Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

Ahmad, Saif; Khan, Shah Alam; Kindelin, Adam; Mohseni, Tasha; Bhatia, Kanchan; Hoda, Nasrul; Ducruet, Andrew F.

doi:10.1007/s12017-019-08569-z

Cited by 40 publications

(23 citation statements)

References 39 publications

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“…It works by inhibiting the 5-LOX/LTB4 and p38-MAPK/JNK/Bax/Caspase-3 pathways (Ahmed et al 2020 ). This protective effect is mediated by suppressing levels of intracellular oxygen free radicals, lipid peroxidation, oxidative DNA damage, and inflammation (Sadeghnia et al 2017 ; Ahmad et al 2019 ). The neuroprotective activities of Boswellia extract and boswellic acids mediated through the inhibition of the oxidative stress were observed also against glutamate toxicity-induced cell injury (Bai et al 2019 ; Rajabian et al 2016 , 2020 ).…”

Section: Potential Therapeutic Effects Of Boswellic Acids/ B Serrata Extract Against Sars-cov-2-induced Modification Omentioning

confidence: 99%

Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly

et al. 2021

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The most severe cases of COVID-19, and the highest rates of death, are among the elderly. There is an urgent need to search for an agent to treat the disease and control its progression. Boswellia serrata is traditionally used to treat chronic inflammatory diseases of the lung. This review aims to highlight currently published research that has shown evidence of potential therapeutic effects of boswellic acids (BA) and B. serrata extract against COVID-19 and associated conditions. We reviewed the published information up to March 2021. Studies were collected through a search of online electronic databases (academic libraries such as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Several recent studies reported that BAs and B. serrata extract are safe agents and have multiple beneficial activities in treating similar symptoms experienced by patients with COVID-19. Because of the low oral bioavailability and improvement of buccal/oral cavity hygiene, traditional use by chewing B. serrata gum may be more beneficial than oral use. It is the cheapest option for a lot of poorer people. The promising effect of B. serrata and BA can be attributed to its antioxidant, anti-inflammatory, immunomodulatory, cardioprotective, anti-platelet aggregation, antibacterial, antifungal, and broad antiviral activity. B. serrata and BA act by multiple mechanisms. The most common mechanism may be through direct interaction with IκB kinases and inhibiting nuclear factor-κB-regulated gene expression. However, the most recent mechanism proposed that BA not only inhibited the formation of classical 5-lipoxygenase products but also produced anti-inflammatory LOX-isoform-selective modulators. In conclusion a small to moderate dose B. serrata extract may be useful in the enhancing adaptive immune response in mild to moderate symptoms of COVID-19. However, large doses of BA may be beneficial in suppressing uncontrolled activation of the innate immune response. More clinical results are required to determine with certainty whether there is sufficient evidence of the benefits against COVID-19.

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Section: Potential Therapeutic Effects Of Boswellic Acids/ B Serrata Extract Against Sars-cov-2-induced Modification Omentioning

confidence: 99%

Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly

et al. 2021

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“…The pMCAO-miR-182 KD group had significantly attenuated the extravasation of Evans blue compared with the pMCAO-WT group ( Figure 2B). Because astrocyte end-feet and endothelial cells TJ proteins are essential for the maintenance of BBB homeostasis, 35,36 we examined the structural integrity of the BBB through double-staining of endothelial cells and astrocytes. The results showed that the BBB structure was relatively complete in the sham group, while the pMCAO-miR-182 KD group had more BBB structures in the infarction area compared with the pMCAO-WT group ( Figure 2C).…”

Section: Mir-182 Knockdown In Mice Reduced Infarct Volume and Presementioning

confidence: 99%

MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

Zhang

Tian

et al. 2020

FASEB j.

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Cerebral ischemia causes damage to the structure and function of the blood‐brain barrier (BBB) and alleviating BBB destruction will be of great significance for the treatment and prognosis of ischemic stroke. Recently, microRNAs have been shown to play a critical role in BBB integrity. However, the potential mechanism by which microRNA‐182 (miR‐182) affects the BBB in ischemic stroke remains unclear. We demonstrated for the first time that cerebral ischemia leads to a significant progressive increase in miR‐182 after pMCAO, and bEnd.3 cells are the primary target cells of miR‐182. In miR‐182 KD transgenic mice, infarct volume, and BBB permeability were attenuated, and tight junction (TJ) proteins increased. Inhibition of miR‐182 with an antagomir reduced OGD‐induced apoptosis of bEnd.3 cells and the loss of ZO‐1 and Occludin. To further explore the mechanism by which miR‐182 regulates BBB integrity, we detected the apoptotic proteins Bcl‐2/Bax and demonstrated that mTOR and FOXO1 were the targets of miR‐182. Inhibition of mTOR/FOXO1 by rapamycin/AS1842856 decreased the ratio of Bcl‐2/Bax and exacerbated TJ protein loss. Taken together, inhibition of miR‐182 protects BBB integrity by reducing endothelial cell apoptosis through the mTOR/FOXO1 pathway. Thus, miR‐182 may be a potential target for the treatment of BBB disruption during cerebral ischemia.

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“…Once drugs and/or chemicals are ingested, they first contact the EC lining of the blood vessels and other cellular matrices before reaching their target sites. Studies have shown that ECs can be easily damaged by various stressors, such as cigarette aerosol, H 2 O 2 , and oxygen-glucose deprivation/reperfusion [ 15 , 16 , 17 ]. These factors can cause DNA damage and inflammation, which eventually lead to death of ECs, and weaken the integrity and function of blood vessels.…”

Section: Introductionmentioning

confidence: 99%

Zearalenone Induces Endothelial Cell Apoptosis through Activation of a Cytosolic Ca2+/ERK1/2/p53/Caspase 3 Signaling Pathway

Lee

2021

Toxins

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Zearalenone (ZEN) is a mycotoxin that has been reported to damage various types of cells/tissues, yet its effects on endothelial cells (ECs) have never been investigated. Therefore, this study investigates the potential effects of ZEN using bovine aortic ECs (BAECs). In this study, we found that ZEN induced apoptosis of BAECs through increased cleavage of caspase 3 and poly ADP-ribose polymerase (PARP). ZEN also increased phosphorylation of ERK1/2 and p53, and treatment with the ERK1/2 or p53 inhibitor reversed ZEN-induced EC apoptosis. Transfection of BAECs with small interfering RNA against ERK1/2 or p53 revealed ERK1/2 as an upstream target of p53 in ZEN-stimulated apoptosis. ZEN increased the production of reactive oxygen species (ROS), yet treatment with the antioxidant did not prevent EC apoptosis. Similarly, blocking of estrogen receptors by specific inhibitors also did not prevent ZEN-induced apoptosis. Finally, chelation of cytosolic calcium (Ca2+) using BAPTA-AM or inhibition of endoplasmic reticulum (ER) Ca2+ channel using 2-APB reversed ZEN-induced EC apoptosis, but not by inhibiting ER stress using 4-PBA. Together, our findings demonstrate that ZEN induces EC apoptosis through an ERK1/2/p53/caspase 3 signaling pathway activated by Ca2+ release from the ER, and this pathway is independent of ROS production and estrogen receptor activation.

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Acetyl-11-keto-β-boswellic acid (AKBA) Attenuates Oxidative Stress, Inflammation, Complement Activation and Cell Death in Brain Endothelial Cells Following OGD/Reperfusion

Cited by 40 publications

References 39 publications

Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly

Boswellic acids/Boswellia serrata extract as a potential COVID-19 therapeutic agent in the elderly

MicroRNA‐182 exacerbates blood‐brain barrier (BBB) disruption by downregulating the mTOR/FOXO1 pathway in cerebral ischemia

Zearalenone Induces Endothelial Cell Apoptosis through Activation of a Cytosolic Ca2+/ERK1/2/p53/Caspase 3 Signaling Pathway

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