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Gedan Jiangya Decoction (GJD), a Chinese herbal medicine composed of six botanical medicines, was designed to treat hypertension (patent published number (CN114246896A)). The overexpression of the ERK (extracellular signal-regulated kinase) signaling pathway is essential in developing left ventricular hypertrophy (LVH). This study aimed to evaluate GJD's effects on LVH in spontaneously hypertensive rats (SHRs) and examine its potential mechanisms on Ras/ERK1/2 pathway regulation. Thirty-five ten-week-old SHRs were randomly assigned to one of five groups: GJD low dosage, medium dose, high dose, model, and captopril. Wistar–Kyoto (WKY) rats served as the control group. All rats received a 6-week treatment. The following parameters were measured: systolic (SBP) and diastolic blood pressure (DBP), left ventricular mass index (LVMI), and serum TGF-beta1. The pathologic structure was determined by H & E staining and Masson. TGF-beta1, Ras, ERK1/2, and C-Fos levels were determined using western blotting and real-time qPCR. SBP, DBP, and LVMI were reduced significantly in the GJD group compared with the model group. GJD inhibited TGF-beta1, Ras, ERK1/2, and C-Fos expression in LVH. In conclusion, GJD reduced the Ras/ERK1/2 pathway expression, which decreased hypertension-induced heart hypertrophy. GJD may protect hypertension-induced myocardial hypertrophy by altering gene expression patterns in the heart. [ABSTRACT FROM AUTHOR]

Primary hypertension is understood as a disease with diverse etiology, a complicated pathological mechanism, and progressive changes. Gedan Jiangya Decoction (GJD), with the patent publication number CN114246896A, was designed to treat primary hypertension. It contains six botanical drugs; however, the underlying mechanism is uncertain. We utilized network pharmacology to predict the active components, targets, and signaling pathways of GJD in the treatment of primary hypertension. We also investigated the potential molecular mechanism using molecular docking and animal experiments. The Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the Protein Database (UniProt), and a literature review were used to identify the active components and related targets of GJD's pharmacological effects. The GeneCards, Online Mendelian Inheritance in Man (OMIM), Therapeutic Target Database (TTD), and DrugBank databases were utilized to identify hypertension-related targets. Based on a Venn diagram of designed intersection targets, 214 intersection targets were obtained and 35 key targets for the treatment of hypertension were determined using the STRING data platform and Cytoscape software. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of key targets revealed that the relevant molecular action pathways of GJD in the treatment of hypertension include the Toll-like receptor, MAPK, PI3K-Akt, and renin-angiotensin signaling pathways. A GJD active ingredient-key target-pathway connection diagram was created using Cytoscape software, and 11 essential active components were selected. Molecular docking was then used to verify the binding activity of key targets and key active ingredients in GJD to treat primary hypertension. The results of this study indicate that AGTR1, AKT1 with puerarin, EDNRA with tanshinone IIA, MAPK14 with daidzein, MAPK8 with ursolic acid, and CHRM2 with cryptotanshinone had high binding activity to the targets with active components, whereas AGTR1 was selected as target genes verified by our experiment. HPLC was utilized to identify the five active ingredients. Experiments in high-salt rats demonstrated that GJD might decrease the expression of AGTR1 in the kidney and thoracic aorta while increasing the expression of eNOS by preventing the activation of the renin-angiotensin pathway, thereby reducing lowering systolic and diastolic blood pressure. [ABSTRACT FROM AUTHOR]

Objective. The aims of this study were to investigate the impact of TAK-242 on the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) signal transduction pathway in rats with hepatic fibrosis (HF) using the liver gut axis and to investigate the molecular mechanism of its intervention on HF. Methods. SPF grade SD male rats were randomly allocated to the control, model, and TAK-242 groups. For 8 weeks, the model and TAK-242 groups received 3 mL·kg-1 (the initial dose 5 mL·kg-1) intraperitoneal injections of 40% CCL4 olive oil solution. TAK-242 (5 mg·kg-1) was administered once a day for 5 days after modeling. The pathological alterations of liver and small intestine tissues in each group were observed using H&E and Masson staining. ELISA was used to measure serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin (DBIL), total bilirubin (TBIL), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). RT-qPCR was utilized to identify the mRNA expression level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB in rat liver and small intestine tissues. The protein level of IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB protein in rat liver and small intestine tissues was determined utilizing Western blot and IHC. Results. TAK-242 significantly reduced AST, ALT, TBIL, and DBIL expression in HF rats' serum (P < 0.01) and alleviated liver tissue injury. Hematoxylin-eosin (H&E) and Masson staining revealed inflammatory cell infiltration and fibrous proliferation in the liver and small intestine tissue in the model group and partial cell swelling in the TAK-242 group, which indicated a considerable improvement compared to the model group. RT-qPCR, Western blot, and IHC data indicated that TAK-242 reduced the IL-1β, IL-6, TNF-α, TLR4, MyD88, and NF-κB expression in the liver and small intestine tissues of HF rats. Conclusion. TAK-242 might downregulate the TLR4/MyD88/NF-κB signal pathway through the liver-gut axis, suppress the inflammatory response, and eventually alleviate HF in rats. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect and possible mechanism of extracts of Xuanshen (Scrophularia Root, Radix Scrophulariae) on liver metabolome in rat model of hyperthyroidism. Methods The rat liver metabolites spectrums effected by Euthyrox and Xuanshen extracts were analyzed by using ultra high performance liquid chromatography-time off light-mass spectrometry (UPLCTOFMS). The difference in metabolites spectrums was studied between blank group and model group by using orthogonal partial least squares-discriminant analysis (OPLS DA). The potential biomarkers were found in liver through variable importance projection (VIP). The interventional effects of Xuanshen extracts were discussed through comparing the difference in content of potential biomarkers. Results There were 21 potential biomarkers found in rat liver in model group, and among them 14 metabolites were significantly called back by Xuanshen extracts. The biosynthesis of glycosylphosphatidylinositol (GPI)-anchor, and metabolisms of arachidonic acid, purine, α-linolenic acid, linoleic acid, glutathione and glycerophospholipid were significantly improved by Xuanshen extracts in Euthyrox induced hyperthyroidism rat model. Conclusion Xuanshen extracts can play a role of treating hyperthyroidism through improving relevant liver potential biomarkers and metabolism pathways in hyperthyroidism rat model. [ABSTRACT FROM AUTHOR]

Rhizoma Dioscoreae Nipponicae (RDN) is an herbal medicine. In the theories of Traditional Chinese Medicine (TCM), the function of RDN is to expel wind and remove dampness. Inflammatory mechanisms play an important role in the pathological process and prognosis of acute gouty arthritis (AGA). The aim of this study was to determine the specially expressed proteins through testing the proteins of the synovium in rats with AGA. The animal model of AGA was set up by Monosodium urate crystal (MSU) combined with hypoxanthine (HX), which was ameliorated in our previous experiment. Blood samples for measurement of serum uric acid were collected prior to sacrifice. Outcomes were assessed (two days after injection) by histological stain and protein quantitation. Three chips of RayBioⓇ Human Label-based Antibody Array I were applied to detect 90 proteins in the synovium tissue of AGA rats. 14 differently expressed proteins were found in the synovium of AGA rats, and nine of them were first found in this model. There were seven up-regulated and seven down-regulated proteins, both TRAIL and Neuropilin-2 could be identified as key contributors to the pathomechanism of AGA. [ABSTRACT FROM AUTHOR]

This study describes the metabonomics of fevers in animal models and the therapeutic effects of Rhizoma coptidis extract (RCE) on them. The rat urinary samples were analyzed by UPLC/ ESI-Q-TOF/MS, combined with principal component analysis (PCA). Nine ions were chosen to characterize the similarities and differences in the responses to fever. The ion at m/z 206.0278 was unambiguously identified to be xanthurenic acid. This study demonstrated that the metabonomic approach can readily distinguish between febrile and healthy individuals. This data support the contention that the metabonomic approach represents a promising new technology for the development of rapid-throughput in vivo fever screening. Furthermore, this approach can detect the interfering effects of RCE. This investigation has led the authors to believe that metabonomics is a valid approach for explaining the therapeutic effects of traditional Chinese medicine on fevers. [ABSTRACT FROM AUTHOR]