Tanshinone IIA therapeutically reduces LPS-induced acute lung injury by inhibiting inflammation and apoptosis in mice

Abstract

Geraniol (GOH), a special type of acyclic monoterpene alcohol, has been widely used to treat many diseases associated with inflammation and apoptosis. Acute lung injury (ALI) is a common clinical disease in humans characterized by pulmonary inflammation and apoptosis. In the present study, we investigated the protective effects of GOH in a mouse model of ALI induced by the intranasal administration of lipopolysaccharide (LPS) and elucidated the underlying molecular mechanisms in RAW 264.7 cells. In vivo, GOH treatment markedly ameliorated pathological injury and pulmonary cell apoptosis and reduced the wet/dry (W/D) weight ratio of lungs, myeloperoxidase (MPO) activity and the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α). In vitro, the levels of pro-inflammatory cytokines, iNOS and COX-2 were significantly increased in LPS-stimulated RAW 264.7 cells, an effect that was decreased by GOH treatment. Moreover, GOH treatment dramatically reduced the expression of Toll-like receptor 4 (TLR4) and then prevented the nuclear factor-κB (NF-κB) activation. GOH treatment also promoted anti-apoptotic Bcl-2 expression and inhibited pro-apoptotic Bax and Caspase-3 expression. Furthermore, knockdown of TLR4 expression exerted a similar effect and inhibited the phosphorylation of p65, as well as the Bax and Caspase-3 expression. Taken together, these results suggest that GOH treatment alleviates LPS-induced ALI via inhibiting pulmonary inflammation and apoptosis, a finding that might be associated with the inhibition of TLR4-mediated NF-κB and Bcl-2/Bax signalling pathways.

Rescue therapy with Tanshinone IIA hinders transition of acute kidney injury to chronic kidney disease via targeting GSK3β

“…This seemingly bimodal effect of Tanshinone IIA has been leveraged to kill cancer cells at high doses, but to protect parenchymal cells at much lower doses. The dose of Tanshinone IIA used in this study was very low (50 mg/kg/d) and had been reported by other studies to be safe2355. No noticeable adverse effect was noted in our animals, according to the observation of body weight, daily behavior and activity and to the analysis of other organ specimens.…”

“…In contrast to the arguable effect on apoptosis, Tanshinone IIA has been reproducibly demonstrated to possess a potent anti-inflammatory activity in animal models of diverse diseases, including chronic kidney disease, ischemic brain injury, endotoxin-associated acute lung injury, ischemic heart disease and atherosclerosis19235556. However, it is largely unknown whether Tanshinone IIA is also beneficial in AKI or whether Tanshinone IIA is able to alter inflammatory injuries in AKI.…”

“…Tanshinone IIA has been proven to be a low toxic and safe agent by numerous clinical and experimental studies19202122. Emerging data suggest that Tanshinone IIA possesses significant anti-inflammatory activities, by which it ameliorates injury in various organ systems, such as the brain, lung and heart23242526272829. Notably, two randomized clinical trials are being undertaken to validate its effect on ischemic heart disease3031.…”

Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro

“…NF-κB is required for maximal transcription of many cytokines, including pro-inflammatory mediator tumor necrosis factor (TNF)-α, and interleukin (IL)-1β. These cytokines are activated by bacterial endotoxin via NF-κB signaling and released in the early stage of ALI [5][6][7]. Besides, the dysregulation of apoptotic pathways is thought to play an important role in the pathogenesis of ALI for the loss of normal functional cells in the lung.…”

Tanshinone IIA represses inflammatory response and reduces radiculopathic pain by inhibiting IRAK-1 and NF-κB/p38/JNK signaling

“…TSA has been demonstrated to exhibit potent anti-inflammatory properties in different cell types, such as RAW 264.7 cells [21], BV-2 cells [22], and osteoclast progenitor cells [23]. Meanwhile, its beneficial anti-inflammatory effects are also observed in different animal models [24][25][26]. Moreover, previous studies demonstrate that TSA exert a series of biochemical effects through its antioxidative [27] and anti-apoptotic [28] properties in addition to it potent anti-inflammatory effect.…”