Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Liu, Xinhua; Wang, Xiling; Xiao, Hong; Wu, Dan; Xin, Xiaoming; Miao, Lei; Zhang, Qiuyan; Zhou, Yang; Liu, Qian; Zhang, Qian; Zhu, Yi‐Zhun

doi:10.1159/000430299

Cited by 12 publications

(8 citation statements)

References 44 publications

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“…A study by Liu et al33 showed that LPS stimulates RAW264.7 macrophages to produce inflammatory reaction and release of inflammatory factors such as inducible nitric oxide synthase (iNOS) and nitric oxide (NO): These changes could be inhibited by administering HO-1 siRNA or PI3K inhibitor LY294002, and these are related to the inhibition of NF-κB activity. This suggested that the expression of HO-1 is closely related to the NF-κB signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

Xue-zheng¹,

2016

NDT

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ObjectiveTo investigate the role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH).MethodsThirty-six adult Sprague Dawley (SD) male rats were randomly divided into sham operation, ICH and zinc protoporphyrin (ZPP) group. Rats (except for the sham operation group) were given 50 μL stereotactic injection of autologous blood from the femoral artery into the caudate nucleus, to establish an ICH model. In addition, rats in the ZPP group were given 10 mg/kg intraperitoneal injection of ZPP. At day 3 postoperative, neurobehavioral changes and brain water content were evaluated, brain tissue HO-1 expression was detected with immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR), brain tissue apoptosis was evaluated with TUNEL method, Caspase 3, Caspase 8 and Caspase 9 activity were detected with colorimetric method, level of TNF-α, IL-1β, IL-6 and IL-8 were measured with the enzyme-linked immunosorbent assay (ELISA), while Bcl-2, Bax, p-NF-κB p65 and p-IκBα protein expression were detected with Western blot.ResultsICH group compared to sham operation: HO-1 positive rate and mRNA expression were increased, neurological deficit score and cell apoptosis rate were increased, Caspase 3, Caspase 8 and Caspase 9 activity were increased, level of TNF-α, IL-1β, IL-6 and IL-8 were increased, Bcl-2 expression was downregulated, Bax, p-NF-κB p65 and p-IκBα expression were upregulated. The differences were statistically significant (P<0.01). ZPP group compared to ICH: HO-1 positive rate and mRNA expression were decreased, neurological deficit score and cell apoptosis rate were decreased, Caspase 3, Caspase 8, Caspase 9 activity were decreased, level of TNF-α, IL-1β, IL-6 and IL-8 were decreased, Bcl-2 expression was upregulated, Bax, p-NF-κB p65 and p-IκBα expression were downregulated, and the differences were statistically significant (P<0.01).ConclusionHO-1 inhibitor, ZPP does have a protective effect on ICH rats. This might be due to its inhibition to the inflammatory reaction and neuronal cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

Xue-zheng¹,

2016

NDT

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“…The control of HO-1 expression occurs primarily at the transcriptional level [34,35] and Nrf2 is one of the most potent transcriptional activators of HO-1. Induction requires Nrf2 nuclear translocation and binding to the antioxidant response element (ARE) controlling expression of HO-1 as well as other phase II antioxidant and stress-inducible genes [36].…”

Section: Discussionmentioning

confidence: 99%

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Tong

Zhang²,

Zhou³

et al. 2016

Cell Physiol Biochem

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Backgrounds/Aims: The selective κ-opioid agonist U50,488H protects heart from myocardial ischemia-reperfusion (MI/R) injury. We examined whether U50,488H is also beneficial for MI/R induced heart failure. Methods: Anesthetized male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia via left anterior descending coronary artery (LAD) occlusion, followed by 4 weeks of reperfusion. Infarct size was examined by Evans blue/triphenyl tetrazolium chloride (TTC) staining. Cardiac function and remodeling were examined by echocardiography and histology. HO-1 gene transcription and expression were measured by RT-PCR and western blot. Results: Compared to vehicle-treated MI/R rats, rats administered a single dose of U50,488H at the beginning of reperfusion exhibited reduced myocardial infarct size, oxidative stress, hypertrophy, and fibrosis, improved mechanical function, and greater neovascularization. U50,488H also increased myocardial heme oxygenase (HO)-1 gene transcription and expression, while pharmacological HO-1 inhibition reversed all protective effects of U50,488H. Furthermore, U50,488H protected control cultured cardiomyoctes against simulated I/R-induced apoptosis but not cultures subjected to shRNA-mediated HO-1 knockdown. Inhibition of HO-1 in the subacute phase of reperfusion reversed the U50,488H-induced increase in neovascularization and suppression of oxidative stress. Finally, U50,488H increased Akt phosphorylation and nuclear translocation of Nrf2, a key HO-1 transcription activator, while inhibition of PI3K-Akt signaling abolished U50,488H-induced Nrf2 nuclear translocation, HO-1 upregulation, and cardioprotection. Conclusion: Activation of HO-1 expression through the PI3K-Akt-Nrf2 pathway may mediate the acute and long-term protective effects of U50,488H against heart failure by enhancing cardiomyocyte survival and neoangiogenesis and by reducing oxidative stress.

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“…Thus, STS has been used in China to treat patients with angina pectoris and coronary artery diseases for many years . To accommodate the cardiovascular protective effects of STS, a novel derivative (ZY‐1A4, introducing an –acetoxyl group at C1) was synthesized and biologically evaluated to test its anti‐inflammatory effects . Mechanistic studies in cultured mouse macrophages revealed that ZY‐1A4 exhibited potent inhibitory effects on LPS‐induced iNOS‐dependent NO production by repressing NF‐ƙB activation and activating anti‐oxidant NRF2/HO‐1 signaling pathway .…”

Section: Structure–activity Relationship Of Tanshinonesmentioning

confidence: 99%

“…166 Mechanistic studies in cultured mouse macrophages revealed that ZY-1A4 exhibited potent inhibitory effects on LPS-induced iNOS-dependent NO production by repressing NF-ƙB activation and activating anti-oxidant NRF2/HO-1 signaling pathway. 166 The potent anti-inflammatory profile of ZY-1A4 indicates that the introduction of the hydrophilic sodium sulfonate and acetoxyl moieties could potentially increase the oral bioavailability and anti-atherosclerotic efficacy of TSN. Interestingly, CTS, with a chemical structure very close to TSN, shows no significant inhibition on macrophage-derived foam cell formation, 167 but displays increased anti-inflammatory effects on LPS-stimulated NO production (IC 50 = 8 μM for TSN, 1.5 μM for CTS).…”

Section: Structure-activity Relationship Of Tanshinonesmentioning

confidence: 99%

Atheroprotective Effects and Molecular Targets of Tanshinones Derived From Herbal Medicine Danshen

Fang

Little

2017

Medicinal Research Reviews

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Abstract:Medicinal plant-derived bioactive compounds modulate multiple therapeutic targets in cardiovascular diseases (CVDs), rendering herb-derived phytochemicals effective against one of the major CVDs-atherosclerosis. Danshen (Salvia milthiorriza Bunge) is a Chinese medicine that has been used in cardio-and cerebro-vascular therapeutic remedies in Asian countries for many years. Emerging evidence from cellular, animal, and clinical studies suggests that major lipophilic tanshinones from Danshen can treat atherosclerotic CVDs. In this review, we highlight recent advances in understanding the molecular mechanisms of tanshinones in treating atherosclerosis, ranging from endothelial dysfunction to chronic inflammation. We also overview new molecular targets of tanshinones, including endothelial nitric oxide synthase, AMP-activated protein kinase, ABC transporter A1, heme oxygenase 1, soluble epoxide hydrolase, 11β-hydroxysteroid dehydrogenase, estrogen receptor, and proprotein convertase subtilisin/kexin type 9. Thus, this review provides a new perspective for advancing our understanding of the "ancient" herb Danshen from "modern" biomedical perspectives, supporting the possibility of exploiting tanshinones and derivatives as effective therapeutics against atherosclerosis-related cardiovascular and metabolic diseases.

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Induction of Heme Oxygenase-1 by Sodium 9-Hydroxyltanshinone IIA Sulfonate Derivative Contributes to Inhibit LPS-Mediated Inflammatory Response in Macrophages

Cited by 12 publications

References 44 publications

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

The role of heme oxygenase-1 (HO-1) in the regulation of inflammatory reaction, neuronal cell proliferation and apoptosis in rats after intracerebral hemorrhage (ICH)

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Atheroprotective Effects and Molecular Targets of Tanshinones Derived From Herbal Medicine Danshen

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