Synthesis and biological evaluations of novel apocynin analogues

Lu, Xiaoyu; Wan, Sainan; Jiang, Jie; Jiang, Xiaojian; Yang, Wenjing; Yu, Pei; Xu, Li; Zhang, Zaijun; Zhang, Gaoxiao; Shan, Luchen; Wang, Yuqiang

doi:10.1016/j.ejmech.2011.03.056

Cited by 15 publications

(19 citation statements)

References 30 publications

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“…In some other researches, apocynin, another well studied natural antioxidant and its analogues were also observed to exert anti-oxidative effect in a dose dependent manner only within a certain range of concentration or dose, and showed a decrease of activity when exceeding the range. 24,25) Herein, 40 mg/kg might exceed the range so that to result in a reverse drop of action with the increase of dosage. The reason will be further studied.…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Chinonin in MPTP-Induced C57BL/6 Mouse Model of Parkinson’s Disease

Feng¹,

Zhang²,

Bao

et al. 2014

Biological & Pharmaceutical Bulletin

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The aims of this study were to investigate the effect of chinonin in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurodegeneration in C57BL/6 mice and to examine the possible mechanisms. The neurotoxin MPTP was employed to create a subacute Parkinson's disease (PD)-like model in C57BL/6 mice. Chinonin (10, 20, 40 mg/kg body weight) was intraperitoneally administered 0.5 h after MPTP (30 mg/kg) injection for 7 d consecutively. Chinonin showed neuroprotective effects in the MPTP-treated mice PD model by ameliorating motor impairment in the catwalk and open-field tests. Consistently, chinonin reduced loss of dopaminergic neurons in the substantia nigra and prevented depletion of dopamine and its metabolites 3-methoxy-4-hydroxy-phenylacetic acid and homovanillic acid in the striatum of mice. Compared with the MPTP group, in the chinonin plus MPTP groups significant increases of superoxide dismutase activity and glutathione levels were observed as well as a distinct reduction of lipid peroxidation product malondialdehyde in the striatum. Taken together, we propose that chinonin exerts neuroprotective effects in C57BL/6 mouse model of PD and these effects may be due to chinonin's antioxidative property. Key words chinonin; Parkinson's disease (PD); neuroprotection; behavior; oxidative stressParkinson's disease (PD) is a major neurodegenerative disorder characterized pathologically by a progressive loss of dopaminergic neurons and clinically by resting tremors, rigidity, slowness of movement and postural instability.1) Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), produces neuropathological and clinical hallmarks in humans, monkeys and mice that closely resemble idiopathic parkinsonism.2,3) MPTP is transformed to the 1-methyl-4-phenylpyridinium ion (MPP + ) by monoamine oxidase type B after administration. 4) Then MPP + is selectively absorbed by the dopaminergic neurons in the substantial nigra via the dopamine transporter and impairs mitochondrial respiration by inhibiting complex I, thereby blocking the production of ATP and lead to the production of reactive oxygen species (ROS). 5) Therefore, MPTP acted as a pro-oxidant in the progress of PD in MPTP-induced mouse.Although the etiologic mechanisms of PD are still obscure, oxidative injury is considered as a pivotal role in disease pathogenesis.6,7) Chinonin (Fig. 1), a natural multi-phenols compound also named Mangifera indica, has been reported to possess anti-oxidative, anti-inflammatory, anti-diabetic, anti-platelet aggregator, antiviral, and anti-depressant properties.8) Given its anti-oxidative property, chinonin have been extensively used in the Indian sub-continent as food additives and in cosmetics and medicines. 9) Besides, chinonin is able to cross the blood brain barrier and has the real potential to ameliorate the oxidative stress observed in neurodegenerative disorders.10,11) Its antioxidant properties have been extensively evaluated in various cell lines, including neurons.12) For example, A...

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Section: Discussionmentioning

confidence: 99%

Protective Effect of Chinonin in MPTP-Induced C57BL/6 Mouse Model of Parkinson’s Disease

Feng¹,

Zhang²,

Bao

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Also known as acetovanillone, apocynin occurs naturally in certain plants (172) and was isolated from the root of Canadian hemp in 1883 and Picrorhiza kurroa in 1971 (73,310). Plants containing the compound have been used as a traditional medicine, for example, for the treatment of jaundice, asthma, liver, and heart problems (219,286).…”

Section: Small-molecule Nox Inhibitors: Progress and Prospectsmentioning

confidence: 99%

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Diebold

Smith

Yang

et al. 2015

Antioxidants & Redox Signaling

106

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Significance: NOX2 is important for host defense, and yet is implicated in a large number of diseases in which inflammation plays a role in pathogenesis. These include acute and chronic lung inflammatory diseases, stroke, traumatic brain injury, and neurodegenerative diseases, including Alzheimer's and Parkinson's Diseases. Recent Advances: Recent drug development programs have targeted several NOX isoforms that are implicated in a variety of diseases. The focus has been primarily on NOX4 and NOX1 rather than on NOX2, due, in part, to concerns about possible immunosuppressive side effects. Nevertheless, NOX2 clearly contributes to the pathogenesis of many inflammatory diseases, and its inhibition is predicted to provide a novel therapeutic approach. Critical Issues: Possible side effects that might arise from targeting NOX2 are discussed, including the possibility that such inhibition will contribute to increased infections and/or autoimmune disorders. The state of the field with regard to existing NOX2 inhibitors and targeted development of novel inhibitors is also summarized. Future Directions: NOX2 inhibitors show particular promise for the treatment of inflammatory diseases, both acute and chronic. Theoretical side effects include pro-inflammatory and autoimmune complications and should be considered in any therapeutic program, but in our opinion, available data do not indicate that they are sufficiently likely to eliminate NOX2 as a drug target, particularly when weighed against the seriousness of many NOX2-related indications. Model studies demonstrating efficacy with minimal side effects are needed to encourage future development of NOX2 inhibitors as therapeutic agents. Antioxid. Redox Signal. 23,

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“…ALA also shields cell membranes via interrelating with glutathione and ascorbic acid, which might conversely regenerate vitamin E (Kennedy & Wan, 2011). These different activities illustrate that ALA works through various processes both physiologically and pharmacologically (Lu et al, 2011b).…”

Section: Introductionmentioning

confidence: 99%

“…ALA has been considered as ''universal antioxidant'', and is recognized to play an important role in mitochondrial dehydrogenase responses (Kennedy & Wan, 2011). ALA could end free radicals, chelates transition metal ions and improve ascorbic acid and cytosolic glutathione state (Lu et al, 2011b). ALA also shields cell membranes via interrelating with glutathione and ascorbic acid, which might conversely regenerate vitamin E (Kennedy & Wan, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…ALA, a B vitamin, is a powerful antioxidant that is lipid-soluble, and reacts chemically with singlet oxygen, peroxyl, hydroxy radicals and hypochlorous radicals (Kennedy & Wan, 2011). ALA is biogenic and one of the most effective antioxidants known (Lu et al, 2011b). ALA has been considered as ''universal antioxidant'', and is recognized to play an important role in mitochondrial dehydrogenase responses (Kennedy & Wan, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cellsin vitro

Wang

Xia²

2013

Drug Delivery

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ALA-loaded nanostructured lipid carrier (ALA-NLC) was designed to improve physicochemical stability and water solubility, and promote sustained release of ALA as well as determine the biocompatibility of ALA-NLC. The ALA-NLC manufactured using hot high-pressure homogenization technique was investigated in terms of size, zeta potential, FTIR analysis and release behavior. In vitro cytotoxicity and biocompatibility were determined by incubating with HaCaT cells using the MTT assay, HE staining and Hoechst 33342 staining. Cell behavior and cellular division of HaCaT cells untreated and treated by ALA-NLC were investigated in real-time images gathered using time-lapse imaging system. The release investigation illustrated that only 6.9% of ALA released in 30 min from ALA-NLC formation, whereas it was 30.3% in free ALA system. ALA-NLC possessed a satisfactory release behavior of sustained release up to 72 h. It showed that ALA-NLC did not exert hazardous effect on HaCaT cells up to 81.9 mg/L without morphological alterations, revealing a satisfactory biocompatibility. Evidence was provided from time-lapse imaging system that cell behavior and cellular division of ALA-NLC treated HaCaT cells were in accordance with the control. These results of this investigation demonstrated that NLC encapsulated ALA formation (ALA-NLC) can improve stability, solubility and release of ALA; ALA-NLC was biocompatible to HaCaT cells.

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Synthesis and biological evaluations of novel apocynin analogues

Cited by 15 publications

References 30 publications

Protective Effect of Chinonin in MPTP-Induced C57BL/6 Mouse Model of Parkinson’s Disease

Protective Effect of Chinonin in MPTP-Induced C57BL/6 Mouse Model of Parkinson’s Disease

NOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress

Alpha-lipoic acid-loaded nanostructured lipid carrier: sustained release and biocompatibility to HaCaT cellsin vitro

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