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  1. Saleem H, Zengin G, Ahmad I, Htar TT, Naidu R, Mahomoodally MF, et al.
    Food Res Int, 2020 11;137:109651.
    PMID: 33233230 DOI: 10.1016/j.foodres.2020.109651
    Anagallis arvensis (L.) is a wild edible food plant that has been used in folklore as a natural remedy for treating common ailments. This study aimed to explore the biochemical properties and toxicity of methanol (MeOH) and dichloromethane (DCM) extracts of A. arvensis (aerial and root parts). Bioactive contents were assessed spectrophotometrically, and the secondary metabolites were identified by UHPLC-MS analysis. DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelating assays were employed to assess antioxidant activity. Inhibitory potential against key enzymes (α-glucosidase, urease, lipoxygenase (LOX), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE)) were also assessed. MTT assay was employed to test toxicity against SW-480, MDA-MB-231, CaSki, MCF-7, and DU-145 cancer cell lines. Methanolic extracts showed highest phenolic (aerial-MeOH: 27.5 mg GAE/g extract; root-MeOH: 21.17 mg GAE/g extract) and flavonoid (aerial-MeOH: 26.15 mg QE/g extract; root-MeOH: 19.07 mg QE/g extract) contents, and potent antioxidant activities. The aerial-MeOH extract was most potent for DPPH (IC50: 231 ug/mL), ABTS (131.12 mg TE/g extract), FRAP (82.97 mg TE/g extract), and CUPRAC (137.15 mg TE/g extract) antioxidant assays. All extracts were cytotoxic towards tested cancer cells with IC50 values ranging from 12.57 to 294.5 µg/mL and conferred a comparatively strong inhibition against α-glucosidase (aerial-DCM extract showed the highest inhibition against α-glucosidase with IC50 value of 20.97 µg /mL), while aerial extracts were also considerably active against BChE (aerial-MeOH IC50: 224.63 µg /mL), LOX (aerial-DCM IC50: 385.7 µg /mL). Likewise, aerial-MeOH extract was most active against urease enzyme (IC50: 129.72 µg /mL). UHPLC-MS investigation of methanolic extracts showed the existence of important phenolics, flavonoids, and saponins, including methyl gallte, quercetin, lanceoletin, and balanitesin, amongst others. Moreover, principal component analysis (PCA) highlighted the correlation amongst bioactive contents and observed biological activities. A. arvensis extracts could be regarded as a natural source of bioactive antioxidants, enzyme inhibitors and anticancer agents and can be further investigated as a lead source for food and pharmaceutical products. However, further studies to isolate, purify, and to characterize its bioactive phytochemicals are needed.
    Matched MeSH terms: Antioxidants/toxicity
  2. Ablat A, Mohamad J, Awang K, Shilpi JA, Arya A
    ScientificWorldJournal, 2014;2014:786130.
    PMID: 24688431 DOI: 10.1155/2014/786130
    The ethanol extract of B. javanica seed was fractionated with solvents of different polarities and tested for antioxidant activities by several assays including DPPH radical scavenging activity, ferric reducing antioxidant power (FRAP), ferrous ion chelating activity (FCA), and nitric oxide radical scavenging activity (NORSA) along with their polyphenolic contents. Antidiabetic activity was evaluated both in vitro and in vivo using a glycogen phosphorylase α (GPα) inhibition assay and oral glucose tolerance test (OGTT) in nondiabetic rats. The ethyl acetate fraction (EAF), rich in tannin, exhibited the strongest antioxidant activities to DPPH, FRAP, and NORSA, except for FCA. The EAF also exerted a dose-depended inhibition of GPα (IC50 = 0.75 mg/ml). Further evaluation of hypoglycemic effect on OGGT indicated that rats treated with EAF (125 mg/kg bw) showed a 39.91% decrease (P < 0.05) in blood glucose levels at 30 min, and continuous fall (P < 0.05) of 28.89% and 20.29% was observed in the following hours (60 and 90 min) compared to the normal control during OGTT. The EAF was applied to polyamide column chromatography, and the resulting tannin-free fraction was tested for both GPα inhibition and antioxidant (DPPH only) activity. The GP α inhibitory activity was retained, while antioxidant activity was lost (4.6-fold) after tannin removal. These results concluded that the GPα inhibitory activity initially detected was primarily due to the compounds other than tannins, whereas antioxidant activity was mainly due to the tannins.
    Matched MeSH terms: Antioxidants/toxicity
  3. Nasir NLM, Kamsani NE, Mohtarrudin N, Tohid SFM, Zakaria ZA
    Pak J Pharm Sci, 2020 Sep;33(5):2009-2016.
    PMID: 33824108
    Muntingia calabura (M. calabura), locally known as "kerukup siam" or "buah ceri" belongs to the family Muntingiaceae and has been scientifically demonstrated to exert various pharmacological activities. The objectives of the current study are to evaluate the antioxidant activities and to determine the subchronic toxicity of 90 days orally-administered methanol extract of M. calabura (MEMC) in male Sprague Dawley rats. The rats were randomly divided into four groups (n=6). Vehicle control received 8% tween 80 and treatment group received 50, 250 and 500 mg/kg of MEMC orally administered daily for 90 days. Blood collection was carried out to obtain the hematological and biochemical profile of the rats. The organs harvested were subjected to histopathological analysis. For the antioxidant test, the extract was subjected to antioxidant study using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging activity, total phenolic content (TPC) and phytochemical screening. Results obtained show that no adverse effects were observed during the experimental period. Hematological and biochemical analysis also showed no significant changes in this toxicity study. Besides, antioxidant analyses revealed that MEMC has higher DPPH- and SOD-radical scavenges activity as well as higher TPC value. In conclusion, M. calabura is safe for consumption and possesses beneficial antioxidant effect.
    Matched MeSH terms: Antioxidants/toxicity*
  4. Zulkawi N, Ng KH, Zamberi R, Yeap SK, Satharasinghe D, Jaganath IB, et al.
    BMC Complement Altern Med, 2017 Jun 30;17(1):344.
    PMID: 28666436 DOI: 10.1186/s12906-017-1845-6
    BACKGROUND: Xeniji, produced by fermenting various types of foods with lactic acid bacteria and yeast, has been commonly consumed as functional food. However, nutrition value, bioactivities and safety of different fermented products maybe varies.

    METHODS: Organic acid and antioxidant profiles of Xeniji fermented foods were evaluated. Moreover, oral acute (5 g/kg body weight) and subchronic toxicity (0.1, 1 and 2 g/kg body weight) of Xeniji were tested on mice for 14 days and 30 days, respectively. Mortality, changes of body weight, organ weight and serum liver enzyme level were measured. Liver and spleen of mice from subchronic toxicity study were subjected to antioxidant and immunomodulation quantification.

    RESULTS: Xeniji was rich in β-carotene, phytonadione, polyphenol, citric acid and essential amino acids. No mortality and significant changes of body weight and serum liver enzyme level were recorded for both oral acute and subchronic toxicity studies. Antioxidant level in the liver and immunity of Xeniji treated mice were significantly upregulated in dosage dependent manner.

    CONCLUSION: Xeniji is a fermented functional food that rich in nutrients that enhanced antioxidant and immunity of mice. Xeniji that rich in β-carotene, phytonadione, polyphenol, citric acid and essential amino acids promote antioxidant and immunity in mice without causing toxic effect.

    Matched MeSH terms: Antioxidants/toxicity
  5. Hayyan M, Looi CY, Hayyan A, Wong WF, Hashim MA
    PLoS One, 2015;10(2):e0117934.
    PMID: 25679975 DOI: 10.1371/journal.pone.0117934
    The cytotoxic potential of ammonium-based deep eutectic solvents (DESs) with four hydrogen bond donors, namely glycerine (Gl), ethylene glycol (EG), triethylene glycol (TEG) and urea (U) were investigated. The toxicity of DESs was examined using In Vitro cell lines and In Vivo animal model. IC50 and selectivity index were determined for the DESs, their individual components and their combinations as aqueous solutions for comparison purposes. The cytotoxicity effect of DESs varied depending on cell lines. The IC50 for the GlDES, EGDES, UDES and TEGDES followed the sequence of TEGDES< GlDES< EGDES< UDES for OKF6, MCF-7, A375, HT29 and H413, respectively. GlDES was selective against MCF-7 and A375, EGDES was selective against MCF-7, PC3, HepG2 and HT29, UDES was selective against MCF-7, PC3, HepG2 and HT29, and TEGDES was selective against MCF-7 and A375. However, acute toxicity studies using ICR mice showed that these DESs were relatively toxic in comparison to their individual components. DES did not cause DNA damage, but it could enhance ROS production and induce apoptosis in treated cancer cells as evidenced by marked LDH release. Furthermore, the examined DESs showed less cytotoxicity compared with ionic liquids. To the best of our knowledge, this is the first time that combined In Vitro and In Vivo toxicity profiles of DESs were being demonstrated, raising the toxicity issue of these neoteric mixtures and their potential applicability to be used for therapeutic purposes.
    Matched MeSH terms: Antioxidants/toxicity
  6. Chew AL, Jessica JJ, Sasidharan S
    Asian Pac J Trop Biomed, 2012 Mar;2(3):176-80.
    PMID: 23569893 DOI: 10.1016/S2221-1691(12)60037-9
    To evaluate antioxidant, antimicrobial and cytotoxic activity of different parts (root, flower, leaf and stem) of Leucas aspera (L. aspera) (Labiatae).
    Matched MeSH terms: Antioxidants/toxicity
  7. Grace-Lynn C, Darah I, Chen Y, Latha LY, Jothy SL, Sasidharan S
    Molecules, 2012 Sep 19;17(9):11185-98.
    PMID: 22992785
    Lantadenes are pentacyclic triterpenoids present in the leaves of the plant Lantana camara. In the present study, in vitro antioxidant activity and free radical scavenging capacity of lantadene A was evaluated using established in vitro models such as ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH•), hydroxyl radical (OH•), nitric oxide radical (NO•), superoxide anion scavenging activities and ferrous ion chelating assay. Interestingly, lantadene A showed considerable in vitro antioxidant, free radical scavenging capacity activities in a dose dependant manner when compared with the standard antioxidant in nitric oxide scavenging, superoxide anion radical scavenging and ferrous ion chelating assay. These findings show that the lantadene A possesses antioxidant activity with different mechanism of actions towards the different free radicals tested. Since lantadene A is a very popular drug in modern medicine, it is a promising candidate for use as an antioxidant and hepatoprotective agent.
    Matched MeSH terms: Antioxidants/toxicity
  8. Lau YS, Ling WC, Murugan D, Mustafa MR
    J Cardiovasc Pharmacol, 2015 Jun;65(6):522-31.
    PMID: 25469805 DOI: 10.1097/FJC.0000000000000185
    Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent "natural" antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47 and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II-induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress-related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress-mediated signaling pathway.
    Matched MeSH terms: Antioxidants/toxicity
  9. Shwter AN, Abdullah NA, Alshawsh MA, Alsalahi A, Hajrezaei M, Almaqrami AA, et al.
    J Ethnopharmacol, 2014 Feb 12;151(3):1194-1201.
    PMID: 24393787 DOI: 10.1016/j.jep.2013.12.044
    ETHNOPHARMACOLOGICAL RELEVANCE: Gynura procumbens is commonly used as a traditional medicinal plant in Malaysia for treatment of many diseases. To investigate the chemopreventive properties of Gynura procumbens on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats.

    METHODS: Five groups of adult male rats were used in this experiment. Normal/control group; the rats were injected subcutaneously with 15 mg/kg of sterile normal saline once a week for two weeks, and orally administered with 10% Tween 20 (5 mL/kg). Carcinogen and treatment groups; the rats were injected subcutaneously each with 15 mg/kg body weight AOM once a week for 2 weeks and were continued to be fed for two months, respectively with 10% Tween 20, 500 and 250mg/kg body weight plant extracts. Reference group; the rats were injected subcutaneously with 15 mg/kg body weight AOM once a week for 2 weeks, and injected intraperitoneally with fluorouracil 35 mg/kg body weight for five consecutive days.

    RESULT: Total ACF detected in methylene blue stained whole mounts of rat colon were 21, 23and 130 in rats fed with 500, 250 mg/kg body weight treatment and carcinogen groups, respectively. Treatment with high and low doses of the plant extract led to83.6% and 82.2% decrease in the total crypts in the groups fed 500 mg/kg and 250 mg/kg Gynura procumbens respectively compared to carcinogen group. Immunohistochemical staining of ACF showed suppressed azoxymethane induced colonic cell proliferation and Bcl-2 expression. Glutathione-S-transfarase and superoxide dismutase activities were higher in treated rats compared to carcinogen groups.

    CONCLUSION: Gynura procumbens reduced the incidence of AOM induced ACF. The findings showed that Gynura procumbens may have antiproliferative and antioxidative properties. Moreover, Gynura procumbens possesses the medicinal properties to prevent colon cancer.

    Matched MeSH terms: Antioxidants/toxicity
  10. Zainol Abidin IZ, Fazry S, Jamar NH, Ediwar Dyari HR, Zainal Ariffin Z, Johari AN, et al.
    Sci Rep, 2020 08 25;10(1):14165.
    PMID: 32843675 DOI: 10.1038/s41598-020-70962-7
    In Malaysia, Piper sarmentosum or 'kaduk' is commonly used in traditional medicines. However, its biological effects including in vivo embryonic toxicity and tissue regenerative properties are relatively unknown. The purpose of this study was to determine zebrafish (Danio rerio) embryo toxicities and caudal fin tissue regeneration in the presence of P. sarmentosum aqueous extracts. The phytochemical components and antioxidant activity of the extract were studied using GC-MS analysis and DPPH assay, respectively. Embryo toxicity tests involving survival, heartbeat, and morphological analyses were conducted to determine P. sarmentosum extract toxicity (0-60 µg/mL); concentrations of 0-400 µg/mL of the extract were used to study tissue regeneration in the zebrafish caudal fin. The extract contained several phytochemicals with antioxidant activity and exhibited DPPH scavenging activity (IC50 = 50.56 mg/mL). Embryo toxicity assays showed that a concentration of 60 μg/mL showed the highest rates of lethality regardless of exposure time. Slower embryogenesis was observed at 40 µg/mL, with non-viable embryos first detected at 50 µg/mL. Extracts showed significant differences (p 
    Matched MeSH terms: Antioxidants/toxicity
  11. Mohamad NE, Keong Yeap S, Beh BK, Romli MF, Yusof HM, Kristeen-Teo YW, et al.
    J Sci Food Agric, 2018 Jan;98(2):534-540.
    PMID: 28631270 DOI: 10.1002/jsfa.8491
    BACKGROUND: Vinegar is widely used as a food additive, in food preparation and as a food supplement. This study compared the phenolic acid profiles and in vivo toxicities, and antioxidant and immunomodulatory effects of coconut, nipah and pineapple juice vinegars, which were respectively prepared via a two-step fermentation using Saccharomyces cerevisiae 7013 INRA and Acetobacter aceti vat Europeans.

    RESULTS: Pineapple juice vinegar, which had the highest total phenolic acid content, also exhibited the greatest in vitro antioxidant capacity compared to coconut juice and nipah juice vinegars. Following acute and sub-chronic in vivo toxicity evaluation, no toxicity and mortality were evident and there were no significant differences in the serum biochemical profiles between mice administered the vinegars versus the control group. In the sub-chronic toxicity evaluation, the highest liver antioxidant levels were found in mice fed with pineapple juice vinegar, followed by coconut juice and nipah juice vinegars. However, compared to the pineapple juice and nipah juice vinegars, the mice fed with coconut juice vinegar, exhibited a higher population of CD4+ and CD8+ T-lymphocytes in the spleen, which was associated with greater levels of serum interleukin-2 and interferon-γ cytokines.

    CONCLUSIONS: Overall, the data suggested that not all vinegar samples cause acute and sub-chronic toxicity in vivo. Moreover, the in vivo immunity and organ antioxidant levels were enhanced, to varying extents, by the phenolic acids present in the vinegars. The results obtained in this study provide appropriate guidelines for further in vivo bioactivity studies and pre-clinical assessments of vinegar consumption. © 2017 Society of Chemical Industry.

    Matched MeSH terms: Antioxidants/toxicity
  12. Samuel AJ, Mohan S, Chellappan DK, Kalusalingam A, Ariamuthu S
    J Ethnopharmacol, 2012 May 7;141(1):396-402.
    PMID: 22421378 DOI: 10.1016/j.jep.2012.02.051
    The roots of Hibiscus vitifolius Linn. (Malvaceae) is used for the treatment of jaundice in the folklore system of medicine in India. This study is an attempt to evaluate the hepatoprotective activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced hepatotoxicity.
    Matched MeSH terms: Antioxidants/toxicity
  13. Abdelwahab SI, Mohan S, Abdulla MA, Sukari MA, Abdul AB, Taha MM, et al.
    J Ethnopharmacol, 2011 Sep 2;137(2):963-70.
    PMID: 21771650 DOI: 10.1016/j.jep.2011.07.010
    Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated.
    Matched MeSH terms: Antioxidants/toxicity
  14. Mazlan M, Sue Mian T, Mat Top G, Zurinah Wan Ngah W
    J Neurol Sci, 2006 Apr 15;243(1-2):5-12.
    PMID: 16442562
    Oxidative stress is thought to be one of the factors that cause neurodegeneration and that this can be inhibited by antioxidants. Since astrocytes support the survival of central nervous system (CNS) neurons, we compared the effect of alpha-tocopherol and gamma-tocotrienol in minimizing the cytotoxic damage induced by H(2)O(2), a pro-oxidant. Primary astrocyte cultures were pretreated with either alpha-tocopherol or gamma-tocotrienol for 1 h before incubation with 100 microM H(2)O(2) for 24 h. Cell viability was then assessed using the MTS assay while apoptosis was determined using a commercial ELISA kit as well as by fluorescent staining of live and apoptotic cells. The uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes were also determined using HPLC. Results showed that gamma-tocotrienol is toxic at concentrations >200 microM but protects against H(2)O(2) induced cell loss and apoptosis in a dose dependent manner up to 100 microM. alpha-Tocopherol was not cytotoxic in the concentration range tested (up to 750 microM), reduced apoptosis to the same degree as that of gamma-tocotrienol but was less effective in maintaining the viable cell number. Since the uptake of alpha-tocopherol and gamma-tocotrienol by astrocytes is similar, this may reflect the roles of these 2 vitamin E subfamilies in inhibiting apoptosis and stimulating proliferation in astrocytes.
    Matched MeSH terms: Antioxidants/toxicity
  15. 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: Antioxidants/toxicity
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