ABSTRACT
The purpose of this study was to investigate the renal protective effect of celastrol on diabetic rats. Furthermore, the mechanism of its action was discussed whether it was related to MAPK/NF-κB signaling pathway. There were a total of 36 rats. Six rats were randomly chosen as the control group. The remaining 30 rats were given 1% streptozotocin intraperitoneal injection (50 mg/kg) and were randomly divided into five groups: the model control group, the low-dose celastrol group, the high-dose celastrol group, the Tripterygium wilfordii polyglycosides group, and the MAPK/NF-κB inhibitor group. After 4 weeks of continuous administration, 24-hr urine volume, urinary protein, blood urea nitrogen, and serum creatinine content were observed, and hematoxylin-eosin (HE) staining of the kidney and liver were evaluated. p38MAPK was designated by immunohistochemical method, and NF-κB p65 in renal tissue was detected by western blotting. Our results showed that celastrol could not only reduce contents of creatinine and urea nitrogen in blood but also reduce excretion of urinary protein in diabetic rats, improve renal pathological injury, and down-regulate the expression of p38MAPK and NF-κB p65. In conclusion, celastrol could protect kidney of diabetic rats by regulating the signal pathway of MAPK/NF-κB, inhibiting inflammation and delaying renal injury.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Kidney , NF-kappa B , Tripterygium , Triterpenes , Animals , Male , Rats , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/drug therapy , Kidney/drug effects , Kidney/pathology , NF-kappa B/drug effects , NF-kappa B/metabolism , Pentacyclic Triterpenes , Rats, Sprague-Dawley , Transcription Factor RelA/metabolism , Tripterygium/chemistry , Triterpenes/pharmacology , Triterpenes/therapeutic useABSTRACT
Benign prostatic hyperplasia (BPH) is a common disease in the current ageing male population. This research aims to study the effects of Kelong-Capsules (KLC) on testosterone-induced BPH. Thirty rats were randomly divided into normal group, model group, and three treatment groups. Three treatment groups were given KLC (3.6 g/kg), KLC (7.2 g/kg), and finasteride (0.9 mg/kg), respectively, for 28 days after establishing the animal model. The BPH rat models were evaluated by Traditional Chinese Medicine (TCM) symptoms and prostate index (PI). Results indicated that three treatment groups all alleviated the pathological changes of prostate and kidney at different levels. Compared with the model group, the PI of the groups treated with KLC (7.2 g/kg) and finasteride decreased significantly. The expressions of NF-E2 related factor 2 (Nrf-2) and quinine oxidoreductase (NQO1) in the group treated with KLC (3.6 g/kg) increased markedly (p < 0.01). The cyclooxygenase-2 (COX-2) protein expression of the group treated with KLC (7.2 g/kg) was increased (p < 0.01). In conclusion, KLC could obviously inhibit the growth of prostate, and KLC (3.6 g/kg) could promote the expressions of Nrf2 and NQO1.
ABSTRACT
BACKGROUND: Pancreatic adenocarcinoma (PAC) is one of the most fatal cancers due to its high degree of malignancy, increasing incidence, high mortality, and unsatisfactory treatment efficacy. Evidence has suggested that numerous microRNAs (miRNAs), including miR-126 and miR-34a, have potent tumor-suppressing effects on PAC, implicating a possible application of miRNA in tumor therapy. However, the therapeutic effect of a single miRNA on pancreatic cancer is limited. METHODS: We simultaneously delivered miR-126 and miR-34a into PAC cells by a carcinoembryonic antigen promoter-driven oncolytic adenovirus (AdCEAp-miR126/34a), and examined the antitumor efficacy of the therapeutic system in in vitro and in vivo experiments. RESULTS: In vitro cytological experiments found that the expression levels of miR-126 and miR-34a were specifically increased in the AdCEAp-miR126/34a-infected PAC cells, and the antitumor efficacy was enhanced in aspects of cancer cell viability, migration, invasion, and apoptosis, by synergistically combining the antitumor effects of overexpressed miR-126 and miR-34a and the oncolytic effect of viral replication specifically in PAC cells. The expression levels of miR-126 target genes (vascular endothelial growth factor-A and SOX2) and miR-34a target genes (cyclin D1, E2F1, and Bcl-2) were markedly decreased in the PAC cells after being infected with AdCEAp-miR126/34a. Notable suppression of the therapeutic system on tumor growth was also proven in established PAC xenograft tumor models in nude mice, which demonstrated that the combination of miR-126 and miR-34a exerts more effective antitumor outcomes than a single miRNA. CONCLUSION: The therapeutic system co-expressing miR-126 and miR-34a mediated by oncolytic adenovirus is a promising system for PAC target therapy.