Curculiginis Rhizoma Ameliorates Kidney-Yang Deficiency in Castrated Rats via PI3K/Akt Signaling Pathway
10.13422/j.cnki.syfjx.20240639
- VernacularTitle:基于PI3K/Akt通路探讨仙茅改善去势大鼠肾阳虚的作用机制
- Author:
Meng YANG
1
;
Lu WANG
2
;
Zijia ZHANG
1
;
Zhengtao WANG
1
;
Ying XU
1
Author Information
1. The MOE Key Laboratory for Standardization of Chinese Medicines and the Shanghai Key Laboratory for Compound Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
2. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
- Publication Type:Journal Article
- Keywords:
Curculiginis Rhizoma;
kidney-Yang deficiency;
network pharmacology;
phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(20):46-53
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the effect and mechanism of Curculiginis Rhizoma in ameliorating kidney-Yang deficiency in castrated rats. MethodThe targets of Curculiginis Rhizoma and male reproductive diseases due to kidney-Yang deficiency were screened from relevant databases by network pharmacology, and key targets were screened out according to topological eigenvalues. After that, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to obtain the pathways of Curculiginis Rhizoma in treating kidney-Yang deficiency. The rat model of kidney-Yang deficiency was established by castration. The rats were assigned into model, testosterone propinate (2 mg·kg-1), and low-, medium-, high-dose (0.14, 0.28, 0.56 g·kg-1, respectively) Curculiginis Rhizoma groups. Another 8 healthy male rats with first incising and then suturing were used as the sham group. The rats were administrated with corresponding agents by gavage once a day for 6 consecutive weeks. During the experiment, the general conditions of rats in each group were observed, and their body mass was recorded. At the end of the experiment, the indexes of accessory sex organs were calculated, and the pathological changes of the seminal vesicle glands and prostate glands were observed by hematoxylin-eosin (HE) staining. The serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay. The results of the network pharmacological prediction were verified by animal experiments, and the expression levels of related genes and proteins were determined by real-time polymerase chain reaction and Western blot, respectively. ResultThe biological functions enriched mainly involved four overexpression modules including regulation of cell responses to various stimuli, metabolic responses, regulation of intracellular signal transduction, and regulation of reproduction. Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway was a significantly enriched pathway for the core target and also a pathway with the highest enrichment factor in the biological process of regulating cell responses to stimuli. The results of animal experiments showed that compared with the model group, low-dose Curculiginis Rhizoma group increased the body weight gain (P<0.05). In addition, high-dose Curculiginis Rhizoma group increased the seminal vesicle gland index and epididymis index (P<0.05). The administration with Curculiginis Rhizoma ameliorate epithelial cell hyperplasia of the seminal vesicle glands, did not attenuate the vacuolar degeneration, mitigated the enlarged vesicular lumen of the prostate gland, changing of epithelial cells of the glands from flattened to cubic and columnar shapes, and cellular disarrangement, and reduced the mesenchymal stroma thickness. Compared with the model group, all the intervention measures elevated the levels of FSH, LH, T, and IL-6 (P<0.05, P<0.01) and up-regulated the mRNA and protein levels of PI3K and the mRNA levels of Akt in the epididymis tissue (P<0.05). ConclusionCurculiginis Rhizoma can alleviate the T level reduction and accessory sex organ atrophy in castrated rats by regulating the PI3K/Akt signaling pathway.