Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis

Yang, Ningning; Chen, Haoyuan; Gao, Yang; Zhang, Sijia; Lin, Qiuchi; Ji, Xuechun; Li, Ning; Xu, Wanying; Liu, Ying; Jin, Shizhu

doi:10.1016/j.biopha.2020.110815

Cited by 10 publications

(12 citation statements)

References 34 publications

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“…Several of the therapeutic agents described are hypothesised to have multiple impacts on different homeostatic and pathophysiological pathways. For example, enoxaparin ( 30 , 31 , 64 , 65 , 111 ) and tanshinone ( 61 ) may have effects that have not yet been classified as direct antifibrotic mechanisms and do not fit into a concrete anti-inflammatory or antioxidative mode of action.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, it is supposed to induce stem cell proliferation and differentiation ( 115 ). A single rat study investigated the effects in a cirrhotic model ( 61 ), where tanshinone improved the histological injury, serological tests, and increased expression of markers indicating newly proliferated stem cells. These effects appeared to be caused by promoting proliferation and differentiation of endogenous liver stem cells.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, a combination of bone-marrow-derived stromal cells and silymarin ameliorated liver tissue damage in a CCl 4 -cirrhotic rat model through immunoregulatory activities. However, antioxidative markers were not investigated in this study (60).…”

Section: Silymarinmentioning

confidence: 95%

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Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

et al. 2021

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Liver cirrhosis is a disease characterised by multiple complications and a poor prognosis. The prevalence is increasing worldwide. Chronic inflammation is ongoing in liver cirrhosis. No cure for the inflammation is available, and the current treatment of liver cirrhosis is only symptomatic. However, several different medical agents have been suggested as potential healing drugs. The majority are tested in rodents, but few human trials are effectuated. This review focuses on medical agents described in the literature with supposed alleviating and curing effects on liver cirrhosis. Twelve anti-inflammatory, five antioxidative, and three drugs with effects on gut microflora and the LPS pathway were found. Two drugs not categorised by the three former categories were found in addition. In total, 42 rodent studies and seven human trials were found. Promising effects of celecoxib, aspirin, curcumin, kahweol, pentoxifylline, diosmin, statins, emricasan, and silymarin were found in cirrhotic rodent models. Few indices of effects of etanercept, glycyrrhizin arginine salt, and mitoquinone were found. Faecal microbiota transplantation is in increasing searchlight with a supposed potential to alleviate cirrhosis. However, human trials are in demand to verify the findings in this review.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

et al. 2021

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“…Recent studies have demonstrated that TIIA-attenuated CCl 4 -induced liver injury and fibrosis inhibit the proliferation and activation of hepatic stellate cells (HSC) [ 22 ]. TIIA reduced liver injury induced by CCl 4 combined with alcohol in a cirrhotic rat model by promoting the proliferation and differentiation of endogenous hepatic stem cells [ 23 ]. Furthermore, TIIA treatment can reduce the production of reactive oxygen species and malondialdehyde, reduce existing reactive oxygen species, and ameliorate steatosis [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Tanshinone IIA Ameliorates Nonalcoholic Steatohepatitis in Mice by Modulating Neutrophil Extracellular Traps and Hepatocyte Apoptosis

Liu

Jia

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Salvia miltiorrhiza Bunge, a traditional Chinese medicine, is widely used in the treatment of a variety of diseases and syndromes. Tanshinone IIA (TIIA), a phenanthrenequinone-class derivative extracted from S. miltiorrhiza, is one of its main active components and has anti-inflammatory effects on various tissues and cells. This study aimed to investigate the beneficial effects of TIIA on nonalcoholic steatohepatitis (NASH) induced in mice using a methionine choline deficiency (MCD) diet and the underlying mechanism of these. Our results reveal that TIIA remarkably ameliorated hepatic steatosis and inflammation and decreased the serum levels of liver dysfunction markers while increasing the levels of serum total cholesterol and triglycerides in MCD-fed mice. TIIA significantly reduced mRNA levels of the inflammatory factors TNF-α, IL-6, and TGF-β. Similarly, TIIA inhibited caspase-3 and Bax-mediated apoptosis in MCD-fed mice. Together, our data indicate that TIIA inhibits the formation of MPO and CitH3 in neutrophil extracellular traps and inhibits apoptosis mediated by caspase-3 and Bax in hepatocytes, thereby mitigating inflammatory progression in an MCD diet-induced NASH mouse model.

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“…31,32 Recently, several studies have explored other potential therapeutic effects of tanshinone IIA and its derivatives in various diseases, including central nervous system disorders, 33 diabetes, 34 cancer, 35 depression 36 and liver diseases. 37,38 Tanshinone IIA and its derivatives also displays a potent beneficial effect in AS by improving endothelial function via multiple processes, including by stabilizing vulnerable AS plaques via the TLR4/MyD88/NF-κB signaling pathway, 39 improving mitochondrial function, 40 alleviating oxidative stress, 41 inhibiting cell death 42,43 and reducing the inflammatory response. 41 Nonetheless, whether STS impacts NLRP3 inflammasome activation and subsequent pyroptosis in endothelial cells, and what the underlying mechanisms could be, remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Sodium Tanshinone IIA Sulfonate Inhibits Vascular Endothelial Cell Pyroptosis via the AMPK Signaling Pathway in Atherosclerosis

Zhu¹,

Chen²,

Guo³

et al. 2022

JIR

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Introduction: Atherosclerosis (AS) is the underlying cause of cardiovascular events. Endothelial cell mitochondrial damage and pyroptosis are important factors contributing to AS. Changes in internal mitochondrial conformation and increase in reactive oxygen species (ROS) lead to the disruption of mitochondrial energy metabolism, activation of the NLRP3 inflammasome and pyroptosis, which in turn affect atherogenesis by impairing endothelial function. AMPK is a core player in the regulation of cellular metabolism, not only by regulating mitochondrial homeostasis but also by regulating cellular inflammatory responses. Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, has significant antioxidant and anti-inflammatory effects, and roles in cardiovascular protection. Purpose: In this study, we investigated whether STS plays a protective role in AS by regulating endothelial cell mitochondrial function and pyroptosis through an AMPK-dependent mitochondrial pathway. Methods and Results: Male ApoE −/− mice and HUVECs were used for the experiments. We found that STS treatment largely abrogated the upregulation of key proteins in aortic vessel wall plaques and typical pyroptosis signaling in ApoE −/− mice fed a western diet, consequently enhancing pAMPK expression, plaque stabilization, and anti-inflammatory responses. Consistently, STS pretreatment inhibited cholesterol crystallization (CC) -induced cell pyroptosis and activated pAMPK expression. In vitro, using HUVECs, we further found that STS treatment ameliorated mitochondrial ROS caused by CC, as evidenced by the finding that STS inhibited mitochondrial damage caused by CC. The improvement of endothelial cell mitochondrial function by STS is blocked by dorsomorphin (AMPK inhibitor). Consistently, the blockade of endothelial cell pyroptosis by STS is disrupted by dorsomorphin. Conclusion:Our results suggest that STS enhances maintenance of mitochondrial homeostasis and inhibits mitochondrial ROS overproduction via AMPK, thereby improving endothelial cell pyroptosis during AS.

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Tanshinone IIA exerts therapeutic effects by acting on endogenous stem cells in rats with liver cirrhosis

Cited by 10 publications

References 34 publications

Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study

Tanshinone IIA Ameliorates Nonalcoholic Steatohepatitis in Mice by Modulating Neutrophil Extracellular Traps and Hepatocyte Apoptosis

Sodium Tanshinone IIA Sulfonate Inhibits Vascular Endothelial Cell Pyroptosis via the AMPK Signaling Pathway in Atherosclerosis

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