Protective effects of 6‐gingerol on 6‐hydroxydopamine‐induced apoptosis in PC12 cells through modulation of SAPK/JNK and survivin activation

Rezazadeh-Shojaee, Farzaneh-Sadat; Ramazani, Elham; Kasaian, Jamal; Tayarani‐Najaran, Zahra

doi:10.1002/jbt.22956

Cited by 14 publications

(10 citation statements)

References 49 publications

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“…A human proximal tubular epithelial cell line (HK-2) was used to determine the cytotoxicity of the peptides via the Resazurin cell viability kit. 58 Briefly, 1 × 10 4 cells/well were plated in 96-well plates (containing 10% serum) and incubated for 12 h; then, the supernatant was discarded. The cells were followed by treatment with various concentrations of peptides for 1 h (without serum) at 37 °C in 5% CO 2 .…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Novel β-Hairpin Antimicrobial Peptides Containing the β-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance

Ouyang

et al. 2022

J. Med. Chem.

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The emergence of multidrug-resistant bacteria has dramatically increased the lethality, level of resistance, and difficulty of treatment. In this study, a series of new antimicrobial peptides (AMPs) based on the β-hairpin structure with the template (XY) 2 RRRF(YX) 2 -NH 2 (X: hydrophobic amino acids; Y: cationic amino acids) were synthesized; surprisingly, almost all of the new peptides have strong antibacterial activity and negligible hemolytic toxicity. Particularly, the therapeutic index (TI) values of F(RI)2R and F(KW)2K reached up to 115.9 and 70.7, respectively. In addition, they did not show induced drug resistance and inhibited the development of antibiotic resistance when combined and used with traditional antibiotics. In addition, their antibacterial mechanism was preliminarily studied. Moreover, the new peptides F(RI)2R and F(KW)2K showed excellent performance in the pulmonary bacterial infection model and low toxicity in mice. In conclusion, F(RI)2R and F(KW)2K are considered new antimicrobial alternatives to address the antimicrobial-resistance crisis.

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Section: ■ Experimental Sectionmentioning

confidence: 99%

Novel β-Hairpin Antimicrobial Peptides Containing the β-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance

Ouyang

et al. 2022

J. Med. Chem.

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“…37 Furthermore, a recent study demonstrated that 6gingerol significantly inhibited 6-OHDA-induced cell apoptosis of PC12 cells, which was accompanied by lower levels of the activated form of stress-activated protein kinase/c-Jun Nterminal kinase (SAPK/JNK). 38 Hence, zingerone, 6-shogaol, and 6-gingerol may be the main ginger components with antioxidant properties in PD.…”

Section: ■ Effects Of Ginger In Oxidative Stress In Pdmentioning

confidence: 99%

“…In particular, 6-shogaol pretreatment has been associated with reduced lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in these cells . Furthermore, a recent study demonstrated that 6-gingerol significantly inhibited 6-OHDA-induced cell apoptosis of PC12 cells, which was accompanied by lower levels of the activated form of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) . Hence, zingerone, 6-shogaol, and 6-gingerol may be the main ginger components with antioxidant properties in PD.…”

Section: Effects Of Ginger In Oxidative Stress In Pdmentioning

confidence: 99%

Elucidating the Beneficial Effects of Ginger (Zingiber officinale Roscoe) in Parkinson’s Disease

Angelopoulou

Paudel

Papageorgiou

et al. 2022

ACS Pharmacol. Transl. Sci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease (AD), and its pathogenesis remains obscure. Current treatment approaches mainly including levodopa and dopamine agonists provide symptomatic relief but fail to halt disease progression, and they are often accompanied by severe side effects. In this context, natural phytochemicals have received increasing attention as promising preventive or therapeutic candidates for PD, given their multitarget pharmaceutical mechanisms of actions and good safety profile. Ginger (Zingiber officinale Roscoe, Zingiberaceae) is a very popular spice used as a medicinal herb throughout the world since the ancient years, for a wide range of conditions, including nausea, diabetes, dyslipidemia, and cancer. Emerging in vivo and in vitro evidence supports the neuroprotective effects of ginger and its main pharmaceutically active compounds (zingerone, 6-shogaol, and 6-gingerol) in PD, mainly via the regulation of neuroinflammation, oxidative stress, intestinal permeability, dopamine synaptic transmission, and possibly mitochondrial dysfunction. The regulation of several transcription factors and signaling pathways, including nuclear factor kappa B (NF-κB), p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol-3-kinase (PI3K)/Ak strain transforming (Akt), extracellular signal-regulated kinase (ERK) 1/2, and AMP-activated protein kinase (AMPK)/proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) have been shown to contribute to the protective effects of ginger. Herein, we discuss recent findings on the beneficial role of ginger in PD as a preventive agent or potential supplement to current treatment strategies, focusing on potential underlying molecular mechanisms.

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“…In addition, 6-gingerol has excellent blood-brain barrier permeability, resulting in direct effects on brain tissue ( Simon et al, 2020 ). Importantly, relevant studies have confirmed that 6-gingerol also exhibits neuroprotective effects against hypoxic-ischemic brain injury ( Zhao et al, 2021 ), cerebral ischemia/reperfusion injury ( Luo Y. et al, 2021 ), amnesia ( Kim et al, 2018 ), acrylonitrile-induced brain damage ( Farombi et al, 2018 ) and Alzheimer’s disease ( Rezazadeh-Shojaee et al, 2021 ). However, the protective effects of 6-gingerol against EBI post-SAH remain unclear.…”

Section: Introductionmentioning

confidence: 99%

“…6-gingerol is a natural compound extracted from ginger and has been reported to exhibit potent effects against oxidation, inflammation, apoptosis and cancer ( Chen et al, 2018 ; de Lima et al, 2018 ; Zhang et al, 2018 ; Luo J. et al, 2021 ; Rezazadeh-Shojaee et al, 2021 ). Previous studies have confirmed that 6-gingerol ameliorates apoptosis under different experimental conditions in various cells and organs, such as hypoxia-induced cardiomyocytes ( Zhang et al, 2019 ), myocardial ischemia/reperfusion injury ( Lv et al, 2021 ), myocardial fibrosis ( Han et al, 2020 ), osteoarthritis ( Abusarah et al, 2017 ), renal damage ( Hegazy et al, 2016 ) and atherosclerosis ( Yang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

6-Gingerol attenuates subarachnoid hemorrhage-induced early brain injury via GBP2/PI3K/AKT pathway in the rat model

et al. 2022

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Numerous studies have elucidated the neuroprotective effect of 6-gingerol in central nervous system diseases. However, the potential role and mechanism of 6-gingerol on early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains poorly understood. Here, we report that 6-gingerol exerts a neuroprotective effect on SAH-induced EBI through the GBP2/PI3K/AKT pathway. A SAH rat model was established by injecting femoral artery blood into the cisterna magna. 6-gingerol or vehicle was injected intraperitoneally 1 hour post-SAH induction. We found that the neurological function score and brain edema of SAH rats were significantly improved after 6-gingerol treatment, as well as neuronal apoptosis was attenuated in SAH rats by Nissl staining assay and TUNEL assay. To further explore potential molecular mechanisms associated with 6-gingerol, RNA sequencing was implemented to investigate the differences in transcriptomes between SAH rats with and without 6-gingerol treatment; and found that the expression of guanylate-binding protein 2 (GBP2) evidently was suppressed with 6-gingerol treatment compared to vehicle group. In addition, dual immunofluorescence was also employed to investigate changes in neurons, astrocytes, and microglia after 6-gingerol treatment. The results showed that GBP2 was expressed in neurons but not astrocytes or microglia. Western blotting analysis results demonstrated that the PI3K/AKT pathway was activated in the SAH rats treated with 6-gingerol. Furthermore, recombinant GBP2 protein and LY294002 (PI3K inhibitor) treatment reversed the effects of 6-gingerol treatment in SAH rats. These results indicate that 6-gingerol suppressed the expression of GBP2 to activate the PI3K/AKT pathway, improve neurologic outcomes, reduce brain edema and neuronal apoptosis. In summary, our findings suggest that 6-gingerol could attenuate EBI post-SAH in rats, and 6-gingerol may serve as a novel candidate neuroprotective drug for SAH-induced EBI.

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Protective effects of 6‐gingerol on 6‐hydroxydopamine‐induced apoptosis in PC12 cells through modulation of SAPK/JNK and survivin activation

Cited by 14 publications

References 49 publications

Novel β-Hairpin Antimicrobial Peptides Containing the β-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance

Novel β-Hairpin Antimicrobial Peptides Containing the β-Turn Sequence of -RRRF- Having High Cell Selectivity and Low Incidence of Drug Resistance

Elucidating the Beneficial Effects of Ginger (Zingiber officinale Roscoe) in Parkinson’s Disease

6-Gingerol attenuates subarachnoid hemorrhage-induced early brain injury via GBP2/PI3K/AKT pathway in the rat model

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