Mangifera indica L. Extract and Mangiferin Modulate Cytochrome P450 and UDP‐Glucuronosyltransferase Enzymes in Primary Cultures of Human Hepatocytes

The aqueous stem bark extract of Mangifera indica L. (MSBE) has been reported to have antioxidant, anti‐inflammatory and analgesic properties. In previous studies, we showed that MSBE and mangiferin, its main component, lower the activity of some cytochrome P‐450 (P450) enzymes in rat hepatocytes and human liver microsomes. In the present study, the effects of MSBE and mangiferin on several P450 enzymes and UDP‐glucuronosyltransferases (UGTs) in human‐cultured hepatocytes have been examined. After hepatocytes underwent a 48‐h treatment with sub‐cytotoxic concentrations of the products (50–250 µg/mL), a concentration‐dependent decrease of the activity of the five P450 enzymes measured (CYP1A2, 2A6, 2C9, 2D6 and 3A4) was observed. For all the activities, a reduction of at least 50% at the highest concentration (250 µg/mL) was observed. In addition, UGT activities diminished. MSBE considerably reduced UGT1A9 activity (about 60% at 250 µg/mL) and lesser effects on the other UGTs. In contrast, 250 µg/mL mangiferin had greater effects on UGT1A1 and 2B7 than on UGT1A9 (about 55% vs. 35% reduction, respectively). Quantification of specific mRNAs revealed reduced CYP3A4 and 3A5 mRNAs content, and an increase in CYP1A1, CYP1A2, UGT1A1 and UGT1A9 mRNAs. No remarkable effects on the CYP2A6, 2B6, 2C9, 2C19, 2D6 and 2E1 levels were observed. Our results suggest that the activity and/or expression of major P450 and UGT enzymes is modulated by MSBE and that potential herb–drugs interactions could arise after a combined intake of this extract with conventional medicines. Therefore, the potential safety risks of this natural product derived by altering the ADMET properties of co‐administered drugs should be examined. Copyright © 2012 John Wiley & Sons, Ltd.     

A New Diarylheptanoid from Barks of Mangifera indica

Objective To study the chemical constituents from the barks of Mangifera indica.Methods The constituents were separated and purified by different methods of chromatography,and their structures were elucidated by IR,MS,1D and 2D NMR techniques.Results Six compounds were isolated from the barks of M.indica.Their structures were identified as mangiferone(1),mangiferin(2),myricetin(3),myricitrin(4),rutin(5),and quercetin(6).Conclusion Mangiferone(1)is a new diarylheptanoid compound isolated from the barks of M.indica.     

Combination of Mangifera indica L. Extract Supplementation Plus Methotrexate in Rheumatoid Arthritis Patients: A Pilot Study

The purpose of the present study was to evaluate the possible therapeutic effects and the safety of Mangifera indica extract (Vimang tablets, 300 mg) combined with methotrexate (MTX) on reducing disease activity in rheumatoid arthritis (RA). Twenty patients with active RA underwent a year of treatment with MTX (12.5 mg/week) associated to non‐steroidal anti‐inflammatory drugs (NSAIDs) and/or prednisone (5–10 mg/day) were randomly allocated to the experimental group (n = 10), that received the extract supplementation (900 mg/day) or preceding usual treatment (n = 10) during 180 days. RA activity was evaluated using the tender and swollen joint counts, erythrocyte sedimentation rate, disease activity score‐28 (DAS 28), visual analogue scale (VAS) and health assessment questionnaire (HAQ). Treatment's efficacy was demonstrated with ACR criteria. Only the patients of MTX‐Vimang group revealed statistically significant improvement in DAS 28 parameters with respect baseline data but no differences were observed between groups. ACR improvements amounted 80% only in MTX‐Vimang group at the 90 days (p < 0.001). In MTX‐Vimang group, 100% of patients decreased NSAIDs administration (p < 0.01) and 70% of those eradicated gastrointestinal side effects (p < 0.01) ensuing of the preceding treatment. Other adverse effects were not reported. Copyright © 2013 John Wiley & Sons, Ltd.     

Mangifera indica L. extract (Vimang) and mangiferin modulate mouse humoral immune responses

The present study investigated the effects of orally administered Vimang (an aqueous extract of Mangifera indica) and mangiferin (the major polyphenol present in Vimang) on mouse antibody responses induced by inoculation with spores of microsporidian parasites. Inoculation induced specific antibody production with an exponential timecourse, peaking after about one month. Vimang significantly inhibited this antibody production from about three weeks post-inoculation, and most markedly by four weeks post-inoculation; by contrast, mangiferin had no significant effect. Determination of Ig isotypes showed that the IgM to IgG switch began about four weeks post-inoculation, with IgG2a predominating. Vimang significantly inhibited IgG production, but had no effect on IgM. Mangiferin did no affect either IgM or IgG2a, but significantly enhanced production of IgG1 and IgG2b. Neither Vimang nor mangiferin enhanced specific antibody secretion by splenic plasma cells from mice inoculated with microsporidian spores, whether administered in vivo before serum extraction or in vitro to the culture medium. Inoculation with spores induced splenomegaly, which was significantly reduced by Vimang and significantly enhanced by mangiferin. These results suggest that components of Mangifera indica extracts may be of potential value for modulating the humoral response in different immunopathological disorders.     

芒果叶的化学成分研究

目的:研究芒果(Mangifera indica L.)叶的化学成分。方法:用甲醇提取及柱色谱等方法进行分离,波谱法鉴定结构。结果:从芒果叶中分离并鉴定了5个化合物,其结构分别为β-谷甾醇(1)、山奈酚(2)、槲皮素(3)、杨梅素(4)和芒果苷(5)。结论:杨梅素为首次从芒果植物中分离得到;实验结果可为芒果的进一步研究开发提供科学依据。     

芒果叶不同组织部位高效液相色谱指纹图谱比较

目的通过考察3个品种芒果叶不同组织部位甲醇提取物的高效液相色谱(HPLC)指纹图谱,并对其HPLC指纹图谱进行比较,为研究和测定芒果叶等叶类药材的HPLC指纹图谱提供方法指导和实验依据。方法Waters symmetry C18(5μm,4.6 mm×250 mm)色谱柱;乙腈∶0.1%磷酸为流动相,梯度洗脱;流速:1.0 ml/min;柱温:25℃;检测波长:216 nm。结果芒果叶不同组织部位的HPLC指纹图谱有明显的差异。结论在研究测定芒果叶等叶类药材指纹图谱时必须注意取样的均匀性。     

芒果叶提取物的镇咳祛痰作用研究

目的探讨芒果叶提取物对小鼠的镇咳、祛痰作用。方法采用水和醇对芒果叶提取,提取物对小鼠进行氨水引咳法和酚红气管排泄法镇咳、祛痰实验。结果芒果叶提取物的镇咳、祛痰作用与对照组比较差异有显著性(P<0.05或0.01)。结论芒果叶提取物具有显著的镇咳、祛痰作用。     

Effect of Mangifera indica L. extract (QF808) on protein and hepatic microsome peroxidation.

The antioxidant activities of QF808, a steam bark extract of Mangifera indica L., were studied on hydroxyl-mediated oxidation of bovine serum albumin (BSA) and in a hepatic microsome system. The extract was effective in reducing the oxidation of BSA, since its half- maximal inhibition concentration (IC(50)) was 0.0049% w/v in the inhibition of carbonyl group formation and lower than 0.0025% w/v in the inhibition of sulfhydryl group loss. QF808 inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate (NADPH), IC(50)= 0.00075% w/v, or non-enzymatically by ascorbic acid, IC(50) = 0.0126% w/v. The extract tested did not inhibit NADPH-dependent cytochrome P-450 reductase activity, since it had no effect on the oxidation rate of NADPH. These results suggest that QF808 has an antioxidant activity, probably due to its ability to scavenge free radicals involved in microsome lipid peroxidation. In addition, QF808 antioxidant profile in vitro is probably similar to its principal polyphenolic component, mangiferin, a glycosylated xanthone.     

Protective effect of Mangifera indica L. extract (Vimang) on the injury associated with hepatic ischaemia reperfusion

The effect of Mangifera indica L. extract (Vimang) on treatment of injury associated with hepatic ischaemia/reperfusion was tested. Vimang protects from the oxidative damage induced by oxygen-based free radicals as shown in several in vitro test systems conducted. The ability of Vimang to reduce liver damage was investigated in rats undergoing right-lobe blood fl ow occlusion for 45 min followed by 45 min of reperfusion. The ischaemia/reperfusion model leads to an increase of transaminase (ALT and AST), membrane lipid peroxidation, tissue neutrophil in filtration, DNA fragmentation, loss of protein -SH groups, cytosolic Ca2+ overload and a decrease of catalase activity. Oral administration of Vimang (50, 110 and 250 mg/kg, b.w.) 7 days before reperfusion, reduced transaminase levels and DNA fragmentation in a dose dependent manner (p < 0.05). Vimang also restored the cytosolic Ca2+ levels and inhibited polymorphonuclear migration at a dose of 250 mg/kg b.w., improved the oxidation of total and non protein sulfhydryl groups and prevented modification in catalase activity, uric acid and lipid peroxidation markers (p < 0.05). These data suggest that Vimang could be a useful new natural drug for preventing oxidative damage during hepatic injury associated with free radical generation.     

Mangifera indica L. extract (Vimang) inhibits 2-deoxyribose damage induced by Fe (III) plus ascorbate

Vimang is an aqueous extract of selected species of Mangifera indica L, used in Cuba as a nutritional antioxidant supplement. Many in vitro and in vivo models of oxidative stress have been used to elucidate the antioxidant mechanisms of this extract. To further characterize the mechanism of Vimang action, its effect on the degradation of 2-deoxyribose induced by Fe (III)-EDTA plus ascorbate or plus hypoxanthine/xanthine oxidase was studied. Vimang was shown to be a potent inhibitor of 2-deoxyribose degradation mediated by Fe (III)-EDTA plus ascorbate or superoxide (O2-). The results revealed that Vimang, at concentrations higher than 50 microM mangiferin equivalent, was equally effective in preventing degradation of both 15 mM and 1.5 mM 2-deoxyribose. At a fixed Fe (III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of Vimang. When ascorbate was replaced by O2- (formed by hypoxanthine and xanthine oxidase) the protective efficiency of Vimang was also inversely related to EDTA concentration. The results strongly indicate that Vimang does not block 2-deoxyribose degradation by simply trapping *OH radicals. Rather, Vimang seems to act as an antioxidant by complexing iron ions, rendering them inactive or poorly active in the Fenton reaction.     

Evaluation of the antidiabetic action of Mangifera indica in mice

The leaves of Mangifera indica were assessed for antidiabetic properties using normoglycaemic, glucose-induced hyperglycaemia and streptozotocin (STZ) induced diabetic mice. The aqueous extract produced a reduction of blood glucose level in normoglycaemic and glucose-induced hyperglycaemia, but did not have any effect on streptozotocin-induced diabetic mice. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity.     

Mangiferin: Possible uses in the prevention and treatment of mixed osteoarthritic pain

Osteoarthritis (OA) pain has been proposed to be a mixed pain state, because in some patients, central nervous system factors are superimposed upon the more traditional peripheral factors. In addition, a considerable amount of preclinical and clinical evidence has shown that, accompanying the central neuroplasticity changes and partially driven by a peripheral nociceptive input, a real neuropathic component occurs that are particularly linked to disease severity and progression. Hence, innovative strategies targeting neuroprotection and particularly neuroinflammation to prevent and treat OA pain could be introduced. Mangiferin (MG) is a glucosylxanthone that is broadly distributed in higher plants, such as Mangifera indica L. Previous studies have documented its analgesic, anti‐inflammatory, antioxidant, neuroprotective, and immunomodulatory properties. In this paper, we propose its potential utility as a multitargeted compound for mixed OA pain, even in the context of multimodal pharmacotherapy. This hypothesis is supported by three main aspects: the cumulus of preclinical evidence around this xanthone, some preliminary clinical results using formulations containing MG in clinical musculoskeletal or neuropathic pain, and by speculations regarding its possible mechanism of action according to recent advances in OA pain knowledge.     

Anthelminthic and antiallergic activities of Mangifera indica L. stem bark components Vimang and mangiferin

This study investigated the antiallergic and anthelmintic properties of Vimang (an aqueous extract of Mangifera indica family stem bark) and mangiferin (the major polyphenol present in Vimang) administered orally to mice experimentally infected with the nematode, Trichinella spiralis. Treatment with Vimang or mangiferin (500 or 50 mg per kg body weight per day, respectively) throughout the parasite life cycle led to a significant decline in the number of parasite larvae encysted in the musculature; however, neither treatment was effective against adults in the gut. Treatment with Vimang or mangiferin likewise led to a significant decline in serum levels of specific anti-Trichinella IgE, throughout the parasite life cycle. Finally, oral treatment of rats with Vimang or mangiferin, daily for 50 days, inhibited mast cell degranulation as evaluated by the passive cutaneous anaphylaxis test (sensitization with infected mouse serum with a high IgE titre, then stimulation with the cytosolic fraction of T. spiralis muscle larvae). Since IgE plays a key role in the pathogenesis of allergic diseases, these results suggest that Vimang and mangiferin may be useful in the treatment of diseases of this type.     

Biological Effects of the Aqueous Extract of Bridelia grandis Stem Bark on Normal and Neoplastic Human Cells: An In Vitro Preliminary Evaluation

The aim of the work is to investigate the effects of Bridelia grandis (Pierre ex Hutch) stem bark water extract on human HeLa cancer cells and normal monocytes treated in vitro, evaluating the morphological modifications with light and electron microscopy. The phytocomplex obtained from B. grandis caused a significant decrease in the mitotic index of both HeLa cancer cells and normal monocytes. In addition, a reduction of the typical aneuploid‐polyploid pattern has been observed in HeLa cells after treatment. Various alterations at fine structural level, both in neoplastic (HeLa cells) and normal (monocytes) cells have been observed. In particular, electron‐dense cells containing condensed mitochondria, autophagic vacuoles and dense spherical cytoplasmic inclusions have been observed. The results show that B. grandis water extracts have an antiproliferative effect on human cells, with a different effect on neoplastic and normal cells. The antiproliferative effect is accompanied by the appearance of various subcellular alterations. The morphological alterations observed are likely to represent the condition of ‘dark cell’ as a possible preliminary phase towards the autophagic and/or apoptotic cell death. Copyright © 2013 John Wiley & Sons, Ltd.     

地桃花水提物的体外抗菌实验研究

目的:探讨地桃花水提物在体外的抗菌作用。方法:采用琼脂二倍稀释法对地桃花水提物进行MIC实验研究。结果:地桃花水提液在体外对金黄色葡萄球菌、铜绿假单胞菌、大肠埃希菌、肺炎链球菌和普通变形杆菌均具一定的抑菌活性,且对金黄色葡萄球菌和普通变形杆菌的抑菌活性更为显著。结论:本研究为地桃花药材水提物的抗菌效用提供了实验依据。     

了哥王抗肿瘤活性部位筛选

目的:研究了哥王95%、75%、50%乙醇提取物、水提物及95%乙醇提取物的石油醚、氯仿、乙酸乙酯、正丁醇萃取部位对肿瘤细胞的增殖抑制作用,确定了哥王抗肿瘤活性部位。方法:采用四甲基偶氮唑盐(MTT)比色法考察了哥王不同提取物及95%乙醇提取物的不同溶剂萃取部位对Hela、SGC-7901、Bel-7402细胞的抗肿瘤活性。结果:了哥王95%乙醇提物对Hela、SGC-7901细胞有良好的抗肿瘤活性,其石油醚、氯仿、乙酸乙酯萃取部位对Hela、SGC-7901细胞均有不同程度的抗肿瘤活性。结论:石油醚、氯仿、乙酸乙酯萃取部位有较强的抗肿瘤活性,初步确定为了哥王抗肿瘤活性部位。     

Anti‐depressant Effects of Aqueous Extract from Acanthopanax senticosus in Mice

In this paper, the anti‐depressant effects of Acanthopanax senticosus extract (ASE) were studied using animal models of depression including the forced swimming and tail suspension tests. The anti‐depressive mechanism of ASE was explored by monitoring the levels of monoamine neurotransmitters including 5‐hydroxytrylamine (5‐HT), norepinephrine (NE), and dopamine (DA), as well as cAMP response element‐binding (CREB) protein expression in the whole brain of mice following the tail suspension test. Our results showed that intragastric administration of ASE at a dose of 2000 mg/kg for seven days significantly reduced the duration of immobility in both the forced swimming test and the tail suspension test. These results indicate that ASE possesses antidepressant‐like properties. Pre‐treatment with 2000 mg/kg of ASE for seven days significantly elevated the levels of 5‐HT, NE, and DA in the whole brain of mice. Moreover, ASE at doses of 1000 and 2000 mg/kg significantly up‐regulated the level of CREB protein. Taken together, these findings suggest that the anti‐depressive mechanism of ASE may be mediated via the central monoaminergic neurotransmitter system and CREB protein expression. Therefore, administration of ASE may be beneficial for patients with depressive disorders. Copyright © 2013 John Wiley & Sons, Ltd.     

Cytoprotective and Anti‐secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models

Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in‐vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+‐ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.     

拳参正丁醇提取物对豚鼠心肌生理特性的影响

目的研究拳参正丁醇提取物对豚鼠离体右心房自律性及收缩特性的影响，并探讨其作用机制。方法采用豚鼠离体右心房测定拳参正丁醇提取物对其自律性、收缩幅度、收缩速度、舒张速度的影响。结果拳参正丁醇提取物可降低豚鼠离体右心房的自律性，降低豚鼠离体右心房的收缩幅度、收缩速度、舒张速度，且具有明显的剂量依赖性。结论拳参正丁醇提取物可抑制豚鼠离体右心房的自律性，降低豚鼠离体右心房的收缩幅度、收缩速度、舒张速度，且具有明显的剂量依赖性。其机制可能与抑制钙离子的内流及改变肌浆网上的钙泵活性有关。     

五色梅根三萜类物质镇痛和抗炎的实验研究

目的：研究五色梅根三萜类物质镇痛和抗炎作用。方法：用扭体法观察镇痛作用；用二甲苯使小鼠致炎观察该药的抗炎作用。结果；五色梅根三萜类物质对醋酸致痛具有明显的镇痛作用．对二甲苯所致炎性水肿也有显著的抑制作用。结论：五色梅根三萜类物质具有较好的镇痛抗炎作用。