Pharmacodynamic structure of deer antler base protein and its mammary gland hyperplasia inhibition mechanism by mediating Raf-1/MEK/ERK signaling pathway activation

Sun, Shiqing; Zhang, Kai; Wang, Yuliang; Zhou, Zijun; Wang, Lihong; Zhao, Hong

doi:10.1039/d2fo03568e

Cited by 7 publications

(2 citation statements)

References 31 publications

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“…Activated RAF kinase phosphorylates the downstream MEK, promoting RAF-mediated activation of MEK. Activated MEK then doubly phosphorylates ERK, which can translocate to the cell nucleus and activate various transcription factors [ 74 , 75 ]. ERK is involved in the proper function of antimicrobial programs in host cells [ 76 , 77 ] and, in particular, plays a crucial role in the regulation of pBD-3 [ 78 ].…”

Section: Discussionmentioning

confidence: 99%

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Xue,

Jia,

Cao

et al. 2024

J Animal Sci Biotechnol

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Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases. Oleanolic acid (OA) is a pentacyclic triterpene that is ubiquitous in plants. Our previous work demonstrated the protective effect of OA on intestinal health, but the underlying molecular mechanisms remain unclear. This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli (ETEC) in piglets. The key molecular role of bile acid receptor signaling in this process has also been explored. Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets (P < 0.05). OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum (P < 0.05). This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets. In addition, as a natural ligand of bile acid receptors, OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR (P < 0.05). Specifically, OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway (P < 0.05). Furthermore, OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR (P < 0.05), thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells. Conclusions In conclusion, our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response, which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Xue,

Jia,

Cao

et al. 2024

J Animal Sci Biotechnol

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“…[ 1 ] The main cause of HMG is the secretion of estradiol (E2) and progesterone (P), which leads to excessive proliferation of mammary epithelial cells and breast tissue hyperplasia. [ 2 ] This disease has a high potential for developing into breast cancer and may be diagnosed as early breast cancer. The incidence of cancer in HMG ranges from 2% to 4%.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology

Li,

Tai,

Zhang

et al. 2024

Medicine

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This study utilized network pharmacology to investigate the effects of Xiaoyaosan (XYS) on the intervention of hyperplasia of mammary glands (HMG) by targeting specific genes and signaling pathways. The active ingredients and targets of XYS, which consisted of 8 traditional Chinese medicines (TCM), were identified using TCMSP. The gene targets associated with HMG were obtained from the GeneCards Database, and the intersection data between the 2 was integrated. Cytoscape 3.8.1 software was used to construct a network diagram illustrating the relationship between compounds, drug active ingredients, target proteins, and the disease. The protein-protein interaction network diagram was generated using STRING, and the core targets were analyzed. A total of 133 active ingredients in XYS and 7662 active ingredient targets were identified. Among them, 6088 targets were related to HMG, and 542 were common targets between the active ingredients and the disease. The protein-protein interaction (PPI) core network contained 15 targets, with 5 key targets playing a crucial role. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses have indicated that XYS has the potential to treat HMG by interfering with the AGE-RAGE signaling pathway in diabetic complications, the MAPK signaling pathway, and the PI3K-Akt signaling pathway. Additionally, molecular docking studies have shown excellent binding properties between the drug components and key targets. Thus, this study provides a theoretical foundation for a better understanding of the pharmacological mechanism and clinical application of XYS in the comprehensive treatment of HMG.

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The anti‐hyperplasia effect of polysaccharide from Prunella vulgaris L. on mammary gland hyperplasia in rats through regulation of the AKT‐FOXO3a signaling pathway and intestinal flora

Zhao,

Yang,

Zhou

et al. 2024

J Sci Food Agric

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BACKGROUNDPrunella vulgaris L., a medicinal and edible homologous plant, is often used to treat conditions such as breast hyperplasia, thyroid enlargement and lymphatic tuberculosis. Research has demonstrated that it is particularly effective in the treatment of mammary gland hyperplasia (MGH). However, the material basis and mechanism of its efficacy are still unclear.RESULTSOur results showed that in rats with MGH, polysaccharide from Prunella vulgaris L. (PVP) led to a reduction in the levels of estradiol, prolactin and malondialdehyde, while simultaneously increasing the concentrations of progesterone (P), superoxide dismutase (SOD), manganese superoxide dismutase (MnSOD) and catalase (CAT) in the serum. In addition, results obtained from 16S rRNA sequencing demonstrated that PVP had the capacity to increase the richness and diversity of the intestinal microbiota in MGH rats, as well as modify the structure of the microbiota. Correlation analysis revealed that the levels of P, SOD, MnSOD and CAT were positively associated with Allobaculum, Romboutsia, Faecalibaculum and Clostridium, while negatively correlated with Turicibacter.CONCLUSIONSThe mechanism of PVP in treating MGH might be through inhibiting the phosphorylation of the AKT‐FOXO3a signaling pathway and then activating the expression of downstream antioxidant enzymes, such as MnSOD and CAT. At the same time, PVP could restore intestinal flora homeostasis in rats with MGH by regulating the flora changes of Allobaculum, Romboutsia, Clostridium and Faecalibaculum, thereby reducing oxidative stress in rats with MGH. © 2024 Society of Chemical Industry.

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Pharmacodynamic structure of deer antler base protein and its mammary gland hyperplasia inhibition mechanism by mediating Raf-1/MEK/ERK signaling pathway activation

Abstract: Mammary gland hyperplasia (MGH) is a common mammary disease whose main pathogenesis is the disruption of estradiol (E2) and progesterone (P) secretion, thereby causing overproliferation of mammary epithelial cells and...

Cited by 7 publications

References 31 publications

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Mechanisms underlying the therapeutic effects of Xiaoyaosan in treating hyperplasia of mammary glands based on network pharmacology

The anti‐hyperplasia effect of polysaccharide from Prunella vulgaris L. on mammary gland hyperplasia in rats through regulation of the AKT‐FOXO3a signaling pathway and intestinal flora

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