Protocatechuic aldehyde prevents ischemic injury by attenuating brain microvascular endothelial cell pyroptosis via lncRNA Xist

Guo, Yan; Yang, Jiehong; Zhou, Huifen; Wang, Yu; Ding, Zhongxiang; Jin, Bo; Wan, Haitong

doi:10.1016/j.phymed.2021.153849

Cited by 26 publications

(19 citation statements)

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“…The occurrence of ischemic disease is related to the coexistence of multiple complex factors, such as inflammation, oxidative stress, blood - brain barrier disorder, platelet activation, and cell apoptosis ( Ge et al, 2019 ; Navis et al, 2019 ; Sarkar et al, 2019 ; Ren et al, 2022 ). In recent years, most of the studies on PCA in the treatment of ischemic diseases have been limited to a single factor, such as pyrolysis ( Guo et al, 2022 ), mitochondrial energy metabolism ( Zeng et al, 2021 ), apoptosis ( Wan et al, 2021 ), or oxidative stress ( Guo et al, 2017 ). To investigate the impact of PCA on ischemic diseases more extensively, our study proposes a novel mechanism by which PCA alleviates OGD/R-induced injury to HUVECs by promoting autophagy and inhibiting apoptosis through SIRT1 axis.…”

Section: Discussionmentioning

confidence: 99%

“…OGD/R model was carried out as described previously ( Guo et al, 2022 ). Briefly, HUVECs were cultured in glucose-free and serum-free Minimum Essential Medium (Gibco, Grand Island, NY, United States) within an anaerobic chamber containing 1% O 2, 5% CO 2 , and 94% N 2 for 10 h at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“… Ji et al (2021) reported that PCA can prevent oxidative stress and restore endothelial function by improving oxidative inactivation of vascular nitric oxide in diabetic conditions. Our previous data also demonstrated that PCA can protect ECs from excessive autophagic damage induced by oxidative stress ( Guo et al, 2021 ) and prevent oxygen-glucose deprivation/reoxygenation (OGD/R)-induced pyroptosis of microvascular ECs in the rat brain ( Guo et al, 2022 ). However, the precise protective effects of PCA on endothelial cell autophagy and apoptosis, and the molecular mechanisms at cellular level, have not been reported.…”

Section: Introductionmentioning

confidence: 96%

“…Oxidative stress-induced apoptosis is the most common form of cell death in endothelial dysfunction ( Zhang and Li, 2020 ). In addition, induction of pyroptosis and disruption of autophagy also play a critical role in endothelial dysfunction ( Peng et al, 2021 ; Guo et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

“…Protocatechualdehyde (PCA) is a main phenolic acid in the root of Salvia miltiorrhiza Bunge (Lamiaceae), a traditional Chinese medicine widely used in the treatment of cardiovascular diseases and ischemic stroke ( Ji et al, 2000 ; Guo et al, 2022 ). PCA has been reported to have many pharmacological uses, such as an antioxidant ( Guo et al, 2017 ) and anti-apoptosis ( Wan et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

et al. 2022

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Background: Oxidative stress-induced endothelial cell death, such as apoptosis and autophagy, plays a critical role in ischemia-reperfusion injury. Protocatechualdehyde (PCA) is a major bioactive component of the traditional Chinese medicine Salvia miltiorrhiza Bunge (Lamiaceae), and it has been proved to be effective in the prevention and treatment of ischemic cardiovascular and cerebrovascular diseases. However, its role in oxidative stress-induced endothelial cell death and its underlying mechanisms remains unclear. This study aims to investigate the effects and mechanisms of PCA on endothelial cell apoptosis and autophagy induced by oxygen-glucose deprivation/reoxygenation (OGD/R) injury.Methods: After OGD/R induction, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of PCA. Cell viability, apoptosis, and autophagy were detected by Cell Counting Kit-8 assay, flow cytometry, and monodansylcadaverine assay, respectively. Western blot was applied to explore the effects of PCA on the expression levels of relevant protein factors.Results: The results show that PCA significantly promoted cell survival rate and cell proliferation and enhanced the antioxidant activity in OGD/R-induced HUVECs. PCA inhibited HUVECs apoptosis, as evidenced by decreased expression of cleaved-caspase-3, Bcl2-associated X (BAX), and increased expression of Bcl-2. PCA induced autophagy by reducing the expression of P62 while increasing the expression of Beclin-1 and LC3 II/I. Meanwhile, PCA enhanced the expression of Sirtuin 1 (SIRT1) and suppressed the expression of P53. When SIRT1 was inhibited by selisistat or SIRT1 small-interfering RNA, the anti-apoptotic and pro-autophagy abilities of PCA were attenuated.Conclusion: These results demonstrated that PCA rescued HUVECs from OGD/R-induced injury by promoting autophagy and inhibiting apoptosis through SIRT1 and could be developed as a potential therapeutic agent against ischemic diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

et al. 2022

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Sodium Butyrate‐Loaded Microspheres With Enhanced Bioavailability for Targeted Treatment of Intestinal Barrier Injury

Lv,

Jiang,

Ouyang

et al. 2024

Adv Healthcare Materials

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Intestinal barrier dysfunction is related to diseases such as inflammatory bowel disease (IBD) and severe acute pancreatitis (SAP). Butyrate and its derivatives (e.g., sodium butyrate (SB)) can alleviate gut inflammatory responses. Nevertheless, these substances usually cannot fully exert protective effects due to low bioavailability. This research aimed to offer microspheres for treating intestinal barrier injury. Sodium alginate solution is prepared to dissolve SB, followed by mixing with chitosan (CS)‐protocatechuic aldehyde (PA)/calcium chloride solution. The required CS‐PA/calcium alginate/SB (CPC/SB) microspheres are formed in this manner. Subsequently, the therapeutic effects of CPC/SB microspheres on intestinal barrier injury through in vivo dextran sulfate sodium salt (DSS)‐induced IBD and sodium taurocholate (STC)‐induced SAP models is explored. Results: The CPC/SB microspheres exhibited excellent antioxidant properties. In vivo bioluminescence imaging experiment confirmed the microspheres effectively targeted the inflammatory gut in IBD. Further in vivo experimental results indicated the microspheres significantly repaired intestinal barrier damage, exerting protective effects in IBD and SAP. Additionally, 16S rDNA sequencing explained the microspheres can regulate the balance between harmful and beneficial bacteria (such as Alistipes, Odoribacter, and Rikenellaceae RC9). This study provides a possible synthetic strategy of microsphere carriers to serve as a potential therapeutic tool for intestinal barrier injury.

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MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions

Zheng,

Zhang,

Wang

et al. 2024

Archiv der Pharmazie

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The NOD‐like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key component of the innate immune system that triggers inflammation and pyroptosis and contributes to the development of several diseases. Therefore, blocking the activation of the NLRP3 inflammasome has therapeutic potential for the treatment of these diseases. MCC950, a selective small molecule inhibitor, has emerged as a promising candidate for blocking NLRP3 inflammasome activation. Ongoing research is focused on elucidating the specific targets of MCC950 as well as assessfing its metabolism and safety profile. This review discusses the diseases that have been studied in relation to MCC950, with a focus on stroke, Alzheimer's disease, liver injury, atherosclerosis, diabetes mellitus, and sepsis, using bibliometric analysis. It then summarizes the potential pharmacological targets of MCC950 and discusses its toxicity. Furthermore, it traces the progression from preclinical to clinical research for the treatment of these diseases. Overall, this review provides a solid foundation for the clinical therapeutic potential of MCC950 and offers insights for future research and therapeutic approaches.

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Protocatechuic aldehyde prevents ischemic injury by attenuating brain microvascular endothelial cell pyroptosis via lncRNA Xist

Cited by 26 publications

References 27 publications

Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

Protocatechualdehyde Rescues Oxygen-Glucose Deprivation/Reoxygenation-Induced Endothelial Cells Injury by Inducing Autophagy and Inhibiting Apoptosis via Regulation of SIRT1

Sodium Butyrate‐Loaded Microspheres With Enhanced Bioavailability for Targeted Treatment of Intestinal Barrier Injury

MCC950 as a promising candidate for blocking NLRP3 inflammasome activation: A review of preclinical research and future directions

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