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Chemical structure of mangiferin (C H O ) 19 18 11
Source publication
The aim of the present study was to investigate the effects of mangiferin (1, 3, 6, 7- Tetrahydroxy-2-[3, 4, 5-trihydroxy-6-(hydroxymethyl) oxan-2-yl] xanthen-9-one), a polyphenol xanthone on multiple pharmacological screening models of Alzheimers disease (AD) viz, in vitro protection against β- amyloid induced neurotoxicity on brain cell line (Neu...
Context in source publication
Context 1
... in various angiosperms and ferns 4 . Canscora decussata 5 , Cyclopia genistoides 6 , Hypericum species 7 , Iris unguicularis 8 , Asplenium montanum 9 , Anemarrhena asphodeloides 10 , Mangifera indica 11 and many others traditional plants used by many communities as food and folklore medicine, have been reported as a source of mangiferin ( Fig. ...
Citations
... inadequate randomization and failure to specify the concentration of diluent used) or lack of control group. One study was rated as 'Definitely high risk of bias' in other bias domains because it did not conduct any statistical analysis for in vitro study and only statistically analyzed the results of the animal study [39]. Hence, this paper is excluded from the review. ...
Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer’s disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
... PCA has structural similarities with gallic acid, which is a wellknown antioxidant compound; its pharmacological activities are due to its antioxidant activities [25]. Mangiferin, a special xanthone commonly called a "super-antioxidant," is well known for its pharmacological properties as an antioxidant and antimalarial [26,27]. Kaempferol, myricetin, and rhamnetin have been found to inhibit the growth of intraerythrocytic malaria parasites [28]. ...
Background:
The search for new antimalarial drugs remains elusive prompting research into antimalarial combinations from medicinal plants due to their cheapness, efficacy and availability. Azadirachta indica (AI), Morinda lucida (ML) and Mangifera indica (MI) have all been reported as potent antimalarial plants.
Purpose:
This study evaluated the efficacy of an antimalarial combination therapeutics prepared from leaves of AI, ML and MI using in vitro, in vivo and molecular methods.
Methods:
Refined extracts of the plants combination was made by partitioning the aqueous extract of plants combinations (AI + MI, AI + ML, MI + ML, AI + MI + ML) using methanol and ethyl acetate consecutively. The resulting ethyl acetate partitioned fraction was evaluated for its antimalarial activity. Molecular docking and molecular dynamics simulation were employed to determine the possible mechanism of action of the constituent of the most active combination against four important P. falciparum proteins.
Results:
The result revealed that the refined extract from combinations AI + ML and MI + ML at 16 mg/kg bodyweight have the highest chemo-suppressive effect of 90.7% and 91.0% respectively compared to chloroquine's 100% at 10 mg/kg. Also, refined extract from MI + ML combination improved PCV levels significantly (p < 0.05) compared to controls. Molecular docking revealed oleanolic acid and ursolic acid as multiple inhibitors of plasmepsin II, hiso-aspartic protease, falcipain-2 and P. falciparum Eonyl acyl-carrier protein reductase with relative stability during 100 ns of simulation.
Conclusion:
The study unveiled the potentials of ML and MI as good candidates for antimalarial combination therapy and further established their use together as revealed in folklore medicine.
... The prophylactic effect of mangiferin in reversing these alterations in biochemical parameters is due to the antioxidant activity in sequestering free radicals and enhancing brain cellular antioxidant defence (Sandhir et al., 2010;Mahdy et al., 2014). In Alzhemier's disease (AD) in vitro model, it has been stated that mangiferin effectively suppress β-amyloid (Aβ) induced neurotoxicity on brain cell via scavenging of ROS (Sethiya and Mishra, 2014). Ample reports implicate that mangiferin possesses free radicals scavenging activity in neuroprotection was mainly ascribed to its nature of C-glucosy linkage along with the presence of polyhydroxy components (Walia et al., 2020;Liu et al., 2021). ...
Huntington’s disease (HD), a neurodegenerative disease, normally starts in the prime of adult life, followed by a gradual occurrence of psychiatric disturbances, cognitive and motor dysfunction. The daily performances and life quality of HD patients have been severely interfered by these clinical signs and symptoms until the last stage of neuronal cell death. To the best of our knowledge, no treatment is available to completely mitigate the progression of HD. Mangiferin, a naturally occurring potent glucoxilxanthone, is mainly isolated from the Mangifera indica plant. Considerable studies have confirmed the medicinal benefits of mangiferin against memory and cognitive impairment in neurodegenerative experimental models such as Alzheimer’s and Parkinson’s diseases. Therefore, this study aims to evaluate the neuroprotective effect of mangiferin against 3-nitropropionic acid (3-NP) induced HD in rat models. Adult Wistar rats (n = 32) were randomly allocated equally into four groups of eight rats each: normal control (Group I), disease control (Group II) and two treatment groups (Group III and Group IV). Treatment with mangiferin (10 and 20 mg/kg, p. o.) was given for 14 days, whereas 3-NP (15 mg/kg, i. p.) was given for 7 days to induce HD-like symptoms in rats. Rats were assessed for cognitive functions and motor coordination using open field test (OFT), novel object recognition (NOR) test, neurological assessment, rotarod and
grip strength tests. Biochemical parameters such as oxidative stress markers and pro-inflammatory markers in brain hippocampus, striatum and cortex regions were evaluated. Histopathological study on brain tissue was also conducted using hematoxylin and eosin (H&E) staining. 3-NP triggered anxiety, decreased recognition memory, reduced locomotor activity, lower neurological scoring, declined rotarod performance and grip strength were alleviated by mangiferin treatment. Further, a significant depletion in brain malondialdehyde (MDA) level, an increase in reduced glutathione (GSH) level, succinate dehydrogenase (SDH), superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in
tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) levels were observed in mangiferin treated groups. Mangiferin also mitigated 3-NP induced histopathological alteration in the brain hippocampus, striatum and cortex sections. It could be inferred that mangiferin protects the brain against oxidative damage and neuroinflammation, notably via antioxidant and antiinflammatory activities. Mangiferin, which has a good safety profile, may be an alternate treatment option for treating HD and other neurodegenerative disorders. The results of the current research of mangiferin will open up new avenues for the
development of safe and effective therapeutic agents in diminishing HD.
... The LOXI activity of each partitioned extract was determined as described (Sethiya & Mishra, 2014) with some modifications. Firstly, 220 µL of 0.2 M borate buffer pH 9.0, 30 µL of the extract in DMSO, and 250 µL of 20,000 U/mL LOX from soybean in 0.2 M borate buffer pH 9.0 were mixed and incubated at 25 • C for 5 min. ...
Background
Bee pollen (BP) is full of useful nutrients and phytochemicals.Its chemical components and bioactivities depend mainly on the type of floral pollen.
Methods
Monofloral BP from Camellia sinensis L., Mimosa diplotricha , Helianthus annuus L., Nelumbo nucifera , Xyris complanata , and Ageratum conyzoides were harvested. Crude extraction and partition were performed to yield solvent-partitioned extracts of each BP. Total phenolic content (TPC) was assayed by the Folin-Ciocalteu method, while the flavonoid content (FC) was measured by the aluminium chloride colorimetric method. Antioxidant capacity was measured by the (i) 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, (ii) 2,2’-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) scavenging activity and its Trolox equivalent antioxidant capacity (TEAC), and (iii) ferric reducing antioxidant power (FRAP). All samples were tested for lipoxygenase inhibitory (LOXI) activity. The most active sample was enriched by silica gel 60 column chromatography (SiG60-CC) and high performance liquid chromatography (HPLC), observing the chemical pattern of each fraction using thin layer chromatography. Chemical structure of the most active compound was analyzed by proton nuclear magnetic resonance and mass spectrometry.
Results
Dichloromethane (DCM)-partitioned BP extracts of H. annuus L. and M. diplotricha (DCMMBP) showed a very high TPC, while DCMMBP had the highest FC. In addition, DCMMBP had the strongest DPPH and ABTS radical scavenging activities (as a TEAC value), as well as FRAP value. Also, DCMMBP (60 µg/mL) gave the highest LOXI activity (78.60 ± 2.81%). Hence, DCMMBP was chosen for further enrichment by SiG60-CC and HPLC. Following this, the most active fraction showed higher antioxidant andLOXI activities with an EC 50 for DPPH and ABTS of 54.66 ± 3.45 µg/mL and 24.56 ± 2.99 µg/mL (with a TEAC value of 2,529.69 ± 142.16 µmole TE/g), respectively, and a FRAP value of 3,466.17 ± 81.30 µmole Fe ²⁺ /g and an IC 50 for LOXI activity of 12.11 ± 0.36 µg/mL. Triferuloyl spermidines were revealed to be the likely main active components.
Conclusions
TPC, FC, and spermidine derivatives played an important role in the antioxidant and antilipoxygenase activities in M. diplotricha bee pollen.
... 114 Mangiferin potentially acts on neurodegeneration and memory impairments often seen in neurological disorders linked with oxidative stress, inflammation, and brain-derived neurotrophic factor (BDNF) pathway. 115 Moreover, the existence of polyphenols in the structure of mangiferin supports the advantageous multifaceted effects of mangiferin to contest AD. 116 Additionally, the mangiferin administration recovers the severity of karyorrhexis formation, number of pyknotic black neurons, karyolysis, and neuronal cell death. 117 ...
Alzheimer's disease (AD), an extensive age‐associated neurodegenerative disorder. In spite of wide‐ranging progress in understanding the AD pathology for the past 50 years, clinical trials based on the hypothesis of amyloid‐beta (Aβ) have reserved worsening particularly at late‐stage human trials. Consequently, very few old drugs are presently used for AD with inadequate clinical consequences and various side effects. We focus on widespread pharmacological and beneficial principles for existing as well as future drugs. Multi‐targeting approaches by means of general antioxidant and anti‐inflammatory mechanisms allied with particular receptor and/or enzyme‐mediated actions in neuroprotection and neurodegeneration. The plant kingdom comprises a vast range of species with an incredible diversity of bioactive metabolites with diverse chemical scaffolds. In recent times, an increasing body of facts recommended the use of phytochemicals to decelerate AD's onset and progression. The definitive goal of AD investigation is to avert the onset of neurodegeneration; thereby it allows successful aging devoid of cognitive decline. At this point, we discussed the neurological protective role of natural products and naturally derived therapeutic agents for AD from various natural polyphenolic compounds and medicinal plants. In conclusion, medicinal plants act as a chief source of different bioactive constituents. This article is protected by copyright. All rights reserved
... According to Jung et al. (2009) andWightman et al. (2020), the presence of mangiferin in mango leaves extract may contribute to a significant role in the inhibition of acetylcholinesterase. An investigation by Sethiya and Mishra (2014) suggested that mangiferin is one of the promising compounds targeted for Alzheimer's disease treatment as past research finding has reported that mangiferin significantly inhibited AChE with the IC 50 value of 55.42 ± 1.52 μg/mL and protects the loss of acetylcholine. The decrease content of acetylcholine is responsible for cognitive function degradation and progression of Alzheimer's diseases. ...
Mango leaves are known to possess many health benefits but the industry only focused on mango fruit production, resulting in abundant leaves being underutilized. In this study, we managed to transform mango leaves into a new fermented drink, which has a pleasant taste through the bio-fermentation process. Different maturity levels of mango leaves were selected; premature leaves (light brown, LBML), intermediate mature leaves (light green, LGML) and mature leaves (green, ML), which were subjected to a fermentation process using bacteria and yeast. Tannin content, organic acids profile and various enzymes functionality activities (e.g. inhibition of tyrosinase, elastase and acetylcholinesterase) studies were determined on fermented mango leaves drink. The reduction of tannins content in all fermented mango leaves resulted in a less astringent taste as a consequence of the microbial action to break down tannins. Acetic, oxalic, kojic and quinic acid are some of the organic acids detected in fermented mango leaves that contributed to its slightly acidic taste. In comparison to non-fermented mango leaves, all fermented samples, particularly LBML drink showed a significant improvement (P<0.05) in tyrosinase inhibition (87.96%). Fermented mango leaves also exhibited good inhibition activity towards elastase (>80%) and acetylcholinesterase (>90%). Further histopathology examination on various rat’s organs (kidney, liver, spleen, and stomach) showed no sign of inflammation symptoms. Through limit toxicological evaluation, the safety consumption rate (IC50 value) for fermented mango leaves was 1000 mL/50 kg of human bodyweight. The improvement functionality activities of fermented mango leaves with a higher inhibition rate against tyrosinase, elastase, and acetylcholinesterase indicate its great potential as a food remedy for anti-ageing treatment.
... In studies, it has exhibited cytoprotective effects [540]. In addition, the compound reversed the amnesia and learning impairment induced by scopolamine in rats, and it showed anticholinesterase and antioxidant activities [541,542]. The compound also was characterized by low toxicity. ...
Acetylcholinesterase (AChE) plays an important role in the pathogenesis of neurodegenerative diseases by influencing the inflammatory response, apoptosis, oxidative stress and aggregation of pathological proteins. There is a search for new compounds that can prevent the occurrence of neurodegenerative diseases and slow down their course. The aim of this review is to present the role of AChE in the pathomechanism of neurodegenerative diseases. In addition, this review aims to reveal the benefits of using AChE inhibitors to treat these diseases. The selected new AChE inhibitors were also assessed in terms of their potential use in the described disease entities. Designing and searching for new drugs targeting AChE may in the future allow the discovery of therapies that will be effective in the treatment of neurodegenerative diseases.
... The importance of this compound lies in its potential for the treatment of neurodegenerative diseases in cellular and animal models, together with its high antioxidant activity and the ability to scavenge hydroxyl radicals. In addition, it reports an important effect on β-amyloid peptide activity and the ability to inhibit acetylcholinesterase (AChE) and lipooxygenase (LOX) enzymes [3]. ...
... The inhibition of the AChE enzyme by the compound mangiferin is quite sign obtaining a value for IC50 of 55.42 ± 1.52 μg/mL in comparison to galantamine, pound used as a standard in AChE assays (IC50: 5.543 ± 0.213 μg/mL). Therefore, its is considered potential to prevent the loss of the neurotransmitter acetylcholine in t gression of Alzheimer's disease [3]. ...
... Regarding the LOX enzyme, mangiferin has presented inhibition results for I 42.28 ± 0.63 μg/mL, which is significant, compared to the routine standard (IC50 0.18 μg/mL). It should be noted that LOX is a key enzyme in inflammatory proces sponsible for the production of leukotrienes and other inflammatory mediators [3] As an antioxidant agent, mangiferin has shown an IC50 value in the DPPH m of 18.50 ± 0.18 μg/mL [3]. This activity corroborates the neuroprotective action of th pound through the pathway of reducing H₂O₂-induced oxidative damage [4]. ...
The genus Asplenium L. comprises about 700 species of terrestrial, epiphytic, and saxicolous habits distributed in temperate and tropical regions around the world, exhibiting a high chemical richness with variable biological activity. In this review, compounds with antioxidant activity that constitute a pharmacological potential in diseases of the central nervous system are detailed. Asplenium nidus L. species presents a high concentration of phenols and flavonoids evidenced by antioxidant activity assays, such as DPPH, FRAP, total phenols, total flavonoids, and ORAC, and represent compounds with bioactive potential, including neuroprotection. The species Asplenium adiantum-nigrum L. presents a high antioxidant potential of its rhizome extracts exhibited in DPPH and ABTS assays, attributed to the high concentration of mangiferin. the xanthone mangiferin is a compound also present in other species of genera, such as Asplenium ceterach L. and Asplenium montanum Willd., in significant amounts. This xanthone has studies on its neuroprotective effect through different targets, some of them being the acetylcholinesterase enzymes, the 5-lipooxygenase enzyme, and the antioxidant activity itself. All these mechanisms of action of mangiferin constitute an object of study for its effect on memory loss, which can be relayed in Alzheimer’s disease.
... En el presente trabajo se utilizó como compuesto de comparación a la mangiferina (1,3,6,7-Tetrahydroxyxantona-C2-β-D-glucósido), debido a que posee una significativa actividad biológica relacionada con la captación de radicales libres, (28) así como la inhibición del estrés oxidativo (29) y la actividad de la enzima 5-LOX. (30) La estructura tridimensional, correspondiente a la difracción de rayos X del cristal ...
Introducción:
Los hongos comestibles, en particular Pleurotus ostreatus, representan una importante fuente de metabolitos bioactivos con propiedades inmunomoduladoras, antioxidantes y antiinflamatorias. Trabajos recientes han demostrado que extractos y compuestos purificados a partir de esta seta, entre ellos, la fracción rica en fenoles, inhiben el factor nuclear kappa B(NF-κB), la cicloxigenasa (COX) y modulan cascadas de señalización relacionadas con el balance redox. De acuerdo con estos antecedentes, dichos compuestos podrían actuar, además, como inhibidores de la enzima 5- lipoxigenasa (5-LOX).
Objetivo:
Evaluar el efecto in silico de trece compuestos fenólicos presentes en la especie Pleurotus ostreatus sobre la enzima 5-LOX, al utilizar como compuesto de referencia la mangiferina.
Métodos:
El acoplamiento se llevó a cabo a través del programa AutoDock 4.2 (http://autodock.scripps.edu) y la estructura de 5 LOX se obtuvo con la base de datos de proteínas, PDB (www.wwpdb.org). Se estimaron la energía libre (ΔG), la constante de disociación (Ki) y la eficiencia de ligando (LE). Se obtuvieron los parámetros de similitud a un fármaco y los relacionados con la absorción, distribución, metabolismo, excreción y toxicidad (ADME/T) de los mejores modelos de acoplamiento.
Resultados:
Los mejores indicadores de ΔG y Ki, correspondieron a los ácidos homogentísico, clorogénico y gentísico, con valores de ΔG (-11,81; -12,28 y -11,67 kcal/moL) y Ki (2,19 10⁻⁹; 9,99 10⁻¹⁰, 2,79 10⁻⁹ M), respectivamente. La eficiencia de ligando alcanzó valores adecuados para estos tres compuestos fenólicos. El modelo de acoplamiento del ácido homogentísico mostró los mejores resultados en cuanto a la similitud a un fármaco y pruebas ADME/T.
Conclusiones:
El estudio in silico reveló las potencialidades de la fracción rica en fenoles de P. ostreatus, y en particular, del ácido homogentísico como inhibidor de la enzima 5 -LOX, y justifica el desarrollo de ensayos confirmativos in vitro/ in vivo que corroboren sus efectos antioxidantes y antinflamatorios.
... Three studies investigated on scopolamine-induced memory deficits (Biradar et al., 2012;Jung et al., 2009;Sethiya and Mishra, 2014) while another two employed aging mice (Biradar et al., 2012;Du et al., 2019). On the other hand, Feng et al. (2017) conducted sleep deprivation (SD)-induced MI while Infante-Garcia et al. (2017) employed amyloid precursor protein/ presenilin 1 (APP/PS1) double transgenic mouse models to investigate the efficacy of mangiferin in cognitive deficits due to Alzheimer's disease. ...
... Mounting evidence confirmed the degeneration of cholinergic neurons in AD patients. Sethiya and Mishra (2014) treated male Sprague-Dawley rats with mangiferin (50 and 100 mg/kg), p.o. whereas in the study by Jung et al. (2009), male ICR swiss albino mice were given mangiferin (10, 20 and 40 mg/kg), p.o. for 14 days. Both findings confirmed the potent effect of mangiferin in reversing the scopolamine-induced cognitive deficits by 1) significant reduction of escape latency, 2) increasing the number of crossing over the platform in MWM and 3) increasing the step-through latency in PAT. ...
Memory impairment (MI) is one of the predominant criteria generally used to identify schizophrenia, dementia and amnesia that are associated with neurodegenerative disorders by evaluating patient’s cognitive symptoms. To date, there is no available treatment that can completely mitigate MI. Currently, there is a trend in recent investigations towards symptomatic therapy approaches using a variety of natural compounds. Mangiferin is one of them that have been investigated extensively. Mangiferin is a naturally occurring potent glucoxilxanthone and is mainly isolated from the Mangifera indica (Mango) plant. This review is aimed at providing a comprehensive overview on the efficacy of mangiferin on MI, based on in-vivo animal studies. After screening through articles identified from Scopus and PubMed based on the inclusion and exclusion criteria, a total of 11 articles between 2009 and 2019 were included. The minimum and maximum dose of mangiferin were 10 and 200 mg/kg respectively and administered over the period of 12–154 days. The results of 11 articles showed that mangiferin effectively improved spatial recognition, episodic aversive events, short- and long-term memories primarily occurring via its antioxidant and anti-inflammatory effects. The outcomes of the review revealed that mangiferin improves memory and cognitive impairment in different animal models, indicating that it has potential preventive and therapeutic roles in MI.
