Oleifera Ethanolic Extract Research Articles

An Evaluation of Anti-hyperlipidemic Activity of Ethanolic Extract of Moringa oleifera on High Fat Induced Hyperlipidemic Rat Model

Background: The art or practice of herbal remedies refers to the use of herbs and herbal treatments for the purpose of maintaining health and preventing, treating, or curing sickness. In some areas, herbal treatments can also be referred to as herbal medicine.
 Aim: The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Moringa oleifera extract in high fat diet-induced hyperlipidemic rats.
 Materials and Methods: Moringa oleifera ethanolic extract was prepared using Soxhlet apparatus. Male rats were made hyperlipidemic by giving high fat diet. M. oleifera was administered in a dose of 250, 500 and 750 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The SGPT, SGOT, total cholesterol,triglyceride, LDL,HDL , Urea and creatinine levels were measured after the treatment.
 Results: For both the SGPT and the SGOT, it was seen that groups 5 and 6 exhibited statistically significant (p< 0.05) outcomes in the case of the SGPT. When conducting the renal function test, it was observed that the levels of creatinine and urea were statistically significant (p< 0.05) in the cases of groups 4, 5, and 6. In the case of high-density lipoprotein (HDL) and low-density lipoprotein (LDL), groups 4, 5, and 6 showed statistically significant findings (p< 0.05) in HDL levels, while groups 5 and 6 showed statistically significant LDL levels. The triglyceride levels in the group were found to be statistically significant (p< 0.05), while the findings obtained from groups 5 and 6 were also found to be statistically significant.
 Conclusion: The study revealed that M. oleifera has anti hyperlipidemic activity.

In-silico Prediction Analysis of Polyphenolic Contents of Ethanolic Extract of Moringa oleifera Leaves

Introduction: Moringa oleifera is widely consumed as a source of nutrients and as traditional medicine for treating myriads of diseases in Southeast Asia, Africa, and South America. Polyphenols are abundantly found in the leaves of Moringa oleifera, particularly astragalin and quercetin, and have shown antioxidant and anti-inflammatory activities. In the present study, the polyphenols in Moringa oleifera leaves were identified and quantified, followed by in-silico pharmacokinetics prediction. Methods: Moringa oleifera ethanolic leaf extract (MOEE) was prepared by macerating dry powdered leaves of Moringa oleifera in 70% ethanol, then subjected to ultra-high-performance liquid chromatography-mass spectrometry (UPHLC-MS/MS) to identify polyphenols and quantification by HPLC. In-silico pharmacokinetic prediction analysis of the polyphenols was performed using the SwissADME web tool. Results: Eight polyphenols were identified, among which astragalin and quercetin were quantified. In-silico prediction analysis using SwissADME demonstrates the drug-likeness of the polyphenols in MOEE based on their physicochemical and ADME (absorption, distribution, metabolism and excretion) properties. MOEE contains polyphenols that can serve as lead compound to developing drugs, but only some are predicted to have high GI absorption index demonstrating their utility in oral medication drug development. Moreover, all the polyphenols determined in this study are predicted to be non-brain permeant, demonstrating their limited utility in developing drugs that target brain-related pathologies. Conclusion: Eight polyphenols were identified by UHPLC/MS analysis of Moringa oleifera leaves. Their ADME pharmacokinetics properties predicted some of the polyphenols as favourable candidates for drug development and lead optimisation, thus positioning the Moringa oleifera as an important source of small molecules for drug development.

Moringa oleifera Ethanolic Extract Prevents Oxidative Damage on Lens Caused by Sodium Valproate Used in Epilepsy Treatment

Moringa oleifera Ethanolic Extract Prevents Oxidative Damage on Lens Caused by Sodium Valproate Used in Epilepsy Treatment

The potential effect of Moringa oleifera ethanolic leaf extract against oxidative stress, immune response disruption induced by abamectin exposure in Oreochromis niloticus

Abamectin (ABM), a naturally fermented product of Streptomyces avermitilis, is applied to pest control in livestock and agriculture fields. The aim of the current study is to evaluate the protective effects of Moringa oleifera leaf ethanolic extract (MOE) on biochemical changes including oxidative stress indices, immune response marker, lipid profiles as well as mRNA expression of immune related genes, and abamectin (ABM, 5% EC) residue levels in Nile tilapia (Oreochromis niloticus) exposed to a sub-lethal concentration (0.5 µg/l) for 28 days. Disturbance in liver and kidney biomarkers was markedly increased in ABM-exposed fish compared to the control group. Malondialdehyde levels in the liver and brain tissues, as well as the activities of glutathione-s-transferase, superoxide dismutase, and glutathione peroxides, all increased significantly in ABM group. Additionally, ABM exposure increased the levels of interleukin 10 beta and growth factor gene expression. On the other hand, fish exposed to ABM had significantly lower serum alkaline phosphatase, creatinine, high-density lipoprotein, glutathione peroxides in brain, glutathione in liver and brain tissues, lysozyme activity, nitric oxide, immunoglobulin M, tumor necrosis factor, and interleukin 1 beta as compared to the control group. The recorded detrimental effects of ABM on tilapia have been overcome by the addition of MOE to the diet (1%) and ameliorating hepato-renal damage and enhancing antioxidant activity, innate immune responses, and upregulating the anti-inflammatory gene expression. Therefore, it could be concluded that MOE dietary supplementation at 1% could be used to counteract the oxidative stress, immune response disruption induced by abamectin exposure in Oreochromis niloticus, and reduce its accumulation in fish tissues.

Ameliorative activities of Moringa oleifera ethanolic leaf extract on Cadmium chloride-induced toxicity in the kidney of adult Wistar rats: A microscopic assessment

Ameliorative activities of Moringa oleifera ethanolic leaf extract on Cadmium chloride-induced toxicity in the kidney of adult Wistar rats: A microscopic assessment

Anti-hemorrhagic activity of ethanol extract of Moringa oleifera leaf on envenomed albino rats

Echis ocellatus (E. ocellatus) is one of the most venomous viper species which constitutes significant economic and health problem all over the world, especially in rural African communities. Moringa oleifera (M. oleifera) is a tropical plant traditionally used in Nigeria for the treatment of many diseases including snakebites. This study, therefore, investigated the anti-haemorrhagic property of ethanol extract of M. oleifera leaf on E. ocellatus envenomed male albino rats. A comprehensive account of the bioactive compounds present in the M. oleifera ethanol leaf extract by means of using Gas Chromatography-Mass Spectrometry (GC–MS) analysis revealed the presence of 9, 12, 15-Octadecatrienoic acid (39.66%), hexadecanoic acid (16.71%), palmitic acid, ethyl ester (14.70%) and phytol (9.81%) as the major components of the leaf extract and some of these components serves as inhibitors of neurotoxins by suitably binding to the snake venom's toxic protein thereby terminating the poisonous effect of the venom. The LD50 of crude E. ocellatus venom was determined to be 0.22 mg/kg while that of ethanol extract of M. oleifera leaf was 800 mg/kg. Envenomation of E. ocellatus venom results in deleterious hematological and histopathological changes in the heart in a dose-dependent manner. Rat given 0.22 mg/kg of E. ocellatus venom (2 mL) and treated with 200 mg/kg, 400 mg/kg and 800 mg/kg of M. oleifera ethanolic leaf extract (2 ml) intradermally show the least heamorrhagic foci at 800 mg/kg of the extract. Pre-incubation of the extract with E. ocellatus venom before injecting animals further enhances the anti-haemorrhagic action of M. oleifera ethanolic leaf extract. Our findings revealed that M. oleifera ethanolic leaf extract is a promising therapeutic agent for the treatment of E. ocellatus snakebite envenomation. Hence, further studies on M. oleifera leaf are warranted.

In vitro Antibacterial Activity of Moringa oleifera Ethanolic Extract against Tomato Phytopathogenic Bacteria

The tomato (Solanum lycopersicum L.) is one of the world’s most important vegetable crops. Still, phytopathogenic bacteria affect the yield and quality of tomato cultivation, like Agrobacterium tumefeciens (At), Clavibacter... | Find, read and cite all the research you need on Tech Science Press

Hepatoprotective effect of Moringa oleifera extract on TNF-\u03b1 and TGF-\u03b2 expression in acetaminophen-induced liver fibrosis in rats

BackgroundIt has been reported that Moringa oleifera (MO) has different medicinal properties. The aim of this study was to evaluate the hepatoprotective role of Moringa oleifera extract on acetaminophen-induced liver fibrosis in albino rats on a biochemical and histological basis. Forty male albino rats were divided into four groups: group I (control group), healthy rates; group II (acetaminophen group), rates received acetaminophen for induction of liver fibrosis; group III (treated group), liver fibrosis of rates treated with Moringa oleifera extract; and group IV (prophylactic group), rates treated with Moringa oleifera extract before and after induction of liver fibrosis. Serum liver function parameters were quantified using a spectrophotometer, while tumor necrosis factor α (TNF-α) and transformed growth factor beta (TGF- β) in liver tissue homogenate by means of enzyme-linked immunosorbent assay (ELISA), and expression of liver tissue TNF-α and TGF-genes was measured by real-time PCR after extraction and purification. Hepatic tissue was also evaluated under a microscope for histopathological changes.ResultsOur results showed a significant decrease in liver enzymes, TNF-α, and TGF-β in the treated and prophylactic groups compared to the acetaminophen group, and our biochemical data were consistent with the histopathological findings confirming the hepatoprotective effect of Moringa oleifera extract.ConclusionsBiochemical parameters and histopathology results provide evidence that Moringa oleifera ethanolic extract has a great potential to prevent and improve liver damage due to its protective activity.

Moringa oleifera ethanolic extract attenuates tilmicosin-induced renal damage in male rats via suppression of oxidative stress, inflammatory injury, and intermediate filament proteins mRNA expression

Tilmicosin (Til) is a popular macrolide antibiotic, widely used in veterinary practice. The present study was designed to address the efficacy of Moringa oleifera ethanolic extract (MOE) in protecting against Tilmicosin (Til) - induced nephrotoxicity in Sprague Dawley rats. Animals were treated once with Til (75 mg/kg bw, subcutaneously), and/or MOE for 7 days (400 or 800 mg/kg bw, by oral gavage). Til-treatment was associated with significantly increased serum levels of creatinine, urea, sodium, potassium and GGT activity, as well as decreased total protein and albumin concentrations. Renal tissue hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were elevated, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were diminished. The levels of renal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) and the mRNA expression of intermediate filament protein encoding genes (desmin, nestin and vimentin) in the kidney were up- regulated with histopathological alterations in renal glomeruli, tubules and interstitial tissue. These toxic effects were markedly ameliorated by co-treatment of MOE with Til, in a dose dependent manner. Taken together, these results indicate that MO at 800 mg/kg protects against Til-induced renal injury, likely by its potent antioxidant and anti-inflammatory properties, which make it suitable to be used as a protective supplement with Til therapy.

Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway to Restore Kidney Tissue from Cobalt-Mediated Oxidative Injury and Inflammation in Rats.

This study aimed to describe the protective efficacy of Moringa oleifera ethanolic extract (MOEE) against the impact of cobalt chloride (CoCl2) exposure on the rat’s kidney. Fifty male rats were assigned to five equal groups: a control group, a MOEE-administered group (400 mg/kg body weight (bw), daily via gastric tube), a CoCl2-intoxicated group (300 mg/L, daily in drinking water), a protective group, and a therapeutic co-administered group that received MOEE prior to or following and concurrently with CoCl2, respectively. The antioxidant status indices (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), oxidative stress markers (hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and malondialdehyde (MDA)), and inflammatory response markers (nitric oxide (NO), tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and C-reactive protein (CRP)) were evaluated. The expression profiles of pro-inflammatory cytokines (nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6)) were also measured by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that CoCl2 exposure was associated with significant elevations of oxidative stress and inflammatory indices with reductions in the endogenous tissue antioxidants’ concentrations. Moreover, CoCl2 enhanced the activity of the NF-κB inflammatory-signaling pathway that plays a role in the associated inflammation of the kidney. MOEE ameliorated CoCl2-induced renal oxidative damage and inflammatory injury with the suppression of the mRNA expression pattern of pro-inflammatory cytokine-encoding genes. MOEE is more effective when it is administered with CoCl2 exposure as a prophylactic regimen. In conclusion, MOEE administration exhibited protective effects in counteracting CoCl2-induced renal injury in rats.

Moringa oleifera extract attenuates the CoCl2 induced hypoxia of rat's brain: Expression pattern of HIF-1α, NF-kB, MAO and EPO

Hypoxia-induced oxidative stress and apoptosis are the major hallmark explanations underlying brain dysfunction. Hypoxia in the current study was induced by Cobalt chloride (CoCl2) treatment in rats. The aim of this experiment was to explore the potential ameliorative potency of Moringa oleifera ethanolic extract (MO) against experimentally induced hypoxia on the structure and function of the rat’s brain. Fifty male rats were allocated to five groups (10 rats each): a control group, a MO-treated group (400 mg/kg bw, orally), a CoCl2-treated group (40 mg/kg bw/day, orally), a prophylaxis group, and a therapeutic co-treated group. Oxidative stress biomarkers and monoamine neurotransmitter were evaluated in brain tissue. In addition, qRT-PCR for expression pattern of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. Glial fibrillary acidic protein (GFAP), apoptotic markers (BCL-2 and caspase 3) were detected immunohistochemically in brain cells. The results revealed a significantly lower concentration of GABA, monoamine neurotransmitter in hypoxic rat’s brain. Moreover, an evident up-regulation of the mRNA expression of HIF-1α, EPO, CYTO, NF-kB, and MAO-A. There was marked encephalopathy manifested by pyknotic neurons with eosinophilic cytoplasm, vacuolations and cerebral congestions in the hypoxic rat brains. Additionally, the score of neuronal expression occupied by GFAP- positive astroglia, Caspase-3 and microglial CD68 were elevated but Bcl-2 expression was found decreased in the hypoxic group than control. The endpoints of this study clearly stated that MO ethanolic extract suggestively counteracted neurotoxic impacts caused by hypoxia, particularly when it administered prior to and concurrently with CoCl2 administration.

Protective Effects of Moringa oleifera extract on Isoniazid and Rifampicin Induced Hepatotoxicity in Rats: Involvment of Adiponectin and Tumor Necrosis Factor-α

H EPATOTOXICITY is the major health problem that is a global concern worldwide especially in Egypt because the liver injury is one of the most ten disease leading to death. There are many factors leading to hepatotoxicity as antibiotics like Isoniazid (INH) and rifampicin (RIF) which are the first line remedies in treatment of tuberculosis. The present study evaluates the possible hepatoprotective effects of Moringa oleifera against the experimentally induced hepatotoxicity with INH/RFP in rats. Forty eight rats (200-250g) were allocated into six groups (8 rats in each group), and treated as follow: group I: received normal saline orally, group II: received INH/ RIF (50 mg/Kg/day of each)for 28 days orally, group III: received Silymarin (50 mg/kg/day) + INH/ RIF for 28 days orally, group IV, V, VI: received Moringa oleifera ethanolic extract (MOEE) (250, 500 and 1000 mg/Kg/day) + INH/ RIF for 28 days respectively. Co-administration of Moringa oleifera with INH/ RIF reduced elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and (bilirubin total &direct) levels but also decreased the elevated malondialdehyde (MDA) & tumor necrosis factor-α (TNF-α) contents in liver homogenate. Moreover, administration of Moringa oleifera increased glutathione peroxidase (GPX) & adiponectin activity. Microscopic examination of Moringa olifera extract administration revealed reduction in the severity of liver damage. It is concluded that Moringa olifera might be considered as adjuvant drug in treatment of liver disorder and or as hepatoprotective therapy with anti-tubercular drugs.

English

Indomethacin is commonly used as an anti-inflammatory and pain relieving medication; however, it has the side effect of gastric ulcer formation which is an actual common gastrointestinal illness that may result in dangerous complications and even death. Various diseases have been treated widely by the use of oriental herbal medicines, this study aims to evaluate the antiulcerative and antioxidative effect of two doses (100 and 50 of Moringa oleifera ethanolic leaf extract; MOELE) on indomethacin plus ethanol-induced oxidative gastric mucosal injury in rats. Sixty adult males Wistar rats weighing 170 to 200 g, were divided into equal six groups. First group of rats were administered saline as a vehicle, second group of rats were given indomethacin (15 mg/kg), third and fourth groups of rats were giving MOELE 100 and 500 mg, fifth group of rats were given indomethacin+ MOELE 100 mg, and sixth group of rats were administered with indomethacin + MOELE (500 mg). To study the effect of MOELE on oxidative gastric mucosal injury in rats, two doses were administered 2 h before ulcer induction by indomethacin plus ethanol. The administration continued for two weeks. All rats were sacrificed 24 h after the last dose. Indomethacin group showed significant increases in lesion index (LI) and increase in malondialdehyde (MDA) level, while there was a decrease in superoxide dismutase (SOD), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities when compared with the control group (G1). MOELE with two doses mentioned before (groups 5 and 6) were effective to reduce stomach LI and oxidative stress markers (MDA) while increasing significantly the antioxidant biomarkers (SOD, GST, and GPx) compared with indomethacin group (G2). A highly significant decrease in MDA accompanied by a marked increase in SOD, GST, and GPx were recorded in group 6. The results concluded that MOELE has an effective antiulcer and antioxidant activities. It can scavenge the free radicals and protect gastric against ulceration. Also, MOELE could ameliorate the ulcerative side effect of indomethacin. Key words: Moringa oleifera, antioxidant enzymes, indomethacin, lesion index, lipid peroxidation.

Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

Physiological response and semen quality of rabbit bucks supplemented with Moringa leaves ethanolic extract during summer season

Exposure of rabbit bucks to summer heat stress reduces their homeostasis and semen quality leading to a temporal subfertility. The potentiality of ethanolic extract of Moringa oleifera leaves (M. oleifera ethanolic extract (MLEE)) to reduce negative impacts of heat stress on physiological and semen quality traits was investigated. A total of 28 adult V-line rabbit bucks were randomly distributed among four experimental groups of seven rabbits each. The first group received water (placebo) and served as a control (M0). The other three groups were given orally MLEE at levels of 50 (M50), 100 (M100) and 150 (M150) mg/kg BW every other day for 12 consecutive weeks during the summer season. Chemical constituents of MLEE were detected by gas chromatography/MS. During the experimental period, ambient temperature and relative humidity were recorded daily and were used to estimate temperature and humidity index. Feed intake, BW, rectal temperature were recorded and blood serum biochemical attributes were determined. Semen samples were collected weekly and were analyzed for semen quality traits. Results showed that MLEE contained high percentages of long-chain fatty acids and antioxidant agents. Feed intake and BW were not affected significantly by the treatment, however rectal temperature was decreased significantly by 0.42°C, 0.24°C and 0.40°C in the M50, M100 and M150 groups, respectively, compared with the M0 group. Treatment with 50 mg/kg BW increased concentration of serum albumin (115%; P<0.05), total antioxidant capacity (132%; P<0.05) and testosterone (160%; P=0.098) as well as seminal plasma initial fructose (127%; P=0.092) compared with the control group. Compared with the control, MLEE supplementation with 50, 100 and 150 mg/kg BW increased significantly sperm concentration by 118%, 151% and 158%, sperm progressive motility by 117%, 120% and 118%, sperm viability by 129%, 137% and 127%, sperm normal morphology by 114%, 113% and 114%, intact acrosome sperm by 109% (on average) and sperm with integrated cell membrane by 109%, 123% and 114%, respectively. In conclusion, MLEE supplementation at a level of 50 mg/kg BW could be effectively used to improve heat tolerance, oxidative status and semen quality of rabbit bucks during summer season.

Molecular mechanisms of the anti-obesity potential effect of Moringa oleifera in the experimental model

ObjectiveTo elucidate the molecular mechanisms of the potent anti-obesity effect of Moringa oleifera Lam. (M. oleifera) ethanolic extract and to clarify the link between these mechanisms and the associated metabolic and vascular risks in the experimental model of visceral obesity. MethodsM. oleifera ethanolic extract was orally administered at 600 mg/kg body weight in obese female rats daily for 12 weeks. At the end of treatment, body weight was determined, and the atherogenic index, coronary artery index, glucose level, insulin resistance status, liver and kidney functions were assessed. Also, the mRNA of leptin, adiponectin and resistin in visceral adipose tissue was determined by quantitative real time-PCR. ResultsThe results showed that M. oleifera extract down-regulated mRNA expression of leptin and resistin, while it up-regulated adiponectin gene expression in obese rats relative to untreated obese control counterparts. This amelioration of genes expression was paralleled by a reduction in body weight and improvement of the atherogenic index and coronary artery index, as well as glucose level and insulin resistance value without adverse effects on liver or kidney functions, versus the untreated obese control ones. ConclusionsIt is reasonable to assume that the anti-obesity, anti-atherogenic and anti-diabetic properties of M. oleifera are mechanistically achieved via working directly on the adipokines of the visceral adipose tissue. Therefore, M. oleifera may be a good therapeutic candidate for the symptoms of metabolic syndrome.

Anti-coccidial Activity of Moringa Oleifera Plant

Moringa Oleifera leaves were screened for its toxicological effect and some pharmacological activities in broiler chicken. Toxicological effect was studied using upgrading oral doses of 75% ethanolic extract in different groups of mice with monitoring the toxicological symptoms and mortality rate. The anti-coccidal activity of Moringa Oleifera powdered leaves for prevention and its 75% ethanolic extract for treatment of coccidiosis were studied in broilers. The obtained result proved that there were no toxicological symptoms or mortalities obtained till oral administration of 6000 mg/kg b. wt. Inclusion of Moringa olifera powder (0.5 and 1%) to broiler's feed were very efficacious and equal to diclazuril (1ppm) in preventing symptoms of coccidiosis associated with experimental infection with mixed Eimeria species. The anti-coccidal activity of Moringa Oleifera powdered leaves and its 75% ethanolic extract were studied on one-day old chicks. The experimental infected chicks with mixed Eimeria species induced severe coccidiosis in non medicated chicks and led to high mortality reached to (26.76%). Addition of 200 and 400ppm of Moringa Oleifera ethanolic extract induced marked curative effect of cocci diosis manifested by reduced mortality percent and improved PM lesion to be 13.3 and 10% respectively compared to 13.3% for group treated with the reference drug (25ppm) toltrazuril.