Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.
Phenolic compounds and antioxidant capacity of acidified methanolic extract prepared from fully ripe bambangan (Mangifera pajang K.) peel cultivated in Sarawak, Malaysia, were analyzed. The total phenolic content (98.3 mg GAE/g) of bambangan peel powder (BPP) was determined by the Folin-Ciocalteu method. BPP showed a strong potency of antioxidant activity and was consistent with that of BHT and vitamin C as confirmed by the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity and FRAP (ferric-reducing antioxidant power) assays. Gallic acid, p-coumaric acid, ellagic acid, protocatechuic acid, and mangiferin were the major compounds among the 16 phenolics that have been identified and quantified in M. pajang peels with 20.9, 12.7, 7.3, 5.4, and 4.8 mg/g BPP, respectively. Peak identities were confirmed by comparing their retention times, UV-vis absorption spectra, and mass spectra with authentic standards. The 16 phenolic compounds identified in M. pajang K. using HPLC-DAD and TSQ-ESI-MS are reported here for the first time.
Furopyridine III, namely 1-(3-amino-4-(4-(tert-butyl)phenyl)-6-(p-tolyl)furo[2,3-b]pyridin-2-yl)ethan-1-one, synthesized from 4-(4-(tert-butyl)phenyl)-2-oxo-6-(p-tolyl)-1,2-dihydropyridine-3-carbonitrile I in two steps. The title compound is characterized by NMR, MS and its X-ray structure. The molecular structure consists of planar furopyridine ring with both phenyl rings being inclined from the furopyridine scaffold to a significant different extent. There are three intramolecular hydrogen bonds within the structure. The lattice is stabilized by N-H…O, H2C-H …π and π…π intermolecular interactions leading to three-dimensional network. Compound III exhibits fluorescent properties, which are investigated. Antimicrobial potential and antioxidant activity screening studies for the title compound III and the heterocyclic derivatives, I and II, show no activity towards neither bacterial nor fungal strains, while they exhibited weak to moderate antioxidant activity compared to reference.
Free radical scavenging activity of 21 tropical plant extracts was evaluated using 1,1-diphenyl-2-picrylhydrazyl assay (DPPH). Total phenolic compounds and flavonoids were determined using Folin-Ciocalteu and HPLC, respectively. Results of the study revealed that all the plants tested exhibited excellent antioxidant activity with IC(50) in the range of 21.3 to 89.6 microg/mL. The most potent activity was demonstrated by Cosmos caudatus (21.3 microg/mL) and Piper betle (23.0 microg/mL) that are not significantly different than that of -tocopherol or BHA. L. inermis extract was found to consist of the highest concentration of phenolics, catechin, epicatechin, and naringenin. High content of quercetin, myricetin, and kaempferol were identified in Vitex negundo, Centella asiatica, and Sesbania grandiflora extracts, respectively. Luteolin and apigenin, on the other hand, were found in Premna cordifolia and Kaempferia galanga extracts. Strong correlation (R = 0.8613) between total phenolic compounds and total flavonoids (R = 0.8430) and that of antioxidant activity of the extracts were observed. The study revealed that phenolic, in particular flavonoids, may be the main contributors to the antioxidant activity exhibited by the plants.
In the present study the extracts of in vivo and in vitro grown plants as well as callus tissue of red clover were tested for their antioxidant activities, using different extraction solvent and different antioxidant assays. The total flavonoid and phenolic contents as well as extraction yield of the extracts were also investigated to determine their correlation with the antioxidant activity of the extracts. Among all the tested extracts the highest amounts of total phenolic and total flavonoids content were found in methanol extract of in vivo grown plants. The antioxidant activity of tested samples followed the order in vivo plant extract > callus extract > in vitro extract. The highest reducing power, 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging, and chelating power were found in methanol extracts of in vivo grown red clover, while the chloroform fraction of in vivo grown plants showed the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, superoxide anion radical scavenging and hydrogen peroxide scavenging compared to the other tested extracts. A significant correlation was found between the antioxidant activity of extracts and their total phenolic and total flavonoid content. According to the findings, the extract of in vitro culture of red clover especially the callus tissue possesses a comparable antioxidant activity to the in vivo cultured plants' extract.
The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases, e.g., Alzheimer's disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer's disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer's disease but not of Parkinson's disease. Melatonin's efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.
This study investigated the cardioprotective effect of N-acetylcysteine (NAC) on isoproterenol (ISO)-induced cardiotoxicity in rats. Male Sprague-Dawley rats were divided into control, NAC alone (100 mg/kg BW orally for 14 days), ISO-control (85 mg/kg BW), and ISO with NAC (for 14 days). Serum creatine kinase-MB and Lactate dehydrogenase were measured. From the heart homogenate lipid hydroperoxides (LPO), superoxide dismutase (SOD), total glutathione (GSH), and 8-isoprostane (IP) were measured. Histopathological examination of the heart was also carried out. There was a significant increase (P free radicals-induced damage to the myocardium.
A new chromanone acid, namely caloteysmannic acid (1), along with three known compounds, calolongic acid (2), isocalolongic acid (3) and stigmasterol (4) were isolated from the stem bark of Calophyllum teysmannii. All these compounds were evaluated for their cytotoxic and antioxidant activities in the MTT and DPPH assays, respectively. The structure of compound 1 was determined by means of spectroscopic methods including 1D and 2D NMR experiments as well as HR-EIMS spectrometry. The stereochemical assignment of compound 1 was done based on the NMR results and X-ray crystallographic analysis. The preliminary assay results revealed that all the test compounds displayed potent inhibitory activity against HeLa cancer cell line, in particular with compound 1 which exhibited the highest cytotoxic activity comparable to the positive control used, cisplatin. However, no significant antioxidant activity was observed for all the test compounds in the DPPH radical scavenging capacity assay.
In spite of many reports on the toxicity of silver nanoparticles (AgNPs), the mechanisms underlying the toxicity are far from clear. A key question is whether the observed toxicity comes from the silver ions (Ag(+)) released from the AgNPs or from the nanoparticles themselves. In this study, we explored the genotoxicity and the genotoxicity mechanisms of Ag(+) and AgNPs. Human TK6 cells were treated with 5 nM AgNPs or silver nitrate (AgNO3) to evaluate their genotoxicity and induction of oxidative stress. AgNPs and AgNO3 induced cytotoxicity and genotoxicity in a similar range of concentrations (1.00-1.75 µg/ml) when evaluated using the micronucleus assay, and both induced oxidative stress by measuring the gene expression and reactive oxygen species in the treated cells. Addition of N-acetylcysteine (NAC, an Ag(+) chelator) to the treatments significantly decreased genotoxicity of Ag(+), but not AgNPs, while addition of Trolox (a free radical scavenger) to the treatment efficiently decreased the genotoxicity of both agents. In addition, the Ag(+) released from the highest concentration of AgNPs used for the treatment was measured. Only 0.5 % of the AgNPs were ionized in the culture medium and the released silver ions were neither cytotoxic nor genotoxic at this concentration. Further analysis using electron spin resonance demonstrated that AgNPs produced hydroxyl radicals directly, while AgNO3 did not. These results indicated that although both AgNPs and Ag(+) can cause genotoxicity via oxidative stress, the mechanisms are different, and the nanoparticles, but not the released ions, mainly contribute to the genotoxicity of AgNPs.
The antioxidant activity of several Malaysian plant extracts was analyzed simultaneously with their pro-oxidant capacity. This ratio represents an index (ProAntidex) of the net free radical scavenging ability of whole plant extracts. We observed that ethanolic extracts of Nephelium lappaceum peel, Fragaria x ananassa leaf, Lawsonia inermis leaf, Syzygium aqueum leaf and grape seed had a lower Pro-Antidex than the commercially available Emblica™ extract which is an antioxidant agent with very low pro-oxidant activity. Among the aqueous extracts, Lawsonia inermis leaf, Nephelium mutobile leaf and grape seed had lower pro-oxidant activity compared to the Emblica™ extract. Among these extracts, aqueous extract of Nephelium mutobile leaf had a very low index of 0.05 compared to 0.69 for Emblica™. Most of the extracts had a far lower ProAntidex compared to the Vitamin C. The index enables us to identify extracts with high net free radical scavenging activity potential. The ProAntidex is beneficial as a screening parameter to the food industries and healthcare.
The phenolic constituents in Piper betle are well known for their antioxidant potential; however, current literature has very little information on their stability under the influence of storage factors. Present study evaluated the stability of total phenolic content (TPC) and antioxidant activity together with individual phenolic constituents (hydroxychavicol, eugenol, isoeugenol and allylpyrocatechol 3,4-diacetate) present in dried Piper betle's extract under different storage temperature of 5 and 25 °C with and without light for a period of six months. Both light and temperature significantly influenced TPC and its corresponding antioxidant activity over time. More than 95% TPC and antioxidant activity was retained at 5 °C in dark condition after 180 days of storage. Hydroxychavicol demonstrated the best stability with no degradation while eugenol and isoeugenol displayed moderate stability in low temperature (5 °C) and dark conditions. 4-allyl-1,2-diacetoxybenzene was the only compound that underwent complete degradation. A new compound, 2,4-di-tert-butylphenol, was detected after five weeks of storage only in the extracts exposed to light. Both zero-order and first-order kinetic models were adopted to describe the degradation kinetics of the extract's antioxidant activity. Zero-order displayed better fit with higher correlation coefficients (R² = 0.9046) and the half-life was determined as 62 days for the optimised storage conditions (5 °C in dark conditions).
Garlic and garlic extracts, through their antioxidant activities, have been reported to provide protection against free radical damage in the body. This study investigated antioxidant properties of garlic compounds representing the four main chemical classes, alliin, allyl cysteine, allyl disulfide, and allicin, prepared by chemical synthesis or purification. Alliin scavenged superoxide, while allyl cysteine and allyl disulfide did not react with superoxide. Allicin suppressed the formation of superoxide by the xanthine/xanthine oxidase system, probably via a thiol exchange mechanism. Alliin, allyl cysteine, and allyl disulfide all scavenged hydroxyl radicals; the rate constants calculated based on deoxyribose competitive assay were 1.4-1.7 x 10(10), 2.1-2.2 x 10(9), and 0.7-1.5 x 10(10) M (1) second(1), respectively. Contrary to previous reports, allicin did not exhibit hydroxyl radical scavenging activity in this study. Alliin, allicin, and allyl cysteine did not prevent induced microsomal lipid peroxidation, but both alliin and allyl cysteine were hydroxyl scavengers, and allyl disulfide was a lipid peroxidation terminator. In summary, our findings indicated that allyl disulfide, alliin, allicin, and allyl cysteine exhibit different patterns of antioxidant activities as protective compounds against free radical damage.
This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of -39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.
A series of N-ethyl phthalimide esters 4(a-n) were synthesized and characterized by spectroscopic studies. Further, the molecular structure of majority of compounds were analysed by single crystal X-ray diffraction studies. The X-ray analysis revealed the importance of substituents on the crystal stability and molecular packing. All the synthesized compounds were tested for in vitro antioxidant activity by DPPH radical scavenging, FRAP and CUPRAC methods. Few of them have shown good antioxidant activity.
A series of six novel heterocyclic chalcone analogues 4(a-f) has been synthesized by condensing 2-acetyl-5-chlorothiophene with benzaldehyde derivatives in methanol at room temperature using a catalytic amount of sodium hydroxide. The newly synthesized compounds are characterized by IR, mass spectra, elemental analysis and melting point. Subsequently; the structures of these compounds were determined using single crystal X-ray diffraction. All the synthesized compounds were screened for their antioxidant potential by employing various in vitro models such as DPPH free radical scavenging assay, ABTS radical scavenging assay, ferric reducing antioxidant power and cupric ion reducing antioxidant capacity. Results reflect the structural impact on the antioxidant ability of the compounds. The IC₀ values illustrate the mild to good antioxidant activities of the reported compounds. Among them, 4f with a p-methoxy substituent was found to be more potent as antioxidant agent.
The Box-Behnken design was applied to optimize the extraction of pectin from Averrhoa bilimbi (ABP) using deep eutectic solvents (DES). The four variables of extraction were percentage of DES (X1), extraction time (X2), temperature (X3), and molar ratio of DES components (X4). The quadratic regression equation was established as a predicted model with R2 value of 0.9375. The optimal condition was X1 = 3.74% (w/v), X2 = 2.5 h, X3 = 80 °C, and X4 = 1:1. No significant difference between the predicted (14.70%) and experimental (14.44%) maximum yield of sample was noted. Characterization of physico-chemical properties characterization of ABP was performed. The main components of ABP were galacturonic acids, arabinoses, and xyloses. ABP also showed good functional properties such as water holding capacity (3.70 g/g), oil holding capacity (2.40 g/g), and foaming capacity (133.33%). The results also showed that ABP exhibited free radical scavenging activity (41.46%) and ferric reducing antioxidant power (1.15 mM).
The aim of the present study was to characterize the phenolic acids, flavonoids, and antioxidant properties of monofloral honey collected from five different districts in Bangladesh. A new high performance liquid chromatography (HPLC) equipped with a UV detector method was developed for the identification of the phenolic acids and flavonoids. A total of five different phenolic acids were identified, with the most abundant being caffeic acid, benzoic acid, gallic acid, followed by chlorogenic acid and trans-cinnamic acid. The flavonoids, kaempferol, and catechin were most abundant, followed by myricetin and naringenin. The mean moisture content, total sugar content, and color characteristics of the honey samples were 18.36 ± 0.95%, 67.40 ± 5.63 g/100 g, and 129.27 ± 34.66 mm Pfund, respectively. The mean total phenolic acids, total flavonoid content, and proline content were 199.20 ± 135.23, 46.73 ± 34.16, and 556.40 ± 376.86 mg/kg, respectively, while the mean FRAP values and DPPH radical scavenging activity were 327.30 ± 231.87 μM Fe (II)/100 g and 36.95 ± 20.53%, respectively. Among the different types of honey, kalijira exhibited the highest phenolics and antioxidant properties. Overall, our study confirms that all the investigated honey samples are good sources of phenolic acids and flavonoids with good antioxidant properties.
The phenolic acid and flavonoid contents of Malaysian Tualang, Gelam, and Borneo tropical honeys were compared to those of Manuka honey. Ferric reducing/antioxidant power assay (FRAP) and the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging activities were also quantified. All honey extracts exhibited high phenolic contents (15.21 ± 0.51- 42.23 ± 0.64 mg/kg), flavonoid contents (11.52 ± 0.27- 25.31 ± 0.37 mg/kg), FRAP values (892.15 ± 4.97- 363.38 ± 10.57 μM Fe[II]/kg), and high IC₅₀ of DPPH radical-scavenging activities (5.24 ± 0.40- 17.51 ± 0.51 mg/mL). Total of 6 phenolic acids (gallic, syringic, benzoic, trans-cinnamic, p-coumaric, and caffeic acids) and 5 flavonoids (catechin, kaempferol, naringenin, luteolin, and apigenin) were identified. Among the Malaysian honey samples, Tualang honey had the highest contents of phenolics, and flavonoids, and DPPH radical-scavenging activities. We conclude that among Malaysian honey samples, Tualang honey is the richest in phenolic acids, and flavonoid compounds, which have strong free radical-scavenging activities.
The aim of the present study was to characterize the physical, biochemical and antioxidant properties of Algerian honey samples (n = 4). Physical parameters, such as pH, moisture content, electrical conductivity (EC), total dissolved solids (TDS), color intensity, total sugar and sucrose content were measured. Several biochemical and antioxidant tests were performed to determine the antioxidant properties of the honey samples. The mean pH was 3.84 ± 0.01, and moisture the content was 13.21 ± 0.16%. The mean EC was 0.636 ± 0.001, and the mean TDS was 316.92 ± 0.92. The mean color was 120.58 ± 0.64 mm Pfund, and the mean 5-hydroxymethylfurfural (HMF) content was 21.49 mg/kg. The mean total sugar and reducing sugar contents were 67.03 ± 0.68 g/mL and 64.72 ± 0.52 g/g, respectively. The mean sucrose content was 2.29 ± 0.65%. High mean values of phenolic (459.83 ± 1.92 mg gallic acid/kg), flavonoid (54.23 ± 0.62 mg catechin/kg), ascorbic acid (159.70 ± 0.78 mg/kg), AEAC (278.15 ± 4.34 mg/kg), protein (3381.83 ± 6.19 mg/kg) and proline (2131.47 ± 0.90) contents, as well as DPPH (39.57% ± 4.18) and FRAP activities [337.77 ± 1.01 µM Fe (II)/100 g], were also detected, indicating that Algerian honey has a high antioxidant potential. Strong positive correlations were found between flavonoid, proline and ascorbic acid contents and color intensity with DPPH and FRAP values. Thus, the present study revealed that Algerian honey is a good source of antioxidants.
This study was conducted to evaluate the effects of evaporation, gamma irradiation and temperature on the total polyphenols, flavonoids and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activities of Tualang honey samples (n = 14) following storage over three, six or twelve months. The mean polyphenol concentrations of the six gamma irradiated honey samples at three, six and twelve months, respectively, were 96.13%, 98.01% and 102.03% higher than the corresponding values of the eight non-gamma irradiated samples. Similarly, the mean values for flavonoids at three, six and twelve months were 111.52%, 114.81% and 110.04% higher, respectively, for the gamma irradiated samples. The mean values for DPPH radical-scavenging activities at three, six and twelve months were also 67.09%, 65.26% and 44.65% higher, respectively, for the gamma irradiated samples. These data indicate that all gamma irradiated honey samples had higher antioxidant potential following gamma irradiation, while evaporation and temperature had minor effects on antioxidant potential.