Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

Guo, Tao; Jiang, Zhongbiao; Tong, Zhongyi; Zhou, Yang; Chai, Xiangping; Xiao, Xianzhong

doi:10.3389/fphys.2020.570441

Cited by 48 publications

(23 citation statements)

References 41 publications

(49 reference statements)

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“…For example, shikonin was shown to be capable of alleviating LPS-induced renal injury and oxidative damage [ 250 ], high glucose-induced renal tubular epithelial cell injury in vitro [ 251 ], and unilateral ureteral obstruction (UUO)-induced tubular apoptosis and macrophage infiltration [ 252 ]. Similar findings were obtained in experimental models of cardiac dysfunction [ 253 ], acute lung [ 254 , 255 , 256 ], liver [ 257 , 258 , 259 , 260 , 261 , 262 ], and ear injuries [ 263 ]. Shikonin also protected against cerebral ischemia/reperfusion- and autoimmune encephalomyelitis-induced brain injury through reducing oxidative stress [ 264 , 265 ] and protected microglial cells against LPS-induced cell death [ 266 ] ( Figure 4 B ).…”

Section: Emerging Areas Of Research Involving Pkm2supporting

confidence: 78%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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Pyruvate kinase is a key regulator in glycolysis through the conversion of phosphoenolpyruvate (PEP) into pyruvate. Pyruvate kinase exists in various isoforms that can exhibit diverse biological functions and outcomes. The pyruvate kinase isoenzyme type M2 (PKM2) controls cell progression and survival through the regulation of key signaling pathways. In cancer cells, the dimer form of PKM2 predominates and plays an integral role in cancer metabolism. This predominance of the inactive dimeric form promotes the accumulation of phosphometabolites, allowing cancer cells to engage in high levels of synthetic processing to enhance their proliferative capacity. PKM2 has been recognized for its role in regulating gene expression and transcription factors critical for health and disease. This role enables PKM2 to exert profound regulatory effects that promote cancer cell metabolism, proliferation, and migration. In addition to its role in cancer, PKM2 regulates aspects essential to cellular homeostasis in non-cancer tissues and, in some cases, promotes tissue-specific pathways in health and diseases. In pursuit of understanding the diverse tissue-specific roles of PKM2, investigations targeting tissues such as the kidney, liver, adipose, and pancreas have been conducted. Findings from these studies enhance our understanding of PKM2 functions in various diseases beyond cancer. Therefore, there is substantial interest in PKM2 modulation as a potential therapeutic target for the treatment of multiple conditions. Indeed, a vast plethora of research has focused on identifying therapeutic strategies for targeting PKM2. Recently, targeting PKM2 through its regulatory microRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has gathered increasing interest. Thus, the goal of this review is to highlight recent advancements in PKM2 research, with a focus on PKM2 regulatory microRNAs and lncRNAs and their subsequent physiological significance.

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Section: Emerging Areas Of Research Involving Pkm2supporting

confidence: 78%

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Puckett

Alquraishi

Chowanadisai

et al. 2021

IJMS

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“…Recent studies have demonstrated that herbal Chinese medicines are therapeutic against cardiovascular diseases. For example, Shikonin (extracted from Chinese herb radix arnebiae) ameliorated cardiac dysfunction and inhibited the activation of NLRP3 inflammasome in lipopolysaccharide (LPS)induced cardiac dysfunction (Guo et al, 2020). Additionally, Songorinea (napelline-type C 20 -diterpene alkaloid in Aconitum carmichaelii Debx.)…”

Section: Introductionmentioning

confidence: 99%

Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway

Wang

Liao

et al. 2021

Front. Pharmacol.

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Septic cardiomyopathy is a common complication of severe sepsis, which is one of the leading causes of death in intensive care units. Therefore, finding an effective therapy target is urgent. Neferine is an alkaloid extracted from the green embryos of mature seeds of Nelumbo nucifera Gaertn., which has been reported to exhibit various biological activities and pharmacological properties. This study aims to explore the protective effects of neferine against lipopolysaccharide (LPS)-induced myocardial dysfunction and its mechanisms. The LPS-induced cardiac dysfunction mouse model was employed to investigate the protective effects of neferine. In this study, we demonstrated that neferine remarkably improved cardiac function and survival rate and ameliorated morphological damage to heart tissue in LPS-induced mice. Neferine also improved cell viability and mitochondrial function and reduced cell apoptosis and the production of reactive oxygen species in LPS-treated H9c2 cells. In addition, neferine significantly upregulated Bcl-2 expression and suppressed cleaved caspase 3 activity in LPS-induced mouse heart tissue and H9c2 cells. Furthermore, neferine also upregulated the phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway in vivo and in vitro. Conversely, LY294002 (a PI3K inhibitor) reversed the protective effect of neferine in LPS-induced H9c2 cells. Our findings thus demonstrate that neferine ameliorates LPS-induced cardiac dysfunction by activating the PI3K/AKT/mTOR signaling pathway and presents a promising therapeutic agent for the treatment of LPS-induced cardiac dysfunction.

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“… 33 Shikonin, a traditional Chinese medicine extract, improved LPS-induced sepsis cardiac dysfunction by SIRT1. 34 We predicted that SIRT1 was the target gene of miR-486-5p through the online biological software miRDB, and miR-486-5p targeting SIRT1 has been demonstrated in non-small cell lung cancer 35 and myocardial ischemia-reperfusion injury. 36 Therefore, we speculate that miR-486-5p may be involved in the progress of sepsis by targeting SIRT1.…”

Section: Discussionmentioning

confidence: 99%

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

Sun

Guo

2021

JIR

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Background As a molecular detection method, miRNA can quickly diagnose and prevent diseases, intervene in disease as early as possible, and reduce mortality. This study was to investigate the potential clinical diagnostic and predictive significance of miR-486-5p in sepsis and its correlation with inflammation and disease severity. Methods The serum miR-486-5p in 108 sepsis, 60 pneumonia-infected, and 101 healthy controls were detected by RT-qPCR. Spearman coefficient detects the correlation between serum miRNA and disease severity indicators (APACHE II, SOFA scores), and inflammation indicators (CRP, PCT), respectively. The diagnostic significance of miR-486-5p in sepsis was analyzed by the ROC curve. Kaplan–Meier estimator and Cox regression hazards analysis of the predictive significance of serum miR-486-5p in 28-day survival from sepsis. Results Serum miR-486-5p was increased in sepsis patients compared with healthy control and pneumonia-infected patients ( P < 0.001). And increased serum miR-486-5p was positively associated with disease severity (SOFA score and APACHE II score) and inflammation (CRP and PCT). Serum miR-486-5p can not only identify sepsis patients from healthy controls (AUC = 0.914) but also significantly distinguish sepsis patients from pneumonia-infected patients (AUC = 0.814), showing good potential as a diagnostic biomarker for sepsis. In addition, serum miR-486-5p was an independent predictor of 28-day survival (log-rank P = 0.012), and patients with high levels of miR-486-5p had a poorer overall 28-day survival (HR = 3.057, 95% CI = 1.385–17.817, P = 0.014). Conclusion miR-486-5p is a potential diagnostic biomarker for sepsis, and its high level is significantly correlated with the disease severity and inflammation. In addition, miR-486-5p were predictive risk factors for 28-day survival in sepsis patients.

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Shikonin Ameliorates LPS-Induced Cardiac Dysfunction by SIRT1-Dependent Inhibition of NLRP3 Inflammasome

Cited by 48 publications

References 41 publications

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

The Role of PKM2 in Metabolic Reprogramming: Insights into the Regulatory Roles of Non-Coding RNAs

Neferine Ameliorates Sepsis-Induced Myocardial Dysfunction Through Anti-Apoptotic and Antioxidative Effects by Regulating the PI3K/AKT/mTOR Signaling Pathway

miR-486-5p Serves as a Diagnostic Biomarker for Sepsis and Its Predictive Value for Clinical Outcomes

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