Efficacy of astragalus combined with renin-angiotensin-aldosterone system blockers in the treatment of stage III diabetic nephropathy: a systematic review and meta-analysis.

OBJECTIVE: To determine the efficacy and safety of Astragalus combined with renin-angiotensin-aldosterone system (RAAS) blockers in treating stage III diabetic nephropathy (DN) by meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Wiley, and Web of Science databases were searched for articles published between August 2007 and August 2022. Clinical studies on Astragalus combined with RAAS blockers for the treatment of stage III DN were included. Meta-analysis was performed by RevMan 5.1 and Stata 14.3 software. RESULTS: A total of 32 papers were included in this meta-analysis, containing 2462 patients from randomized controlled trials, with 1244 receiving the combination treatment and 1218 solely receiving RAAS blockers. Astragalus combined with RAAS blockers yielded a significantly higher total effective rate (TER) (mean difference [MD] 3.63, 95% confidence interval [CI] 2.59-5.09) and significantly reduced urinary protein excretion rate (UPER), serum creatinine (Scr), blood urine nitrogen (BUN) and glycosylated hemoglobin (HbAlc) levels. In subgroup analysis, combining astragalus and angiotensin receptor blocker significantly lowered fasting plasma glucose (FPG) and 24 h urinary protein (24hUTP) levels, compared with the combined astragalus and angiotensin-converting enzyme inhibitor treatment. Meanwhile, the latter significantly decreased the urinary microprotein (ß2-MG). Importantly, the sensitivity analysis confirmed the study's stability, and publication bias was not detected for UPER, BUN, HbAlc, FPG, or ß2-MG. However, the TER, SCr, and 24hUTP results suggested possible publication bias. CONCLUSIONS: The astragalus-RAAS blocker combination treatment is safe and improves outcomes; however, rigorous randomized, large-scale, multi-center, double-blind trials are needed to evaluate its efficacy and safety in stage III DN.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are commonly used to treat diabetic neuropathy (DN) and Astragalus membranaceus components are known to improve DN symptoms.We aimed to establish the efficacy and safety of using Astragalus combined with RAAS inhibitors.Astragalus combined with RAAS inhibitors enhances the total effective rate of diabetic neuropathy response to treatment and reduces urinary protein excretion rate, serum creatinine, blood urea nitrogen and HbAlc.Sensitivity analysis affirms study stability, while publication bias was detected for total effective rate, serum creatinine, and 24 h urinary protein levels.

Exploring the potential mechanisms of Danshen against COVID-19 via network pharmacology analysis and molecular docking.

Danshen, a prominent herb in traditional Chinese medicine (TCM), is known for its potential to enhance physiological functions such as blood circulation, immune response, and resolve blood stasis. Despite the effectiveness of COVID-19 vaccination efforts, some individuals still face severe complications post-infection, including pulmonary fibrosis, myocarditis arrhythmias and stroke. This study employs a network pharmacology and molecular docking approach to investigate the potential mechanisms underlying the therapeutic effects of candidate components and targets from Danshen in the treatment of complications in COVID-19. Candidate components and targets from Danshen were extracted from the TCMSP Database, while COVID-19-related targets were obtained from Genecards. Venn diagram analysis identified common targets. A Protein-Protein interaction (PPI) network and gene enrichment analysis elucidated potential therapeutic mechanisms. Molecular docking evaluated interactions between core targets and candidate components, followed by molecular dynamics simulations to assess stability. We identified 59 potential candidate components and 123 targets in Danshen for COVID-19 treatment. PPI analysis revealed 12 core targets, and gene enrichment analysis highlighted modulated pathways. Molecular docking showed favorable interactions, with molecular dynamics simulations indicating high stability of key complexes. Receiver operating characteristic (ROC) curves validated the docking protocol. Our study unveils candidate compounds, core targets, and molecular mechanisms of Danshen in COVID-19 treatment. These findings provide a scientific foundation for further research and potential development of therapeutic drugs.

Experimental Verification of Erchen Decoction Plus Huiyanzhuyu Decoction in the Treatment of Laryngeal Squamous Cell Carcinoma Based on Network Pharmacology.

BACKGROUND: The prescription of Chinese herbal medicine (CHM) consists of multiple herbs that exhibit synergistic effects due to the presence of multiple components targeting various pathways. In clinical practice, the combination of Erchen decoction and Huiyanzhuyu decoction (EHD) has shown promising outcomes in treating patients with laryngeal squamous cell carcinoma (LSCC). However, the underlying mechanism by which EHD exerts its therapeutic effects in LSCC remains unknown. METHODS: Online databases were utilized for the analysis and prediction of the active constituents, targets, and key pathways associated with EHD in the treatment of LSCC. The protein-protein interaction (PPI) network of common targets was constructed and visualized using Cytoscape 3.8.1 software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the functional roles of core targets within the PPI network. Protein clustering was conducted utilizing the MCODE plug-in. The obtained results highlight the principal targets and pathways involved. Subsequently, clinical samples were collected to validate alterations in the levels of these main targets through Western blotting (WB) and immunohistochemistry (IHC). Furthermore, both in vivo and in vitro experiments were conducted to investigate the therapeutic effects of EHD on healing LSCC and elucidate its underlying mechanism. Additionally, to ensure experimental reliability and reproducibility, quality control measures utilizing HPLC were implemented for EHD herbal medicine. RESULTS: The retrieval and analysis of databases in EHD medicine and LSCC disease yielded a total of 116 overlapping targets. The MCODE plug-in methods were utilized to acquire 8 distinct protein clusters through protein clustering. The findings indicated that both the first and second clusters exhibited a size greater than 6 scores, with key genes PI3K and ErbB occupying central positions, while the third and fourth clusters were associated with proteins in the PI3K, STAT3, and Foxo pathways. GO functional analysis reported that these targets had associations mainly with the pathway of p53 mediated DNA damage and negative regulation of cell cycle in terms of biological function; the death-induced signaling complex in terms of cell function; transcription factor binding and protein kinase activity in terms of molecular function. The KEGG enrichment analysis demonstrated that these targets were correlated with several signaling pathways, including PI3K-Akt, FoxO, and ErbB2 signaling pathway. On one hand, we observed higher levels of key genes such as P-STAT3, P-PDK1, P-Akt, PI3K, and ErbB2 in LSCC tumor tissues compared to adjacent tissues. Conversely, FOXO3a expression was lower in LSCC tumor tissues. On the other hand, the key genes mentioned above were also highly expressed in both LSCC xenograft nude mice tumors and LSCC cell lines, while FOXO3a was underexpressed. In LSCC xenograft nude mice models, EHD treatment resulted in downregulation of P-STAT3, P-PDK1, PI3K, P-AKT, and ErbB2 protein levels but upregulated FOXO3a protein level. EHD also affected the levels of P-STAT3, P-PDK1, PI3K, P-AKT, FOXO3a, and ErbB2 proteins in vitro: it inhibited P-STAT3, P-AKT, and ErbB2, while promoting FOXO3a; however, it had no effect on PDK1 protein. In addition, HPLC identified twelve compounds accounting for more than 30% within EHD. The findings from this study can serve as valuable guidance for future experimental investigations. CONCLUSION: The possible mechanism of EHD medicine action on LSCC disease is speculated to be closely associated with the ErbB2/PI3K/AKT/FOXO3a signaling pathway.

Mechanism of network pharmacology of Erzhi Pill and Erxian Decoction in treating climacteric syndrome with "treating the same disease with different methods": A review.

Network pharmacology and molecular docking methods were used in the present study to clarify the molecular mechanism of two traditional Chinese medicine prescriptions of climacteric syndrome. Based on oral availability and drug similarity, the main active components of Erzhi Pill and Erxian Decoction were screened through the platform of traditional Chinese medicine system pharmacology. The target database of climacteric syndrome was established by using GENECARD, OMIM, PharmGKB, Targets and Drugbank. The "component - target" network diagram was constructed using Cytoscape software (version 3.8.2). Topology analysis, module analysis, and GO and KEGG enrichment analyses were used to explore the core target and action pathway of Erzhi Pill-Erxian Decoction for treating climacteric syndrome of same disease with different treatments. There were 16 active components and 103 corresponding targets found in Erzhi Pill; 69 active components and 121 corresponding targets were found in Erxian Decoction; and 100 potential targets were found in Erzhi Pill and Erxian Decoction. Through network analysis, topology and module analysis, TP53, AKT1, Jun, ESR1, IL1B, CASP3, MMP9, PTGS2, HIF1A, MYC and EGFR could be considered as potential targets of the 2 prescriptions for alleviating climacteric syndrome. The effects of Erzhi pill and Erxian Decoction on climacteric syndrome are mainly in the pathway of lipid and atherosclerosis, AGE-RAGE signaling pathway and PI3K-Akt signaling pathway in diabetic complications. The active components in Erzhi Pill - Erxian Decoction, such as quercetin, show considerable potential as a candidate drug for the treatment of climacteric syndrome.

Meta-analysis of the efficacy of Er Chen Tang in the adjuvant treatment of obesity: A study protocol for systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the efficacy of Er Chen Tang in the adjuvant treatment of obesity. METHODS: A computerized search of databases such as CNKI, Wanfang, Wipro, EMBase, Web of Science, PubMed, and Cochrane Library was performed to collect randomized controlled trials on the application of Er Cheng Tang for the treatment of obesity and to track the references included in the literature, with a timeframe from the establishment of the library to October 2023 for the searches. After selection of trials, extraction of information and assessment of methodological quality were done independently by 2 evaluators, meta-analysis was performed using RevMan 5.3 software and the quality of evidence was evaluated using the Cochrane system. RESULTS: Six studies were included, with a total of 438 study participants. They were randomized into trial and control groups. The total cholesterol, triglyceride, low-density lipoprotein cholesterol, body mass index, and visceral fat area values before treatment were compared between the 2 groups, and the differences were not statistically significant (all P > .05). After treatment, the indicators of the experimental group were significantly better than those of the control group, and the differences were all statistically significant (P < .05). CONCLUSION: The adjuvant treatment of obesity with Er Chen Tang can improve the symptoms faster and is favorable to the reduction of various risk indicators. However, due to the lack of high-quality literature, the theoretical support of large-sample double-blind randomized trials is still needed in the future.

Effect of herbal medicine on postoperative nausea and vomiting after laparoscopic surgery: A systematic review and meta-analysis.

BACKGROUND: Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting (PONV), especially after laparoscopic surgery, remains limited. This review aimed to evaluate the efficacy and safety of herbal medicine as an alternative therapy to prevent and manage nausea and vomiting after laparoscopic surgery compared with untreated, placebo, and Western medicine groups. METHODS: We searched 11 databases, including EMBASE, PubMed, and the Cochrane Library, to collect randomized controlled trials (RCTs) of herbal medicines on PONV after laparoscopic surgery on July 7, 2022. Two independent reviewers screened and selected eligible studies, extracted clinical data, and evaluated the quality of evidence using the Cochrane risk-of-bias tool. The primary outcome was the incidence of PONV, whereas the secondary outcomes included the frequency and intensity of PONV, symptom improvement time, antiemetic requirement frequency, and incidence of adverse events. Review Manager Version 5.3. was used for the meta-analysis. RESULTS: We identified 19 RCTs with 2726 participants comparing herbal medicine with no treatment, placebo, and Western medicine. The findings showed that compared with no treatment, herbal medicine demonstrated significant effects on vomiting incidence (risk ratio [RR] = 0.43, 95% confidence interval [CI] 0.32-0.57, P < .00001). Compared with placebo, herbal medicine revealed a significant effect on the severity of nausea 12 hours after laparoscopic surgery (standardized mean difference = -2.04, 95% CI -3.67 to -0.41, P = .01). Herbal medicines showed similar effects with Western medicine on the incidence of postoperative nausea (RR = 0.94, 95% CI 0.63-1.42, P = .77) and vomiting (RR = 0.68, 95% CI 0.25-1.84, P = .45). Furthermore, comparing the experimental group containing herbal medicine and control group excluding herbal medicine, adverse events were considerably lower in the group with herbal medicine (RR = 0.45, 95% CI 0.27-0.72, P = .001). CONCLUSION: Herbal medicine is an effective and safe treatment for nausea and vomiting secondary to laparoscopic surgery. However, the number of studies was small and their quality was not high; thus, more well-designed RCTs are warranted in the future.

Exploring the potential of Huangqin Tang in breast cancer treatment using network pharmacological analysis and experimental verification.

AIMS OF THIS STUDY: This study aims to investigate the potential of Huangqin Tang (HQT), a traditional Chinese medicine formulation, in the treatment of breast cancer (BC) through a comprehensive approach integrating network pharmacology, molecular docking, and experimental validation. METHODS: Chemical composition and target information of HQT were collected using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Disease-related target genes were obtained from the GeneCards database. Network pharmacological analysis, including construction of compound-disease-target networks and protein-protein interaction networks, was performed. Molecular docking simulations were conducted to evaluate the binding affinity between HQT components and key targets. Experimental validation was carried out using cell viability assays, clone formation assays, flow cytometry, Western blotting, and pathway analysis. RESULTS: A total of 210 candidate targets were identified. Network analysis revealed STAT3, AKT1, MAPK3 etc. as central targets. Enrichment analysis suggested HQT may exert anti-tumor effects through regulating lipid metabolism and inflammation related pathways. Molecular docking showed that the key compounds baicalein, wogonin, kaempferol and quercetin all bound effectively to MAPK1. The binding of baicalein to IL6 and naringenin to TNF-α was also relatively stable. The experimental results demonstrated that HQT effectively inhibited the proliferation of breast cancer cells, with IC50 values of 2.334 mg/mL and 1.749 mg/mL in MCF-7 cells at 24 h and 48 h, and IC50 values of 1.286 mg/mL and 1.496 mg/mL in MDA-MB-231 cells at 24 h and 48 h, respectively. Furthermore, HQT induced cell cycle arrest at the G2/M phase in breast cancer cells and downregulated the expression of related proteins including CDK1, Cyclin B1, CDK2, and Cyclin E. Additionally, HQT promoted apoptosis in breast cancer cells by upregulating the expression of Bak and CC-3, while downregulating the expression of Bcl-2. Notably, HQT also exhibited regulatory effects on the HIF-1 signaling pathway. CONCLUSIONS: This study provides insights into the potential multi-component and multi-target mechanisms of HQT against BC, suggesting it may achieve therapeutic effects through regulating inflammatory response and cancer-related pathways via the identified active compounds and targets. The findings highlight the importance of integrating traditional medicine with modern approaches for the development of novel cancer therapies.

Experimental verification about treatment of Bu-Shen-Yi-Jing-Fang in Alzheimer's disease by the analysis of the feasible signaling pathway of network pharmacology.

CONTEXT: Bu-shen-yi-jing-fang (BSYJF) has been reported to reduce amyloid-ß (Aß)1-42 deposition in the brain of APP/PS1 mice and ameliorate cognitive function. However, its neuroprotective mechanism remains unclear. OBJECTIVE: This study aims to investigate whether BSYJF exerts a protective effect on Aß1-42-induced oxidative stress injury and explore its possible mechanism. MATERIALS AND METHODS: The platform databases TCMSP, Swiss, TTD, DrugBank, and GeneCards were used to mine the targets of Alzheimer's disease (AD) and BSYJF. The platform databases STRING and Metascape were used to build the interaction network of the target protein, and Cytoscape software was used to analyze this network and screen out the key pathways. Aß1-42-treated SKNMC cells were established to verify the mechanism of BSYJF and the key proteins. The downstream proteins and antioxidants as well as apoptosis and ferroptosis of the PI3K/AKT/Nrf2 signaling pathway were validated using an in vitro SKNMC cell model experiment. The expression levels of related proteins were detected using Western blotting. Flow cytometry and immunofluorescence staining were used to analyze apoptosis and ferroptosis. RESULTS: Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis considered the key signal pathways, mainly involving the PI3K/AKT signaling pathway. Experimental validation demonstrated that BSYJF treatment markedly increased the activity of the PI3K/AKT pathway, which could exert anti-AD effects. CONCLUSIONS: Our data provided compelling evidence that the protective effects of BSYJF might be associated with their regulation of the PI3K/AKT/Nrf2 signaling pathway. These studies offered a potential therapy for natural herbal medicine treatment of AD.

The Antihypertensive Effects and Mechanisms of Huotan Jiedu Tongluo Decoction in Rats with H-Type Hypertension.

H-type hypertension, which is a specific form of hypertension characterized by elevated plasma homocysteine (Hcy) levels, has become a major public health challenge worldwide. This study investigated the hypotensive effects and underlying mechanisms of Huotan Jiedu Tongluo decoction (HTJDTLD), a highly effective traditional Chinese medicine formula commonly used to treat vascular stenosis. Methionine was used to induce H-type hypertension in rats, and HTJDTLD was administered intragastrically. Then, the systolic and diastolic blood pressures of the caudal artery of rats were measured by noninvasive rat caudal manometry. Histological assessment of the aorta was performed by hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to measure Hcy levels, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting were used to determine the mRNA and protein levels of Glucose regulatory protein 78 (GRP78), Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), c-Jun N-terminal kinases (JNK), and caspase-3. The results showed that HTJDTLD significantly lowered blood pressure, alleviated histopathological lesions, and decreased Hcy levels after methionine treatment. Moreover, HTJDTLD significantly inhibited the gene and protein expression of GRP78, JNK, TRAF2, and caspase 3, which are involved mainly in the endoplasmic reticulum (ER) stress-induced apoptosis pathway. Overall, the results indicated that HTJDTLD had effective antihypertensive effects in rats with H-type hypertension and revealed the antihypertensive mechanisms associated with inhibition of ER stress-induced apoptosis pathway activation.

Chemical composition analysis of Qingyan dropping pills using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

RATIONALE: This study developed a method for the rapid classification and identification of the chemical composition of Qingyan dropping pills (QDP) to provide the theoretical basis and data foundation for further in-depth research on the pharmacological substance basis of the formula and the selection of quality control indexes. METHODS: Ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and data postprocessing technology were used to analyze the chemical composition of QDP. The fragmentation information on possible characteristic fragments and related neutral losses was summarized based on the literature and was compared with the MS data obtained from the assay, and thus a rapid classification and identification of chemical components in QDP could be achieved. RESULTS: A total of 73 compounds were identified, namely 24 flavonoids, 14 terpenoids, 30 organic acids and their esters, 3 alkaloids, and 2 phenylpropanoids. CONCLUSIONS: In this study, UHPLC-Q-TOF-MS and data postprocessing technology were used to realize the rapid classification and identification of the chemical constituents of QDP, which provided a comprehensive, efficient, and fast qualitative analysis method, a basis for further quality control and safe medication of QDP.

Integrated multicomponent analysis based on ultra-high-performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry and network pharmacology to elucidate the effective constituents and potential mechanism of Zhibai Dihuang pill in treating childhood precocious puberty.

RATIONALE: Childhood precocious puberty (CPP) is a common pediatric endocrine disorder with significant associated risks. Zhibai Dihuang pill (ZBDHP), a classic recipe of the Qing dynasty with its efficacy of nourishing yin and clearing heat, can downregulate the expression of ESR1 in the uterus and ovaries, thereby inhibiting CPP. However, as of now, the main active ingredients and pharmacological mechanisms of ZBDHP remain unclear. METHODS: A comprehensive approach was proposed using ultra-high-performance liquid chromatography coupled with quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS) and network pharmacology to explore the potentially active constituents of ZBDHP and reveal the underlying mechanisms against CPP. Molecular docking was used to verify the possible mechanisms. RESULTS: A total of 214 constituents derived were identified via UHPLC-Q-Exactive Orbitrap-MS, and 12 of them were definitely characterized using reference standards. Subsequently, compounds tetrahydropalmatine, alisol C, 25-anhydroalisol A 11-acetate, hispidone, cavidine, alisol E, melianone, neogitogenin, denudatin B, and 16ß-hydroperoxyalisol B with related targets PIK3CA, HSD11B1, CYP19A1, AR, PTGS2, CDK2, NR3C1, MMP2, MMP1, and MAPK1 were regarded as key components and targets for ZBDHP treating CPP using the compound-target-pathway network. Besides, the results revealed that the pathways conduced obviously to therapeutic efficacy, including pathways in cancer, neuroactive ligand-receptor interaction, and cyclic adenosine monophosphate（cAMP） signaling pathways. Molecular docking indicated that PIK3CA, HSD11B1, and CYP19A1 exhibited high affinities to corresponding compounds. Overall, the study determined the multicomponent, multitarget, and multipathway mechanisms of ZBDHP against CPP. CONCLUSIONS: This study provided a new method for exploring the chemical constituents and pharmacology mechanism of traditional Chinese medicine.

Evidence Construction of Chuankezhi Injection Against Chronic Obstructive Pulmonary Disease: A Systematic Review and Network Pharmacology.

Objective: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology. Research Methods: Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. Results: A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure. Conclusion: This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.

Determination of the signaling proteins responsible for the antioxidant potential of the Yishenhuoxue formula for treating asthenospermia in rats.

Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant potential of traditional Chinese medicine, the Yishenhuoxue (YSHX) formula, in treating polyglycosides of Tripterygium wilfordii (GTW)-induced asthenospermia in rats. Fifty male rats were randomly divided into the normal, model, and treatment groups. HE staining was used to evaluate the improvement of spermatogenic function of rats, and TBA reaction, qRT-PCR, Western Blot and other methods were used to determine the changes of oxidative stress indicators and to evaluate the improvement of antioxidant capacity of rats by YSHX. Comparison with the model group showed significant improvement in pathological damage caused by GTW to seminiferous tubules. MDA and NO content in rat testes decreased, especially in middle- and high-dosage groups. No significant changes were observed in SOD and CAT activity or mRNA expression. GSH-Px activity and GSH mRNA expression were significantly higher in the low-dosage group than in the model group. Compared to the model group, GR activity was significantly lower in the middle and high dosage groups, while the mRNA expression was higher. The PKC-beta level increased, while p-ERK1/2, NF-κB, and the ratio of p-ERK1/2*(ERK1/2)-1 decreased significantly in the treatment groups. Therefore, YSHX can alleviate GTW-induced testicular damage, enhance GSH-Px activity, regulate GSH redox cycling, and mitigate oxidative stress injury. Furthermore, YSHX can promote PKC-beta expression and inhibit the phosphorylation of ERK1/2 and NF-κB. Using YSHX may be an effective way to increase sperm motility via the PKC-ERK1/2-NF-ĸB axis.

Unraveling the treatment effects of huanglian jiedu decoction on drug-induced liver injury based on network pharmacology, molecular docking and experimental validation.

Huanglian Jiedu Decoction (HJD) is a well-known Traditional Chinese Medicine formula that has been used for liver protection in thousands of years. However, the therapeutic effects and mechanisms of HJD in treating drug-induced liver injury (DILI) remain unknown. In this study, a total of 26 genes related to both HJD and DILI were identified, which are corresponding to a total of 41 potential active compounds in HJD. KEGG analysis revealed that Tryptophan metabolism pathway is particularly important. The overlapped genes from KEGG and GO analysis indicated the significance of CYP1A1, CYP1A2, and CYP1B1. Experimental results confirmed that HJD has a protective effect on DILI through Tryptophan metabolism pathway. In addition, the active ingredients Corymbosin, and Moslosooflavone were found to have relative strong intensity in UPLC-Q-TOF-MS/MS analysis, showing interactions with CYP1A1, CYP1A2, and CYP1B1 through molecule docking. These findings could provide insights into the treatment effects of HJD on DILI.

Efficacy of an herbal formula Guixiong Yimu San in preventing retained placenta and improving reproductive performance in cows.

Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P < 0.01, OR = 0.335), a lower puerperal metritis risk (8.8% vs. 20.1%, P < 0.01, OR = 0.369), and a reduced need for additional therapeutic antibiotics (11.2% vs. 26.1%, P < 0.01, OR = 0.342). We observed increases in the first service conception rate (59.7% vs. 49.1%, P < 0.01) and conception rate within 305 days postpartum (93.2% vs. 85.5%, P < 0.01) in the GYS group than in the control group. A significant decrease was observed in the number of services per conception (1.8 ± 1.1 vs. 2.1 ± 1.4, P < 0.01) and the calving-to-conception interval (83.6 ± 39.6 vs. 96.6 ± 52.5 days, P < 0.01) between the two groups. Additionally, GYS treatment increased milk yield on days 7, 14, and 28 postpartum without affecting milk fat, milk protein, somatic cell count (SCC), or milk urea nitrogen (MUN) on days 7 and 28 postpartum. Accordingly, the GYS was effective and safe in preventing retained placenta and to improve reproductive performance in cows. Therefore, it could be a prophylactic intervention for superior postpartum fertility in cows.

Shen'ge Formula Protects Cardiac Function in Rats with Pressure Overload-Induced Heart Failure.

Background: In China, Shen'ge formula (SGF), a Traditional Chinese Medicine blend crafted from ginseng and gecko, holds a revered place in the treatment of cardiovascular diseases. However, despite its prevalent use, the precise cardioprotective mechanisms of SGF remain largely uncharted. This study aims to fill this gap by delving deeper into SGF's therapeutic potential and underlying action mechanism, thus giving its traditional use a solid scientific grounding. Methods: In this study, rats were subjected to abdominal aortic constriction (AAC) to generate pressure overload. Following AAC, we administered SGF and bisoprolol intragastrically at specified doses for two distinct durations: 8 and 24 weeks. The cardiac function post-treatment was thoroughly analyzed using echocardiography and histological examinations, offering insights into SGF's influence on vital cardiovascular metrics, and signaling pathways central to cardiac health. Results: SGF exhibited promising results, significantly enhanced cardiac functions over both 8 and 24-week periods, evidenced by improved ejection fraction and fractional shortening while moderating left ventricular parameters. Noteworthy was SGF's role in the significant mitigation of myocardial hypertrophy and in fostering the expression of vital proteins essential for heart health by the 24-week mark. This intervention markedly altered the dynamics of the Akt/HIF-1α/p53 pathway, inhibiting detrimental processes while promoting protective mechanisms. Conclusion: Our research casts SGF in a promising light as a cardioprotective agent in heart failure conditions induced by pressure overload in rats. Central to this protective shield is the modulation of the Akt/HIF-1α/p53 pathway, pointing to a therapeutic trajectory that leverages HIF-1α promotion and p53 nuclear transport inhibition.

Jianpi-Tiaoqi decoction inhibits tumour proliferation and lung metastasis in tumour-bearing mice with triple-negative breast cancer.

Traditional Chinese medicine, specifically the Jianpi Tiaoqi (JPTQ) decoction, has been explored for its role in treating breast cancer, particularly in inhibiting lung metastasis in affected mice. Our study evaluated the effects of JPTQ on several factors, including tumour growth, apoptosis, angiogenesis, epithelial-to-mesenchymal transition (EMT) and immune microenvironment regulation. We used bioluminescence imaging to observe in situ tumour growth and potential lung metastasis. Transcriptomic analysis provided insights into gene expression, whereas flow cytometry was used to examine changes in specific immune cells, such as CD4+ T cells and myeloid-derived suppressor cells. Several essential proteins and genes, including vascular endothelial growth factor (VEGF), matrix metalloprotein-9 (MMP-9) and B-cell lymphoma 2 (Bcl-2), were assessed through quantitative real-time polymerase chain reaction, western blotting and immunohistochemistry. Our findings showed that JPTQ treatment inhibited tumour proliferation in cancer-bearing mice. Bioluminescence imaging and pathological analysis indicated a reduction in lung metastasis. Transcriptome analysis of lung and tumour tissues indicated that the genes associated with EMT, angiogenesis, proliferation and apoptosis were regulated in the JPTQ-treated group. Kyoto Encyclopedia of Genes and Genomes analysis suggested enrichment of immune-related pathways. Flow cytometry indicated that JPTQ treatment reduced the proportion of monocyte-myeloid-derived suppressor cells in the lung and increased the number of CD4+ T cells in the peripheral blood and the number of T helper 1 (Th1) cells in the spleen (P < 0.05). E-cadherin and cleaved caspase 3 were upregulated, whereas Snail, Bcl-2, Ki67 and VEGF were downregulated in the lung and tumour tissues; moreover, the expression of MMP-9 was downregulated in the lung tissue (P < 0.05). In essence, JPTQ not only inhibits tumour growth in affected mice, but also promotes positive immune responses, reduces angiogenesis, boosts tumour cell apoptosis, reverses EMT and decreases breast cancer lung metastasis.

Association of Cytokines with Clinical Indicators in Patients with Drug-Induced Liver Injury.

Objective: To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury (DILI) caused by different drugs and their correlation with clinical indicators. Method: The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests (RUCAM) scoring criteria and clinically diagnosed with DILI. Based on Chinese herbal medicine, cardiovascular drugs, non-steroidal anti-inflammatory drugs (NSAIDs), anti-infective drugs, and other drugs, patients were divided into five groups. Cytokines were measured by Luminex technology. Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results: 73 patients were enrolled. Age among five groups was statistically different ( P = 0.032). Alanine aminotransferase (ALT) ( P = 0.033) and aspartate aminotransferase (AST) ( P = 0.007) in NSAIDs group were higher than those in chinese herbal medicine group. Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in patients with Chinese herbal medicine (IL-6: P < 0.001; TNF-α: P < 0.001) and cardiovascular medicine (IL-6: P = 0.020; TNF-α: P = 0.001) were lower than those in NSAIDs group. There was a positive correlation between ALT ( r = 0.697, P = 0.025), AST ( r = 0.721, P = 0.019), and IL-6 in NSAIDs group. Conclusion: Older age may be more prone to DILI. Patients with NSAIDs have more severe liver damage in early stages of DILI, TNF-α and IL-6 may partake the inflammatory process of DILI.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway.

BACKGROUND: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. METHODS: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. RESULTS: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. CONCLUSION: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.