Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats

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Abstract

Introduction

We investigated the effects of zerumbone (1 and 10 mg/kg) against hyperactivity, anxiety and memory impairment in scopolamine-induced dementia in Sprague-Dawley rats.

Methods

Open field tests, elevated plus maze and Morris water maze were performed to assess general locomotor activity, anxiety-like behaviours and learning and memory processes respectively in rats pretreated with scopolamine.

Results

Scopolamine-treated rats showed high total activity, stereotype, and total distance travelled in the open field arena, reduced number of entries to open arms, decreased the percentage of time spent in open arms and higher escape latency time in the Morris water maze test. Interestingly, single administration of zerumbone (1 and 10 mg/kg) reversed the hyperactivity, anxiety-like behaviours, and learning impairment effects of scopolamine in the three experimental model studied respectively.

Discussion

Our findings demonstrated that the scopolamine-induced impairment of learning and memory was reversed by the administration of zerumbone. As a conclusion, our findings presented the positive effects of zerumbone on dementia-like behaviours in the animal model used and could possibly contribute for future research to manage hyperactivity, anxiety, and learning disabilities.

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Most cited references 15

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2014 Alzheimer's disease facts and figures.

(2014)

This report discusses the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality rates, costs of care, and overall effect on caregivers and society. It also examines the impact of AD on women compared with men. An estimated 5.2 million Americans have AD. Approximately 200,000 people younger than 65 years with AD comprise the younger onset AD population; 5 million are age 65 years or older. By mid-century, fueled in large part by the baby boom generation, the number of people living with AD in the United States is projected to grow by about 9 million. Today, someone in the country develops AD every 67 seconds. By 2050, one new case of AD is expected to develop every 33 seconds, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. In 2010, official death certificates recorded 83,494 deaths from AD, making AD the sixth leading cause of death in the United States and the fifth leading cause of death in Americans aged 65 years or older. Between 2000 and 2010, the proportion of deaths resulting from heart disease, stroke, and prostate cancer decreased 16%, 23%, and 8%, respectively, whereas the proportion resulting from AD increased 68%. The actual number of deaths to which AD contributes (or deaths with AD) is likely much larger than the number of deaths from AD recorded on death certificates. In 2014, an estimated 700,000 older Americans will die with AD, and many of them will die from complications caused by AD. In 2013, more than 15 million family members and other unpaid caregivers provided an estimated 17.7 billion hours of care to people with AD and other dementias, a contribution valued at more than $220 billion. Average per-person Medicare payments for services to beneficiaries aged 65 years and older with AD and other dementias are more than two and a half times as great as payments for all beneficiaries without these conditions, and Medicaid payments are 19 times as great. Total payments in 2014 for health care, long-term care, and hospice services for people aged 65 years and older with dementia are expected to be $214 billion. AD takes a stronger toll on women than men. More women than men develop the disease, and women are more likely than men to be informal caregivers for someone with AD or another dementia. As caregiving responsibilities become more time consuming and burdensome or extend for prolonged durations, women assume an even greater share of the caregiving burden. For every man who spends 21 to more than 60 hours per week as a caregiver, there are 2.1 women. For every man who lives with the care recipient and provides around-the-clock care, there are 2.5 women. In addition, for every man who has provided caregiving assistance for more than 5 years, there are 2.3 women.

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Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite.

Daisuke Takahashi, Koichi Koshimizu, Junji Terao … (2002)

Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.

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Zerumbone abolishes NF-kappaB and IkappaBalpha kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion.

Yasunari Takada, Bharat B. Aggarwal, Akira Murakami (2005)

Zerumbone found in subtropical ginger Zingiber zerumbet Smith exhibits antiproliferative and antiinflammatory activities but underlying molecular mechanisms are poorly understood. As several genes that regulate proliferation and apoptosis are regulated by nuclear factor (NF)-kappaB, we hypothesized that zerumbone mediates its activity through the modulation of NF-kappaB activation. We found that zerumbone suppressed NF-kappaB activation induced by tumor necrosis factor (TNF), okadaic acid, cigarette smoke condensate, phorbol myristate acetate, and H2O2 and that the suppression was not cell type specific. Interestingly, alpha-humulene, a structural analogue of zerumbone lacking the carbonyl group, was completely inactive. Besides being inducible, constitutively active NF-kappaB was also inhibited. NF-kappaB inhibition by zerumbone correlated with sequential suppression of the IkappaBalpha kinase activity, IkappaBalpha phosphorylation, IkappaBalpha degradation, p65 phosphorylation, p65 nuclear translocation, and p65 acylation. Zerumbone also inhibited the NF-kappaB-dependent reporter gene expression activated by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK but not that activated by the p65 subunit of NF-kappaB. NF-kappaB-regulated gene products, such as cyclin D1, COX-2, MMP-9, ICAM-1, c-Myc, survivin, IAP1, IAP2, XIAP, Bcl-2, Bcl-xL, Bfl-1/A1, TRAF1 and FLIP, were all downregulated by zerumbone. This downregulation led to the potentiation of apoptosis induced by cytokines and chemotherapeutic agents. Zerumbone's inhibition of expression of these NF-kappaB-regulated genes also correlated with the suppression of TNF-induced invasion activity. Overall, our results indicated that zerumbone inhibits the activation of NF-kappaB and NF-kappaB-regulated gene expression induced by carcinogens and that this inhibition may provide a molecular basis for the prevention and treatment of cancer by zerumbone.

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Author and article information

Contributors

Enoch Kumar Perimal

Journal

Journal ID (nlm-ta): Alzheimers Dement (N Y)

Journal ID (iso-abbrev): Alzheimers Dement (N Y)

Title: Alzheimer's & Dementia : Translational Research & Clinical Interventions

Publisher: Elsevier

ISSN (Electronic): 2352-8737

Publication date PMC-release: 22 October 2019

Publication date Collection: 2019

Publication date (Electronic): 22 October 2019

Volume: 5

Pages: 637-643

Affiliations

[a ]Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia

[b ]Department of Genetics, Harvard Medical School, Boston, MA, USA

[c ]Center for Drug Research, Universiti Sains Malaysia, Gelugor, Penang, Malaysia

[d ]Flinders Digital Health Research Centre, College of Nursing and Health Sciences, Flinders University of South Australia, Adelaide, SA, Australia

[e ]Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, University of Adelaide, Adelaide, SA, Australia

Author notes

[∗ ]Corresponding author. Tel.: +61474015688; Fax: +60389472774. enoch@ 123456upm.edu.my enoch.perimal@ 123456adelaide.edu.au

Article

Publisher ID: S2352-8737(19)30070-8

DOI: 10.1016/j.trci.2019.09.009

PMC ID: 6819871

PubMed ID: 31687471

SO-VID: cfac4429-1fc0-4de2-89bf-62ea04e4e834

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Effect of zerumbone on scopolamine-induced memory impairment and anxiety-like behaviours in rats

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Abstract

Introduction

Methods

Results

Discussion

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Embodied Memory

Most cited references 15

2014 Alzheimer's disease facts and figures.

Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the alpha,beta-unsaturated carbonyl group is a prerequisite.

Zerumbone abolishes NF-kappaB and IkappaBalpha kinase activation leading to suppression of antiapoptotic and metastatic gene expression, upregulation of apoptosis, and downregulation of invasion.

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Contributors

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