Tuo-Min-Ding-Chuan Decoction Alleviates Airway Inflammations in the Allergic Asthmatic Mice Model by Regulating TLR4-NLRP3 Pathway-Mediated Pyroptosis: A Network Pharmacology and Experimental Verification Study.

Background: Tuo-Min-Ding-Chuan Decoction (TMDCD) is an effective traditional Chinese medicine (TCM) formula granule for allergic asthma (AA). Previous studies proved its effects on controlling airway inflammations, while the specific mechanism was not clear. Methods: We conducted a network pharmacology study to explore the molecular mechanism of TMDCD against AA with the public databases of TCMSP. Then, HUB genes were screened with the STRING database. DAVID database performed GO annotation and KEGG functional enrichment analysis of HUB genes, and it was verified with molecular docking by Autodock. Then, we built a classic ovalbumin-induced allergic asthma mice model to explore the mechanism of anti-inflammation effects of TMDCD. Results: In the network pharmacology study, we found out that the potential mechanism of TMDCD against AA might be related to NOD-like receptor (NLR) signaling pathway and Toll-like receptor (TLR) signaling pathway. In the experiment, TMDCD showed remarkable effects on alleviating airway inflammations, airway hyperresponsiveness (AHR), and airway remodeling in the asthmatic mice model. Further molecular biology and immunohistochemistry experiments suggested TMDCD could repress TLR4-NLRP3 pathway-mediated pyroptosis-related gene transcriptions to inhibit expressions of target proteins. Conclusion: TMDCD could alleviate asthmatic mice model airway inflammations by regulating TLR4-NLRP3 pathway-mediated pyroptosis.

Molecular Mechanism Underlying Effects of Wumeiwan on Steroid-Dependent Asthma: A Network Pharmacology, Molecular Docking, and Experimental Verification Study.

Background: Steroid-dependent asthma (SDA) is characterized by oral corticosteroid (OCS) resistance and dependence. Wumeiwan (WMW) showed potentials in reducing the dose of OCS of SDA patients based on our previous studies. Methods: Network pharmacology was conducted to explore the molecular mechanism of WMW against SDA with the databases of TCMSP, STRING, etcetera. GO annotation and KEGG functional enrichment analysis were conducted by metascape database. Pymol performed the molecular docking. In the experiment, the OVA-induced plus descending dexamethasone intervention chronic asthmatic rat model was conducted. Lung pathological changes were analyzed by H&E, Masson, and IHC staining. Relative expressions of the gene were performed by real-time PCR. Results: A total of 102 bioactive ingredients in WMW were identified, as well as 191 common targets were found from 241 predicted targets in WMW and 3539 SDA-related targets. The top five bioactive ingredients were identified as pivotal ingredients, which included quercetin, candletoxin A, palmidin A, kaempferol, and beta-sitosterol. Besides, 35 HUB genes were obtained from the PPI network, namely, TP53, AKT1, MAPK1, JUN, HSP90AA1, TNF, RELA, IL6, CXCL8, EGFR, etcetera. GO biological process analysis indicated that HUB genes were related to bacteria, transferase, cell differentiation, and steroid. KEGG pathway enrichment analysis indicated that the potential mechanism might be associated with IL-17 and MAPK signaling pathways. Molecular docking results supported these findings. H&E and Masson staining proved that WMW could reduce airway inflammation and remodeling of model rats, which might be related to the downward expression of IL-8 proved by IHC staining and real-time PCR. Conclusion: WMW could be a complementary and alternative therapy for SDA by reducing airway inflammation.

Xuefu Zhuyu decoction improves asthma-induced asthenozoospermia based on network pharmacology and in vivo experiment.

This study aimed to verify that Xuefu Zhuyu decoction (XFZYD) can improve asthenozoospermia caused by asthma, and explore its potential mechanism. Ovalbumin solution is used to induce asthma rat models. Sperm concentration and motility are used to evaluate semen quality. Immunohistochemistry (IHC), Western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) are used to detect proteins and mRNA related to rat testis tissue. Haematoxylin and eosin (H&E) staining was used to observe changes in testicular tissues. Through network pharmacology, eriodictyol, 18-ß-glycyrrhetinic acid, naringenin, chrysin and Hispidulin were prominent active ingredients of XFZYD. We found that XFZYD regulates the expression levels of albumin (ALB), vascular endothelial growth factor A (VEGFA), interleukin 6 (IL-6) protein and mRNA, thereby improving the histopathological morphology of the testis, increasing the concentration and motility of spermatozoa. We suggest that future research can increase the detection of hormones and oxidative stress and other related indicators, so as to conduct more in-depth exploration.

Study on the Mechanism of Jiawei Shengjiang Powder in Improving Male Asthma-Induced Asthenospermia Based on Network Pharmacology and Bioinformatics.

BACKGROUND: Jiawei Shengjiang Powder (JWSJP) is a classical Chinese medicinal formula, which has been widely applied in the treatment of asthma and complications for many years due to its curative effect. AIM: To verify the effect of JWSJP in improving abnormal sperm motility caused by asthma and to explore its potential mechanism. MATERIALS AND METHODS: The active compounds of JWSJP were obtained from high performance liquid chromatography tandem mass spectrometry and the Traditional Chinese Medicine System Pharmacology. The key active components and targets of JWSJP were predicted based on network pharmacological analysis and bioinformatics research. Rats were randomly divided into normal, model and treatment groups. The rat model of allergic asthma was induced by intraperitoneal injection of ovalbumin solution. The experiment judged improvement of semen quality by evaluating sperm motility, and detected the expression of related proteins in testicular tissue of Sprague-Dawley rats by RT-qPCR and Western blot methods. Hematoxylin and eosin (HE) staining was used to observe the changes in testicular tissue structure in rats. RESULTS: Through the analysis of network pharmacology and bioinformatics, it was found that beta-sitosterol, quercetin, gallic acid, pelargonidin and kaempferol were the key active components of Jiawei Shengjiang Powder. Tumor necrosis factor (TNF), interleukin-6 (IL-6) and insulin (INS) genes are crucial targets of JWSJP in the treatment of spermatogenic dysfunction caused by acute asthma. After 8 weeks of intervention, compared with the model group, the treatment group had significantly improved sperm motility (P < 0.05). There were significant differences in TNF, IL6, and INS proteins in the treatment group, and the HE staining of testicular tissue structure in the treatment group was significantly improved. CONCLUSION: JWSJP can improve the abnormal sperm motility induced by asthma, and its mechanism may be related to the expression of related proteins and mRNA of TNF, IL6, and INS.

Traditional Chinese medicine on treating ureteral calculi: A systematic review and meta-analysis protocol.

BACKGROUND: Ureteral calculi generally refer to the temporary obstruction of the human body after the ureteral stenosis. When the ureteral stones are not discharged in time, they can grow in the original site, causing the patient to have corresponding clinical manifestations, such as: renal colic, hematuria, etc, when severe, can cause renal obstruction and hydronephrosis, seriously endangering the patient's health. Ureteral calculi usually occur in young and middle-aged people. The peak age of the disease is between 20 and 50 years old. It also occurs in the young and middle-aged labor force. The men incidence rate is 2 to 3 times that of women. Ureteral calculi is one of the current refractory diseases, and the effect after treatment with integrated Chinese and Western medicine is remarkable. METHODS AND ANALYSIS: We will search for PubMed, Cochrane Library, AMED, EMbase, WorldSciNet; Nature, Science online and China Journal Full-text Database (CNKI), China Biomedical Literature CD-ROM Database (CBM), and related randomized controlled trials included in the China Resources Database. The time is limited from the construction of the library to November 2018. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata13.0 software for meta-analysis of the effectiveness, recurrence rate, and symptom scores of ureteral. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for ureteral. Because all of the data used in this systematic review and meta-analysis has been published, this review does not require ethical approval. Furthermore, all data will be analyzed anonymously during the review process Trial.Registration number: PROSPERO CRD42019137095.