Anti-inflammatory Effect of Tanshinone I in Neuroprotection Against Cerebral Ischemia–Reperfusion Injury in the Gerbil Hippocampus

Abstract

Tanshinone I (TsI) is an important lipophilic diterpene extracted from Danshen (Radix Salvia miltiorrhizae) and has been used in Asia for the treatment of cerebrovascular diseases such as ischemic stroke. In this study, we examined the neuroprotective effect of TsI against ischemic damage and its neuroprotective mechanism in the gerbil hippocampal CA1 region (CA1) induced by 5 min of transient global cerebral ischemia. Pre-treatment with TsI protected pyramidal neurons from ischemic damage in the stratum pyramidale (SP) of the CA1 after ischemia-reperfusion. The pre-treatment with TsI increased the immunoreactivities and protein levels of anti-inflammatory cytokines [interleukin (IL)-4 and IL-13] in the TsI-treated-sham-operated-groups compared with those in the vehicle-treated-sham-operated-groups; however, the treatment did not increase the immunoreactivities and protein levels of pro-inflammatory cytokines (IL-2 and tumor necrosis factor-α). On the other hand, in the TsI-treated-ischemia-operated-groups, the immunoreactivities and protein levels of all the cytokines were maintained in the SP of the CA1 after transient cerebral ischemia. In addition, we examined that IL-4 injection into the lateral ventricle did not protect pyramidal neurons from ischemic damage. In conclusion, these findings indicate that the pre-treatment with TsI can protect against ischemia-induced neuronal death in the CA1 via the increase or maintenance of endogenous inflammatory cytokines, and exogenous IL-4 does not protect against ischemic damage.

Neuroprotection of Ischemic Preconditioning is Mediated by Anti-inflammatory, Not Pro-inflammatory, Cytokines in the Gerbil Hippocampus Induced by a Subsequent Lethal Transient Cerebral Ischemia

“…ischemia)-groups. It was reported that the maintenance or increase of anti-inflammatory cytokines such as IL-4 and IL-13 might be related with neuroprotection against ischemic damage [20,39]. In addition, our present finding regarding neuroprotection by IPC is supported by reports that showed that IL-4 and IL-13 might contribute to more delayed and less neuronal damage after transient cerebral ischemia [39,43].…”

“…Cellular inflammatory responses display important roles in ischemic injury and anti-inflammatory treatments in ischemic stroke must be beneficial [19]. We recently reported that pretreatment with tanshinone I increased levels of anti-inflammatory cytokines in the gerbil hippocampus; however, the treatment did not increase levels of pro-inflammatory cytokines [20]. On the basis of these papers, in order to examine whether anti-inflammatory markers are responsible for neuroprotection following ischemic insult, we investigated alterations in IL-2 and TNF-a as pro-inflammatory cytokines and IL-4 and IL-13 as anti-inflammatory cytokines in the IPC-induced gerbil brain following a subsequent transient cerebral ischemia; in addition, we discussed the relationship between neuroprotection and inflammatory cytokines in the IPC-induced hippocampus after transient cerebral ischemia.…”

Reactive oxygen species‐mediated phosphorylation of p38 signaling is critically involved in apoptotic effect of Tanshinone I in colon cancer cells

“…Despite multibiological activities of Tan I such as anti‐inflammatory (Park et al, ), antitumor (Jing et al, ; Lu, Wang, & Wang, ; Zhou, Zhang, Wang, & Sun, ), and antibacterial effect (Lee, Lee, Noh, & Hong, ), its antitumor mechanism is not fully understood compared with another component Tan IIA from Dansen. Thus, in the current study, the underlying mechanisms of Tan I from S .…”

Effects of Salvia miltiorrhiza on CNS Neuronal Injury and Degeneration: A Plausible Complementary Role of Tanshinones and Depsides

“…Pretreatment with TSI had several effects against cerebral I/R injury in the gerbil hippocampus [48]. It increased the immunoreactivities and protein levels of anti-inflammatory cytokines IL-4 and IL-13, but did not increase the immunoreactivities and protein levels of proinflammatory cytokines IL-2 and TNF-α.…”