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Fulltext The effects of E'Jiao on body composition, bone marrow adiposity and skeletal redox status in ovariectomised rats

Ekeuku SO, Chin KY, Qian J, Zhang Y, Qu H, Ahmad F, et al.

Int J Med Sci, 2023;20(13):1711-1721.
PMID: 37928881 DOI: 10.7150/ijms.84604

Background: Menopause is accompanied by increased oxidative stress, partly contributing to weight gain and bone marrow adiposity. Traditional Chinese medication, E'Jiao, has been demonstrated to reduce excessive bone remodelling during oestrogen deprivation, but its effects on body composition and bone marrow adiposity during menopause remain elusive. Objective: To determine the effects of E'Jiao on body composition, bone marrow adiposity and skeletal redox status in ovariectomised (OVX) rats. Methods: Seven groups of three-month-old female Sprague Dawley rats were established (n=6/group): baseline, sham, OVX control, OVX-treated with low, medium or high-dose E'Jiao (0.26, 0.53, 1.06 g/kg, p.o.) or calcium carbonate (1% in tap water, ad libitum). The supplementation was terminated after 8 weeks. Whole-body composition analysis was performed monthly using dual-energy X-ray absorptiometry. Analysis of bone-marrow adipocyte numbers and skeletal antioxidant activities were performed on the femur. Results: Increased total mass, lean mass, and bone marrow adipocyte number were observed in the OVX control versus the sham group. Low-dose E'Jiao supplementation counteracted these changes. Besides, E'Jiao at all doses increased skeletal catalase and superoxide dismutase activities but lowered glutathione levels in the OVX rats. Skeletal malondialdehyde level was not affected by ovariectomy but was lowered with E'Jiao supplementation. However, peroxisome proliferator-activated receptor gamma protein expression was not affected by ovariectomy or any treatment. Conclusion: E'Jiao, especially at the low dose, prevented body composition changes and bone marrow adiposity due to ovariectomy. These changes could be mediated by the antioxidant actions of E'Jiao. It has the potential to be used among postmenopausal women to avoid adiposity.

Matched MeSH terms: Oxidation-Reduction
Fulltext Metabolic and genetic screening of electromagnetic hypersensitive subjects as a feasible tool for diagnostics and intervention

De Luca C, Thai JC, Raskovic D, Cesareo E, Caccamo D, Trukhanov A, et al.

Mediators Inflamm, 2014;2014:924184.
PMID: 24812443 DOI: 10.1155/2014/924184

Growing numbers of "electromagnetic hypersensitive" (EHS) people worldwide self-report severely disabling, multiorgan, non-specific symptoms when exposed to low-dose electromagnetic radiations, often associated with symptoms of multiple chemical sensitivity (MCS) and/or other environmental "sensitivity-related illnesses" (SRI). This cluster of chronic inflammatory disorders still lacks validated pathogenetic mechanism, diagnostic biomarkers, and management guidelines. We hypothesized that SRI, not being merely psychogenic, may share organic determinants of impaired detoxification of common physic-chemical stressors. Based on our previous MCS studies, we tested a panel of 12 metabolic blood redox-related parameters and of selected drug-metabolizing-enzyme gene polymorphisms, on 153 EHS, 147 MCS, and 132 control Italians, confirming MCS altered (P < 0.05-0.0001) glutathione-(GSH), GSH-peroxidase/S-transferase, and catalase erythrocyte activities. We first described comparable-though milder-metabolic pro-oxidant/proinflammatory alterations in EHS with distinctively increased plasma coenzyme-Q10 oxidation ratio. Severe depletion of erythrocyte membrane polyunsaturated fatty acids with increased ω 6/ ω 3 ratio was confirmed in MCS, but not in EHS. We also identified significantly (P = 0.003) altered distribution-versus-control of the CYP2C19∗1/∗2 SNP variants in EHS, and a 9.7-fold increased risk (OR: 95% C.I. = 1.3-74.5) of developing EHS for the haplotype (null)GSTT1 + (null)GSTM1 variants. Altogether, results on MCS and EHS strengthen our proposal to adopt this blood metabolic/genetic biomarkers' panel as suitable diagnostic tool for SRI.

Matched MeSH terms: Oxidation-Reduction
Antioxidative/Antimicrobial effects of galangal and alpha-tocopherol in minced beef

Cheah PB, Gan SP

J Food Prot, 2000 Mar;63(3):404-7.
PMID: 10716573

The antioxidant and microbial stabilities of galangal (Alpinia galanga) extract in raw minced beef were examined at 4 +/- 1 degree C. Raw minced beef containing galangal extracts (0 to 0.10%, wt/wt) were prepared. Lipid oxidation during refrigerated storage was assessed by monitoring malonaldehyde formation, using the thiobarbituric acid reactive substances method. In minced beef, added galangal extract improved oxidative stability. Galangal extract at higher concentrations of 0.05% and 0.10% (wt/wt) were also found to extend the shelf-life of minced beef. Addition of alpha-tocopherol (0.02%, wt/wt) to galangal extract (0.05%, wt/wt) were observed to increase the oxidative but not the microbial stability of minced beef during the storage of 7 days. Galangal extract may prove useful in inhibiting lipid oxidation and increasing microbial stability of minced meat.

Matched MeSH terms: Oxidation-Reduction
Fulltext Effect of CO(2) enrichment on synthesis of some primary and secondary metabolites in ginger (Zingiber officinale Roscoe)

Ghasemzadeh A, Jaafar HZ

Int J Mol Sci, 2011 Feb 10;12(2):1101-14.
PMID: 21541046 DOI: 10.3390/ijms12021101

The effect of two different CO(2) concentrations (400 and 800 μmol mol(-1)) on the photosynthesis rate, primary and secondary metabolite syntheses and the antioxidant activities of the leaves, stems and rhizomes of two Zingiber officinale varieties (Halia Bentong and Halia Bara) were assessed in an effort to compare and validate the medicinal potential of the subterranean part of the young ginger. High photosynthesis rate (10.05 μmol CO(2) m(-2)s(-1) in Halia Bara) and plant biomass (83.4 g in Halia Bentong) were observed at 800 μmol mol(-1) CO(2). Stomatal conductance decreased and water use efficiency increased with elevated CO(2) concentration. Total flavonoids (TF), total phenolics (TP), total soluble carbohydrates (TSC), starch and plant biomass increased significantly (P ≤ 0.05) in all parts of the ginger varieties under elevated CO(2) (800 μmol mol(-1)). The order of the TF and TP increment in the parts of the plant was rhizomes > stems > leaves. More specifically, Halia Bara had a greater increase of TF (2.05 mg/g dry weight) and TP (14.31 mg/g dry weight) compared to Halia Bentong (TF: 1.42 mg/g dry weight; TP: 9.11 mg/g dry weight) in average over the whole plant. Furthermore, plants with the highest rate of photosynthesis had the highest TSC and phenolics content. Significant differences between treatments and species were observed for TF and TP production. Correlation coefficient showed that TSC and TP content are positively correlated in both varieties. The antioxidant activity, as determined by the ferric reducing/antioxidant potential (FRAP) activity, increased in young ginger grown under elevated CO(2). The FRAP values for the leaves, rhizomes and stems extracts of both varieties grown under two different CO(2) concentrations (400 and 800 μmol mol(-1)) were significantly lower than those of vitamin C (3107.28 μmol Fe (II)/g) and α-tocopherol (953 μmol Fe (II)/g), but higher than that of BHT (74.31 μmol Fe (II)/g). These results indicate that the plant biomass, primary and secondary metabolite synthesis, and following that, antioxidant activities of Malaysian young ginger varieties can be enhanced through controlled environment (CE) and CO(2) enrichment.

Matched MeSH terms: Oxidation-Reduction
Fulltext Changes in nutritional metabolites of young ginger (Zingiber officinale Roscoe) in response to elevated carbon dioxide

Ghasemzadeh A, Jaafar HZ, Karimi E, Ashkani S

Molecules, 2014 Oct 16;19(10):16693-706.
PMID: 25325154 DOI: 10.3390/molecules191016693

The increase of atmospheric CO2 due to global climate change or horticultural practices has direct and indirect effects on food crop quality. One question that needs to be asked, is whether CO2 enrichment affects the nutritional quality of Malaysian young ginger plants. Responses of total carbohydrate, fructose, glucose, sucrose, protein, soluble amino acids and antinutrients to either ambient (400 μmol/mol) and elevated (800 μmol/mol) CO2 treatments were determined in the leaf and rhizome of two ginger varieties namely Halia Bentong and Halia Bara. Increasing of CO2 level from ambient to elevated resulted in increased content of total carbohydrate, sucrose, glucose, and fructose in the leaf and rhizome of ginger varieties. Sucrose was the major sugar followed by glucose and fructose in the leaf and rhizome extract of both varieties. Elevated CO2 resulted in a reduction of total protein content in the leaf (H. Bentong: 38.0%; H. Bara: 35.4%) and rhizome (H. Bentong: 29.0%; H. Bara: 46.2%). In addition, under CO2 enrichment, the concentration of amino acids increased by approximately 14.5% and 98.9% in H. Bentong and 12.0% and 110.3% in H. Bara leaf and rhizome, respectively. The antinutrient contents (cyanide and tannin) except phytic acid were influenced significantly (P ≤ 0.05) by CO2 concentration. Leaf extract of H. Bara exposed to elevated CO2 exhibited highest content of cyanide (336.1 mg HCN/kg DW), while, highest content of tannin (27.5 g/kg DW) and phytic acid (54.1 g/kg DW) were recorded from H.Bara rhizome grown under elevated CO2. These results demonstrate that the CO2 enrichment technique could improve content of some amino acids and antinutrients of ginger as a food crop by enhancing its nutritional and health-promoting properties.

Matched MeSH terms: Oxidation-Reduction
Assessment of antioxidant activity in Victorian marine algal extracts using high performance thin-layer chromatography and multivariate analysis

Agatonovic-Kustrin S, Morton DW, Ristivojević P

J Chromatogr A, 2016 Oct 14;1468:228-235.
PMID: 27670751 DOI: 10.1016/j.chroma.2016.09.041

The aim of this study was to develop and validate a rapid and simple high performance thin layer chromatographic (HPTLC) method to screen for antioxidant activity in algal samples. 16 algal species were collected from local Victorian beaches. Fucoxanthin, one of the most abundant marine carotenoids was quantified directly from the HPTLC plates before derivatization, while derivatization either with 2,2-diphenyl-1-picrylhydrazyl (DPPH) or ferric chloride (FeCl3) was used to analyze antioxidants in marine algae, based on their ability to scavenge non biological stable free radical (DPPH) or to chelate iron ions. Principal component analysis of obtained HPTLC fingerprints has classified algae species into 5 groups according to their chemical/antioxidant profiles. The investigated brown algae samples were found to be rich in non-and moderate-polar compounds and phenolic compounds with antioxidant activity. Most of the phenolic iron chelators also have shown free radical scavenging activity. Strong positive and significant correlations between total phenolic content and DPPH radical scavenging activity showed that, phenolic compounds, including flavonoids are the main contributors of antioxidant activity in these species. The results suggest that certain brown algae possess significantly higher antioxidant potential when compared to red or green algae and could be considered for future applications in medicine, dietary supplements, cosmetics or food industries. Cystophora monilifera extract was found to have the highest antioxidant concentration, followed by Zonaria angustata, Cystophora pectinate, Codium fragile, and Cystophora pectinata. Fucoxanthin was found mainly in the brown algae species. The proposed methods provide an edge in terms of screening for antioxidants and quantification of antioxidant constituents in complex mixtures. The current application also demonstrates flexibility and versatility of a standard HPTLC system in the drug discovery. Proposed methods could be used for the bioassay-guided isolation of unknown natural antioxidants and subsequent identification if combined with spectroscopic identification.

Matched MeSH terms: Oxidation-Reduction
Is the Mitochondrial Function of Keloid Fibroblasts Affected by Cytoglobin?

Jusman SWA, Azzizah IN, Sadikin M, Hardiany NS

Malays J Med Sci, 2021 Apr;28(2):39-47.
PMID: 33958959 DOI: 10.21315/mjms2021.28.2.4

Background: A keloid is a benign skin tumour characterised by excessive proliferation of fibroblasts, a process that requires a sufficient amount of energy. The energy needs are associated with adequate oxygen (O2) flow and well-functioning mitochondria. It is known that cytoglobin (CYGB) has a function in O2 distribution. The aim of the present study was to explore whether the inhibition of CYGB expression caused impaired mitochondrial function of keloid fibroblasts.
Methods: An in vitro study was conducted on a keloid fibroblast derived from our previous study. The study was carried out in the laboratory of the Biochemistry & Molecular Biology Department, Faculty of Medicine, Universitas Indonesia (FMUI), from July to December 2018. CYGB expression was inhibited by small interfering ribonucleic acid (siRNA) and CYGB. Analysis of mitochondrial function was observed through peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), a mitochondrial biogenesis marker and the activity of the succinate dehydrogenase (SDH) enzyme in mitochondria.
Results: The CYGB gene and protein were downregulated after treatment with CYGB siRNA. Inhibition of CYGB expression with siRNA also tended to decrease the levels of PGC-1α messenger ribonucleic acid (mRNA) and protein, as well as SDH enzyme activity.
Conclusion: Inhibition of CYGB expression with siRNA tended to decrease mitochondrial biogenesis and function. This may be useful for understanding the excessive proliferation of fibroblasts in keloids and for development of treatment for keloids.

Matched MeSH terms: Oxidation-Reduction
Fulltext Palm oil and palm olein frying applications

Ismail R

Asia Pac J Clin Nutr, 2005;14(4):414-9.
PMID: 16326649

Several million tones of palm oil and palm olein are used annually in the world for frying. This paper will discuss their frying performances in three major applications - industrial production of potato chips/crisps, industrial production of pre-fried frozen French fries and in fast food outlets. In the first study, about four tones of potato chips were continuously fried 8 hours a day and five days a week. The palm olein used (with proper management) performed well and was still in excellent condition and usable at the end of the trial. This was reflected in its low free fatty acid (FFA) content of around 0.23%, peroxide value of 4 meq/kg, anisidine value of 16, low polar and polymer contents of 10% and 2%, respectively, induction period (OSI) of 21 hours and high content of tocopehrols and tocotrienols of 530 ppm even after >1900 hours. In the second study in which an average 12 tones pre-fried frozen French fries were continuously fried a day for 5 days a week, palm oil performed excellently as reflected by its low FFA of 0.34%, food oil sensor reading of 1.1, low polar and polymer contents of 17% and 2.8%, respectively, over the 12 days of trial. In the third study in which palm shortening, palm oil and palm olein were simultaneously used to intermittently fry chicken parts in the laboratory simulating the conditions in fast food outlets, the three frying oils also performed very satisfactorily as reflected by their reasonably low FFA of <1%, smoke points of >180 degrees C, and polar and polymer contents of <25% and <6%, respectively, after 5 days of consecutive frying. All the quality indicators did not exceed the maximum discard points for frying oils/fats in the three applications, while the fried food product was well accepted by the in-house train sensory panel using a-nine point hedonic score.

Matched MeSH terms: Oxidation-Reduction
Performance of phytochemical antioxidant systems in refined-bleached-deodorized palm olein during frying

Jaswir I, Che Man YB, Hassan TH

Asia Pac J Clin Nutr, 2005;14(4):402-13.
PMID: 16326648

Antioxidants are important inhibitory compounds against the oxidative deterioration of food. This study investigated the effects of various phytochemical antioxidant systems [oleoresin rosemary (OR), oleoresin sage (OS) and citric acid (CA)] on the physico-chemical characteristics of refined, bleached and deodorized (RBD) palm olein during the frying of potato chips. The effects of various mixtures of the antioxidants on the oil was also studied in repeated deep frying. The response surface methodology was used to optimize the composition of mixed antioxidants used. A comparative study was carried out with synthetic antioxidants. Samples of the oil after frying were analyzed for different physical and chemical properties. OR and OS were found to be effective phytochemical antioxidants protecting RBD palm olein against oxidative deterioration during frying.

Matched MeSH terms: Oxidation-Reduction
Fulltext Analysis of the xplAB-containing gene cluster involved in the bacterial degradation of the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine

Chong CS, Sabir DK, Lorenz A, Bontemps C, Andeer P, Stahl DA, et al.

Appl Environ Microbiol, 2014 Nov;80(21):6601-10.
PMID: 25128343 DOI: 10.1128/AEM.01818-14

Repeated use of the explosive compound hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) on military land has resulted in significant soil and groundwater pollution. Rates of degradation of RDX in the environment are low, and accumulated RDX, which the U.S. Environmental Protection Agency has determined is a possible human carcinogen, is now threatening drinking water supplies. RDX-degrading microorganisms have been isolated from RDX-contaminated land; however, despite the presence of these species in contaminated soils, RDX pollution persists. To further understand this problem, we studied RDX-degrading species belonging to four different genera (Rhodococcus, Microbacterium, Gordonia, and Williamsia) isolated from geographically distinct locations and established that the xplA and xplB (xplAB) genes, which encode a cytochrome P450 and a flavodoxin redox partner, respectively, are nearly identical in all these species. Together, the xplAB system catalyzes the reductive denitration of RDX and subsequent ring cleavage under aerobic and anaerobic conditions. In addition to xplAB, the Rhodococcus species studied here share a 14-kb region flanking xplAB; thus, it appears likely that the RDX-metabolizing ability was transferred as a genomic island within a transposable element. The conservation and transfer of xplAB-flanking genes suggest a role in RDX metabolism. We therefore independently knocked out genes within this cluster in the RDX-degrading species Rhodococcus rhodochrous 11Y. Analysis of the resulting mutants revealed that XplA is essential for RDX degradation and that XplB is not the sole contributor of reducing equivalents to XplA. While XplA expression is induced under nitrogen-limiting conditions and further enhanced by the presence of RDX, MarR is not regulated by RDX.

Matched MeSH terms: Oxidation-Reduction
Fulltext Inhibition of oxidative stress and lipid peroxidation by anthocyanins from defatted Canarium odontophyllum pericarp and peel using in vitro bioassays

Khoo HE, Azlan A, Ismail A, Abas F, Hamid M

PLoS One, 2014;9(1):e81447.
PMID: 24416130 DOI: 10.1371/journal.pone.0081447

Canarium odontophyllum, also known as CO, is a highly nutritious fruit. Defatted parts of CO fruit are potent sources of nutraceutical. This study aimed to determine oxidative stress and lipid peroxidation effects of defatted CO pericarp and peel extracts using in vitro bioassays. Cell cytotoxic effect of the CO pericarp and peel extracts were also evaluated using HUVEC and Chang liver cell lines. The crude extracts of defatted CO peel and pericarp showed cytoprotective effects in t-BHP and 40% methanol-induced cell death. The crude extracts also showed no toxic effect to Chang liver cell line. Using CD36 ELISA, NAD(+) and LDL inhibition assays, inhibition of oxidative stress were found higher in the crude extract of defatted CO peel compared to the pericarp extract. Hemoglobin and LDL oxidation assays revealed both crude extracts had significantly reduced lipid peroxidation as compared to control. TBARS values among defatted CO pericarp, peel, and cyanidin-3-glucoside showed no significant differences for hemoglobin and LDL oxidation assays. The protective effects of defatted CO parts, especially its peel is related to the presence of high anthocyanin that potentially offers as a pharmaceutical ingredient for cardioprotection.

Matched MeSH terms: Oxidation-Reduction/drug effects
Fulltext Antioxidant potential, cytotoxic activity and total phenolic content of Alpinia pahangensis rhizomes

Phang CW, Malek SN, Ibrahim H

BMC Complement Altern Med, 2013 Oct 01;13:243.
PMID: 24083445 DOI: 10.1186/1472-6882-13-243

BACKGROUND: Alpinia pahangensis, a wild ginger distributed in the lowlands of Pahang, Malaysia, is used by the locals to treat flatulence. In this study, the antioxidant and cytotoxic activities of the crude aqueous methanol and fractionated extracts of Alpinia pahangensis against five different cancer and one normal cell lines were investigated. The total phenolic content of each extract and its fractions were also quantified. This is the first report on the antioxidant and cytotoxic activities of Alpinia pahangensis extract.
METHODS: In the current study, the crude methanol and fractionated extract of the rhizomes of Alpinia pahangensis were investigated for their antioxidant activity using four different assays namely, the DPPH scavenging activity, superoxide anion scavenging, β-carotene bleaching and reducing power assays whilst their phenolic contents were measured by the Folin-Ciocalteu's method.In vitro neutral red cytotoxicity assay was employed to evaluate the cytotoxic activity against five different cancer cell lines, colon cancer (HCT 116 and HT-29), cervical cancer (Ca Ski), breast cancer (MCF7) and lung cancer (A549) cell lines, and one normal cell line (MRC-5). The extract that showed high cytotoxic activity was further investigated for its chemical constituents by GC-MS (gas chromatography-mass spectrometry) analysis.
RESULTS: The ethyl acetate fraction showed the strongest DPPH radical scavenging (0.35 ± 0.094 mg/ml) and SOD activities (51.77 ± 4.9%) whilst the methanol extract showed the highest reducing power and also the strongest antioxidant activity in the β-carotene bleaching assays in comparison to other fractions. The highest phenolic content was found in the ethyl acetate fraction, followed by the crude methanol extract, hexane and water fractions. The results showed a positive correlation between total phenolic content with DPPH radical scavenging capacities and SOD activities. The hexane fraction showed potent cytotoxic effect against KB, Ca Ski and HCT 116 cell lines with IC₅₀ of 5.8 ± 0.1 and 9.1 ± 2.0 ug/ml, respectively. The major components of hexane fraction analysed by GC-MS analysis were mostly methyl esters.
CONCLUSIONS: The current study suggests that the methanol extract and ethyl acetate fraction of A. pahangensis is a potential source of natural antioxidant for protective as well as prevention of life-threatening diseases. The hexane fraction of A. pahangensis may have the potential to be developed into therapeutic option for treating cancer.

Matched MeSH terms: Oxidation-Reduction/drug effects
Fulltext The antioxidant activity of new coumarin derivatives

Kadhum AA, Al-Amiery AA, Musa AY, Mohamad AB

Int J Mol Sci, 2011;12(9):5747-61.
PMID: 22016624 DOI: 10.3390/ijms12095747

The antioxidant activity of two synthesized coumarins namely, N-(4,7-dioxo-2- phenyl-1,3-oxazepin-3(2H,4H,7H)-yl)-2-(2-oxo-2H-chromen-4-yloxy)acetamide 5 and N-(4-oxo-2-phenylthiazolidin-3-yl)-2-(2-oxo-2H-chromen-4-yloxy)acetamide 6 were studied with the DPPH, hydrogen peroxide and nitric oxide radical methods and compared with the known antioxidant ascorbic acid. Compounds 5 and 6 were synthesized in a good yield from the addition reaction of maleic anhydride or mercaptoacetic acid to compound 4, namely N'-benzylidene-2-(2-oxo-2H-chromen-4-yloxy)acetohydrazide. Compound 4 was synthesized by the condensation of compound 3, namely 2-(2-oxo-2H-chromen-4-yloxy) acetohydrazide, with benzaldehyde. Compound 3, however, was synthesized from the addition of hydrazine to compound 2, namely ethyl 2-(2-oxo-2H-chromen-4-yloxy)acetate, which was synthesized from the reaction of ethyl bromoacetate with 4-hydroxycoumarin 1. Structures for the synthesized coumarins 2-6 are proposed on the basis of spectroscopic evidence.

Matched MeSH terms: Oxidation-Reduction/drug effects
2-Methoxy-1,4-naphthoquinone (MNQ) induces apoptosis of A549 lung adenocarcinoma cells via oxidation-triggered JNK and p38 MAPK signaling pathways

Ong JY, Yong PV, Lim YM, Ho AS

Life Sci, 2015 Aug 15;135:158-64.
PMID: 25896662 DOI: 10.1016/j.lfs.2015.03.019

The compound 2-methoxy-1,4-naphthoquinone (MNQ) was previously shown to be cytotoxic against several cancer cell lines, but its mode of action is poorly understood. In this study, we aimed to explore the molecular mechanism of MNQ-induced cytotoxicity of A549 lung adenocarcinoma cells.

Matched MeSH terms: Oxidation-Reduction/drug effects
Celastrol attenuates mitochondrial dysfunction and inflammation in palmitate-mediated insulin resistance in C3A hepatocytes

Abu Bakar MH, Sarmidi MR, Tan JS, Mohamad Rosdi MN

Eur J Pharmacol, 2017 Mar 15;799:73-83.
PMID: 28161417 DOI: 10.1016/j.ejphar.2017.01.043

Accumulating evidence indicates that mitochondrial dysfunction-induced inflammation is among the convergence points for the greatest hallmarks of hepatic insulin resistance. Celastrol, an anti-inflammatory compound from the root of Tripterygium Wilfordii has been reported to mitigate insulin resistance and inflammation in animal disease models. Nevertheless, the specific mechanistic actions of celastrol in modulating such improvements at the cellular level remain obscure. The present study sought to explore the mechanistic roles of celastrol upon insulin resistance induced by palmitate in C3A human hepatocytes. The hepatocytes exposed to palmitate (0.75mM) for 48h exhibited reduced both basal and insulin-stimulated glucose uptake, mitochondrial dysfunction, leading to increased mitochondrial oxidative stress with diminished fatty acid oxidation. Elevated expressions of nuclear factor-kappa B p65 (NF-κB p65), c-Jun NH(2)-terminal kinase (JNK) signaling pathways and the amplified release of pro-inflammatory cytokines including IL-8, IL-6, TNF-α and CRP were observed following palmitate treatment. Consistently, palmitate reduced and augmented phosphorylated Tyrosine-612 and Serine-307 of insulin receptor substrate-1 (IRS-1) proteins, respectively in hepatocytes. However, celastrol at the optimum concentration of 30nM was able to reverse these deleterious occasions and protected the cells from mitochondrial dysfunction and insulin resistance. Importantly, we presented evidence for the first time that celastrol efficiently prevented palmitate-induced insulin resistance in hepatocytes at least, via improved mitochondrial functions and insulin signaling pathways. In summary, the present investigation underlines a conceivable mechanism to elucidate the cytoprotective potential of celastrol in attenuating mitochondrial dysfunction and inflammation against the development of hepatic insulin resistance.

Matched MeSH terms: Oxidation-Reduction/drug effects
Fulltext Antioxidant capacities and total phenolic contents increase with gamma irradiation in two types of Malaysian honey

Hussein SZ, Yusoff KM, Makpol S, Yusof YA

Molecules, 2011 Jul 27;16(8):6378-95.
PMID: 21796076 DOI: 10.3390/molecules16066378

Two types of monofloral Malaysian honey (Gelam and Nenas) were analyzed to determine their antioxidant activities and total phenolic and flavonoid contents, with and without gamma irradiation. Our results showed that both types of honey can scavenge free radicals and exhibit high antioxidant-reducing power; however, Gelam honey exhibited higher antioxidant activity (p < 0.05) than Nenas honey, which is in good correlation (r = 0.9899) with its phenolic contents. Interestingly, we also noted that both irradiated honeys have higher antioxidant activities and total phenolic and flavonoid contents compared to nonirradiated honeys by Folin-Ciocalteu and UV-spectrophotometry methods, respectively. However, HPLC analysis for phenolic compounds showed insignificant increase between irradiated and nonirradiated honeys. The phenolic compounds such as: caffeic acid, chlorogenic acid, ellagic acid, p- coumaric acid, quercetin and hesperetin as indicated by HPLC method were found to be higher in Gelam honey versus Nenas honey. In conclusion, irradiation of honey causes enhanced antioxidant activities and flavonoid compounds.

Matched MeSH terms: Oxidation-Reduction/radiation effects
Fulltext Counteracting the Ramifications of UVB Irradiation and Photoaging with Swietenia macrophylla King Seed

Mahendra CK, Abidin SAZ, Htar TT, Chuah LH, Khan SU, Ming LC, et al.

Molecules, 2021 Apr 01;26(7).
PMID: 33916053 DOI: 10.3390/molecules26072000

In this day and age, the expectation of cosmetic products to effectively slow down skin photoaging is constantly increasing. However, the detrimental effects of UVB on the skin are not easy to tackle as UVB dysregulates a wide range of molecular changes on the cellular level. In our research, irradiated keratinocyte cells not only experienced a compromise in their redox system, but processes from RNA translation to protein synthesis and folding were also affected. Aside from this, proteins involved in various other processes like DNA repair and maintenance, glycolysis, cell growth, proliferation, and migration were affected while the cells approached imminent cell death. Additionally, the collagen degradation pathway was also activated by UVB irradiation through the upregulation of inflammatory and collagen degrading markers. Nevertheless, with the treatment of Swietenia macrophylla (S. macrophylla) seed extract and fractions, the dysregulation of many genes and proteins by UVB was reversed. The reversal effects were particularly promising with the S. macrophylla hexane fraction (SMHF) and S. macrophylla ethyl acetate fraction (SMEAF). SMHF was able to oppose the detrimental effects of UVB in several different processes such as the redox system, DNA repair and maintenance, RNA transcription to translation, protein maintenance and synthesis, cell growth, migration and proliferation, and cell glycolysis, while SMEAF successfully suppressed markers related to skin inflammation, collagen degradation, and cell apoptosis. Thus, in summary, our research not only provided a deeper insight into the molecular changes within irradiated keratinocytes, but also serves as a model platform for future cosmetic research to build upon. Subsequently, both SMHF and SMEAF also displayed potential photoprotective properties that warrant further fractionation and in vivo clinical trials to investigate and obtain potential novel bioactive compounds against photoaging.

Matched MeSH terms: Oxidation-Reduction/drug effects
Melatonin improves cognitive behavior, oxidative stress, and metabolism in tumor-prone lethal giant larvae mutant of Drosophila melanogaster

Wong KC, Sankaran S, Jayapalan JJ, Subramanian P, Abdul-Rahman PS

Arch Insect Biochem Physiol, 2021 May;107(1):e21785.
PMID: 33818826 DOI: 10.1002/arch.21785

Mutant lethal giant larvae (lgl) flies (Drosophila melanogaster) are known to develop epithelial tumors with invasive characteristics. The present study has been conducted to investigate the influence of melatonin (0.025 mM) on behavioral responses of lgl mutant flies as well as on biochemical indices (redox homeostasis, carbohydrate and lipid metabolism, transaminases, and minerals) in hemolymph, and head and intestinal tissues. Behavioral abnormalities were quantitatively observed in lgl flies but were found normalized among melatonin-treated lgl flies. Significantly decreased levels of lipid peroxidation products and antioxidants involved in redox homeostasis were observed in hemolymph and tissues of lgl flies, but had restored close to normalcy in melatonin-treated flies. Carbohydrates including glucose, trehalose, and glycogen were decreased and increased in the hemolymph and tissues of lgl and melatonin-treated lgl flies, respectively. Key enzymes of carbohydrate metabolism showed a significant increment in their levels in lgl mutants but had restored close to wild-type baseline levels in melatonin-treated flies. Variables of lipid metabolism showed significantly inverse levels in hemolymph and tissues of lgl flies, while normalization of most of these variables was observed in melatonin-treated mutants. Lipase, chitinase, transaminases, and alkaline phosphatase showed an increment in their activities and minerals exhibited decrement in lgl flies; reversal of changes was observed under melatonin treatment. The impairment of cognition, disturbance of redox homeostasis and metabolic reprogramming in lgl flies, and restoration of normalcy in all these cellular and behavioral processes indicate that melatonin could act as oncostatic and cytoprotective agents in Drosophila.

Matched MeSH terms: Oxidation-Reduction/drug effects
Fulltext A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose

Dear JW, Ng ML, Bateman DN, Leroy Sivappiragasam P, Choi H, Khoo BBJ, et al.

Clin Transl Sci, 2021 Jul;14(4):1476-1489.
PMID: 33742775 DOI: 10.1111/cts.13009

N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.

Matched MeSH terms: Oxidation-Reduction/drug effects
Fulltext Involvement of salicylic acid on antioxidant and anticancer properties, anthocyanin production and chalcone synthase activity in ginger (Zingiber officinale Roscoe) varieties

Ghasemzadeh A, Jaafar HZ, Karimi E

Int J Mol Sci, 2012 Nov 13;13(11):14828-44.
PMID: 23203096 DOI: 10.3390/ijms131114828

The effect of foliar application of salicylic acid (SA) at different concentrations (10-3 M and 10-5 M) was investigated on the production of secondary metabolites (flavonoids), chalcone synthase (CHS) activity, antioxidant activity and anticancer activity (against breast cancer cell lines MCF-7 and MDA-MB-231) in two varieties of Malaysian ginger, namely Halia Bentong and Halia Bara. The results of high performance liquid chromatography (HPLC) analysis showed that application of SA induced the synthesis of anthocyanin and fisetin in both varieties. Anthocyanin and fisetin were not detected in the control plants. Accordingly, the concentrations of some flavonoids (rutin and apigenin) decreased significantly in plants treated with different concentrations of SA. The present study showed that SA enhanced the chalcone synthase (CHS) enzyme activity (involving flavonoid synthesis) and recorded the highest activity value of 5.77 nkat /mg protein in Halia Bara with the 10-5 M SA treatment. As the SA concentration was decreased from 10-3 M to 10-5 M, the free radical scavenging power (FRAP) increased about 23% in Halia Bentong and 10.6% in Halia Bara. At a concentration of 350 μg mL-1, the DPPH antioxidant activity recorded the highest value of 58.30%-72.90% with the 10-5 M SA treatment followed by the 10-3 M SA (52.14%-63.66%) treatment. The lowest value was recorded in the untreated control plants (42.5%-46.7%). These results indicate that SA can act not only as an inducer but also as an inhibitor of secondary metabolites. Meanwhile, the highest anticancer activity against MCF-7 and MDA-MB-231 cell lines was observed for H. Bara extracts treated with 10-5 M SA with values of 61.53 and 59.88%, respectively. The results suggest that the high anticancer activity in these varieties may be related to the high concentration of potent anticancer components including fisetin and anthocyanin. The results thus indicate that the synthesis of flavonoids in ginger can be increased by foliar application of SA in a controlled environment and that the anticancer activity in young ginger extracts could be improved.

Matched MeSH terms: Oxidation-Reduction/drug effects

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