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Contribution of human UDP-glucuronosyltransferases to the antioxidant effects of propolis, artichoke and silymarin
Conclusion: In conclusion, this study provides a possible molecular mechanism for protective antioxidant effects associated with the herbal drugs propolis, artichoke and silymarin. The herbal drug-mediated transcriptional upregulation of human detoxifying UGT1A enzymes via activation of AhR and Nrf2 leads to reduced hydrogen peroxide and oxidative stress. Because of UGT1A activation, the intake of these drugs could affect the therapeutic efficacy of other drugs when these also undergo metabolism by glucuronidation.Graphical abstract
Source: Phytomedicine - August 10, 2018 Category: Drugs & Pharmacology Source Type: research

Inhibition of SETD7 protects cardiomyocytes against hypoxia/reoxygenation-induced injury through regulating Keap1/Nrf2 signaling
This study aimed to investigate the potential role of SETD7 in hypoxia/reoxygenation (H/R)-induced apoptosis of rat cardiomyocytes and reveal the underlying mechanism. Our results demonstrated that SETD7 expression was significantly up-regulated in cardiomyocytes in response to H/R injury. The inhibition of SETD7 by siRNA-mediated gene silencing significantly suppressed H/R-induced apoptosis and decreased the production of reactive oxygen species (ROS). The overexpression of SETD7 markedly enhanced H/R-induced apoptosis and ROS production. Moreover, the knockdown of SETD7 reduced the expression of Keap1 and promoted the ex...
Source: Biomedicine and Pharmacotherapy - July 12, 2018 Category: Drugs & Pharmacology Source Type: research

Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2.
CONCLUSIONS: Sesn2 promoted the transfer of nuclear Nrf2 to the cytoplasm, it decreased the expressions of Nrf2 and its downstream proteins, Srx1 and Trx1. Meanwhile, it increased the cerebral ischemia-reperfusion injury by changing the distribution of Nrf2. PMID: 29917204 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - June 20, 2018 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

The apoptotic effect of Zoledronic acid on the nasopharyngeal carcinoma cells via ROS mediated chloride channel activation.
This article is protected by copyright. All rights reserved. PMID: 29884989 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - June 8, 2018 Category: Drugs & Pharmacology Authors: Wang L, Gao H, Yang X, Liang X, Tan Q, Chen Z, Zhao C, Gu Z, Yu M, Zheng Y, Huang Y, Zhu L, Jacob TJC, Wang L, Chen L Tags: Clin Exp Pharmacol Physiol Source Type: research

Suppression of Nrf2 confers chemosensitizing effect through enhanced oxidant-mediated mitochondrial dysfunction.
In this study, we investigated the mechanism of this chemosensitizing effect. MAIN METHODS: KKU-100 cells were used in the study. Nrf2 expression was knocked down by siRNA and expression was validated by reverse transcription and polymerase chain reaction. Cytotoxicity was assessed by sulforhodamine B method. Intracellular reactive oxygen species (ROS) was examined by fluorescent dye, dichlorofluorescin diacetate method and mitochondrial transmembrane potential was assessed by JC1 dye assay. KEY FINDINGS: Cytotoxicity of cisplatin (Cis) in KKU-100 cells was enhanced by knockdown of Nrf2 expression. The enhanced c...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - March 5, 2018 Category: Drugs & Pharmacology Authors: Sompakdee V, Prawan A, Senggunprai L, Kukongviriyapan U, Samathiwat P, Wandee J, Kukongviriyapan V Tags: Biomed Pharmacother Source Type: research

Invited submission to the Diamond Jubilee Special Issue of Biochemical PharmacolLeptin induces SIRT1 expression through activation of NF-E2-related factor 2: implications for obesity-associated colon carcinogenesis.
In conclusion, leptin might play a role in colon carcinogenesis by inducing Nrf2-dependent SIRT1 overexpression. PMID: 29427626 [PubMed - as supplied by publisher]
Source: Biochemical Pharmacology - February 7, 2018 Category: Drugs & Pharmacology Authors: Song NY, Lee YH, Na HK, Baek JH, Surh YJ Tags: Biochem Pharmacol Source Type: research

Baicalein and baicalin alleviate acetaminophen-induced liver injury by activating Nrf2 antioxidative pathway: the involvement of ERK1/2 and PKC.
This study investigated the protection of baicalin and its aglycone baicalein against APAP-induced hepatotoxicity and its mechanism. Baicalein and baicalin alleviated APAP-induced hepatotoxicity both in vitro and in vivo. Moreover, baicalin-provided this protection was not diminished in hepatocytes or mice treated with β-glucuronidase inhibitor. Results of liver glutathione (GSH) and reactive oxygen species (ROS) formation demonstrated the alleviation of baicalein and baicalin on APAP-induced liver oxidative stress injury. Baicalein and baicalin induced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) ...
Source: Biochemical Pharmacology - January 12, 2018 Category: Drugs & Pharmacology Authors: Shi L, Hao Z, Zhang S, Wei M, Lu B, Wang Z, Ji L Tags: Biochem Pharmacol Source Type: research

Gliclazide, a KATP channel blocker, inhibits vascular smooth muscle cell proliferation through the CaMKK β-AMPK pathway.
In this study, we investigated the inhibitory effect of gliclazide on vascular smooth muscle cell (VSMC) proliferation and tried to identify the underlying signaling pathway. We first investigated the effect of gliclazide-induced AMP-activated protein kinase (AMPK) activation on the proliferation of VSMCs. Gliclazide induced phosphorylation of AMPK in a dose- and time-dependent manner and inhibited VSMC proliferation following stimulation by platelet-derived growth factor (PDGF). However, KATP channel openers and Kir6.1 siRNA prevented gliclazide-mediated inhibition of VSMC proliferation. Gliclazide also increased the leve...
Source: Vascular Pharmacology - January 11, 2018 Category: Drugs & Pharmacology Authors: Lee KY, Kim JR, Choi HC Tags: Vascul Pharmacol Source Type: research

Heme oxygnease-1 induction by methylene blue protects RAW264.7 cells from hydrogen peroxide-induced injury.
Abstract Althoughmethylene blue (MB) has showed strong antioxidant effect, its effect related with heme oxygenase-1(HO-1) is still unclear. Thus, we investigated the effects of MB on HO-1 protein content and enzyme activity, and its protective effect against hydrogen peroxide (H2O2)- induced oxidative damage in RAW264.7 macrophage. The cellviability and the release of lactate dehydrogenase of RAW264.7 were determined. The mitochondrial functions were valuated through these indexes: content of adenosine triphosphate, superoxide dismutase, concentration of reactive oxygen species and mitochondrial membrane potential...
Source: Biochemical Pharmacology - January 5, 2018 Category: Drugs & Pharmacology Authors: Zhang XT, Sun XQ, Wu C, Chen JL, Yuan JJ, Pang QF, Wang ZP Tags: Biochem Pharmacol Source Type: research

Heme oxygenase-1 induction by rosiglitazone via PKC α/AMPKα/p38 MAPKα/SIRT1/PPARγ pathway suppresses lipopolysaccharide-mediated pulmonary inflammation.
In this study, we found that upregulation of HO-1 in vitro or in vivo by rosiglitazone attenuated VCAM-1 gene expression and monocyte adhesion to HPAEpiCs challenged with lipopolysaccharide (LPS). The inhibitory effects of rosiglitazone on LPS-mediated responses were reversed by transfection with HO-1 siRNA. LPS-induced VCAM-1 expression was mediated through NF-κB activation which was attenuated by rosiglitazone via suppressing p65 activation and translocation into the nucleus. Moreover, pretreatment with the inhibitor of PKCs (H7), PKCα (Gö6976), AMPKα (Compound C), p38 MAPKα (p38i VIII), SIRT1 (Sirtinol), or PPARγ ...
Source: Biochemical Pharmacology - January 5, 2018 Category: Drugs & Pharmacology Authors: Cho RL, Lin WN, Wang CY, Yang CC, Hsiao LD, Lin CC, Yang CM Tags: Biochem Pharmacol Source Type: research

Zerumbone Protects Human Skin Keratinocytes against UVA-irradiated Damages through Nrf2 Induction.
Abstract Ultraviolet A (UVA) irradiation is toxic to skin as it penetrates deep into the dermis and damages cellular components through excessive reactive oxygen species (ROS) production, which accelerates photoaging and skin cancer. We evaluated the dermato-protective efficacies of zerumbone (natural sesquiterpene of Zingiber zerumbet) in UVA-irradiated human skin keratinocyte (HaCaT) cells and mouse epidermis. Zerumbone pretreatment (2-10 μM) substantially suppressed UVA (15 J/cm2)-induced HaCaT cell death and lactate dehydrogenase release in a dose-dependent manner. UVA-induced excessive ROS production, DNA si...
Source: Biochemical Pharmacology - December 19, 2017 Category: Drugs & Pharmacology Authors: Yang HL, Lee CL, Korivi M, Liao JW, Rajendran P, Wu JJ, Hseu YC Tags: Biochem Pharmacol Source Type: research

Acacetin attenuates mice endotoxin-induced acute lung injury via augmentation of heme oxygenase-1 activity
AbstractAcacetin, a natural product, has a wide spectrum of biological activities such as antioxidant properties. In the present study, we examined whether Acacetin has any beneficial role on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and, if so, whether its effect is mediated via heme oxygenase-1 (HO-1), an antioxidant enzyme playing an important role in ALI. Male BALB/c mice were stimulated with LPS intratracheal instillation to induce ALI. Acacetin was administrated 2  h after LPS challenge. Samples were harvested 10 h after LPS administration. We demonstrated that LPS challenge significantly induced lun...
Source: Inflammopharmacology - October 7, 2017 Category: Drugs & Pharmacology Source Type: research

Methyleugenol protects against t-BHP-triggered oxidative injury by induction of Nrf2 dependent on AMPK/GSK3 β and ERK activation
Publication date: Available online 19 September 2017 Source:Journal of Pharmacological Sciences Author(s): Junfeng Zhou, Xiaoyuan Ma, Yan Cui, Yang Song, Lei Yao, Yuanyuan Liu, Shanshan Li Methyleugenol (Mlg), a natural ingredient of many herbs and used as a flavoring substance in dietary products, inhibits inflammation and oxidative stress. The aim of the study is to explore the antioxidative potential of Mlg against tert-butyl hydroperoxide (t-BHP)-triggered oxidative injury and the involvement of antioxidative mechanisms. Our findings indicated that Mlg exposure significantly alleviated t-BHP-stimulated cytotoxicity,...
Source: Journal of Pharmacological Sciences - September 20, 2017 Category: Drugs & Pharmacology Source Type: research

Triptolide induces Sertoli cell apoptosis in mice via ROS/JNK-dependent activation of the mitochondrial pathway and inhibition of Nrf2-mediated antioxidant response.
This study aimed to delineate the molecular mechanisms of TP-induced testicular injury in vitro and in vivo. TP (5-50000 nmol/L) dose-dependently decreased the viability of TM4 Sertoli cells with an IC50 value of 669.5-269.45 nmol/L at 24 h. TP (125, 250, and 500 nmol/L) dose-dependently increased the accumulation of ROS, the phosphorylation of JNK, mitochondrial dysfunction and activation of the intrinsic apoptosis pathway in TM4 cells. These processes were attenuated by co-treatment with the antioxidant N-acetyl cysteine (NAC, 1 mmol/L). Furthermore, TP treatment inhibited the translocation of Nrf2 from cytoplasm into th...
Source: Acta Pharmacologica Sinica - September 14, 2017 Category: Drugs & Pharmacology Authors: Wang Y, Guo SH, Shang XJ, Yu LS, Zhu JW, Zhao A, Zhou YF, An GH, Zhang Q, Ma B Tags: Acta Pharmacol Sin Source Type: research

Cinnamaldehyde protects human dental pulp cells against oxidative stress through the Nrf2/HO-1-dependent antioxidant response.
This study examined the intracellular signaling mechanisms of CA on the oxidative stress response in human dental pulp cells (hDPCs). The results showed that CA did not have any cell cytotoxicity or cause morphological changes at concentrations up to 50µM. A CA treatment strongly up-regulated the cellular protein level of heme oxygenase-1 (HO-1) and promoted Nrf2 translocation to the nucleus. CA-mediated Nrf2/HO-1 activation reduced the level of reactive oxygen species and protected the hDPCs from H2O2-induced oxidative stress, which induces apoptosis. Moreover, HO-1 depletion by siRNA attenuated the CA-mediated cell prot...
Source: European Journal of Pharmacology - September 4, 2017 Category: Drugs & Pharmacology Authors: Kim NY, Ahn SG, Kim SA Tags: Eur J Pharmacol Source Type: research

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