Mechanism of Yanghe Pingchaun granules on airway remodeling in asthmatic rats based on IL-6/JAK2/STAT3 signaling axis

Objective: To investigate the effects of Yanghe Pingchuan Granules on airway remodeling in asthmatic rats, and to explore the mechanism of Interleukin-6/Janus kinase 2/ Signal transducing activator of transcription 3(IL-6/JAK2/STAT3) signal axis. Methods: We separated 42 healthy male SD rats into two groups, a control group (7) and a model group (35).The model group was sensitized with a combination of ovalbumin (OVA) and aluminum hydroxide for 2 weeks, while the control group was given an equal amount of physiological saline.After 2 weeks, the modeling group was randomly divided into Model group, Yanghe Pingchuan Granules high, medium and low dose groups and Dexamethasone group, each group consisted of 7 animals. After 4 weeks, OVA atomization and gavage were used for stimulation and treatment. Yanghe Pingchuan Granules high, middle and low groups were given 15.48, 7.74, 3.87 g∙kg-1 Yanghe Pingchuan Granules daily, dexamethasone group was given 0.0625 mg∙kg-1 dexamethasone daily, and the other groups were given the same amount of normal saline. HE, PAS and Masson staining were used to observe the lung histopathological changes in rats. The levels of interleukin-6, IL-23 and IL-17A were detected by ELISA. The expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 in lung tissues were detected by Western blot. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of IL-6, JAK2 and STAT3 in rat lung tissue. Results: The lung tissue structure of the model group was severely damaged compared to the control group, accompanied by a great many of inflammatory cell infiltration, goblet cell hyperplasia, subepithelial collagen fiber deposition and airway epithelial thickening were more obvious. The expressions of IL-6, IL- 23 and IL-17A in serum were significantly increased (P<0.01), the protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and the mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly increased (P<0.01);Compared with the model group, inflammatory cell infiltration, goblet cell proliferation, subepithelial collagen fiber deposition and airway epithelial thickening were significantly reduced in each administration group, and the expressions of IL-6, IL-23 and IL-17A in serum were significantly decreased (P< 0.01). The protein expression levels of JAK-2, P-JAK2, STAT3 and P-STAT3 and mRNA expression levels of IL-6, JAK2 and STAT3 in lung tissue were significantly decreased (P<0.01). Conclusion: Yanghe Pingchuan Granules can significantly alleviate airway remodeling in asthmatic rats, and its mechanism may be through inhibiting the IL-6/JAK2/STAT3 signal axis.

Role of Yanghe Huayan Decoction in ER-PI3K/Akt/mTOR pathway of endocrine-resistant breast cancer cells with low mTOR expression

Objective:To study the mechanism of action of Yanghe Huayan Decoction on endocrine-resistant cells(MCF-7R/mTOR cells)with low expression of mTOR;Methods:CCK-8 assay and cell clone assay were used to detect cell proliferation and clonal ability,and flow cytometry was used to detect cell apoptosis.The changes of cytokines in ER-PI3K/Akt/mTOR signaling pathway were analyzed by blot and QPCR.Results:Yanghe Huayan Decoction could significantly affect the proliferation(p<0.05)and cloning ability(p<0.05)of MCF-7R/mTOR cells,promote cell apoptosis(p<0.01),and downregulate the expression of ER,PI3K,AKT,mTOR and p-mTOR(p<0.05).Conclusion:Yanghe Huayan Decoction can regulate the ER-PI3K/Akt/mTOR signaling pathway with multiple targets,and the use of combined mTOR inhibitors can regulate the ER-PI3K/Akt/mTOR signaling pathway more significantly.

The clinical application of Yanghe Decoction

Yanghe Decoction is a representative prescription of such prescriptions as warming up the yang and dissipating the cold.It has the functions of warming the blood and dispelling cold and stagnation.Yanghe Decoction has effects on many diseases.The principle of this kind of disease is blood deficiency and yang,and the clinical manifestation is cold stagnation.Such diseases often occur in multiple systems and in multiple aspects.This article summarizes the compatibility of Yanghe Decoction and its clinical application by reviewing the related literature analysis in recent years,and provides a broad idea for the application of Yanghe Decoction.

Potential Mechanisms of Yanghe Decoction in the Treatment of Soft Tissue Sarcoma and Arteriosclerosis Obliterans Based on Network Pharmacology

Objective The objective of this study was to investigate potential mechanisms of Yanghe Decoction(YHD)in treating soft tissue sarcoma(STS)and arteriosclerosis obliterans(ASO)based on the use of network pharmacology.Methods Candidate compounds and potential targets were identifed through the TCM Systems Pharmacology database and a comprehensive literature search.Related targets of STS and ASO were collected in the GeneCards database,DisGeNET database,and Drugbank database.Furthermore,The STRING 11.0 database was used to determine protein-protein interaction(PPI)networks;common targets were obtained and imported into Cytoscape 3.7.2.Then,a PPI network comprising common targets was drawn,and network topology analysis was performed to screen for key shared targets.Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key shared targets were performed by using Metascape software.Subsequently.a compound-target-pathway network was constructed via Cytoscape 3.7.2.Results The following signaling pathways were found to be associated with the mechanisms of YHD in treating STS and ASO:AGE-RAGE signaling pathway,IL-17 signaling pathway;HIF-1 signaling pathway,TNF signaling pathway,interactions between cytokines and cytokine receptors,Th17 cell differentiation,and NOD-like receptor signaling pathway.Among the compounds and targets involved in these pathways,quercetin,luteolin,and kaempferol were found to be core compounds,and TNF,IL-6,and MAPK1 were found to be core targets.Conclusion Taken together,our findings elucidated that potential mechanisms of YHD in treating STS and ASO involved cellular proliferation/differentiation,angiogen-esis,inflammation,immune responses,oxidative stress,and other related signaling pathways.

Yanghe decoction(阳和汤)attenuated pain hypersensitivity induced by michigan cancer foundation-7 injection in rats with bone metastases from breast cancer by inhibiting transient receptor potential ankyrin 1

OBJECTIVE:To study the effect and underlying mechanisms of Chinese medicine Yanghe decoction(阳和汤)on pain relief in a rat model of bone metastasis of breast cancer induced by michigan cancer foundation-7(MCF-7).METHODS:Bone pain was induced in the tibia of rats injected with MCF-7 cells.The Chinese herbal remedy was used to decoct Yanghe decoction for the treatment of bone pain rats.The behavior study was carried out to evaluate the paw mechanical withdraw threshold and thermal withdraw latency.Liquid chromatography-mass spectrometry,Western blotting,quantitative real-time polymerase chain reaction,enzyme-linked immunosorbent assay(ELISA),immunohistochemical(IHC)staining were performed for analysis.RESULTS:Yanghe decoction could improve the defensive behavior similar to the transient receptor potential ankyrin 1(TRPA1)inhibitor.In morphology study,Yanghe decoction could attenuate the cellular growth as well as inflammatory infiltration in the metastasis group.Furthermore,Yanghe decoction downregulated the TRPA1 expression on the dorsal root ganglion from the metastatic rats at both transcriptional and protein level.Yanghe decoction alleviated the inflammation in metastatic tissues by hematoxylin-eosin and IHC analysis,and Yanghe decoction also reduced the inflammatory cytokines production in the serum including tumor necrosis factor-αand interleukin-6,interleukin-1 beta by ELISA.As the cytochromec oxidase subunit II/prostaglandin E2(PGE2)is required for cancer development,Yanghe decoction reduced the expression of PGE2 in the tissue and serum.CONCLUSION:Taken together,Yanghe decoction protected the rats from breast cancer bone metastasis through TRPA1 signaling mediated neuropathic pain and additional immune modulation in tumor microenvironment.

STAGES OF THE NEOTECTONIC MOVEMENT IN THE MENYUAN BASIN, QINGHAI PROVINCE

The Menyuan Basin is a structural basin located inside the Qilianshan Mountains, the northern edge of Qinghai—Tibet Plateau, the surface of which is about 3000m ASL. To the south of this basin is the Dabanshan Mountain and to the north, the Lenglongling Mountain, which are 4000m ASL.. The neotectonic movement within this area is intense and can be divided into 6 stages.1 The basic data for identifying the stages of the neotectonic movement (1) Deformation of Tertiary deposit: Of the Tertiary system, only Baiyanghe Formation exists in the studied area, distributing at the boundary and under the bottom of the basin with Quaternary deposits discontinuously overlying it. Baiyanghe Formation has been intensely offset and folded, the folding dose not appear in Quaternary deposits. Its exact age remains unknown.(2) Deformation of Quaternary deposits: Most of Quaternary deposits belong to glacial and fluvial deposits, which have been offset and uplifted or sunk by neotectonic movement.(3) Deformation of the geomorphic surfaces: In the studied area exist many types and many orders of geomorphic surfaces, including 2 orders of planation surfaces, 3 orders of glacial platforms, 3 orders of river terraces and 2 orders of alluvial fans. Their ages are dated or comparatively estimated. All of them have been offset and uplifted or subsided by neotectonic movement. They are the time scales for dividing the stages of neotectonic movement.

Research Progress on Classical Prescriptions in Treating Mammary Glands Hyperplasia

According to Zhongjing Zhang's academic thought,gynecological diseases mostly result from deficiency,accumulated cold,and qi stagnation,so the treatment of gynecological miscellaneous diseases should take qi and blood as the general principle,and focus on the liver.The pathogenesis of mammary glands hyperplasia(MGH)is liver and kidney deficiency,disharmony of the thoroughfare vessel and the conception vessel,the causes of which are emotional imbalance,liver qi depression,and failure of transportation due to spleen deficiency.The superficial causes include qi stagnation,phlegm coagulation,and blood stasis,which are mainly related to the liver,spleen,kidney,the thoroughfare vessel,and the conception vessel.In clinical treatment of MGH,Xiaochaihu Decoction or Sini Powder can be used for qi stagnation syndrome,Xiao Xianxiong Decoction for phlegm coagulation syndrome,Guizhi Fuling Pill or Dahuang Zhechong Pill for spleen deficiency syndrome,and Wenjing Decoction for the deficiency-cold syndrome.