Protective effects of oleanolic acid on oxidative stress and the expression of cytokines and collagen by the AKT/NF-κB pathway in silicotic rats

Abstract

Oleanolic acid (OA), a natural pentacyclic triterpenoid, has been reported to have several benefits and medicinal properties. However, its protective effects against silica‑induced lung injury and fibrosis remain to be elucidated. The aim of the present study was to investigate the effects of OA on oxidative stress, and the expression of cytokines and collagen in silicotic rats. Male rats were induced by intratracheal instillation of silicosis (250 mg/kg), with the exception of the control group (NS). The rats in the OA group were intragastrically administered with OA (60 mg/kg/d). The rats in the solvent control group were gavaged daily with 0.6% sodium carboxymethyl cellulose (10 ml/kg) solution for 56 consecutive days. The data showed that OA significantly attenuated the extent of silicosis fibrosis by histopathologic analysis of the lung tissues. In addition, oxidative stress activated by silica exposure, as evidenced by increasing of malondialdehyde content, and activities of superoxide dismutase and glutathione peroxidase in the lung, was regulated by treatment with OA. Furthermore, enzyme‑linked immunosorbent assay analysis showed that OA significantly decreased the levels of tumor necrosis factor‑α and transforming growth factor‑β1. Immunohistochemistry analysis showed that OA significantly decreased collagen types I and III. In investigating the mechanisms underlying the action of OA, it was found that OA decreased the level of phosphorylated AKT1, which in turn inactivated the transcriptional of nuclear factor (NF)‑κB in the development and progress of silicosis. In conclusion, these results suggested that the protective effects of OA were due, at least in part, to its anti‑oxidant activity and its ability to decrease the expression of cytokines and collagen by modulating the AKT/NF‑κB pathway.

HO-1 alleviates cholesterol-induced oxidative stress through activation of Nrf2/ERK and inhibition of PI3K/AKT pathways in endothelial cells

“…Several studies have shown that oxidative stress can decrease the expression of several survival signaling molecules, including PI3K, p-AKT and Bcl-2. PI3K pathway activation is involved in cell proliferation and cell survival in response to cytokines and growth factors (34)(35)(36). In the present study, it was found that the ratio of p-AKT/AKT was decreased following stimulation with cholesterol, indicating that the PI3K/AKT signaling pathway was inhibited by stimulation of cholesterol.…”

Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

“…Several recent studies investigated the antioxidant activity of OA in different disease models. For example, OA was found to reduce oxidative stress in silicotic rats by modulating the Akt/NF-κB pathway [32]. Moreover, OA suppressed oxidative stress by regulating the stanniocalcin-1 pathway in a cell model of Alzheimer's disease treatment [33], as well as repressed oxidative stress via the SIRT3/NF-κB axis in an in vitro osteoarthritis cell model [34].…”

Clinical efficacy of acetylcysteine combined with tetrandrine tablets on patients with silicosis and its effect on exercise tolerance and pulmonary function

“…Silicosis is an irreversible chronic disease that continues to deteriorate. The treatment is based on the principle of avoiding complications as far as possible and needs long-term medication, and the quality of life of patients will be seriously affected with the development of the disease (5). The silicotic lung has the characteristics of high medical costs, high disability rate and high mortality rate, heavy financial burden and psychological pressure on the patient's family, and no special drugs have been developed for the treatment of silicosis so far, therefore, the treatment can only be the basis of controlling and delaying the development of the disease, and the main purpose is to improve the immune function and quality of life of patients at the same time (6).…”