-week therapy period. Furthermore, Western blotting (WB) and immunofluorescence (IF) were employed to identify the levels of Nrf2 expression in the mitochondria, cytoplasm, and nucleus of the myocardium. Additionally, transmission electron microscopy and enzyme-linked immunosorbent assay (ELISA) were utilized to measure mitochondrial morphology and pro-inflammatory cytokine levels, respectively. Furthermore, Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques were employed to quantify the levels of marker proteins associated with myocardial fibrosis, cardiac inflammation, oxidative stress, and mitochondrial dysfunction. ResultsQGZS inhibited weight gain and depressed systolic and mean arterial pressures in high-fat-fed SHRs. Echocardiographic results demonstrated that QGZS prevented the increase in left ventricular mass, restricted the growth of left ventricular diameter, and improved ejection fraction (EF), fractional shortening (FS), and the ratio of early diastolic peak velocity of transmitral flow (E) to late diastolic peak velocity (A) in high-fat-fed SHRs. This suggested that QGZS prevented ventricular remodeling and protected cardiac systolic and diastolic functions. H&E and WGA staining showed that QGZS improved cardiomyocyte disorders and restricted cardiomyocyte hypertrophy. The underlying mechanisms, QGZS attenuated the oxidative stress state, including reducing the generation of reactive oxygen species (ROS) in the myocardium, revitalizing the antioxidant enzyme system, and protecting mitochondrial function. Moreover, QGZS alleviated the pro-inflammatory state in high-fat-fed SHRs. What's more, QGZS significantly increased the expression level of Nrf2 in nuclei and mitochondria in rat heart tissues, exerting a proximate Nrf2 agonist effect. ConclusionsQGZS exerted cardioprotective effects, in part due to its increasing expression of Nrf2 protein in the heart, which promoted Nrf2 nuclear expression.

Spectrum–effect relationship combined with bioactivity evaluation to discover the main anxiolytic active components of Baihe Dihuang decoction

Ethnopharmacological relevanceAnxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear. Aim of the studyTo screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment. MethodsThe UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors. ResultsIn the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines. ConclusionThe butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.

Exploring the therapeutic mechanisms of Sijunzi decoction in the treatment of sarcopenia: Key targets and signaling pathways.

Sarcopenia, an age-associated condition, negatively impacts the quality of life. This study investigates the mechanism of Sijunzi decoction (SJZD), a traditional Chinese formula, against sarcopenia. Active compounds and potential targets of SJZD for sarcopenia were gathered from databases. Hub targets were identified using protein-protein interaction networks, with GO and KEGG analyses suggesting potential pathways. Molecular docking was used to assess compound-target affinity. A lipopolysaccharide-induced sarcopenia rat model was used to verify the targets. Sijunzi decoction contains 92 compounds and 47 targets for sarcopenia. The top 10 hub targets comprise AKT1, ALB, INS, IL6, TNF, TP53, VEGFA, SIRT1, CAT and FOS. GO and KEGG analyses indicate involvement in steroid hormone response, vesicle lumen, receptor agonist activity, and FoxO and HIF-1 signaling pathways. Validation experiments showed that SJZD alleviates sarcopenia by downregulating SIRT1, IL-6, TNF and AKT1. Sijunzi decoction treats sarcopenia by targeting SIRT1, IL-6, TNF and AKT1, potentially involving FoxO and HIF-1 signaling pathways. This highlights SJZD's potential for sarcopenia treatment.

Insight into the mechanism of Xiao–Chai–Hu–Tang alleviates irinotecan-induced diarrhea based on regulating the gut microbiota and inhibiting Gut β-GUS

BackgroundIrinotecan (CPT-11, Camptosar@) is a first-line drug for metastatic colorectal cancer. CPT-11-induced diarrhea, which is closely related to the concentrations of β-glucuronidase (β-GUS) and SN-38 in the gut, largely limits its clinical application. PurposeHerein, Xiao–Chai–Hu–Tang (XCHT), a traditional Chinese formula, was applied to mitigate CPT-11-induced toxicity. This study initially explored the mechanism by which XCHT alleviated diarrhea, especially for β-GUS from the gut microbiota. MethodsFirst, we examined the levels of the proinflammatory cytokines and the anti-inflammatory cytokines in the intestine. Furthermore, we researched the community abundances of the gut microbiota in the CPT-11 and XCHT-treated mice based on 16S rRNA high-throughput sequencing technology. Meanwhile, the level of SN-38 and the concentrations of β-GUS in intestine were examined. We also resolved the 3D structure of β-GUS from gut microbiota by X-ray crystallography technology. Moreover, we used virtual screening, SPR analysis, and enzyme activity assays to confirm whether the main active ingredients from XCHT could selectively inhibit β-GUS. ResultsIn XCHT-treated mice, the levels of the proinflammatory cytokines decreased, the anti-inflammatory cytokines increased, and the community abundances of beneficial Firmicutes and Bacteroidota improved in the gut microbiota. We also found that the concentrations of β-GUS and the level of SN-38, the major ingredient that induces diarrhea in the gut, significantly decreased after coadministration of XCHT with CPT-11 in the intestine. Additionally, we revealed the structural differences of β-GUS from different gut microbiota. Finally, we found that EcGUS had good affinity with baicalein and meanwhile could be selectively inhibited by baicalein from XCHT. ConclusionsOverall, XCHT could relieve the delayed diarrhea induced by CPT-11 through improving the abundance of beneficial gut microbiota and reduced inflammation. Furthermore, based on the three-dimensional structure, baicalein, especially, could be used as a candidate EcGUS inhibitor to alleviate CPT-11-induced diarrhea.

Xinshubao tablet ameliorates myocardial injury against heart failure via the DCN/PPARα/PGC-1α/P300 pathway

Heart failure (HF) is a complex clinical syndrome with impaired ventricular ability due to structural or functional cardiac disorders. A traditional Chinese formula named Xinshubao tablet (XSB) is reported to protect cardiomyocytes and decrease the risk of HF clinically; however, the underlying mechanism of XSB on decreasing HF risk is not elucidated yet. Therefore, our study aimed to investigate the therapeutic efficacy and underlying mechanism of XSB by using HF model rats and H9c2 cells with oxygen glucose deprivation. Echocardiographic and pathological features of animal experiment showed that XSB treatment effectively improved cardiac function and ameliorated myocardial injury after 4 weeks of treatment. Cellular experiments indicated that XSB pretreatment significantly inhibited apoptosis and increased mitochondrial energy metabolism. Furthermore, in vivo and in vitro experiments both demonstrated that XSB suppressed oxidative stress and inflammatory response. Our results further revealed that the potential protective mechanism of XSB was closely associated with the DCN/PPARα/PGC-1α/P300 signaling pathway. Our findings provide novel mechanistic insights for HF treatment and a pharmacological basis for the therapeutic application of XSB against cardiovascular disorders.

Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion——From the perspective of glial-vascular unit

Ethnopharmacological relevanceIschemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. Aim of the studyThis study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). Materials and methodsModels of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36 g/kg/day), JDHXD-M group (10.71 g/kg/day), JDHXD-H group (21.42 g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. ResultsIn rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). ConclusionsOur investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.

Post-Exposure Prophylaxis for COVID-19: A Systematic Review.

SARS-CoV-2 cause pneumonia can spread across the lung and lead to acute respiratory distress syndrome (ARDS) in severe cases. Post-exposure prophylaxis has shown great potential to prevent the transmission of some viral infections; however, such results for COVID-19 are still inconclusive. Therefore, the aim of this study was to systematically review the resources that utilized postexposure prophylaxis (PEP) for COVID-19 and the possible clinical benefits of such drugs. An organized search of relevant literature was done using the keywords and search queries on public databases of Cochrane, PubMed, Web of Science and Scopus from December 2019 to August 23, 2021. Original resources that had the inclusion criteria were included after two-phase title/abstract and full-text screenings. This review adhered to the Preferred Reporting Items for Systematic Reviews and MetaAnalysis (PRISMA) statement. Out of 841 retrieved records 17 resources were appropriate to include in the systematic review. Hydroxychloroquine with a daily dose of 400-800 mg and a duration of 5-14 days was the most frequently used agent for PEP. Chloroquine was recommended to use to control treatment in patients with mild to severe COVID-19 pneumonia. Other agents like Lopinavir-ritonavir (LPV/r), angiotensinconverting enzyme inhibitors (ACEIs), Angiotensin receptor blockers (ARBs), Vitamin D, arbidol, thymosin drugs, and Xin guan no.1 (XG.1, a Chinese formula medicine) have also been applied in some studies. Current evidence demonstrated no established clinical benefits of any drug as PEP in individuals with COVID-19. However, scarce indication occurs for the beneficial effects of some agents, but more studies are needed to explore such effects.

Exploring the Unique Morphological and Syntactic Features of Singlish (Singapore English)

Singapore is home to a number of significant ethnic groups, including Chinese, Malay, and Tamil, whose contributions have shaped the distinctive characteristics of Singlish in comparison to standard English. This study aims to examine the morphological and syntactic characteristics of Singlish, an English-based creole spoken in Singapore, emphasizing its impact on interethnic communication. Using comparative analysis, Singlish's morphological and syntactic characteristics were compared to those of standard English and the languages of the three largest ethnic groups in Singapore (Chinese, Malay, and Tamil). Examining grammatical patterns, word order, sentence structure, and the use of particular linguistic features would be required. The findings demonstrate that Singlish utilizes distinctive syntactic patterns that frequently incorporate Malay, Chinese, and Tamil grammatical formulas. Singlish, in contrast to standard English, lacks subject and object pronouns and frequently employs "sentence-ending particles" such as what, leh, lor, hah, and meh, in addition to lah. In addition, the copula be is frequently omitted before adjectives, nouns, and locatives in Singlish. In addition, the presence of word repetition and word drop in Singlish can be traced back to the Chinese dialect Hokkien. The Singaporean government has attempted to discourage the use of Singlish; however, this has sparked controversy due to the significance of the language in interethnic communication and its reflection of interethnic identity. As a result, Singlish is a fascinating subject for linguistic and sociological study, with significant implications for language education and policy.

Traditional Chinese formulas reduce hospitalization for infection among patients with systemic lupus erythematosus in Taiwan

IntroductionSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with many associated comorbidities. Disease activity and the long-term use of steroids or immunosuppressants are related to infection in SLE. Thus, identifying a safe complementary medicine, which can reduce inflammation and symptoms and can be used in conjunction with conventional SLE drugs, is necessary. MethodsThis study was designed to determine whether traditional Chinese medicine (TCM) formulas are associated with the infectious hospitalization rate of patients with SLE. A population-based retrospective cohort study covering 23,084 patients that were diagnosed with SLE from 1999 to 2009 was conducted. ResultsA total of 2638 incident cases of hospitalization among patients with SLE were due to infectious diseases. TCM users were significantly associated with a decreased risk of hospitalization for infectious diseases (hazard ratios = 0.85, 95% CI = 0.78–0.92). Other risk factors that were associated with increased risks of infectious hospitalization were old age, gender (male), hospitalization due to infectious diseases 1 year prior to diagnosis, low amount of insurance, comorbidities, and use of steroids and immunosuppressive agents. ConclusionThis study showed that TCM formulas were significantly associated with a decreased risk of infectious hospitalization among patients with SLE. TCM formulas may be used as a part of SLE treatments to decrease infectious hospitalization in SLE in the future. Health promotion programs can be planned in accordance with the risk factors associated with the increased risk of infectious hospitalization of SLE in response to disease burden and cost.

Liang-Ge-San inhibits dengue virus serotype 2 infection by reducing caveolin1-induced cytoplasmic heat shock protein 70 translocation into the plasma membrane

Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n=10) and AG129 mice (n=8) were used to examine the protective effects of LGS. It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.