RESUMO
Electroacupuncture (EA) is a popular therapeutic therapy for premature ovarian insufficiency (POI). However, little has been known about the underlying processes of EA therapy. To investigate the benefit of EA and reveal the mechanism, thirty SD female rats were allocated into the control, model, sham, EA, and GnRHa groups at random. Vaginal smears were used to monitor the rats' estrous cycle. Serum liver and renal function (ALT, AST, BUN, and Cr), sex hormone (FSH, E2, and AMH), oxidative stress markers (SOD, GSH, and MDA), and inflammatory cytokine (IL6, IL1ß, and TNFα) levels were measured by enzyme-linked immunosorbent assay (ELISA). Their ovary morphology was observed by hematoxylin-eosin staining. Transmission electron microscope was used to remark the ultrastructure of the granulocytes. Protein and gene expressions of Keap1/Nrf2/HO-1 pathway were detected by western blot and RT-PCR. Compared with the model group, in the EA group, the levels of serum sex hormones recovered to normal levels. Moreover, it reduced oxidative stress in rats, as demonstrated by increased SOD and GSH levels and decreased MDA levels. Meanwhile, Keap1 mRNA and protein expression dropped considerably in the EA group, while the mRNA and protein expressions of Nrf2 and HO-1 increased. We found that preventive EA might rescue rats with CTX-induced ovarian dysfunction. The anti-inflammatory and antioxidative stress properties of EA, which elevated the Keap1/Nrf2/HO-1 signaling pathway, might be the underlying mechanism. Furthermore, as compared to GnRHa, electroacupuncture did not raise the burden of the liver (ALT and AST) or the kidney (BUN and Cr). Electroacupuncture has a meaningful impact and a sufficient level of safety, making it useful for therapeutic setting in POI.
Assuntos
Eletroacupuntura , Insuficiência Ovariana Primária , Animais , Ciclofosfamida , Feminino , Inflamação , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/terapia , RNA Mensageiro/metabolismo , Ratos , Superóxido Dismutase/metabolismoRESUMO
The roots of Codonopsis cordifolioidea (classified as campanulaceae cordifolioidea), locally known as Tsoong, have been used as a tonic food. The major components isolated from Tsoong have been demonstrated to present antihuman immunodeficiency virus1 activities and cytotoxicity against various tumor cell lines. However, the possible effects of the novel compound isolated from Tsoong, cordifoliketones A, on pancreatic ductal adenocarcinoma (PDAC) cells, are still unknown. In the present study, cordifoliketones A extractions were prepared from Tsoong, and the possible effects on PDAC cell growth, apoptosis, migration and invasion in vitro and in vivo were exlored. The cytotoxicity assay, apoptosis assay, western blotting, migration and invasion assay, and a PDAC cell (AsPC1, BxPC3 and PANC1) xenograft mice model were employed. The results demonstrated that treatment with cordifoliketones A: i) inhibited proliferation and promoted apoptosis of PDAC cells; ii) significantly induced apoptosis and altered expression of apoptosisassociated proteins in a dosedependent manner; iii) suppressed migration and invasion of PDAC cells in a dosedependent manner; and iv) restrained the growth of PDAC neoplasm in nude mice. Furthermore, cordifoliketones A demonstrated noncytotoxic activity in a panel of normal human cells, including hTERTHPNE, 293, hepatocyte HL7702 and HL1 cells. Therefore, these data indicated that cordifoliketones A may be a potential candidate compound for the prevention of PDAC cell proliferation and metastasis, presumably by induction apoptosis and inhibiting viability, invasion and migration of PDAC cells.