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Fulltext Neuroprotective effects of 1`δ-1`-acetoxyeugenol acetate on Aβ(25-35) induced cognitive dysfunction in mice

Jayasingh Chellammal HS, Veerachamy A, Ramachandran D, Gummadi SB, Manan MM, Yellu NR

Biomed Pharmacother, 2019 Jan;109:1454-1461.
PMID: 30551397 DOI: 10.1016/j.biopha.2018.10.189

The progressive accumulation of amyloid beta (Aβ) peptide is neurotoxic and leads to Alzheimer's type dementia. Accumulation of Aβ has been associated with dysfunction of hypothalamic-pituitary-adrenal (HPA) axis and elevated pro-inflammatory cytokines. In this study, we investigated the effect of 1`δ-1`-acetoxyeugenol acetate (DAEA), isolated from Alpinia galanga (L.), on Aβ(25-35) induced neurodegeneration in mice. Mice were treated with three different doses of DAEA (12.5 mg/kg, 25 mg/kg and 50 mg/kg) for 28 days. Aβ(25-35) was injected by intracerebroventricular (i.c.v.) injection on the 15th day of 28 days. Open field, water maze and step-down inhibitory tests were performed on the 27th day to determine the habituation memory, spatial learning, and short- and long-term memory, respectively. Acetylcholinesterase (AChE), Corticosterone, biogenic amines (serotonin and dopamine), tumour necrosis factor-α (TNF-α), and antioxidant parameters such as superoxide dismutase, catalase, glutathione peroxidase and vitamin C were evaluated in brain homogenates after behavioural tests to ascertain the cognitive improvement through neuro-immune-endocrine modulation. The DAEA treatment with 25 mg/kg and 50 mg/kg resulted in significant (p < 0.001) improvement of habituation memory and step-down inhibitory avoidance task. In spatial learning, the cognitive improvement was significantly improved (p < 0.001) by reduction in escape latency. In the biochemical study, the significant (p < 0.001) reduction of AChE indicates the preeminent neuroprotection. Corticosterone and TNF-α were significantly (p < 0.01) reduced and biogenic amines were increased with antioxidant markers, which signify the potential influence of DAEA on neuroprotection. Our investigation revealed that the drug DAEA attenuates stress mediated through the HPA axis and regulates the neuroendocrine and neuroimmune function to improve the cognition. DAEA could be a potential lead candidate for the treatment of neurodegeneration.

Matched MeSH terms: Catalase/metabolism
Fulltext Gastroprotective activity of a novel Schiff base derived dibromo substituted compound against ethanol-induced acute gastric lesions in rats

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.

Matched MeSH terms: Catalase/metabolism
Fulltext Alpinia zerumbet (Pers.): Food and Medicinal Plant with Potential In Vitro and In Vivo Anti-Cancer Activities

Zahra MH, Salem TAR, El-Aarag B, Yosri N, El-Ghlban S, Zaki K, et al.

Molecules, 2019 Jul 08;24(13).
PMID: 31288458 DOI: 10.3390/molecules24132495

BACKGROUND/AIM: Plants play an important role in anti-cancer drug discovery, therefore, the current study aimed to evaluate the biological activity of Alpinia zerumbet (A. zerumbet) flowers.
METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.
RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.
CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.

Matched MeSH terms: Catalase/metabolism
Activation of Nrf2 signaling by sitagliptin and quercetin combination against β-amyloid induced Alzheimer's disease in rats

Li Y, Tian Q, Li Z, Dang M, Lin Y, Hou X

Drug Dev Res, 2019 09;80(6):837-845.
PMID: 31301179 DOI: 10.1002/ddr.21567

The objective of this study was to evaluate the neuroprotective effect of sitagliptin (Sita), quercetin (QCR) and its combination in β-amyloid (Aβ) induced Alzheimer's disease (AD). Male Sprague-Dawley rats, weighing between 220 and 280 g were used for experiment. Rats were divided into 5 groups (n = 10) and the groups were as follows: (a) Sham control; (b) Aβ injected; (c) Aβ injected + Sita 100; (d) Aβ injected + QCR 100; and (e) Aβ injected + Sita 100 + QCR 100. Cognitive performance was observed by the Morris water maze (MWM), biochemical markers, for example, MDA, SOD, CAT, GSH, Aβ1-42 level, Nrf2/HO-1 expression and histopathological study of rat brain were estimated. Pretreatment with Sita, QCR and their combination showed a significant increase in escape latency in particular MWM cognitive model. Further co-administration of sita and QCR significantly reduced Aβ1-42 level when compared with individual treatment. Biochemical markers, for example, increased SOD, CAT and GSH, decreased MDA were seen, and histopathological studies revealed the reversal of neuronal damage in the treatment group. Additionally, Nrf2/HO-1 pathway in rat's brain was significantly increased by Sita, QCR and their combination. Pretreatment with QCR potentiates the action of Sita in Aβ induced AD in rats. The improved cognitive memory could be because of the synergistic effect of the drugs by decreasing Aβ1-42 level, antioxidant activity and increased expression of Nrf2/HO-1 in rat brain.

Matched MeSH terms: Catalase/metabolism
Chlorella vulgaris modulates the expression of senescence-associated genes in replicative senescence of human diploid fibroblasts

Jaafar F, Durani LW, Makpol S

Mol Biol Rep, 2020 Jan;47(1):369-379.
PMID: 31642042 DOI: 10.1007/s11033-019-05140-8

Human diploid fibroblasts (HDFs) cultured in vitro have limited capacity to proliferate after population doubling is repeated several times, and they enter into a state known as replicative senescence or cellular senescence. This study aimed to investigate the effect of Chlorella vulgaris on the replicative senescence of HDFs by determining the expression of senescence-associated genes. Young and senescent HDFs were divided into untreated control and C. vulgaris-treated groups. A senescence-associated gene transcription analysis was carried out with qRT-PCR. Treatment of young HDFs with C. vulgaris reduced the expression of SOD1, CAT and CCS (p

Matched MeSH terms: Catalase/metabolism
Gold nanoparticles synthesized from Euphorbia fischeriana root by green route method alleviates the isoprenaline hydrochloride induced myocardial infarction in rats

Zhang T, Dang M, Zhang W, Lin X

J. Photochem. Photobiol. B, Biol., 2020 Jan;202:111705.
PMID: 31812087 DOI: 10.1016/j.jphotobiol.2019.111705

The procurance of gold nanoparticles in the plant extracts is an excellent way to attain nanomaterials natural and eco-friendly nanomaterials. The Dehydrated roots of Chinese Euphorbia fischeriana flowering plant are called "Lang-Du". In this study, the retrieving of gold nanoparticles from Euphorbia fischeriana root was amalgamated by standard procedure. Fabricated gold nanoparticles were portrayed through the investigations of ultraviolet and visible spectrophotometry (UV-Vis), Fourier transform infrared spectroscopy (FTIR), High resolution transmission electron microscopy (HRTEM) and X-ray diffraction (XRD). The UV-Vis and FTIR results explicated the obtained particles were sphere-shaped and the terpenoids of Euphorbia fischeriana had strong communications with gold surface. The HRTEM and XRD images exposed the produced gold nanoparticles had an extreme composition of crystal arrangement and excellent uniformed size of particles. In our study, the Isoprenaline induced myocardial damage established the elevation in TBARS, LOOH of heart tissues and notable decline in antioxidant enzymes SOD, CAT, GPx, and GSH. This biochemical result was additionally proved by histopathological assessment. Remarkably, the pretreatment with EF-AuNps(50 mg/kg b.w) illustrated stabilized levels of serum creatine and cardiotropins in myocardial infarcted animals. And further we understood the essential function of NF-ƙB, TNF-α, IL-6 signaling molecules and its way progression in the development of vascular tenderness.

Matched MeSH terms: Catalase/metabolism
Fulltext In vivo acute toxicity and anti-gastric evaluation of a novel dichloro Schiff base: Bax and HSP70 alteration

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.

Matched MeSH terms: Catalase/metabolism
Fulltext In Vitro and In Vivo Anticancer Activity of the Most Cytotoxic Fraction of Pistachio Hull Extract in Breast Cancer

Seifaddinipour M, Farghadani R, Namvar F, Bin Mohamad J, Muhamad NA

Molecules, 2020 Apr 13;25(8).
PMID: 32295069 DOI: 10.3390/molecules25081776

Pistacia (Pistacia vera) hulls (PV) is a health product that has been determined to contain bioactive phytochemicals which have fundamental importance for biomedical use. In this study, PV ethyl acetate extraction (PV-EA) fractions were evaluated with the use of an MTT assay to find the most cytotoxic fraction, which was found to be F13b1/PV-EA. After that, HPTLC was used for identify the most active compounds. The antioxidant activity was analyzed with DPPH and ABTS tests. Apoptosis induction in MCF-7 cells by F13b1/PV-EA was validated via flow cytometry analysis and a distinctive nuclear staining method. The representation of genes like Caspase 3, Caspase 8, Bax, Bcl-2, CAT and SOD was assessed via a reverse transcription (RT_PCR) method. Inhabitation of Tubo breast cancer cell development was examined in the BALB-neuT mouse with histopathology observations. The most abundant active components available in our extract were gallic acid and the flavonoid quercetin. The F13b1/PV-EA has antiradical activity evidence by its inhibition of ABTS and DPPH free radicals. F13b1/PV-EA displayed against MCF-7 a suppressive effect with an IC50 value of 15.2 ± 1.35 µg/mL. Also, the expression of CAT, SOD, Caspase 3, Caspase 8 and Bax increased and the expression of Bcl-2 decreased. F13b1/PV-EA dose-dependently inhibited tumor development in cancer-induced mice. Thus, this finding introduces F13b1/PV-EA as an effectual apoptosis and antitumor active agent against breast cancer.

Matched MeSH terms: Catalase/metabolism
Intracellular ROS scavenging and antioxidant regulation of WL15 from cysteine and glycine-rich protein 2 demonstrated in zebrafish in vivo model

Guru A, Lite C, Freddy AJ, Issac PK, Pasupuleti M, Saraswathi NT, et al.

Dev Comp Immunol, 2021 Jan;114:103863.
PMID: 32918928 DOI: 10.1016/j.dci.2020.103863

Antioxidant peptides are naturally present in food, especially in fishes, and are considered to contain rich source of various bioactive compounds that are structurally heterogeneous. This study aims to identify and characterize the antioxidant property of the WL15 peptide, derived from Cysteine and glycine-rich protein 2 (CSRP2) identified from the transcriptome of a freshwater food fish, Channa striatus. C. striatus is already studied to contain high levels of amino acids and fatty acids, besides traditionally known for its pharmacological benefits in the Southeast Asian region. In our study, in vitro analysis of WL15 peptide exhibited strong free radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), superoxide anion radical and hydrogen peroxide (H2O2) scavenging assay. Further, to evaluate the cytotoxicity and dose-response, the Human dermal fibroblast (HDF) cells were used. Results showed that the treatment of HDF cells with varying concentrations (10, 20, 30, 40 and 50 μM) of WL15 peptide was not cytotoxic. However, the treatment concentrations showed enhanced antioxidant properties by significantly inhibiting the levels of free radicals. For in vivo assessment, we have used zebrafish larvae for evaluating the developmental toxicity and for determining the antioxidant property of the WL15 peptide. Zebrafish embryos were treated with the WL15 peptide from 4 h of post-fertilization (hpf) to 96 hpf covering the embryo-larval developmental period. At the end of the exposure period, the larvae were exposed to H2O2 (1 mM) for inducing generic oxidative stress. The exposure of WL15 peptide during the embryo-larval period showed no developmental toxicity even in higher concentrations of the peptide. Besides, the WL15 peptide considerably decreased the intracellular reactive oxygen species (ROS) levels induced by H2O2 exposure. WL15 peptide also inhibited the H2O2-induced caspase 3-dependent apoptotic response in zebrafish larvae was observed using the whole-mount immunofluorescence staining. Overall results from our study showed that the pre-treatment of WL15 (50 μM) in the H2O2-exposed zebrafish larvae, attenuated the expression of activated caspase 3 expressions, reduced Malondialdehyde (MDA) levels, and enhanced antioxidant enzymes, including superoxide dismutase (SOD) and catalase (CAT). The gene expression of antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxide (GPx) and γ-glutamyl cysteine synthetase (GCS) was found to be upregulated. In conclusion, it can be conceived that pre-treatment with WL15 could mitigate H2O2-induced oxidative injury by elevating the activity and expression of antioxidant enzymes, thereby decreasing MDA levels and cellular apoptosis by enhancing the antioxidant response, demonstrated by the in vitro and in vivo experiments.

Matched MeSH terms: Catalase/metabolism
Anti-ulcerogenic effect of methanolic extract of Elaeagnus conferta Roxb. seeds in Wistar rats

Gupta M, Gulati M, Kapoor B, Kumar B, Kumar R, Kumar R, et al.

J Ethnopharmacol, 2021 Jul 15;275:114115.
PMID: 33852947 DOI: 10.1016/j.jep.2021.114115

ETHNOPHARMACOLOGICAL RELEVANCE: Elaeagnus conferta Roxb. (Elaeagnaceae) is a subtropical shrub mainly native to India, Vietnam, Malaysia and South China, whose various parts are used for treatment of diabetes, gastric ulcers, pain, oxidative stress and pulmonary disorders. Though the other parts of the plant have been reported for their ethnic use i.e. fruits as astringent locally and for cancer systemically, leaves for body pain and flowers for pain in chest and the seeds are mentioned as edible, there is no report per se on the medicinal use of seeds. Based on the fact that seeds of closely resembling species i.e. Elaeagnus rhamnoides has demonstrated significant anti-gastroulcerative property, the probability of the seeds of E. conferta possessing similar activity seemed quite significant.
AIM OF THE STUDY: Phytochemical investigation and assessment of pharmacological mechanism(s) involved in anti-ulcer effect of methanolic extract of the seeds of E. conferta.
MATERIALS AND METHODS: Bioactive phytoconstituents were isolated by column chromatography. These were identified by spectroscopic techniques including infrared (IR) spectroscopy, nuclear magnetic resonance (NMR) and mass spectrometry. Methanolic extract (MEC) of the seeds was prepared by cold maceration and its anti-ulcerogenic potential was evaluated using indomethacin (50 mg/kg) and water immersion stress models in male rats. The animals were pre-treated with different doses of MEC (400 and 800 mg/kg) and the therapeutic effect was compared with standard drug i.e. ranitidine (RANT; 50 mg/kg). The ameliorative effects of MEC were investigated on gastric juice pH, total acidity, free acidity and ulcer index. The assays of malionaldehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH) and pro-inflammatory cytokines i.e. interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were carried out to find out the possible mechanism(s) of protection. Further, histopathological changes were also studied.
RESULTS: Chromatography studies and further confirmation by spectroscopic techniques revealed the presence of four different compounds in MEC i.e oleic acid (1), stearic acid (2), ascorbic acid (3) and quercetin (4). MEC exhibited anti-ulcerogenic effect in dose dependent manner which may be attributed to suppression of pro-inflammatory cytokines (IL-6, TNF-α) and MDA (112.7%), and up-regulation of protective factors such as CAT (90.48%), SOD (92.77%) and GSH (90.01%). Ulcer inhibition, reduction in total and free acidity and increase in gastric juice pH were observed in MEC treated rats as compared to disease control animals. Histopathological findings confirmed decreased cell infiltration, less epithelial cell damage and regeneration of gastric mucosa in dose dependent manner.
CONCLUSIONS: The anti-ulcer effect of MEC may be attributed to its ability to scavenge free radicals and anti-inflammatory property via suppression of TNF-α and IL-6, thus offers a complete and holistic approach for management of peptic ulcer.

Matched MeSH terms: Catalase/metabolism
Pharmacological evaluation of vanillic acid in rotenone-induced Parkinson's disease rat model

Sharma N, Khurana N, Muthuraman A, Utreja P

Eur J Pharmacol, 2021 Jul 15;903:174112.
PMID: 33901458 DOI: 10.1016/j.ejphar.2021.174112

In the present study, we investigated the anti-Parkinson's effect of vanillic acid (VA) (12 mg/kg, 25 mg/kg, 50 mg/kg p.o.) against rotenone (2 mg/kg s.c.) induced Parkinson's disease (PD) in rats. The continuous administration of rotenone for 35 days resulted in rigidity in muscles, catalepsy, and decrease in locomotor activity, body weight, and rearing behaviour along with the generation of oxidative stress in the brain (rise in the TBARS, and SAG level and reduced CAT, and GSH levels). Co-treatment of VA and levodopa-carbidopa (100 mg/kg + 25 mg/kg p.o.) lead to a significant (P

Matched MeSH terms: Catalase/metabolism
Fulltext Physiological and biochemical responses of selected weed and crop species to the plant-based bioherbicide WeedLock

Hasan M, Mokhtar AS, Mahmud K, Berahim Z, Rosli AM, Hamdan H, et al.

Sci Rep, 2022 Nov 15;12(1):19602.
PMID: 36379972 DOI: 10.1038/s41598-022-24144-2

WeedLock is a broad-spectrum plant-based bioherbicide that is currently on the market as a ready-to-use formulation. In this study, we investigated the physiological and biochemical effects of WeedLock (672.75 L ha-1) on Ageratum conyzoides L., Eleusine indica (L.) Gaertn, Zea mays L., and Amaranthus gangeticus L. at four different time points. WeedLock caused significant reductions in chlorophyll pigment content and disrupted photosynthetic processes in all test plants. The greatest inhibition in photosynthesis was recorded in A. conyzoides at 24 h post-treatment with a 74.88% inhibition. Plants treated with WeedLock showed increased malondialdehyde (MDA) and proline production, which is indicative of phytotoxic stress. Remarkably, MDA contents of all treated plants increased by more than 100% in comparison to untreated. The activity of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) was elevated following treatment with WeedLock. Significant increases were observed in the SOD activity of A. conyzoides ranging from 69.66 to 118.24% from 6 to 72 h post-treatment. Our findings confirm that WeedLock disrupts the normal physiological and biochemical processes in plants following exposure and that its mode of action is associated with ROS (reactive oxygen species) production, similar to that of PPO (protoporphyrinogen oxidase) inhibitors, although specific site-of-action of this novel bioherbicide warrants further investigation.

Matched MeSH terms: Catalase/metabolism

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