Anti-inflammatory,antioxidant, anti-cholinesterase activity and mutagenicity of South African medicinal orchids

While the role of various processes in inflammatory-related degenerative disorders is still being researched, many avenues of research have concentrated on the treatment and/or prevention of these disorders. Inflammatory-responses, the cholinergic system and oxidative stress have often been linked to the symptoms prevalent in aged persons and Alzheimer's patients. The current research explored the selective inhibition of cyclooxygenase (COX) enzymes, antioxidant and anti-cholinesterase activities of selected South African orchid extracts, currently traded in herbal markets along the east coast of South Africa. Out of a total of 53 evaluated extracts, significant anti-inflammatory activity was observed in nearly 40% of extracts in the COX-1 assay and 25% of extracts in the COX-2 assay. Overall, the DCM root extract of Ansellia africana was the most potent, the DCM tuber extract of Eulophia hereroensis was the only extract to significantly inhibit both COX enzymes, while all Bulbophyllum scaberulum organic root extracts exhibited COX-2 selective inhibitory activity. Bulbophyllum scaberulum DCM root extract was also the most effective anti-cholinesterase extract, performing better than galanthamine. In the single electron transfer (SET) (2,2′-diphenylpicrylhydrazyl (DPPH) free radical scavenging assay and ferric reducing antioxidant power (FRAP) reaction based assays, E. petersii pseudobulb and A. africana root extracts performed better than other extracts. In the hydrogen atom transfer (HAT) (β-carotene/linoleic acid assay) reaction-based assay, the leaf extract of Tridactyle tridentata and root extracts of Cyrtorchis arcuata and E. hereroensis exhibited the best antioxidant effects. The mutagenicity (Salmonella/microsome assay) was also determined. Organic leaf and root extracts of C. arcuata produced no genotoxic effects in comparison to the other tested species. None of the crude extracts tested demonstrated mutagenic effects using S. typhimurium strain TA98 with metabolic activation. The results obtained in this study validate the use of certain orchid species in South African traditional medicine for inflammation-related degenerative disorders.     

Anti-inflammatory, antioxidant and analgesic amides

The synthesis of some new aryl acetic acids and amides and a pharmacochemical study and quantitative structure-activity relationships (QSAR) on them are described. The compounds were screened for their biological activity using the carrageenin induced rat paw oedema model and a significant inhibition of oedema occurred (44.1-80.1%) at a concentration of 0.01 mmol/1 kg. The analgesic activity, based on the inhibition of acetic acid-induced writhing in rats was also found to be significant. The compounds were found to interact with the stable free radical 1,1-diphenylhydrazyl DPPH and with DMSO (for hydroxyl radicals). The compounds were screened for radical scavenging activity with the xanthine/xanthine oxidase system for O2-* and for inhibition of soybean lipoxygenase (LOX). The results are discussed in terms of the structural and physicochemical characteristics of the compounds.     

Anti-inflammatory and antioxidant activity of coumarins designed as potential fluorescent zinc sensors

A series of coumarin analogs, designed and synthesised as potential fluorescent zinc probes were evaluated for their biological activity as anti-inflammatory and antioxidant agents. The effect of the synthesised compounds on inflammation, using the carrageenin-induced rat paw oedema model, was studied. In general, the compounds were found to be potent anti-inflammatory agents (26.5-64%). Compound 5 was found to interact significantly with 1,1-diphenyl-2-picryl-hydrazyl stable free radical (DPPH) whereas the remainder were inactive in this assay. The compounds inhibit in general the soybean lipoxygenase and scavenge superoxide anion radicals. The anti-inflammatory activity seems to be connected with their reducing activity. Their RM values were determined as an expression of their lipophilicity. Theoretical calculations of their lipophilicity as clog P were performed indicating that only a poor relationship exists between their lipophilicity and anti-inflammatory activity.     

Anti-inflammatory, antiarthritic and analgesic activity of a herbal formulation (DRF/AY/4012)

Anti-inflammatory, antiarthritic and analgesic effect of a herbal product (DRF/AY/4012) was evaluated in animal models. Herbal product treatment induced a dose dependent anti-inflammatory activity in acute inflammatory models (carrageenin and egg-albumin induced rat hind paw edema). It also elicited promising anti-inflammatory activity in chronic inflammatory models (cotton pellet granuloma and Freund's adjuvant induced polyarthritis in rats). Further, the product inhibited the increased level of serum lysosomal enzyme activity viz. serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase and the lipid peroxidation in liver. In Freund's adjuvant induced polyarthritis, herbal product reduced the increased level of hydroxy proline, hexosamine and total protein content in edematous tissue. The product also exhibited mild to moderate analgesic activity in acetic acid induced writhing in mice. The LD50 value of the herbal product was more than 16 gm/kg by oral route in mice. The product has distinct advantages over the existing agents and deserves further developmental studies.     

Comparative antioxidant activity of individual herbal components used in Ayurvedic medicine

Four aqueous extracts from different parts of medicinal plants used in Ayurveda (an ancient Indian Medicine) viz., Momardica charantia Linn (AP1), Glycyrrhiza glabra (AP2), Acacia catechu (AP3), and Terminalia chebula (AP4) were examined for their potential as antioxidants. The antioxidant activity of these extracts was tested by studying the inhibition of radiation induced lipid peroxidation in rat liver microsomes at different doses in the range of 100-600 Gy as estimated by thiobarbituric acid reactive substances (TBARS). Of all these extracts, AP4 showed maximum inhibition in the TBARS formation and hence is considered the best antioxidant among these four extracts. The extracts were found to restore antioxidant enzyme superoxide dismutase (SOD) from the radiation induced damage. The antioxidant capacities were also evaluated in terms of ascorbate equivalents by different methods such as cyclic voltammetry, decay of ABTS(.-) radical by pulse radiolysis and decrease in the absorbance of DPPH radicals. The results were found to be in agreement with the lipid peroxidation data and AP4 showed maximum value of ascorbate equivalents. Therefore AP4, with high antioxidant activity, is considered as the best among these four extracts.     

Total phenolic content, flavonoid concentration, antioxidant and antimicrobial activity of methanol extracts from three Seseli L. taxa

The present study describes the total phenolic content, concentrations of flavonoids and in vitro antioxidant and antimicrobial activity of methanol extracts from Seseli pallasii Besser, S. libanotis (L.) Koch ssp. libanotis and S. libanotis (L.) Koch ssp. intermedium (Rupr.) P. W. Ball, growing wild in Serbia. The total phenolic content in the extracts was determined using Folin-Ciocalteu reagent and their amounts ranged between 84.04 to 87.52 mg GA (gallic acid)/g. The concentrations of flavonoids in the extracts varied from 4.75 to 19.37 mg Qu (quercetin)/g. Antioxidant activity was analyzed using DPPH reagent. Antioxidant activity ranged from 0.46 to 4.63 IC₅₀ (mg/ml) and from 1.98 to 2.19 mg VitC (vitamin C)/g when tested with the DPPH and ABTS reagents, respectively, using BHA and VitC as controls. The antimicrobial activity of the extracts was investigated using a micro-well dilution assay for the most common human gastrointestinal pathogenic bacterial strains: Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 9027, Salmonella enteritidis ATCC 13076, Bacillus cereus ATCC 10876, Listeria monocytogenes ATCC15313, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 10231. This finding suggests that Seseli species may be considered as a natural source of antioxidants and antimicrobial agents.     

Anti-inflammatory and antimicrobial activities of novel pyrazole analogues

A new sequence of pyrazole derivatives (1–6) was synthesized from condensation technique under utilizing ultrasound irradiation. Synthesized compounds were characterized from IR, ¹H NMR, ¹³C NMR, Mass and elemental analysis. Synthesized compounds (1–6) were screened for antimicrobial activity. Among the compounds 3 (MIC: 0.25 μg/mL) was exceedingly antibacterially active against gram negative bacteria of Escherichia coli and compound 4 (MIC: 0.25 μg/mL) was highly active against gram positive bacteria of Streptococcus epidermidis compared with standard Ciprofloxacin. Compound 2 (MIC: 1 μg/mL) was highly antifungal active against Aspergillus niger proportionate to Clotrimazole. Synthesized compounds (1–6) were screened for anti-inflammatory activity and the compound 2-((5-hydroxy-3-methyl-1H-pyrazol-4-yl)(4-nitrophenyl)methyl)hydrazinecarboxamide (4) was better activity against anti-inflammatory when compared with standard drugs (Diclofenac sodium). Compounds (2, 3 and 4) are the most important molecules and hence the need to develop new drugs of antibacterial, antifungal and anti-inflammatory agents.     

Total phenolic content and antioxidant activity of plants used in traditional Romanian herbal medicine

A number of herbal plants from Romania widely used as natural food additives or for health promotion in traditional medicine were investigated for their antioxidant activity. Methanol extracts were obtained from plants belonging to the Lamiaceae family (lavender Lavandula angustifolia L.; lemon balm Melissa officinalis; sage Salvia officinalis; oregano Origanum vulgare L.; rosemary Rosmarinus officinalis L.; thyme Thymus vulgaris L.; mullein Verbascum phlomoides; mint Mentha longifolia), Clusiaceae family (St John’s wort Hypericum perforatum L.), and Compositae family (elecampane Inula helenium). Total phenolic concentration was determined using the Folin-Ciocalteu phenol reagent method, while total flavonoids were measured using the aluminium chloride colorimetric method. Relationships between total antioxidant activity and composition of plant extracts were evaluated. Origanum vulgare extract showed the highest antioxidant activity and total phenolic content compared to the other plants extracts. A positive correlation was observed between total antioxidant activity and total phenolic content of the analyzed extracts.     

Synthesis of thiazole-based substituted piperidinone oximes: Profiling of antioxidant and antimicrobial activity

The synthesis of novel thiazole-based piperidinone oximes and screening of their antioxidant and antimicrobial activity are described. The obtained results revealed that the electronic effects of active substituents at C-4 terminals of phenyl rings on either side of piperidinone skeleton, as well as at 2-hydrazinyl thiazole, played a major role in development of antioxidant and antimicrobial activity. Antioxidant activity seems to be based also on radical dissipating ability of the thiazole ring. The nucleophilic character of sulfur in thiazole and lipophilic nature of piperidinone skeleton substantially influenced the observed antimicrobial activity of thiazole-based piperidinone oximes. Among the synthesized compounds, 2,6-bis(4-hydroxy-3-methoxyphenyl)-1-methylpiperidin-4-one O-(2-(2-(4-hydroxy-3-methoxybenzylidene)hydrazinyl)thiazol-4-yl) oxime exhibited excellent antioxidant activity whereas compound 2,6-bis(4-chloro phenyl)-1-methylpiperidin-4-one O-(2-(2-(4-nitrobenzylidene)hydrazinyl)thiazol-4-yl)oxime emerged as an outstanding antimicrobial agent.     

红豆树种子化学成分及其抗氧化和抑菌活性研究

为研究红豆树种子的化学组成及生物活性。本文采用气相色谱-质谱联用技术(GC-MS)对其甲醇提取物的化学成分进行了鉴定,并首次采用不同极性溶剂对红豆树种子的生物活性物质进行萃取;同时,利用DPPH法、ABTS法和抑菌圈法评价红豆树种子生物活性物质的体外抗氧化及抑菌活性。结果表明,从红豆树种子萃取物中共检测出化合物12个,占萃取物总量的89.03%;种子萃取物的主要成分为5-羟甲基糠醛(52.98%)、D-阿洛糖(7.24%)、2,3-二甲氧基-10,11-二氢二苯并(b,f)恶庚英-10-醇(6.51%)、甲基丁香酚(4.53%)、2,3-二氢-3,5-二羟基-6-甲基-4H-吡喃-4-酮(4.45%)、黄樟素(3.75%)、α-松油醇(3.31%)、2,6-二甲氧基苯酚(2.01%),此8种成分占总量的84.78%。红豆树种子正丁醇、乙酸乙酯和石油醚等萃取物对DPPH和ABTS自由基均具有显著的抗氧化活性,且抗氧化活性与萃取物浓度呈线性相关。当红豆树种子正丁醇、乙酸乙酯和石油醚等萃取物浓度为10.0 mg/mL时,正丁醇萃取物对大肠杆菌、绿脓杆菌和鼠伤寒沙门氏菌的抑菌效果最佳;乙酸乙酯萃取物对枯草芽孢杆菌的抑菌效果最佳;石油醚萃取物对金黄色葡萄球菌和苏云金芽孢杆菌的抑菌效果最佳。研究结果为红豆树种子资源的开发和综合利用提供了数据支持。     

Anti-inflammatory and analgesic effects and molecular mechanisms of JCICM-6, a purified extract derived from an anti-arthritic Chinese herbal formula

The anti-inflammatory and anti-nociceptive effects and the molecular mechanisms of JCICM-6, a purified extract derived from an anti-arthritic Chinese herbal formula composed of Caulis Sinomenii, Aconiti laterralis Preparata, Rhizoma Curcumae longae, Radix Paeoniae albae, and Cortex Moutan, were examined for the first time. JCICM-6 was prepared using pharmaceutical extraction technology, purified by Amberlite XAD-7HP polymeric resin. Pharmacologically, in carrageenan-induced edema and carrageenan-evoked thermal hyperalgesia in paws of rats, the oral administration of JCICM-6 at dosages of 0.4, 0.8, and 1.6 g/kg demonstrated significant inhibition with a dose-dependent manner. Mechanistic studies showed that JCICM-6 effectively decreased the production of the pro-inflammatory cytokines of IL-6 and IL-1β and expression of COX-2 and iNOS proteins, and simultaneously elevated the level of anti-inflammatory cytokine IL-4 in the carrageenan-injected rat paw tissues and exudates. The positive reference drug, indomethacin at a dosage of 10 mg/kg, demonstrated inhibitory potency in both rat models, but it could not augment the production of IL-4, indicating JCICM-6 and indomethacin might possess different pharmacological properties and molecular mechanisms although both have anti-inflammatory and analgesic effects in rats. These results suggest that JCICM-6 would be a valuable candidate for further investigation as a new anti-arthritic drug.     

Synthesis,antioxidant, and antimicrobial evaluation of some 2-arylbenzimidazole derivatives

A series of 2-arylbenzimidazole derivatives (3a–3p and 4a–4i) were synthesized and evaluated as potential antioxidant and antimicrobial agents. Their antioxidant properties were evaluated by various in vitro assays including hydroxyl radical (HO) scavenging, superoxide radical anion (O₂^?) scavenging, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, and ferric reducing antioxidant power. Results demonstrated that compounds with hydroxyl group at the 5-position of benzimidazole ring had a comparable or better antioxidant activity in comparison to standard antioxidant tert-butylhydroquinone (TBHQ). Markedly, compound 4h that showed the highest HO scavenging activity (EC₅₀ = 46 μM) in vitro had a significant reduction of 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH)-induced intracellular oxidative stress and H₂O₂-induced cell death. In addition, these compounds showed moderate to good inhibitory activity against Staphylococcus aureus selectively at noncytotoxic concentrations.     

Biocatalytic preparation of acylated derivatives of flavonoid glycosides enhances their antioxidant and antimicrobial activity

Enzymatic synthesis of acylated derivatives of a monosaccharidic flavonoid chrysoeriol-7-O-beta-D-(3'-E-p-coumaroyl)-glucopyranoside as well as of a disaccharidic flavonoid chrysoeriol-7-[6'-O-acetyl-beta-D-allosyl-(1-->2)-beta-D-glucopyranoside], isolated from Greek endemic plants, was performed using an immobilized Candida antarctica lipase in non-toxic organic solvents. The influence of the reaction parameters such as the molar ratio of acyl donor to flavonoid, as well as the nature of the acyl donor, on the performance of the biocatalytic process was pointed out using the acylation of naringin as a model reaction. With vinyl laurate as acyl donor, the highest conversion was observed at relatively high molar ratio (>or=10), using acetone as solvent. Lipase exhibits specificity towards primary alcohol of the glucose moiety of both flavonoid glycosides. The introduction of an acyl group into glucosylated flavonoids significantly improved their antioxidant activity towards both LDL and serum model in vitro. Furthermore, the acylated derivative of disaccharidic flavonoid increased its antimicrobial activity against two Gram-positive bacteria.     

Anti-inflammatory activity of hydroxydihydrocarvone

Hydroxydihydrocarvone (HC) is a synthetic intermediate obtained by hydration of the natural compound (R)-(-)-carvone. The aim of the present study was to investigate the possible anti-inflammatory activity of orally administered HC. Toxicity, motor coordination, tail immersion test, as well as carrageenan-induced paw edema and myeloperoxidase (MPO) activity or peritonitis were all evaluated in rodents. HC was force-fed to the animals 1 h before the stimulus. The lethal dose 50% (LD50) of orally administered HC was 1259 mg/kg. No changes in motor coordination were recorded in HC-treated mice in the rotarod test. The time of response to the thermoceptive stimulus in the tail immersion test was longer in HC-treated animals (50, 100, and 200 mg/kg) than in the vehicle-treated group. HC also significantly decreased the area under curve of carrageenan-induced rat paw edema at 100 and 200 mg/kg and MPO activity at 200 mg/kg. Carrageenan-induced neutrophil recruitment to the peritoneal cavity was significantly reduced by HC at doses of 100 or 200 mg/kg, but not 50 mg/kg. These findings demonstrate that orally administered HC exerts antinociceptive and anti-inflammatory activities in rats and mice.     

Glutathione peroxidase-like activity of caeruloplasmin as an important lung antioxidant.

The copper-containing plasma protein caeruloplasmin (Cp) has been shown to possess several oxidase activities, but with the exception of its ferrous ion oxidising (ferroxidase) activity which so far appear to be of minor biological relevance. Recently, Kim and colleagues (Kim et al. (1998) FEBS Lett. 431, pp. 473-475) observed that Cp can catalytically remove hydrogen peroxide in the presence of thiols. Here, we show that Cp can remove both hydrogen peroxide and lipid hydroperoxides at physiologically relevant concentrations of reduced glutathione known to be present in lung and lung lining fluid. The glutathione peroxidase-like activity of Cp together with its ferroxidase activity would completely remove the primary reactants required for both Fenton chemistry and lipid peroxidation.