• SAURABH YADAV Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra, India.
  • MUKTI SHARMA Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra, India.
  • NARAYANAN GANESH Jawaharlal Nehru Cancer Hospital and Research Center, Bhopal, India.
  • SHALINI SRIVASTAVA Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra, India.
  • M. M. SRIVASTAVA Department of Chemistry, Dayalbagh Educational Institute, Dayalbagh, Agra, India.


Objective: Unexplored in-vivo anti-melanoma bio-efficacy of the plant Madhuca longifolia (bark) has been carried out against C57BL/6 mice.

Methods: Optimized experimental conditions of phytofabrication of gold nanoparticles were as follows: flavonoid content (1 ml, 0.5 mg/ml), sodium tetrachloroaurate dihydrate solution (2 ml, 1 mM), and sonication (15 min, 20 KHz) at pH 4. The optical properties; ultraviolet-visible spectrophotometer (UV-Vis), particles size and zeta potential (Zetasizer), miller indices; X-ray diffraction (XRD), morphology; field emission-scanning electron microscope (FE-SEM), particle size; high resolution-transmission electron microscopy (HR-TEM), surface roughness; atomic force microscopy (AFM) and elemental composition; and energy dispersive X-rays (EDX) of flavonoid loaded gold nanoparticles. In-vivo anti-melanoma bio-efficacy has been carried out against C57BL mice. Radioisotopic, hematological, and histopathological studies were carried out using standard procedures.

Results: Redox potential of the total flavonoid extracted from the bark of the plant (Madhuca longifolia) has been used for the fabrication of flavonoid loaded gold nanoparticles (F@AuNp) and confirmed for the first time their significant anti-melanoma bio-efficacy. The finding is supported by hematological and histopathological studies carried out in the organs (liver, kidney, and intestine) of C57BL mice. The significant enhancement in phytofabricated F@AuNp compared to native bark extract of the plant has been assigned to enhanced stay period and nanosizing, biocompatibility, nontoxic nature, and enhanced beneficial payload to the cancerous cells.

Conclusion: Such phytofabricated gold nanoparticles possess an admirable prospect for the expansion of herbal nanomedicine for anti-melanoma bio-efficacy.

Keywords: Madhuca longifolia, Flavonoid, Gold nanoparticles, Enhanced bio-efficacy


1. Jiang TL, Salmon SE, Liu RM. Activity of camptothecin, harriangtonin, cantharidin and curcumae in the human tumor stem cell assay. Eur J Cancer Clin Oncol 1983;19:263-70.
2. Cragg GM, Schepartz SA, Suffness M, Grever MR. The taxol supply crisis. New policies for handling the large-scale production of novel natural product anticancer and anti-hiv agents. J Nat Prod 1993;56:1657-68.
3. Maryam M, Go R, Yien CY, Nazer M. Vinka alkaloids. Int J Prev Med 2013;4:1231-5.
4. Sznarkowska A, Kostecka A, Meller K, Bielawski KP. Inhibition of cancer antioxidant defence by natural compounds. Oncotarget 2017;8:15996-16.
5. Acharya A, Das I, Chandhok D, Saha T. Redox regulation in cancer a double-edged sword with therapeutic potential. Oxid Med Cell Longev 2010;3:23-34.
6. Kumari A, Kumar V, Yadav SK. Nanotechnology: A tool to enhance therapeutic values of natural plant products. Trends Med Res 2012;7:34-42.
7. Khan T, Gurav P. Phytonanotechnology: Enhancing delivery of plant based anti-cancer drugs. Front Pharmacol 2018;8:1-14.
8. Silva CO, Pinho JO, Lop JM. Review current trends in cancer nanotheranostics: Metallic, polymeric, and lipid-based systems. Pharmaceutics 2019;11:1-40.
9. Brown SD, Nativo P, Smith JA, Stirling D, Edwards PR, Venugopal B, et al. Gold nanoparticles for the improved anticancer drug delivery of the active component of oxaliplatin. J Am Chem Soc 2010;132:4678-84.
10. Cabuzu D, Ciraj A, Puiu R, Grumezescu AM. Biomedical applications of gold nanoparticles. Curr Top Med Chem 2015;15:1605-13.
11. Venkatachalam P, Sangeetha P, Geetha N, Sahi SV. Phyto-fabrication of bioactive molecules encapsulated metallic silver nanoparticles from Cucumis sativus L. and its enhanced wound healing potential in rat model. J Nanomater 2015;2015:1-9.
12. Ahmed S, Ahmad M, Swami BL, Ikram SA. Review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: A green expertise. J Adv Res 2016;7:17-28.
13. Chung IM, Park I, Seung-Hyun K, Thiruvengadam M, Rajakumar G. Plant-mediated synthesis of silver nanoparticles: Their characteristic properties and therapeutic applications. Nanoscale Res Lett 2016;11:1-14.
14. Gholipourmalekabai M, Mobaraki M, Ghaffari M, Zarebkohan A, Omrani VF, Urbanska AM, et al. Targeted drug delivery based on gold nanoparticles derivatives. Curr Pharm Des 2017;23:2918-29.
15. Vijayaraghavan K, Ashokkumar T. Plant-mediated biosynthesis of metallic nanoparticles: A review of literature, factors affecting synthesis, characterization techniques and applications. J Environ Chem Eng 2017;5:4866-83.
16. Du Y, Long X, Ami J, Richey MD, Philippe B, Marion FE, et al. Synthesis and evaluation of doxorubicin-loaded gold nanoparticles for tumor-targeted drug delivery. Bioconjug Chem 2018;29:420-30.
17. Ebrahiminezhad A, Zare-Hoseinabadi A, Sarmah AK, Taghizadeh S, Ghasemi Y, Berenjian A. Plant mediated synthesis and applications of iron nanoparticles. Mol Biotechnol 2018;60:154-68.
18. Burlacu E, Tanase C, Coman NA, Berta L. A review of bark-extract-mediated green synthesis of metallic nanoparticles and their applications. Molecules 2019;24:1-18.
19. Ahmad S, Munir S, Zeb N, Ullah A, Khan B, Ali J, et al. Green nanotechnology: A review on green synthesis of silver nanoparticles-an eco-friendly approach. Int J Nanomedicine 2019;14:5087-107.
20. Lee KX, Shameli K, Teow SY, Jahangirian H, Moghaddam RR, Webster TJ. Recent developments in the facile bio-synthesis of gold nanoparticles (AuNPs) and their biomedical applications. Int J Nanomedicine 2020;15:275-300.
21. Kumar A, Thakur RC, Raja W. Mustard oil assisted green synthesis of nanomagnetites. J Mater Environ Sci 2015;6:1105-10.
22. Kittiwisut S, Kraisit P. Physicochemical characterization of propranol-loaded chitosan nanoparticles for a buccal drug delivery system. Int J App Pharm 2020;12:243-7.
23. Yadav P, Singh D, Mallik A, Nayak S. Madhuca longifolia (Sapotaceae): A review of its traditional uses, phytochemistry and pharmacology. Int J Biomed Res 2012;3:291-305.
24. Akshatha KN, Murthy MS, Lakshmidevi N. Ethanomedical uses of Madhuca longifolia-A review. Int J Life Sci Pharm Res 2013;3:44-53.
25. Indus S, Annika D. Cytotoxic and antioxidant potential of Madhuca indica flowers. World J Pharm Pharm Sci 2013;5:389-91.
26. Patel PK, Prajapati NK, Dubey BK. Madhuca indica: A review of its medicinal property. Int J Pharma Sci Res 2012;3:1285-93.
27. Ramadan MF, Mohdaly AA, Assiri AM, Tadros M, Niemeyer B. Functional characteristics, nutritional value and industrial applications of Madhuca longifolia seeds: An overview. J Food Sci Technol 2016;53:2149-57.
28. Jerine PS, Prince SE. Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress, and cytokine formation. Biomed Pharmacother 2018;98:45-51.
29. Thirulalaisamy R, Vaijayanthimala M, Govingaraju S, Subramanian A. Phytochemical screening and GC-MS analysis of Madhuca longifolia (L) Macbr. Int J Adv Sci Eng 2015;2:88-93.
30. Annalakshmi R, Mahalakshmi S, Charles A, Sahayam CS. GC-MS and HPTLC analysis of leaf extract of Madhuca longifolia (Koenig) Linn. Drug Invent Today 2013;5:76-80.
31. Inganakal TS, Udupi RH, Swamy P. A new triterpene from Madhuca longifolia L. leaves. Int J Bio Pharma Res 2012;3:718-21.
32. Medhe S, Bansal P, Roy SK, Rajan MG, Srivastava MM. Combination and nanotech enhancement in anti-breast cancer efficacy: Dietary chemo preventing agent. Bionanoscience 2013;3:295-301.
33. Medhe S, Bansal P, Srivastava MM. Enhanced antioxidant activity of gold nanoparticles embedded 3, 6-dihydroxyflavone: A combinational study. Appl Nanosci 2014;4:153-61.
34. Sharma M, Yadav S, Srivastava MM, Ganesh N, Srivastava S. Promising anti-inflammatory bio-efficacy of saponin loaded silver nanoparticles prepared from the plant Madhuca longifolia. Asian J Nanosci Mater 2018;1:244-61.
35. Yadav S, Sharma M, Ganesh N, Srivastava S, Srivastava MM. Bioactive principle loaded gold nanoparticles as potent anti-melanoma agent: Green synthesis, characterization and in-vitro bio-efficacy. Asian J Green Chem 2019;3:492-507.
36. Yadav S, Sharma M, Ganesh N, Srivastava S, Srivastava MM. Enhanced anti-melanoma bio-efficacy of flavonoid loaded gold nanoparticles prepared from the plant Madhuca longifolia on the mice and human melanoma cell lines. J Appl Chem 2019;8:833-43.
37. Sharma M, Yadav S, Ganesh N, Srivastava MM, Srivastava S. Bio-fabrication and characterization of flavonoid loaded Ag, Au, Au-Ag bimetallic nanoparticles using seed extract of the plant Madhuca longifolia for the enhancement in wound healing bio-efficacy. Prog Biomater 2019;8:51-63.
38. Feleszko W, Mlynarczuk I, Olszewska D, Jalili A, Grzela T, Lasek W, et al. Lovastatin potentiates antitumor activity of doxorubicin in murine melanoma via an apoptosis dependent mechanism. Int J Cancer 2002;100:111-8.
39. Corbett T, Valeriote F, Lorusso P, Polin L, Panchapor C, Pugh S. In-vivo methods for screening and preclinical testing. In: Teicher B, editor. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials and Approval. Totowa, NJ: Humana Press, Inc.; 1998. p. 75-99.
40. Kamal R, Dhawan DK, Chadha VD. Physiological uptake and retention of radio-labelled resveratrol loaded gold nanoparticles (Tc99m-Res- AuNp) in colon cancer tissue. Nanomedicine 2018;14:1059-71.
41. Krajian AA. Tissue cutting and staining. In: Frasnkel S, Reitman S, editors. Gradwohl’s Clinical Laboratory Methods and Diagnosis. Saint Louis, USA: Mosby Co.; 1963. p. 16-39.
42. Ravishankar D, Rajora AK, Greco F, Osborn HM. Flavonoids as prospective compounds for anti-cancer therapy. Int J Biochem Cell B 2013;45:2821-31.
43. Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, et al. A review: Flavonoids in cancer and apoptosis. Cancers 2019;11:1-40.
44. Chaudhary A, Bhandari A, Pandurangan A. Antioxidant potential and total phenolic content of methanolic bark extracts of Madhuca indica (Koenig) Gmelin. Anc Sci Life 2012;31:132-36.
45. Gupta VK, Singh R, Sharma B. Phytochemicals mediated signalling pathways and their implications in cancer chemotherapy: Challenges and opportunities in phytochemicals based drug development: A Review. Biochem Compounds 2017;5:1-15.
46. Oboh G, Akomolafe TL, Adetuyi AO. Inhibition of cyclophosphamide-induced oxidative stress in brain by dietary inclusion of red dye extracts from sorghum (Sorghum bicolor) stem. J Med Food 2010;13:1075-80.
47. Bleicher RJ, Ruth K, Sigurdson ER, Beck JR, Ross E, Wong YN, et al. Time to surgery and breast cancer survival in the united states. JAMA Oncol 2016;2:330-9.
48. Liu J, Guo W, Xu B, Ran F, Chu M, Fu H, et al. Angiogenesis inhibition and cell cycle arrest induced by treatment with pseudolarix acid b alone or combined with 5-fluorouracil. Acta Biochim Biophys Sin 2012;44:490-502.
49. Debnath S, Mukherjee A, Karan S, Debnath M, Chatterjee TK. Induction of apoptosis, anti-proliferation, tumor-angiogenic suppression and down-regulation of dalton’s ascitic lymphoma (dal) induced tumorigenesis by poly-l-lysine: A mechanistic study. Biomed Pharmacother 2018;102:1064-76.
50. Thummar VR, Parasuraman S, Basu D, Raveendran R. Evaluation of in-vivo antitumor activity of cleistanthin B in swiss albino mice. J Tradit Med Complement Ther 2015;6:383-8.
51. Bryer E, Henary D. Chemotherapy-induced anaemia: Etiology, pathophysiology, and implications for contemporary practice. Int J Clin Transfus Med 2018;6:21-31.
52. Shaul ME, Fridlender ZG. Cancer-related circulating and tumor-associated neutrophils-subtypes, sources and function. FEBS J 2018;285:4316-42.
53. Lima SR, Veiga VF Jr., Christo HB, Pinto AC, Fernandes PD. In-vivo and in-vitro studies on the anticancer activity of Copaifera multijuga hayne and its fractions. Phytother Res 2003;17:1048-53.
54. Mustapha N, Bzeouich IM, Ghedira K, Hennebelle T, Ghedira LC. Compounds isolated from the aerial part of Crataegus azarolus inhibit growth of B16F10 melanoma cells and exert a potent inhibition of the melanin synthesis. Biomed Pharmacother 2015;69:139-44.
55. Purushotham G, PadmaY, Nabiha Y, Venkata RR. In-vitro evaluation of anti-proliferative, anti-inflammatory and pro-apoptotic activities of the methanolic extracts of Andrographis nallamalayana Ellis on A375 and B16F10 melanoma cell lines.3 Biotech 2016;212:1-11.
56. Spera KD, Figueiredo PA, Santos PC, Barbosa FC, Alves CP, Dokkedal AN, et al. Genotoxicity, anti-melanoma and antioxidant activities of Hymenaea courbaril L. seed extract. An Acad Bras Cienc 2019;91:1-10.
57. Jin S, Kim KC, Kim JS, Jang K, Hyun TK. Anti-melanoma activities and phytochemical compositions of Sorbus commixta fruit extracts. Plants 2020;9:1-9.
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How to Cite
YADAV, S., M. SHARMA, N. GANESH, S. SRIVASTAVA, and M. M. SRIVASTAVA. “ANTI-MELANOMA BIO-EFFICACY OF THE PLANT MADHUCA LONGIFOLIA AND ITS ENHANCEMENT USING BIOACTIVE PRINCIPLE LOADED GOLD NANOPARTICLE”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 13, no. 10, Aug. 2020, pp. 142-9, doi:10.22159/ajpcr.2020.v13i10.38832.
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