Efficiency of Traditional Chinese medicine targeting the Nrf2/HO-1 signaling pathway

Li, Bin; Nasser, Maher; Masood, Muqaddas; Adlat, Salah; Huang, Yufei; Yang, Baofeng; Luo, Chaochao; Jiang, Nan

doi:10.1016/j.biopha.2020.110074

Cited by 65 publications

(27 citation statements)

References 103 publications

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“…Normally, under physiological conditions, of low the activity of Nrf2 activity is maintained at a low level via its distribution in the cytoplasm in the Nrf2-keap1 complex [ 54 ]. After activation, Nrf2 is phosphorylated, dissociates from the complex, and is then released to translocate into the nucleus, where it induces downstream expression of HO-1 and SOD, which eliminate ROS [ 55 ]. To further identify the pathway through which PQQ supplementation protects cells from oxidative stress, we determined the key genes involved in the Nrf2-mediated antioxidant response.…”

Section: Discussionmentioning

confidence: 99%

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Huang

Fan

Han

et al. 2021

J Animal Sci Biotechnol

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Background Oxidative stress is a main cause of piglet gut damage and diarrhea. Pyrroloquinoline quinone (PQQ), is a novel redox cofactor with antioxidant properties. However, the effect and mechanism that PQQ supplementation decreases oxidative injury in weaned pigs is not understood. Therefore, the aim of this study is to confirm the effect of PQQ on regulating redox status in weaned pigs and the mechanism for antioxidant function by porcine intestinal epithelial cell line (IPEC-J2) challenged with H2O2. Results Experiment 1, 144 Duroc × Landrace × Yorkshire pigs (weaned at 28 d) were allocated to four groups: received a basal diet (control) and diets supplemented with 0.15%, 0.30% and 0.45% PQQ, respectively. On d 28, growth performance, diarrhea incidence and redox factors were measured. Experiment 2, IPEC-J2 were treated with or without PQQ in the presence or absence of H2O2 for indicated time points. Experiment 3, IPEC-J2 were transfected with or without Nrf2 siRNA, then treated according to Experiment 2. The cell viability, redox factors, protein of tight junctions and Nrf2 pathway were determined. In vivo, PQQ supplementation demonstrated dose-related improvements in average daily gain, and gain to feed ratio (Linear P < 0.05). During d 0–28, compared to controls, 0.45% PQQ supplementation for pigs decreased diarrhea incidence and MDA content in liver and jejunum, and increased concentration of SOD in liver; 0.3% PQQ supplementation decreased ileal and liver MDA concentration; and 0.15% PQQ supplementation decreased ileal MDA concentration (P < 0.05). In vitro, compared to cells cultured with H2O2, pre-treatment with PQQ increased cell viability, tight junction proteins expression including ZO-1, ZO-2, Occludin and Claudin-1; and decreased ROS concentration and level of Caspase-3 (P < 0.05); as well as upregulated the ratio of Bcl-2 to Bax and protein expression of nuclear Nrf2, HO-1. Notably, Nrf2 knockdown by transfection with Nrf2 siRNA largely abrogated the positive effects of PQQ pretreatment on H2O2-induced intracellular changes. Conclusions PQQ administration attenuated oxidative stress in weaned pigs which is associated with activation of Nrf2/HO-1 pathway.

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Section: Discussionmentioning

confidence: 99%

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Huang

Fan

Han

et al. 2021

J Animal Sci Biotechnol

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“…Colchicine and oral ginsenosides both appear to provide therapeutic benefit by activating xenobiotic defenses in the liver, a proposed mechanism that is shared by many other TCM-derived molecules ( Li et al, 2021a ; Li et al, 2020 ). Furthermore, many herbal remedies, as well as pure molecules derived from them, are known to cause drug-drug interactions by inducing or inhibiting cytochrome P450s and drug transporters ( Pal and Mitra, 2006 ).…”

Section: Case Studiesmentioning

confidence: 99%

Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses

Shi

Weng

Mitchison

2021

eLife

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Traditional herbal medicines, which emphasize a holistic, patient-centric view of disease treatment, provide an exciting starting point for discovery of new immunomodulatory drugs. Progress on identification of herbal molecules with proven single agent activity has been slow, in part because of insufficient consideration of pharmacology fundamentals. Many molecules derived from medicinal plants exhibit low oral bioavailability and rapid clearance, leading to low systemic exposure. Recent research suggests that such molecules can act locally in the gut or liver to activate xenobiotic defense pathways that trigger beneficial systemic effects on the immune system. We discuss this hypothesis in the context of four plant-derived molecules with immunomodulatory activity: indigo, polysaccharides, colchicine, and ginsenosides. We end by proposing research strategies for identification of novel immunomodulatory drugs from herbal medicine sources that are informed by the possibility of local action in the gut or liver, leading to generation of systemic immune mediators.

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“…erefore, HO-1 plays a critical role in preserving cardiac homeostasis and attenuating heart injury. e modulation of Nrf2/Keap1/HO-1 signaling is known to regulate cardiac ischemia-reperfusion injury, hypertensive heart disease, coronary heart disease, and arrhythmia [38]. Modulation of Nrf2/Keap1/HO-1 signaling treats cardiovascular diseases by alleviating oxidative stress in cardiomyocytes, enhancing the cellular antioxidant defense system, and upregulating the viability of cardiomyocytes.…”

Section: Nrf2 Pathway and Cardiovascular Diseasesmentioning

confidence: 99%

Ling‐Gui‐Zhu‐Gan Decoction Protects H9c2 Cells against H₂O₂‐Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO‐1 Signaling Pathway

Wang

Tang

Zhai

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Objectives. Ling-Gui-Zhu-Gan decoction (LGZGD) is a potentially effective treatment for heart failure, and it showed significant anti-inflammatory potential in our previous studies. However, its ability to ameliorate heart failure through regulation of oxidative stress response is still unknown. This study was aimed to investigate the protective effect of LGZGD-containing serum on H2O2-induced oxidative injury in H9c2 cells and explore the underlying mechanism. Methods. Eighteen rats were randomly divided into two groups: the blank control group and LGZGD group. The LGZGD group rats were administrated with 8.4 g/kg/d LGZGD for seven consecutive days through gavage, while the blank control group rats were given an equal volume of saline. The serum was extracted from all the rats. To investigate the efficacy and the underlying mechanism of LGZGD, we categorized the H9c2 cells into groups: the control group, model group, normal serum control (NSC) group, LGZGD group, LGZGD + all-trans-retinoic acid (ATRA) group, and ATRA group. Malonedialdehyde (MDA) and superoxide dismutase (SOD) were used as markers for oxidative stress. Dichlorodihydrofluorescin diacetate (DCFH-DA) staining was used to measure the levels of reactive oxygen species (ROS). The apoptosis rate was detected using flow cytometry. The expression levels of pro-caspase-3, cleaved-caspase-3, Bcl-2, Bax, Keap1, Nrf2, and HO-1 were measured using western blotting. The mRNA levels of Keap1, Nrf2, and HO-1 were measured using RT-qPCR. Results. The LGZGD attenuated injury to H9c2 cells and reduced the apoptosis rate. It was also found to upregulate the SOD activity and suppress the formation of MDA and ROS. The expression levels of pro-caspase-3 and Bcl-2 were significantly increased, while those of cleaved-caspase-3 and Bax were decreased in the LGZGD group compared with the model group. As compared with the model group, the LGZGD group demonstrated decreased Keap1 protein expression and significantly increased Nrf2 nuclear expression and Nrf2-mediated transcriptional activity. ATRA was found to reverse the LGZGD-mediated antioxidative and antiapoptotic effect on injured H9c2 cells induced by H2O2. Conclusion. Our results demonstrated that LGZGD attenuated the H2O2-induced injury to H9c2 cells by inhibiting oxidative stress and apoptosis via the Nrf2/Keap1/HO-1 pathway. These observations suggest that LGZGD might prevent and treat heart failure through regulation of the oxidative stress response.

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Efficiency of Traditional Chinese medicine targeting the Nrf2/HO-1 signaling pathway

Cited by 65 publications

References 103 publications

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses

Ling‐Gui‐Zhu‐Gan Decoction Protects H9c2 Cells against H₂O₂‐Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO‐1 Signaling Pathway

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Efficiency of Traditional Chinese medicine targeting the Nrf2/HO-1 signaling pathway

Cited by 65 publications

References 103 publications

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Pyrroloquinoline quinone regulates the redox status in vitro and in vivo of weaned pigs via the Nrf2/HO-1 pathway

Immunomodulatory drug discovery from herbal medicines: Insights from organ-specific activity and xenobiotic defenses

Ling‐Gui‐Zhu‐Gan Decoction Protects H9c2 Cells against H2O2‐Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO‐1 Signaling Pathway

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Ling‐Gui‐Zhu‐Gan Decoction Protects H9c2 Cells against H₂O₂‐Induced Oxidative Injury via Regulation of the Nrf2/Keap1/HO‐1 Signaling Pathway