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

Li, Wei; Zhang, Yu; Cui-yan, Xing; Zhang, Mengyuan

doi:10.1016/j.intimp.2015.06.032

Cited by 31 publications

(23 citation statements)

References 45 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JNK, a key intracellular kinase of the MAPK pathway, plays an important role in chronic pain and astrocytic activation ( 42 , 43 ). The overexpression of p-JNK can be detected in many types of pain models.…”

Section: Discussionmentioning

confidence: 99%

The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain

Guo

Bai

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Bone cancer pain (BCP) is one of the most difficult and intractable tasks for pain management, which is associated with spinal 'neuron-astrocytic' activation. The activation of the c-Jun N-terminal kinase (JNK)/chemokine (C-C motif) ligand (CCL2) signaling pathway has been reported to be critical for neuropathic pain. Rolipram (ROL), a selective phosphodiesterase 4 inhibitor, possesses potent anti-inflammatory and anti-nociceptive activities. The present study aimed to investigate whether the intrathecal administration of ROL has an analgesic effect on BCP in rats, and to assess whether the inhibition of spinal JNK/CCL2 pathway and astrocytic activation are involved in the analgesic effects of ROL. The analgesic effects of ROL were evaluated using the Von Frey and Hargreaves tests. Immunofluorescence staining was used to determine the number of c-Fos immunoreactive neurons, and the expression of spinal astrocytes and microglial activation on day 14 after tumor cell inoculation. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α] and chemokines (CCL2), and western blot analysis was then used to examine the spinal phosphodiesterase 4 (PDE4), ionized calcium binding adapter molecule-1 (IBA-1) and JNK levels on day 14 after tumor cell inoculation. The results revealed that ROL exerted a short-term analgesic effect in a dose-dependent manner, and consecutive daily injections of ROL exerted continuous analgesic effects. In addition, spinal 'neuron-astrocytic' activation was suppressed and was associated with the downregulation of spinal IL-1β, IL-6 and TNF-α expression, and the inhibition of PDE4B and JNK levels in the spine was also observed. In addition, the level of CCL2 was decreased in the rats with BCP. The JNK inhibitor, SP600125, decreased CCL2 expression and attenuated pain behavior. Following co-treatment with ROL and SP600125, no significant increases in thermal hyperalgesia and CCL2 expression were observed compared with the ROL group. Thus, our findings suggest that the analgesic effects of ROL in BCP are mainly mediated through the inhibition of 'neuron-astrocytic' activation, which occurs via the suppression of spinal JNK/CCL2 signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain

Guo

Bai

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…Starting day 1, mice were randomly assigned to receive daily Tanshinone IIA (50 mg/kg/d, Jiangsu Carefree Group Co., Nanjing, China) in corn oil [TS(E)] according to the doses safely used in animal models in published studies22232425262728293031323334353637 or an equal volume of corn oil by gavage. For late Tanshinone IIA treatment [TS(L)] treatment, some folic acid-injured mice were fed daily with Tanshinone IIA by gavage starting day 5.…”

Section: Methodsmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%

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

Jiang

Zhu

Xiang

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Acute kidney injury (AKI) remains challenging for clinical practice and poses a risk of developing progressive chronic kidney disease (CKD) with no definitive treatment available yet. Tanshinone IIA, an active ingredient of Chinese herbal Salvia miltiorrhiza, has been widely used in Asia for the remarkable organoprotective activities. Its effect on established AKI, however, remains unknown. In mice with folic acid-induced AKI, delayed treatment with Tanshinone IIA, commenced early or late after injury, diminished renal expression of kidney injury markers, reduced apoptosis and improved kidney dysfunction, concomitant with mitigated histologic signs of AKI to CKD transition, including interstitial fibrosis and tubular atrophy, and with an ameliorated inflammatory infiltration in tubulointerstitium and a favored M2-skewed macrophage polarization. Mechanistically, Tanshinone IIA blunted glycogen synthase kinase (GSK)3β overactivity and hyperactivation of its downstream mitogen-activated protein kinases that are centrally implicated in renal fibrogenesis and inflammation. Inhibition of GSK3β is likely a key mechanism mediating the therapeutic activity of Tanshinone IIA, because sodium nitroprusside, a GSK3β activator, largely offset its renoprotective effect. In confirmatory studies, rescue treatment with Tanshinone IIA likewise ameliorated ischemia/reperfusion-induced kidney destruction in mice. Our data suggest that Tanshinone IIA represents a valuable treatment that improves post-AKI kidney salvage via targeting GSK3β.

show abstract

“…Therefore, Tan-IIA is widely used in the treatment of cardiovascular disease [ 1 , 2 , 3 ]. A large amount of researches show that Tan-IIA exhibits various pharmacological activities, including anti-inflammatory [ 4 ], anti-oxidative [ 5 ], anti-fibrosis [ 6 ], modulation of collagen metabolism [ 7 ], anti-tumor [ 8 ] and so on.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos

Wang

et al. 2017

Molecules

View full text Add to dashboard Cite

Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos. The LC50 values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96 hpf were 18.5 μM and 12.8 μM, respectively, and the teratogenicity was manifested at a concentration of about 1 µM. The main endpoints of teratogenicity were scoliosis, malformation of tail, and pericardium edema. Our findings displayed the potential cardiotoxicity and severe impact on the abnormal development of Tan-IIA in zebrafish embryo at high concentrations, which may help avoid the risk of its clinical application.

show abstract

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

Cited by 31 publications

References 45 publications

The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain

The analgesic effect of rolipram is associated with the inhibition of the activation of the spinal astrocytic JNK/CCL2 pathway in bone cancer pain

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

Evaluation of Tanshinone IIA Developmental Toxicity in Zebrafish Embryos

Contact Info

Product

Resources

About