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  1. Rad SK, Movafagh A
    Recent Pat Food Nutr Agric, 2021;12(1):45-57.
    PMID: 32807070 DOI: 10.2174/2212798411666200817120307
    BACKGROUND: Cinnamomum cassia (C. cassia) is an evergreen tree in China and Southern and Eastern Asia. In traditional medicine, cinnamon is widely used due to its many bioactivity effects.

    OBJECTIVE: The present novel study aims to evaluate and make a comparison of antioxidant and antiproliferative activities of different extractions of C. cassia bark using seven solvents having different polarities. Solvents polarity gradients start with the solvent of lower polarity, n-hexane, and end with water as the highest polar solvent. Among the extracts, acetone extract contains the highest phenolic and flavonoid contents; therefore, it is assessed for the ability to protect DNA from damage.

    METHODS: The extracts are evaluated for total phenolic, flavonoid contents and antioxidant activities, using FRAP, DPPH, superoxide, and hydroxyl and nitric oxide radicals scavenging assays. DNA damage protecting activity of the acetone extract is studied with the comet assay. Each of the extracts is studied for its antiproliferative effect against, MCF-7, MDA-MB-231(breast cancer), and HT29 (colon cancer), using MTT assay.

    RESULTS: The acetone extract exhibited the highest FRAP value, phenolic and flavonoids contents when compared to the other extracts and could protect 45% mouse fibroblast cell line (3T3-L1) from DNA damage at 30 μg/ml. The lowest IC50 value in DPPH, superoxide, and hydroxyl radicals scavenging was noticed in the ethyl acetate extract. IC50 value obtained for the hexane extract was the lowest compared to the other extracts in scavenging nitric oxide radicals. The hexane extract showed the highest antiproliferative effect against cancer cells followed by the chloroform extract. The ethyl acetate extract inhibited the proliferation of only MCF-7 by IC50 of 100 μg/ml, while the other extracts exhibited no IC50 in all the cancer cells.

    CONCLUSION: C. cassia showed promising antioxidant and anticancer activities with significant DNA damage protecting effect.

  2. Zadeh-Ardabili PM, Rad SK
    Biotechnol Rep (Amst), 2019 Jun;22:e00341.
    PMID: 31061816 DOI: 10.1016/j.btre.2019.e00341
    Although inflammation is a reactive to injurious stimuli and considered as beneficial process in body, but it causes some discomforts, such as pain. Murine dietary contains appreciable amounts of fatty acids and antioxidants which encourages researchers to focus on their potential therapeutic effects. This study is aimed to examine the analgesic and anti-inflammatory activity of Neptune krill oil (NKO) and fish oil (FO) in rodent model which are two well-known sources of rich content of n-3 polyunsaturated fatty acids (n-3 PUFAs), mostly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). NKO and FO were used at the same dose of 500 mg and also balanced at similar doses of EPA: 12 in NKO vs. 12 in FO wt%, DHA: 7 NKO vs. 8 FO wt%. Application of NKO and FO in acetic acid-induced writhing effect, hot plate, and formalin induced test, indicated the nociceptive activity of the two tested drugs in comparison with normal saline. Also, the anti-inflammatory effect of these supplements was confirmed by carrageenan test. Analysis of cytokines levels in the blood samples of the mice after induction inflammation by carrageenan indicated decreased levels of those proteins compared to that in the normal groups. Both tested drugs, effectively could reduce severe inflammation and pain in rodents in comparison with the references drugs (depends on the tests); however, NKO was found to be more effective.
  3. Zadeh-Ardabili PM, Rad SK, Rad SK, Movafagh A
    Sci Rep, 2020 Aug 11;10(1):13797.
    PMID: 32782307 DOI: 10.1038/s41598-020-70338-x
    An amendment to this paper has been published and can be accessed via a link at the top of the paper.
  4. Zadeh-Ardabili PM, Rad SK, Rad SK, Movafagh A
    Sci Rep, 2019 Dec 27;9(1):19953.
    PMID: 31882885 DOI: 10.1038/s41598-019-56360-8
    Oxidative stress has significant role in pathophysiology of any kind of depression through actions of free radicals, non-radical molecules, and unbalancing antioxidant systems in body. In the current study, antidepressant responses of fish oil (FO), Neptune krill oil (NKO), vitamin B12 (Vit B12), and also imipramine (IMP) as the reference were studied. Natural light was employed to induce stress in the animals followed by oral administration of the drugs for 14 days. The antidepressant effect was assessed by tail suspension test (TST) and forced swimming test (FST), antioxidant enzymes and oxidative stress markers were then measured in the brain tissue of the animals. The administration of FO and NKO could significantly reduce the immobility of the animals; while, increasing climbing and swimming time compared to the normal saline in CUS-control group in TST and FST, similarly to IMP but not with Vit B12. Vit B12 could not effect on SOD activity and H2O2 level, but, cause decrease of the malondialdihydric (MDA) level and CAT activity, as well as increased the GPx and GSH activities. The rest treatments led to decrease of MDA, H2O2 levels and CAT activity and increase of GPx, SOD, GSH activities.
  5. Saremi K, Rad SK, Khalilzadeh M, Hussaini J, Majid NA
    Acta Biochim Biophys Sin (Shanghai), 2020 Jan 02;52(1):26-37.
    PMID: 31889181 DOI: 10.1093/abbs/gmz140
    Chlorine is shown to possess anti-gastric ulcer activity, since it can inactivate Helicobacter pylori, which is regarded as one of the most common risk factors for causing gastric problems. In the current study, the gastroprotective property of a novel dichloro-substituted Schiff base complex, 2, 2'- [-1, 2-cyclohexanediylbis(nitriloethylidyne)] bis(4-chlorophenol) (CNCP), against alcohol-induced gastric lesion in SD rats was assessed. SD rats were divided into four groups, i.e. normal, ulcer control, testing, and reference groups. Ulcer area, gastric wall mucus, and also gastric acidity of the animal stomachs were measured. In addition, antioxidant activity of CNCP was evaluated and its safe dose was identified. Immunohistochemistry staining was also carried to evaluate two important proteins, i.e. Bcl2-associated X protein (Bax) and heat shock protein 70 (HSP70). Moreover, the activities of super oxide dismutase and catalase, as well as the levels of prostaglandin E2 (PGE2) and malondialdehyde (MDA) were also measured. Antioxidant activity of CNCP was approved via the aforementioned experiments. Histological evaluations showed that the compound possesses stomach epithelial defense activity. Additionally, periodic acid-Schiff staining exhibited over-expression of HSP70 and down-expression of Bax protein in the CNCP-treated rats. Moreover, CNCP caused deceased MDA level and elevated PGE2 level, and at the same time increased the activities of the two enzymes.
  6. Rad SK, Kanthimathi MS, Abd Malek SN, Lee GS, Looi CY, Wong WF
    PLoS One, 2015;10(12):e0145216.
    PMID: 26700476 DOI: 10.1371/journal.pone.0145216
    BACKGROUND: Cinnamomum cassia bark is a popular culinary spice used for flavoring and in traditional medicine. C. cassia extract (CE) induces apoptosis in many cell lines. In the present study, particular differences in the mechanism of the anti-proliferative property of C. cassia on two breast cancer cell lines, MCF-7 and MDA-MB-231, were elucidated.

    METHODOLOGY/PRINCIPAL FINDINGS: The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells (IC50, 34 ± 3.52 and 32.42 ± 0.37 μg/ml, respectively). Oxidative stress due to disruption of antioxidant enzyme (SOD, GPx and CAT) activity is suggested as the probable cause for apoptosis initiation. Though the main apoptosis pathway in both cell lines was found to be through caspase-8 activation, caspase-9 was also activated in MDA-MB-231 cells but suppressed in MCF-7 cells. Gene expression studies revealed that AKT1, the caspase-9 suppressor, was up-regulated in MCF-7 cells while down-regulated in MDA-MB-231 cells. Although, AKT1 protein expression in both cell lines was down-regulated, a steady increase in MCF-7 cells was observed after a sharp decrease of suppression of AKT1. Trans-cinnamaldehyde and coumarin were isolated and identified and found to be mainly responsible for the observed anti-proliferative activity of CE (Cinnamomum cassia).

    CONCLUSION: Activation of caspase-8 is reported for the first time to be involved as the main apoptosis pathway in breast cancer cell lines upon treatment with C. cassia. The double effects of C. cassia on AKT1 gene expression in MCF-7 cells is reported for the first time in this study.

  7. Saremi K, Rad SK, Tayeby F, Abdulla MA, Karimian H, Majid NA
    BMC Pharmacol Toxicol, 2019 Feb 15;20(1):13.
    PMID: 30770761 DOI: 10.1186/s40360-019-0292-z
    BACKGROUND: Basic function of bromine in body is to activate pepsin production in gastritis with low acidity. The present study encompasses a broad in vivo study to evaluate gastroprotective activity of a novel dibromo substituted Schiff base complex against Sprague Dawley (SD) rats.

    METHODS: 2, 2'-[1, 2-cyclohexanediylbis (nitriloethylidyne)]bis(4-bromophenol) (CNBP) is synthesized via a Schiff base reaction, using the related ketone and diamine as the starting materials. SD rats are divided as normal, ulcer control (5 ml/kg of 10% Tween 20), testing (10 and 20 mg/kg of CNBP) and reference groups (omeprazole 20 mg/kg). Except for the normal group, the rest of the groups are induced gastric ulcer by ethanol 1 h after the pre-treatment. Ulcer area, gastric wall mucus, and acidity of gastric content of the animal stomachs are measured after euthanization. Antioxidant activity of the compound is tested by Ferric reducing antioxidant power (FRAP) test and safety of the compound is identified through acute toxicity by [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, activities of superoxide dismutase (SOD), catalase (CAT), levels of prostaglandins E2 (PGE2) and also malondialdehyde (MDA) are determined.

    RESULTS: Antioxidant activity of CNBP was approved via FRAP assay. Vast shallow hemorrhagic injury of gastric glandular mucosa was observed in the ulcer group compared to the CNBP-treated animals. Histological evaluations confirmed stomach epithelial defense effect of CNBP with drastic decrease of gastric ulceration, edema and leucocytes penetration of submucosal stratum. Immunostaining exhibited over-expression in HSP70 protein in CNBP-treated groups compared to that of the ulcer group. Also, gastric protein analysis showed low levels of MDA, PGE2 and high activity of SOD and CAT.

    CONCLUSIONS: CNBP with noticeable antioxidant property showed gastroprotective activity in the testing rodents via alteration of HSP70 protein expression. Also, antioxidant enzyme activities which were changed after treatment with CNBP in the animals could be elucidated as its gastroprotective properties.

  8. Zadeh-Ardabili PM, Rad SK, Rad SK, Khazaài H, Sanusi J, Zadeh MH
    Sci Rep, 2017 10 30;7(1):14365.
    PMID: 29085045 DOI: 10.1038/s41598-017-14765-3
    Spinal cord injury (SCI) occurs following different types of crushes. External and internal outcomes of SCI are including paralysis, cavity, and cyst formation. Effects of dietary derived antioxidants, such as palm vitamin E on central nervous system (CNS) encourage researchers to focus on the potential therapeutic benefits of antioxidant supplements. In the present study, experiments were carried out to evaluate the neuro-protective effect of the palm vitamin E on locomotor function and morphological damages induced SCI. Seventy-two male rats (Sprague-Dawley) were randomly divided into four groups: sham (laminectomy); control (supplemented with the palm vitamin E at a dose of 100 mg/kg/day); untreated-SCI (partial crush, 30-33% for 20 sec); treated-SCI (partial crush, 30-33% for 20 sec supplemented with the palm vitamin E at a dose of 100 mg/kg/day). The treatment with the palm vitamin E significantly improved the hind limb locomotor function, reduced the histopathological changes and the morphological damage in the spinal cord. Also, the palm vitamin E indicated a statistically significant decrease in the oxidative damage indicators, malondialdehyde (MDA) level and glutathione peroxidase (GPx) activity in the treated-SCI compared to the untreated-SCI.
  9. Rad SK, Arya A, Karimian H, Madhavan P, Rizwan F, Koshy S, et al.
    Drug Des Devel Ther, 2018;12:3999-4021.
    PMID: 30538427 DOI: 10.2147/DDDT.S173970
    The pathophysiological link between type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) has been suggested in several reports. Few findings suggest that T2DM has strong link in the development process of AD, and the complete mechanism is yet to be revealed. Formation of amyloid plaques (APs) and neurofibrillary tangles (NFTs) are two central hallmarks in the AD. APs are the dense composites of β-amyloid protein (Aβ) which accumulates around the nerve cells. Moreover, NFTs are the twisted fibers containing hyperphosphorylated tau proteins present in certain residues of Aβ that build up inside the brain cells. Certain factors contribute to the aetiogenesis of AD by regulating insulin signaling pathway in the brain and accelerating the formation of neurotoxic Aβ and NFTs via various mechanisms, including GSK3β, JNK, CamKII, CDK5, CK1, MARK4, PLK2, Syk, DYRK1A, PPP, and P70S6K. Progression to AD could be influenced by insulin signaling pathway that is affected due to T2DM. Interestingly, NFTs and APs lead to the impairment of several crucial cascades, such as synaptogenesis, neurotrophy, and apoptosis, which are regulated by insulin, cholesterol, and glucose metabolism. The investigation of the molecular cascades through insulin functions in brain contributes to probe and perceive progressions of diabetes to AD. This review elaborates the molecular insights that would help to further understand the potential mechanisms linking T2DM and AD.
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