Natural products targeting ER stress pathway for the treatment of cardiovascular diseases

Choy, Ker Woon; Murugan, Dharmani Devi; Mustafa, Mohd Rais

doi:10.1016/j.phrs.2018.04.013

Cited by 90 publications

(60 citation statements)

References 146 publications

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“…ER is also recognized as a major site of the biosynthesis of cholesterol and lipids [17], as evidenced by involvement of GRP78 in regulating lipid metabolism of cancer cells and its localization in ER [18]. Additionally, GRP78 modulates antioxidant activities of glutathione and NAD(P)H:quinone oxidoreductase by inducing activation of protein kinase RNA-like endoplasmic reticulum kinase and nuclear factor erythroid 2 p45-related factor 2 [19], contributing the protection of cancer cells from oxidative stress-induced damage [20,21]. Increased formation of cell surface GRP78−PI3K complexes in cancer cells confers a beneficial effects on cell survival and resistance to reactive oxygen species (ROS)-induced lipotoxicity [13,22].…”

Section: Introductionmentioning

confidence: 99%

Impairment of Membrane Lipid Homeostasis by Bichalcone Analog TSWU-BR4 Attenuates Function of GRP78 in Regulation of the Oxidative Balance and Invasion of Cancer Cells

Lee

Wang

Chan

et al. 2020

Cells

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The specialized cholesterol/sphingolipid-rich membrane domains termed lipid rafts are highly dynamic in the cancer cells, which rapidly assemble effector molecules to form a sorting platform essential for oncogenic signaling transduction in response to extra- or intracellular stimuli. Density-based membrane flotation, subcellular fractionation, cell surface biotinylation, and co-immunoprecipitation analyses of bichalcone analog ((E)-1-(4-Hydroxy-3-((4-(4-((E)-3-(pyridin-3-yl)acryloyl)phenyl)piperazin-1-yl)methyl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one (TSWU-BR4)-treated cancer cells showed dissociation between GRP78 and p85α conferring the recruitment of PTEN to lipid raft membranes associated with p85α. Ectopic expression of GRP78 could overcome induction of lipid raft membrane-associated p85α–unphosphorylated PTEN complex formation and suppression of GRP78−PI3K−Akt−GTP-Rac1-mediated and GRP78-regulated PERK−Nrf2 antioxidant pathway and cancer cell invasion by TSWU-BR4. Using specific inducer, inhibitor, or short hairpin RNA for ASM demonstrated that induction of the lipid raft membrane localization and activation of ASM by TSWU-BR4 is responsible for perturbing homeostasis of cholesterol and ceramide levels in the lipid raft and ER membranes, leading to alteration of GRP78 membrane trafficking and subsequently inducing p85α–unphosphorylated PTEN complex formation, causing disruption of GRP78−PI3K−Akt−GTP-Rac1-mediated signal and ER membrane-associated GRP78-regulated oxidative stress balance, thus inhibiting cancer cell invasion. The involvement of the enrichment of ceramide to lipid raft membranes in inhibition of NF-κB-mediated MMP-2 expression was confirmed through attenuation of NF-κB activation using C2-ceramide, NF-κB specific inhibitors, ectopic expression of NF-κB p65, MMP-2 promoter-driven luciferase, and NF-κB-dependent reporter genes. In conclusion, localization of ASM in the lipid raft membranes by TSWU-BR4 is a key event for initiating formation of ceramide-enriched lipid raft membrane platforms, which causes delocalization of GRP78 from the lipid raft and ER membranes to the cytosol and formation of p85α–unphosphorylated PTEN complexes to attenuate the GRP78-regulated oxidative stress balance and GRP78−p85α−Akt−GTP-Rac1−NF-κB−MMP-2-mediated cancer cell invasion.

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Section: Introductionmentioning

confidence: 99%

Impairment of Membrane Lipid Homeostasis by Bichalcone Analog TSWU-BR4 Attenuates Function of GRP78 in Regulation of the Oxidative Balance and Invasion of Cancer Cells

Lee

Wang

Chan

et al. 2020

Cells

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“…Mangiferin (Mg), a natural glucosyl xanthone, is mainly extracted from mangos, mango leaves, and stem barks. In the past decades, Mg is known to its various pharmacological properties , such as anti‐oxidation , anticancer , antidiabetes , anti‐inflammation , and cardiovascular protection . Zhao et al .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotection of mangiferin against oxidative damage via arousing Nrf2 signaling pathway in PC12 cells

et al. 2019

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Accumulating evidence demonstrates that oxidative stress is involved in the pathogenesis and progression of neurodegeneration. As NF-E2-related factor 2 (Nrf2) plays a crucial role in maintaining cellular redox homeostasis, small molecules with the ability in activation of Nrf2 pathway are promising neuroprotective agents. Mangiferin (Mg) is a xanthone glucoside extracted from mangoes and papayas, and has been reported to possess multiple pharmacological activities. In this study, we investigated neuroprotective effects of Mg in the neuron-like rat pheochromocytoma cell line (PC12 cells). Mg scavenges different kinds of free radicals in vitro and attenuates hydrogen peroxide-or 6-hydroxydopamine-induced cell death. After treatment with Mg, a range of antioxidant genes governed by Nrf2 were upregulated, and the expressions and activities of these gene products were also elevated. Moreover, knockdown of Nrf2 antagonized the protective effect of Mg, indicating that Nrf2 is an essential factor in this cytoprotective process. In summary, our study demonstrates that Mg is a potent antioxidant that can provide neuroprotection against oxidative stress-mediated damage of PC12 cells. © 2019 BioFactors, 45(3):381-392, 2019

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“…Similar to coptisine, berberine exerts cardiovascular protection, lipid‐lowering, vascular‐relaxing and anti‐atherosclerosis properties. Besides, berberine also prevents multiple pathophysiologic processes such as myocardial injury, neurohormonal activation and oxidative stress . Accordingly, further efforts could focus on coptisine's effect on myocardial injury biomarkers (eg cardiac troponins), neurohormonal activation biomarkers (eg norepinephrine, ET‐1) and oxidative/nitroxidative stress biomarkers (eg nitrotyrosine, MPO).…”

Section: Future Prospectsmentioning

confidence: 99%

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

Luo

Deng

et al. 2019

J Cellular Molecular Medi

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Coptisine is a natural small‐molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as ‘coptisine’ in combination of ‘each pivotal pathway target’. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti‐cancer, anti‐inflammatory, CAD ameliorating or anti‐bacterial drug through regulating the signalling transduction of pathways such as NF‐κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non‐liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase‐1‐involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano‐ or microrods strategies or applying salt‐forming process to coptisine, can it be introduced to clinical trial.

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Natural products targeting ER stress pathway for the treatment of cardiovascular diseases

Cited by 90 publications

References 146 publications

Impairment of Membrane Lipid Homeostasis by Bichalcone Analog TSWU-BR4 Attenuates Function of GRP78 in Regulation of the Oxidative Balance and Invasion of Cancer Cells

Impairment of Membrane Lipid Homeostasis by Bichalcone Analog TSWU-BR4 Attenuates Function of GRP78 in Regulation of the Oxidative Balance and Invasion of Cancer Cells

Neuroprotection of mangiferin against oxidative damage via arousing Nrf2 signaling pathway in PC12 cells

Coptisine fromCoptis chinensisexerts diverse beneficial properties: A concise review

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