Network Pharmacology and Molecular Docking Reveal the Antioxidant
Potential of Mangiferin from Mango Peel

Guangjie      Zhang; Peiyu      Xue; Hongmei      Zhao; Tianzhu      Guan; Zheng      Ma

doi:10.2174/1570180820666230403090658

Abstract

Background: As one of the main by-products of mango production, the mango peel is rich in multiple polyphenols, such as mangiferin. Therefore, there is an urgent need to explore the potential mechanism of mangiferin for nutrition intervention of oxidative stress-related diseases.

Methods: Mangiferin was extracted and purified from the mango peel and was identified by the reverse phase high-performance liquid chromatography. The antioxidant potential of mangiferin was determined in vitro (potassium ferricyanide reducing capacity, DPPH, hydroxyl radicals scavenging ability, and superoxide anion radicals reducing capacity). In order to explore the potential mechanism for the antioxidant activity of mangiferin, a combination of network pharmacology and molecular docking approaches was performed.

Results: The purity of mangiferin from the mango peel was ≥ 95.0%, and its antioxidant activity was confirmed by different in vitro assays. ALB, ESR1, CASP8, CASP3, BCL2L1, CXCL8, AKT1, CTNNB, and EGFR were identified as the potential oxidative stress-related targets of mangiferin. These results suggested that mangiferin might play a key role in the antioxidant process through multi-targets.

Conclusion: Integrated with network pharmacology and molecular docking methods, this work demonstrated the potential mechanism of mangiferin for nutrition intervention of oxidative stress-related diseases.

Keywords: Mango peel, mangiferin, antioxidant potential, network pharmacology, molecular docking, RP-HPLC.

« Previous Next »

[1]
Marçal, S.; Pintado, M. Mango peels as food ingredient / additive: Nutritional value, processing, safety and applications. Trends Food Sci. Technol.,  2021, 114, 472-489.
 [http://dx.doi.org/10.1016/j.tifs.2021.06.012]

[2]
Hu, K.; Dars, A.G.; Liu, Q.; Xie, B.; Sun, Z. Phytochemical profiling of the ripening of Chinese mango (Mangifera indica L.) cultivars by real-time monitoring using UPLC-ESI-QTOF-MS and its potential benefits as prebiotic ingredients. Food Chem.,  2018, 256, 171-180.
 [http://dx.doi.org/10.1016/j.foodchem.2018.02.014] [PMID:  29606434]

[3]
Parniakov, O.; Barba, F.J.; Grimi, N.; Lebovka, N.; Vorobiev, E. Extraction assisted by pulsed electric energy as a potential tool for green and sustainable recovery of nutritionally valuable compounds from mango peels. Food Chem.,  2016, 192, 842-848.
 [http://dx.doi.org/10.1016/j.foodchem.2015.07.096] [PMID:  26304419]

[4]
Wu, J.Y.; Ding, H.Y.; Wang, T.Y.; Tsai, Y.L.; Ting, H.J.; Chang, T.S. Improving aqueous solubility of natural antioxidant mangiferin through glycosylation by maltogenic amylase from Parageobacillus galactosidasius DSM 18751. Antioxidants,  2021, 10(11), 1817.
 [http://dx.doi.org/10.3390/antiox10111817] [PMID:  34829688]

[5]
Amrouche, T.A.; Yang, X.; Capanoglu, E.; Huang, W.; Chen, Q.; Wu, L.; Zhu, Y.; Liu, Y.; Wang, Y.; Lu, B. Contribution of edible flowers to the Mediterranean diet: Phytonutrients, bioactivity evaluation and applications. Food Front.,  2022, 3(4), 592-630.
 [http://dx.doi.org/10.1002/fft2.142]

[6]
Ma, Y.; Liu, Y.; Ma, Y.; Jiang, N.; Wang, L.; Wang, B.; Niu, W.; Hu, Y.; Lin, Q.; Yu, B. Mangiferin relieves lipopolysaccharide-induced injury by up-regulating miR-181a via targeting PTEN in ATDC5 cells. Front. Pharmacol.,  2020, 11, 137.
 [http://dx.doi.org/10.3389/fphar.2020.00137] [PMID:  32210798]

[7]
Ullah, H.; Khan, A.; Daglia, M. The focus on foods for special medical purposes and food supplements in age‐related disorders. Food Front.,  2022, 3(3), 353-357.
 [http://dx.doi.org/10.1002/fft2.163]

[8]
Zou, H.; Ye, H.; Zhang, J.; Ren, L. Recent advances in nuclear receptors-mediated health benefits of blueberry. Phytomedicine,  2022, 100, 154063.
 [http://dx.doi.org/10.1016/j.phymed.2022.154063] [PMID:  35344717]

[9]
Zhang, J.; Zhao, J.; Sun, Y.; Liang, Y.; Zhao, J.; Zou, H.; Zhang, T.; Ren, L. GR-mediated anti-inflammation of α-boswellic acid: Insights from in vitro and in silico studies. Food Chem. Toxicol.,  2021, 155, 112379.
 [http://dx.doi.org/10.1016/j.fct.2021.112379] [PMID:  34197882]

[10]
Ansary, J.; Regolo, L.; Machì, M.; Salinari, A.; Cianciosi, D. Evaluation of the in vitro bioaccessibility of phenolic compounds of black cumin (BARI‐1cumin) methanolic extract. eFood,  2022, 3(3), e15.
 [http://dx.doi.org/10.1002/efd2.15]

[11]
An, L.; Feng, F. Network pharmacology-based antioxidant effect study of zhi-zi-da-huang decoction for alcoholic liver disease. Evid. Based Complement. Alternat. Med.,  2015, 2015, 1-6.
 [http://dx.doi.org/10.1155/2015/492470] [PMID:  25922610]

[12]
Zhang, Y.; Wu, X.; Wang, X.; Zeng, Y.; Liao, Y.; Zhang, R.; Zhai, F.; Zeng, Z. Grey relational analysis combined with network pharmacology to identify antioxidant components and uncover its mechanism from Moutan Cortex. Front. Pharmacol.,  2021, 12, 748501.
 [http://dx.doi.org/10.3389/fphar.2021.748501] [PMID:  34690779]

[13]
Cui, S.; Chen, S.; Wu, Q.; Chen, T.; Li, S. A network pharmacology approach to investigate the anti-inflammatory mechanism of effective ingredients from Salvia miltiorrhiza. Int. Immunopharmacol.,  2020, 81, 106040.
 [http://dx.doi.org/10.1016/j.intimp.2019.106040] [PMID:  31818704]

[14]
Zhang, J.; Pavek, P.; Kamaraj, R.; Ren, L.; Zhang, T. Dietary phytochemicals as modulators of human pregnane X receptor. Crit. Rev. Food Sci. Nutr.,  2021, 1-23. (EPub a had of print)
 [http://dx.doi.org/10.1080/10408398.2021.1995322] [PMID: 34698593]

[15]
Zhao, J.; Sun, Y.; Yuan, C.; Li, T.; Liang, Y.; Zou, H.; Zhang, J.; Ren, L. Quercetin ameliorates hepatic fat accumulation in high-fat diet-induced obese mice via PPARs. Food Funct.,  2023, 14(3), 1674-1684.
 [http://dx.doi.org/10.1039/D2FO03013F] [PMID:  36691903]

[16]
Zou, H.; Ye, H.; Kamaraj, R.; Zhang, T.; Zhang, J.; Pavek, P. A review on pharmacological activities and synergistic effect of quercetin with small molecule agents. Phytomedicine,  2021, 92, 153736.
 [http://dx.doi.org/10.1016/j.phymed.2021.153736] [PMID:  34560520]

[17]
Higbee, J.; Solverson, P.; Zhu, M.; Carbonero, F. The emerging role of dark berry polyphenols in human health and nutrition. Food Front.,  2022, 3(1), 3-27.
 [http://dx.doi.org/10.1002/fft2.128]

[18]
Ruiz-Montañez, G.; Ragazzo-Sánchez, J.A.; Calderón-Santoyo, M. Velázquez-de la, C.G.; Ramírez de, L.J.A.; Navarro-Ocaña, A. Evaluation of extraction methods for preparative scale obtention of mangiferin and lupeol from mango peels (Mangifera indica L.). Food Chem.,  2014, 159, 267-272.
 [http://dx.doi.org/10.1016/j.foodchem.2014.03.009] [PMID:  24767054]

[19]
Huang, X.; Ai, C.; Yao, H.; Zhao, C.; Xiang, C.; Hong, T.; Xiao, J. Guideline for the extraction, isolation, purification, and structural characterization of polysaccharides from natural resources. eFood,  2022, 3(6), e37.
 [http://dx.doi.org/10.1002/efd2.37]

[20]
Lerma-Torres, J.M.; Navarro-Ocaña, A.; Calderón-Santoyo, M.; Hernández-Vázquez, L.; Ruiz-Montañez, G.; Ragazzo-Sánchez, J.A. Preparative scale extraction of mangiferin and lupeol from mango (Mangifera indica L.) leaves and bark by different extraction methods. J. Food Sci. Technol.,  2019, 56(10), 4625-4631.
 [http://dx.doi.org/10.1007/s13197-019-03909-0] [PMID:  31686694]

[21]
Loan, N.T.T.; Long, D.T.; Yen, P.N.D.; Hanh, T.T.M.; Pham, T.N.; Pham, D.T.N. Purification process of mangiferin from Mangifera indica L. leaves and evaluation of its bioactivities. Processes,  2021, 9(5), 852.
 [http://dx.doi.org/10.3390/pr9050852]

[22]
Schieber, A.; Berardini, N.; Carle, R. Identification of flavonol and xanthone glycosides from mango (Mangifera indica L. Cv. “Tommy Atkins”) peels by high-performance liquid chromatography-electrospray ionization mass spectrometry. J. Agric. Food Chem.,  2003, 51(17), 5006-5011.
 [http://dx.doi.org/10.1021/jf030218f] [PMID:  12903961]

[23]
Zhu, F.; Li, J.; Ma, Z.; Li, J.; Du, B. Structural identification and in vitro antioxidant activities of anthocyanins in black chokeberry (Aronia melanocarpa lliot). eFood,  2021, 2(4), 201-208.
 [http://dx.doi.org/10.53365/efood.k/143829]

[24]
Zeng, C.; Luo, S.; Feng, S.; Chen, T.; Zhou, L.; Yuan, M.; Huang, Y.; Liao, J.; Ding, C. Phenolic composition, antioxidant and anticancer potentials of extracts from Rosa banksiae Ait. flowers. Molecules,  2020, 25(13), 3068.
 [http://dx.doi.org/10.3390/molecules25133068] [PMID:  32640514]

[25]
Singh, R.P.; Chidambara Murthy, K.N.; Jayaprakasha, G.K. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J. Agric. Food Chem.,  2002, 50(1), 81-86.
 [http://dx.doi.org/10.1021/jf010865b] [PMID:  11754547]

[26]
Zhao, G.; Xiang, Z.; Ye, T.; Yuan, Y.; Guo, Z. Antioxidant activities of Salvia miltiorrhiza and Panax notoginseng. Food Chem.,  2006, 99(4), 767-774.
 [http://dx.doi.org/10.1016/j.foodchem.2005.09.002]

[27]
Qu, Y.; Li, C.; Zhang, C.; Zeng, R.; Fu, C. Optimization of infrared-assisted extraction of Bletilla striata polysaccharides based on response surface methodology and their antioxidant activities. Carbohydr. Polym.,  2016, 148, 345-353.
 [http://dx.doi.org/10.1016/j.carbpol.2016.04.081] [PMID:  27185148]

[28]
Leng, Y.; Ren, L.; Niu, S.; Zhang, T.; Zhang, J. In vitro and in silico investigations of endocrine disruption induced by metabolites of plasticizers through glucocorticoid receptor. Food Chem. Toxicol.,  2021, 155, 112413.
 [http://dx.doi.org/10.1016/j.fct.2021.112413] [PMID:  34273429]

[29]
Ren, L.; Niu, S.; Sun, Y.; Liang, Y.; Zhao, J.; Zhang, T.; Zhang, J. Anti-inflammatory action of betulin and its potential as a dissociated glucocorticoid receptor modulator. Food Chem. Toxicol.,  2021, 157, 112539.
 [http://dx.doi.org/10.1016/j.fct.2021.112539] [PMID:  34500009]

[30]
Liang, Y.; Zhang, T.; Zhao, J.; Li, C.; Zou, H.; Li, F.; Zhang, J.; Ren, L. Glucocorticoid receptor-mediated alleviation of inflammation by berberine: In vitro, in silico and in vivo investigations. Food Funct.,  2021, 12(23), 11974-11986.
 [http://dx.doi.org/10.1039/D1FO01612A] [PMID:  34747965]

[31]
Ren, L.; Zhang, J.; Zhang, T. Immunomodulatory activities of polysaccharides from Ganoderma on immune effector cells. Food Chem.,  2021, 340, 127933.
 [http://dx.doi.org/10.1016/j.foodchem.2020.127933] [PMID:  32882476]

[32]
Fernández-Ponce, M.T.; Casas, L.; Mantell, C.; Martínez de la Ossa, E. Use of high pressure techniques to produce Mangifera indica L. leaf extracts enriched in potent antioxidant phenolic compounds. Innov. Food Sci. Emerg. Technol.,  2015, 29, 94-106.
 [http://dx.doi.org/10.1016/j.ifset.2015.04.006]

[33]
Moayedi, A.; Hashemi, M.; Safari, M. Valorization of tomato waste proteins through production of antioxidant and antibacterial hydrolysates by proteolytic Bacillus subtilis: Optimization of fermentation conditions. J. Food Sci. Technol.,  2016, 53(1), 391-400.
 [http://dx.doi.org/10.1007/s13197-015-1965-2] [PMID:  26787958]

[34]
Saha, S.; Sadhukhan, P.; Sinha, K.; Agarwal, N.; Sil, P.C. Mangiferin attenuates oxidative stress induced renal cell damage through activation of PI3K induced Akt and Nrf-2 mediated signaling pathways. Biochem. Biophys. Rep.,  2016, 5, 313-327.
 [http://dx.doi.org/10.1016/j.bbrep.2016.01.011] [PMID:  28955838]

[35]
Morales, M.; Zapata, K.; Sagaste, C.A.; Angulo, A.A.; Rojano, B. Optimization of the ultrasound-assisted extraction of polyphenol, mangiferin, and its antioxidant expressionin mango peel (Mangifera indica) using response surface methodology. Acta Sci. Pol. Technol. Aliment.,  2020, 19(1), 5-14.
 [PMID: 32227693]

[36]
Wang, L.; Lin, J.; Li, W. Pharmacological mechanism of danggui-sini formula for intervertebral disc degeneration: A network pharmacology study. BioMed Res. Int.,  2021, 2021, 1-12.
 [http://dx.doi.org/10.1155/2021/5165075] [PMID:  34805401]

[37]
Sundarrajan, S.; Lulu, S.; Arumugam, M. Deciphering the mechanism of action of wrightia tinctoria for psoriasis based on systems pharmacology approach. J. Altern. Complement. Med.,  2017, 23(11), 866-878.
 [http://dx.doi.org/10.1089/acm.2016.0248] [PMID:  28604055]

[38]
Dennis, G., Jr; Sherman, B.T.; Hosack, D.A.; Yang, J.; Gao, W.; Lane, H.C.; Lempicki, R.A. DAVID: Database for annotation, visualization, and integrated discovery. Genome Biol.,  2003, 4(5), P3.
 [http://dx.doi.org/10.1186/gb-2003-4-5-p3] [PMID:  12734009]

[39]
Roncaglia, P.; Martone, M.E.; Hill, D.P.; Berardini, T.Z.; Foulger, R.E.; Imam, F.T.; Drabkin, H.; Mungall, C.J.; Lomax, J. The gene ontology (GO) cellular component ontology: Integration with SAO (Subcellular Anatomy Ontology) and other recent developments. J. Biomed. Semantics,  2013, 4(1), 20.
 [http://dx.doi.org/10.1186/2041-1480-4-20] [PMID:  24093723]

[40]
Qiao, B.; He, Y.; Gao, X.; Liu, H.; Rao, G.; Su, Q.; Ruan, Z.; Tang, Z.; Hu, L. Curcumin attenuates AFB1-induced duck liver injury by inhibiting oxidative stress and lysosomal damage. Food Chem. Toxicol.,  2023, 172, 113593.
 [http://dx.doi.org/10.1016/j.fct.2022.113593] [PMID:  36596445]

[41]
Qiu, W.; Zhang, X.; Pang, X.; Huang, J.; Zhou, S.; Wang, R.; Tang, Z.; Su, R. Asiatic acid alleviates LPS-induced acute kidney injury in broilers by inhibiting oxidative stress and ferroptosis via activation of the Nrf2 pathway. Food Chem. Toxicol.,  2022, 170, 113468.
 [http://dx.doi.org/10.1016/j.fct.2022.113468] [PMID:  36244460]

[42]
Xia, J.; Hu, J.; Zhang, R.; Liu, W.; Zhang, H.; Wang, Z.; Jiang, S.; Wang, Y.; Li, W. Icariin exhibits protective effects on cisplatin-induced cardiotoxicity via ROS-mediated oxidative stress injury in vivo and in vitro. Phytomedicine,  2022, 104, 154331.
 [http://dx.doi.org/10.1016/j.phymed.2022.154331] [PMID:  35878553]

[43]
Yu, T.; He, Y.; Chen, H.; Lu, X.; Ni, H.; Ma, Y.; Chen, Y.; Li, C.; Cao, R.; Ma, L. Li; Lei, Y.; Luo, X.; Zheng, C. Polysaccharide from Echinacea purpurea plant ameliorates oxidative stress-induced liver injury by promoting Parkin-dependent autophagy. Phytomedicine,  2022, 104, 154311.
 [http://dx.doi.org/10.1016/j.phymed.2022.154311] [PMID:  35843188]

[44]
Graiet, I.; Hamdi, H.; Abid-Essefi, S.; Eyer, J. Fludioxonil, a phenylpyrrol pesticide, induces Cytoskeleton disruption, DNA damage and apoptosis via oxidative stress on rat glioma cells. Food Chem. Toxicol.,  2022, 170, 113464.
 [http://dx.doi.org/10.1016/j.fct.2022.113464] [PMID:  36228901]

[45]
Wang, Y.F.; Chang, Y.; Zhang, X.; Gao, M.T.; Zhang, Q.; Li, X.; Zhang, L.; Yao, W.F. Salidroside protects against osteoporosis in ovariectomized rats by inhibiting oxidative stress and promoting osteogenesis via Nrf2 activation. Phytomedicine,  2022, 99, 154020.
 [http://dx.doi.org/10.1016/j.phymed.2022.154020] [PMID:  35278902]

[46]
Gao, Y.; Bian, C.; Li, N.; Yao, K.; Xiao, L.; Yang, Z.; Guan, T. Exploring the binding mechanism and adverse toxic effects of chiral phenothrin to human serum albumin: Based on multi-spectroscopy, biochemical and computational approach. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2022, 282, 121659.
 [http://dx.doi.org/10.1016/j.saa.2022.121659] [PMID:  35930945]

[47]
Guan, T-Z.; Bian, C-F.; Li, N.; Gao, Y.; Ren, C-X.; Zheng, X-F.; Hang, S-J.; Li, Q.; Yang, Z-Q.; Min, E-H. Molecular mechanism of Guihuang traditional drink in prevention of thrombotic diseases explored through network pharmacology, quantum chemical calculation, and molecular docking-based strategy. Chin. J. Anal. Chem.,  2023, 51(2), 100216.
 [http://dx.doi.org/10.1016/j.cjac.2022.100216]

[48]
Zhang, T.; Zhong, S.; Li, T.; Zhang, J. Saponins as modulators of nuclear receptors. Crit. Rev. Food Sci. Nutr.,  2020, 60(1), 94-107.
 [http://dx.doi.org/10.1080/10408398.2018.1514580] [PMID:  30582348]

[49]
Bernardi, M.; Ricci, C.S.; Zaccherini, G. Role of human albumin in the management of complications of liver cirrhosis. J. Clin. Exp. Hepatol.,  2014, 4(4), 302-311.
 [http://dx.doi.org/10.1016/j.jceh.2014.08.007] [PMID:  25755577]

[50]
Kinoshita, H.; Watanabe, K.; Azma, T.; Feng, G.G.; Akahori, T.; Hayashi, H.; Sato, M.; Fujiwara, Y.; Wakatsuki, A. Human serum albumin and oxidative stress in preeclamptic women and the mechanism of albumin for stress reduction. Heliyon,  2017, 3(8), e00369.
 [http://dx.doi.org/10.1016/j.heliyon.2017.e00369] [PMID:  28808694]

[51]
Zhu, H.; Zhang, L.; Jia, H.; Xu, L.; Cao, Y.; Zhai, M.; Li, K.; Xia, L.; Jiang, L.; Li, X.; Zhou, Y.; Liu, J.; Yu, S.; Duan, W. Tetrahydrocurcumin improves lipopolysaccharide-induced myocardial dysfunction by inhibiting oxidative stress and inflammation via JNK/ERK signaling pathway regulation. Phytomedicine,  2022, 104, 154283.
 [http://dx.doi.org/10.1016/j.phymed.2022.154283] [PMID:  35779282]

[52]
Wang, S.; Han, Q.; Wei, Z.; Wang, Y.; Xie, J.; Chen, M. Polystyrene microplastics affect learning and memory in mice by inducing oxidative stress and decreasing the level of acetylcholine. Food Chem. Toxicol.,  2022, 162, 112904.
 [http://dx.doi.org/10.1016/j.fct.2022.112904] [PMID:  35257813]

[53]
Shafiey, S.I.; Abo-Saif, A.A.; Abo-Youssef, A.M.; Mohamed, W.R. Protective effects of rivaroxaban against cisplatin-induced testicular damage in rats: Impact on oxidative stress, coagulation, and p–NF–κB/VCAM-1 signaling. Food Chem. Toxicol.,  2022, 169, 113419.
 [http://dx.doi.org/10.1016/j.fct.2022.113419] [PMID:  36122812]

[54]
Julien, O.; Wells, J.A. Caspases and their substrates. Cell Death Differ.,  2017, 24(8), 1380-1389.
 [http://dx.doi.org/10.1038/cdd.2017.44] [PMID:  28498362]

[55]
Kang, R.; Li, R.; Dai, P.; Li, Z.; Li, Y.; Li, C. Deoxynivalenol induced apoptosis and inflammation of IPEC-J2 cells by promoting ROS production. Environ. Pollut.,  2019, 251, 689-698.
 [http://dx.doi.org/10.1016/j.envpol.2019.05.026] [PMID:  31108302]

Rights & Permissions Print Cite

Article Metrics

26

2

Journal Information

For Authors

For Editors

For Reviewers

Explore Articles

Open Access

Open Access Articles

For Visitors

DOI https://dx.doi.org/10.2174/1570180820666230403090658	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X

Letters in Drug Design & Discovery

Network Pharmacology and Molecular Docking Reveal the Antioxidant Potential of Mangiferin from Mango Peel

Abstract

Related Journals

Related Books

Related Articles