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Current Cancer Therapy Reviews


ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Research Article

Bioactive Extracts of Ziziphus mauritiana Induces Apoptosis in A549 Human Lung Epithelial Carcinoma Cells through the Generation of Reactive Oxygen Species

Author(s): Om Prakash, Shazia Usmani *, Amresh Gupta, Asif Jafri , Mohammad Fahad Ullah, Shadma Wahab, Md Arshad and Sudheer Kumar

Volume 18, Issue 1, 2022

Published on: 05 August, 2021

Page: [57 - 68] Pages: 12

DOI: 10.2174/1573394717666210805115802

Price: $65


Background: In recent years, novel metabolites isolated from botanical sources have been attracted much attention due to their traditional and therapeutic significance. The ethnopharmacological studies suggest that Ziziphus mauritiana is a common remedy against several kinds of ailments.

Objective: The current study has evaluated the MeOH extract of Ziziphus mauritiana leaves (ZME) through physicochemical, phytochemical, and chromatographic fingerprinting analysis, which displayed an array of biometabolites of pharmacological significance, including flavonoids.

Methods: The extract was further examined for anticancer activities, which revealed promising anticancer properties against human lung epithelial carcinoma cells (A549) and induction of apoptosis impart by ROS. The oxidative stress was evaluated in terms of production and accumulation of cytosolic extent of ROS, whereas anticancer perspective was determined by MTT assay, cell morphology analysis, followed by nuclear condensation for the examination of apoptosis induction.

Results: Finding suggests that the MeOH extract of ZME markedly exhibited promising anticancer activity against the A549 lung epithelial carcinoma cell. The ZME was found to be most active in the MTT assay against A549 cells, while it was less toxic to normal cells. The intracellular ROS generation was remarkably induced by ZME, which correlated with the ability of the flavonoidrich fractions in the MeOH extract to inhibit cell growth and might induce apoptosis.

Conclusion: The present study provides useful insight concerning the promising anticancer potential of ZME against A549 lung carcinomas. However, the clinical correlation will be required for its authorization and the discovery of significant and least noxious novel agents against lung carcinomas.

Keywords: Complementary therapy, Ziziphus mauritiana Lam., HPTLC fingerprinting, A549 lung cancer, reactive oxygen species, apoptosis.

Graphical Abstract
Wang, R.; Willem, B. The Rotterdam criteria for polycystic ovary syndrome: Evidence-based criteria. Human Reproduction 2017; 32: 261-4.
Abdelazim, I.A.; Elsawah, W.F. Metabolic syndrome among infertile women with polycystic ovary syndrome. Asian Pac J Reprod 2015; 4: 44-8.
Prakash O, Usmani S, Gupta A, Singh R, Singh N, Ved A. Bioactive polyphenols as promising natural medicinal agents against cancer: The emerging trends and prospective goals. Curr Bioact Compd 2020; 16: 243-64. b
Deshpande MS, Tondare PR, Paygude SV, Apte KG, Parab PB. Evaluation of antioxidant, antiinflammatory and adipocyte differentiation inhibitory potential of Ziziphus mauritiana bark extract. Pharmacogn J 2013; 5: 205-10.
Talmale S, Bhujade A, Patil M. Anti-allergic and anti-inflammatory properties of Zizyphus mauritiana root bark. Food Funct 2015; 6(9): 2975-83.
[] [PMID: 26189881]
Koley TK, Kau C, Nagal S, Walia S, Sarika SJ. Antioxidant activity and phenolic content in genotypes of Indian jujube Zizyphus mauritiana Lamk. Arab J Chem 2016; 9: S1044-55.
Batool M, Afzal S, Afzal K, et al. SHORT COMMUNICATION-Anticancer activity of Ziziphus mauritiana roots against human breast cancer cell line. Pak J Pharm Sci 2019; 32(4): 1715-6.
[PMID: 31608895]
Tagne RS, Telefo BP, Talla E, et al. Bio-guided fractionation of MeOH extract of Ziziphus mauritiana Lam. bark and effect of the most active fraction on cancer cell lines. Asian Pac J Trop Dis 2015; 4: 307-12.
Bhatia A, Mishra T. Hypoglycemic activity of Ziziphus mauritiana aqueous ethanol seed extract in alloxan-induced diabetic mice. Pharm Biol 2010; 48(6): 604-10.
[] [PMID: 20645731]
Jarald EE, Joshi SB, Jain DC. Antidiabetic activity of extracts and fraction of Zizyphus mauritiana. Pharm Biol 2009; 4: 328-34.
Priyanka C, Kumar P, Bankar SP, Karthik L. in vitro antibacterial activity and gas chromatography–mass spectroscopy analysis of acacia karoo and Ziziphus mauritiana extracts. J Taibah Univ Med Sci 2015; 9: 13-9.
Dahiru D, Sini JM, John AL. Antidiarrhoeal activity of Ziziphus mauritiana root extract in rodents. Afr J Biotechnol 2006; 5: 941-5.
Meera S, Bhargavi YR. Evaluation of wound-healing effect of Ziziphus mauritiana L. leaf extract in rats. Interna J Green Pharmacy 2014; 4: 263-6.
Mishra T, Bhatia A. Augmentation of expression of immunocytes’ functions by seed extract of Ziziphus mauritiana (Lamk.). J Ethnopharmacol 2010; 127(2): 341-5.
[] [PMID: 19887103]
Afzal S, Batool M, Ch BA, Ahmad A, Uzair M, Afzal K. Immunomodulatory, cytotoxicity, and antioxidant activities of roots of Ziziphus mauritiana. Pharmacogn Mag 2017; 13(Suppl. 2): S262-5.
[] [PMID: 28808390]
Dahiru D, Obidoa O. Evaluation of the antioxidant effects of Ziziphus mauritiana Lam. Leaf extracts against chronic ethanol-induced hepatotoxicity in rat liver. Afr J Tradit Complement Altern Med 2007; 5(1): 39-45.
[] [PMID: 20162053]
Choi SH, Ahn JB, Kozukue N, Levin CE, Friedman M. Distribution of free amino acids, flavonoids, total phenolics, and antioxidative activities of Jujube (Ziziphus jujuba) fruits and seeds harvested from plants grown in Korea. J Agric Food Chem 2011; 59(12): 6594-604.
[] [PMID: 21574660]
Thanatcha R, Pranee A. Extraction and characterization of mucilage in Ziziphus mauritiana Lam. Int Food Res J 2011; 18: 201-12.
Mojtaba D, Reza EK, Sahari MA. Utilization of jujube fruit Ziziphus mauritiana lam. extracts as natural antioxidants in stability of frying oil. Int J Food Prop 2016; 19: 789-801.
Pawlowska AM, Camangi F, Bader A, Braca A. Flavonoids of Zizyphus jujuba and Zizyphus spina-christi L Wild Rhamnaceae fruits. Food Chem 2000; 112: 858-62.
Cheng G, Bai Y, Zhao Y, et al. Flavonoids from Ziziphus jujuba Mill var. spinasa. Tetrahedron 2000; 56: 8915-20.
Pareek S. Nutritional composition of jujube fruit. Emir J Food Agric 2013; 25: 463-70.
Jamilian, M.; Samimi, M.; Mirhosseini, N.; Ebrahimi, FA.; Aghadavod, E.; Talaee, R.; Jafarnejad, S.; Hashemi Dizaji, S.; Asemi, Z. The influences of vitamin D and omega-3 co-supplementation on clinical, metabolic and genetic parameters in women with polycystic ovary syndrome. J Affect Disord 2018; 238(32): 38.
Anonymous . The Ayurveda Pharmacopoeia of India The Controller of Publications, Control Lines New Delhi: Ministry of health and family welfare, department of indian systems of medicines and homeopathy, Government of India. 2001; 1.
Faghfoori, Z.; SiavashFazelian, S.; Mahdi shadnoush, M.; Reza Goodarzi, R. Nutritional management in women with polycystic ovary syndrome: A review study. Diabetes Metab Syndrome 2017; S1871-4021(17), 30011-30015.
World Health Organization. Quality control methods for herbal materials 2011.
Mohammadi, M. Oxidative stress and polycystic ovary syndrome: A brief review. Int J Prev Med 2019; 10: 86.
Chang CC, Yang MH, Wen HM, Chern JC. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Yao Wu Shi Pin Fen Xi 2002; 10: 178-82.
Srivastava G, Singh MP. Pharmacognostic standardization and chromatographic fingerprint analysis on triterpenoidal constituents of the medicinally important plant Artocarpus heterophyllus by high-performance thin layer chromatography technique. J Repo in Pharma Sci 2019; 8: 1-12.
Blainski A, Lopes GC, de Mello JCP. Application and analysis of the folin ciocalteu method for the determination of the total phenolic content from Limonium brasiliense L. Molecules 2013; 18(6): 6852-65.
[] [PMID: 23752469]
McDonald S, Prenzler PD, Antolovich M, Robards K. Phenolic content and antioxidant activity of olive extracts. Food Chem 2001; 73: 73-84.
Medini F, Fellah H, Ksouri R, Abdelly C. Total phenolic, flavonoid and tannin contents and antioxidant and antimicrobial activities of organic extracts of shoots of the plant Limonium delicatulum. J Taibah Univ Sci 2014; 8: 216-24.
Srivastava G, Gupta A, Singh MP, Mishra A. Pharmacognostic standardization and chromatographic fingerprint analysis on triterpenoids constituents of the medicinally important plant Plumeria rubra f. rubra by HPTLC technique. Pharmacogn J 2017; 9: 135-41.
Ahmad A, Husain A, Mujeeb M, Khan SA, Alhadrami HAA, Bhandari A. Quantification of total phenol, flavonoid content and pharmacognostical evaluation including HPTLC fingerprinting for the standardization of Piper nigrum Linn. fruits. Asian Pac J Trop Biomed 2015; 5: 101-7.
Itankar PR, Sawant DB, Tauqeer M, Charde SS. High performance thin layer chromatography fingerprinting, phytochemical and physico-chemical studies of anti-diabetic herbal extracts. Ayu 2015; 36(2): 188-95.
[] [PMID: 27011722]
Brand WW, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. Lebensm Wiss Technol 1995; 28: 25-30.
Aksoy L, Kolay E, Ağılönü Y, Aslan Z, Kargıoğlu M. Free radical scavenging activity, total phenolic content, total antioxidant status, and total oxidant status of endemic Thermopsis turcica. Saudi J Biol Sci 2013; 20(3): 235-9.
[] [PMID: 23961240]
Ahmed M, Saeed F, Ahmad M, Saeed F, Jahan N. Evaluation of insecticidal and antioxidant activity of selected medicinal plants. J Pharmacogn Phytochem 2013; 2: 153-8.
Patel RM, Patel NJ. In vitro antioxidant activity of coumarin compounds by DPPH, superoxide and nitric oxide free radical scavenging methods. J Adv Pharm Educ Res 2011; 1: 52-68.
Koleva II, van Beek TA, Linssen JP, de Groot A, Evstatieva LN. Screening of plant extracts for antioxidant activity: A comparative study on three testing methods. Phytochem Anal 2002; 13(1): 8-17.
[] [PMID: 11899609]
Marvibaigi M, Amini N, Supriyanto E, et al. Antioxidant activity and ros-dependent apoptotic effect of Scurrula ferruginea (jack) danser methanol extract in human breast cancer cell MDA-MB-231. PLoS One 2016; 11(7): e0158942.
[] [PMID: 27410459]
Ahamad MS, Siddiqui S, Jafri A, Ahmad S, Afzal M, Arshad M. Induction of apoptosis and antiproliferative activity of naringenin in human epidermoid carcinoma cell through ROS generation and cell cycle arrest. PLoS One 2014; 9(10): e110003. a
[] [PMID: 25330158]
Remila S, Atmani-Kilani D, Delemasure S, et al. Antioxidant, cytoprotective, anti-inflammatory and anticancer activities of Pistacia lentiscus anacardiaceae leaf and fruit extracts. Eur J Integr Med 2015; 7: 274-86.
Cragg GM, Newman DJ, Snader KM. Natural products in drug discovery and development. J Nat Prod 1997; 60(1): 52-60.
[] [PMID: 9014353]
Jafri A, Siddiqui S, Rais J, et al. Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation. EXCLI J 2019; 18: 154-64. a
[] [PMID: 31217779]
Prakasham RS, Hymavathi M, Subba Rao Ch, et al. Evaluation of antineoplastic activity of extracellular asparaginase produced by isolated Bacillus circulans. Appl Biochem Biotechnol 2010; 160(1): 72-80.
[] [PMID: 19543838]
Jafri A, Bano S, Rais J, et al. Phytochemical screening of Sterculia foetida seed extract for anti-oxidant, anti-microbial activity, and detection of apoptosis through reactive oxygen species ROS generation, mitochondrial membrane potential MMP decrease, and nuclear fragmentation in human osteosarcoma cells. J Histotechnol 2019; 42: 68-79. b
Ahmad A, Husain A, Mujeeb M, Siddiqui NA, Damanhouri ZA, Bhandari A. Physicochemical and phytochemical standardization with HPTLC fingerprinting of Nigella sativa L. seeds. Pak J Pharm Sci 2014; 27(5): 1175-82. b
[PMID: 25176375]
Tyagi P, Chauhan AK. Aparna. Optimization and characterization of functional cookies with addition of Tinospora cordifolia as a source of bioactive phenolic antioxidants. Lebensm Wiss Technol 2020; 130: 109639.
Roopashree TS, Dang R, Rani RHS, Narendra C. Antibacterial activity of antipsoriatic herbs: Cassia tora, Momordica charantia and Calendula officinalis. Int J Appl Res Nat Prod 2008; 1: 20-8.
Hadi SM, Bhat SH, Azmi AS, Hanif S, Shamim U, Ullah MF. Oxidative breakage of cellular DNA by plant polyphenols: A putative mechanism for anticancer properties. Semin Cancer Biol 2007; 17(5): 370-6.
[] [PMID: 17572102]
Bravo L. Polyphenols: chemistry, dietary sources, metabolism, and nutritional significance. Nutr Rev 1998; 56(11): 317-33.
[] [PMID: 9838798]
Agati G, Azzarello E, Pollastri S, Tattini M. Flavonoids as antioxidants in plants: Location and functional significance. Plant Sci 2012; 196: 67-76.
[] [PMID: 23017900]
Marques MR, Paz DD, Batista LP, Barbosa CO, Araújo MA, dos Reis MA. An in vitro analysis of the total phenolic content, antioxidant power, physical, physicochemical, and chemical composition of Terminalia catappa Linn. fruits. Food Sci Technol (Campinas) 2012; 32: 209-13.
Severo J, Lima CS, Coelho MT, Rufatto AR, Rombaldi CV, Silva JA. Antioxidant and phytochemical activity in Physalis fruits (Physalis peruviana, L.) during repening and storage. Revista Brasileira de Agrociência 2010; 16: 77-82.
Ajazuddin S, Saraf S. Evaluation of physicochemical and phytochemical properties of Safoof-E-Sana, a Unani polyherbal formulation. Pharmacognosy Res 2010; 2(5): 318-22.
[] [PMID: 21589760]
Alhakmani F, Kumar S, Khan SA. Estimation of total phenolic content, C antioxidant and anti-inflammatory activity of flowers of Moringa oleifera. Asian Pac J Trop Biomed 2013; 3(8): 623-7.
[] [PMID: 23905019]
Usmani S, Ahmad M, Arshad H. Cellular oxidative stress and antiproliferative effects of Cordia dichotoma Linn. seeds extract and their fractions on human cervix epitheloid HeLa and human lung A549 carcinoma cells. Eur J Integr Med 2018; 21: 1-10.
Usmani S, Khatoon S. HPTLC fingerprinting and antioxidant potential of MeOH extract of Digera muricata. J Chem Pharm Res 2015; 7: 661-5.
Eleazu CO, Eleazu KC, Awa E, Chukwuma SC. Comparative study of the phytochemical composition of the leaves of five Nigerian medicinal plants. Journal of Biotechnology and Pharmaceutical Research 2012; 3: 42-6.
Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016; 1863(12): 2977-92.
[] [PMID: 27646922]

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