Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

Liu, Yawei; Huang, Yi-Tsau

doi:10.1371/journal.pone.0103229

Cited by 30 publications

(30 citation statements)

References 55 publications

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“…Moreover, tanshinone IIA attenuated LPS-induced mRNA expressions of CCL2, CCL3, CCL5, IL-1β, TNF-α, IL-6, ICAM-1, iNOS and α-SMA in HSC-T6 cells. The present results demonstrated that tanshinone IIA decreased LPS-induced HSC activation [33] .…”

Section: Inhibitory Effect Of Tanshinone Iia On Rat Hepatic Satellitesupporting

confidence: 67%

“…and his colleagues determined whether tanshinone IIA protects neurons against Aβ (25-35)-induced cytotoxicity and detected the association of this protective effect with calpain and the p35/Cdk5 pathway. The results showed that tanshinone IIA protected neurons against the neurotoxicity of Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), increased the viability of neurons, decreased expression of phosphorylated tau in neurons induced by Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), improved the impairment of the cell ultra-structure (such as nuclear condensation and fragmentation, and neurofibril collapse). Further more, the authors found that tanshinone IIA possessed neuroprotective action and the protection may involve in calpain and the p35/Cdk5 pathway.…”

Section: A N T I -I N F L a M M A T O R Y E F F E C T S O F Tanshinonmentioning

confidence: 99%

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Tanshinones as Possible Therapeutic Agents for Cardiovascular, Cerebral, Hepatic, and Bone Diseases

Yagi

Takeo

2015

Journal of Gastroenterology and Hepatology Research

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The root of Salvia miltiorrhiza (Tan shen) has been used as a traditional drug for circulatory disorders including ischemic diseases such as angina pectoris. Effective components protecting the myocardium against ischemia-induced metabolic disturbances; tanshinone IIA, tanshinone I, tanshinone V, tanshinone VI, and dihydrotanshinone were isolated. Among them, we found tanshinone VI as the most effective and possible agent with cardioprotection against ischemia/reperfusion injury in Langendorff manner by using rat isolated hearts. We have shown that the possible mechanisms underlying an enhancement of post-hypoxic contractile recovery of perfused hearts may be exerted via an enhancement of energy restoration and an attenuation of Ca2+ overload in the reoxygenated myocardium. We also found another beneficial effect of tanshinone VI on cardiac remodeling in primary cultured cardiomyocytes and cardiac fibroblasts. It is generally accepted that cardiac remodeling such as cardiac hypertrophy and fibrosis enhances the development and progression of heart failure following various cardiac diseases including acute myocardial infarction. Treatment of cardiomyocytes and cardiac fibroblasts with tanshinone VI attenuated humoral factor-induced cellular hypertrophy and fibro-sis under in vitro experimental conditions. Thus, tanshinone VI may be a possible agent for attenuating the development of cardiac remodeling such as cardiac hypertrophy and fibrosis, which may lead to cardiac contractile dysfunction. Furthermore, inhibition of tanshinone VI to bone resorption through the prevention of osteoclast differentiation by inhibiting receptor activator of NFκB ligand (RANKL) expression and NFκB induction, was exhibited. Pharmacological suppression of NFκB and RANKL induced by tanshinone VI in vivo may be an effective approach to improve bone loss suppressing osteoclastic bone resorption in rheumatoid arthritis. Anti-inflammatory effect of tanshinone I, having a similar abietane structure to tanshinone VI, is shown on neuroprotection against cerebral ischemia-reperfusion injury in the gerbil hippocampus, and apoptosis in activated hepatic satellite cells (HSCs). Neuroprotection of tanshinone IIA against cerebral ischemia/ reperfusion injury through inhibition of macrophage migration inhibitory factor and tanshinone IIA-mediated HSC-T6 apoptosis through Akt inhibition and ERK-Bax-caspase-3/9 signaling pathways are presented. Tanshinone IIA decreased the lipopolysaccharide-induced activation of rat hepatic satellite cells. Possible therapeutic effects of tanshinones VI, I, and IIA on cardiac contractile failure, cerebral infarction, born resorption, and apoptosis of hepatic satellite cells are discussed.

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Section: Inhibitory Effect Of Tanshinone Iia On Rat Hepatic Satellitesupporting

confidence: 67%

Section: A N T I -I N F L a M M A T O R Y E F F E C T S O F Tanshinonmentioning

confidence: 99%

Tanshinones as Possible Therapeutic Agents for Cardiovascular, Cerebral, Hepatic, and Bone Diseases

Yagi

Takeo

2015

Journal of Gastroenterology and Hepatology Research

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“…These results indicated that inhibition of JNK in the spinal dorsal horn of SNL rats was consistent with the analgesic effect of TIIAS. Recent studies have indicated that in some pathological processes, activation of JNK can be inhibited by TIIAS, especially in the signal transduction of anti-inflammatory and anti-apoptotic pathways [ 39 - 42 ]. The pro-inflammatory cytokines, especially TNF-α and IL-1β, induced by peripheral nerve injury, are essential triggers for the activation of JNK in spinal astrocytes underlying the development of neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain

Tang

Zhu

et al. 2015

J Neuroinflammation

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BackgroundNeuropathic pain (NP) continues to be challenging to treat due to lack of effective drugs. Accumulating evidence elucidated that glia-mediated inflammatory reactions play a pivotal role in the introduction and development of NP. Besides, activation of the c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) pathway in astrocytes has been reported to be critical for spinal astrocytic activation and neuropathic pain development after spinal nerve ligation (SNL). Tanshinone IIA, a major active component of a traditional Chinese drug, Danshen, possesses potent immuno-suppressive activities. The present study was undertaken to assess whether intraperitoneal administration of tanshinone IIA sulfonate (TIIAS) has analgesic effect on SNL-induced neuropathic pain and whether the inhibition of astrocytic activation and JNK/MCP-1 pathway is involved in the analgesic effect of TIIAS.MethodsThe effects of TIIAS on SNL-induced mechanical allodynia were assessed by behavioral testing. Immunofluorescence histochemical staining was used to detect changes of spinal astrocytes and spinal pJNK expression and localization. Immunofluorescence histochemistry and Western blot analysis were used to quantify the SNL-induced spinal pJNK expression after TIIAS administration. Enzyme-linked immunosorbent assay (ELISA) was used to detect the SNL-induced spinal expression of pro-inflammatory cytokines and MCP-1.ResultsOur results indicated that intraperitoneal TIIAS up-regulated the mechanical paw withdrawal threshold (PWT) of NP, while astrocytic activation was suppressed and accompanied by the down-regulation of IL-1β and TNF-α expression, as well as JNK phosphorylation in the spinal dorsal horn. Additionally, the release of MCP-1 was dose dependently decreased. After co-treatment with TIIAS and JNK inhibitor (SP600125), no significant increases in mechanical PWT and MCP-1 expression were observed compared with the TIIAS-treated group.ConclusionsThe present results suggest that the analgesic effects of TIIAS in neuropathic pain are mainly mediated by the down-regulation of SNL-induced astrocytic activation, which is via the inhibition of JNK/MCP-1 pathway.

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“…NF-jB activation in neurons is mediated primarily by the binding of p50 and p65 to the jB DNA recognition sequence. Interleukin-1b (IL-1b) and proinflammatory cytokines tumor necrosis factor-a (TNF-a) are known as stimuli that more strongly activate neuronal NFjB, than other agents like L-glutamate [14,15]. Therefore, inhibitors of the NF-jB pathway may become important alternatives in preventing further anti-neuroinflammation in the microglial over-activation.…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA Rescued the Impairments of Primary Hippocampal Neurons Induced by BV2 Microglial Over-Activation

Wang

Yang

2015

Neurochem Res

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Activated microglia plays an important role in monitoring the microenvironment and prune neural process in healthy neural tissue, in order to maintain synaptic homeostasis. However, hyperactive microglia may release various cytotoxic factors and induce neuroinflammation, which cause neuronal damages leading to neurodegenerative diseases. Tanshinone IIA (TSA), an extract from traditional Chinese medicine, features potent anti-apoptotic and anti-inflammatory effects both in vitro and in vivo. But little is known on the effects of TSA on microglial-over-activation-induced neural impairments. In this study, by employing murine BV2 cell lines as well as the combinations of ELISA assay, immunostaining, western blotting analysis and RT-PCR, we found that TSA has the potential to exhibit anti-inflammatory effects. We hereby demonstrated that TSA rescued neural growth and development in the primary cultured hippocampal neurons from impairments caused by BV2 microglial over-activation insult. The results show that TSA attenuated the BV2 cell activation by lipopolysaccharide (LPS) stimulation through suppressing the NF-кB signal pathway. Also, conditioned mediums (CM) from TSA treated and activated BV2 cells protected against LPS-CM-induced neuronal death. Furthermore, TSA treatment could recover the inhibitory effects of LPS-CM on growth cone extension, neurite sprouting and outgrowth, as well as spinogenesis. Our findings support that TSA is capable of inhibiting BV2 cell over-activation thus has potential protective effects in the cultured hippocampal neurons. This study may lay a foundation for using TSA to restore cerebral injuries after severe neuroinflammation.

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Inhibitory Effect of Tanshinone IIA on Rat Hepatic Stellate Cells

Cited by 30 publications

References 55 publications

Tanshinones as Possible Therapeutic Agents for Cardiovascular, Cerebral, Hepatic, and Bone Diseases

Tanshinones as Possible Therapeutic Agents for Cardiovascular, Cerebral, Hepatic, and Bone Diseases

Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain

Tanshinone IIA Rescued the Impairments of Primary Hippocampal Neurons Induced by BV2 Microglial Over-Activation

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