Biological and phytochemical analysis of fractionated extracts of Ziziphus nummularia against pathogenic bacteria, oxidative stress and cytotoxicity
DOI:
https://doi.org/10.15835/nbha52313663Keywords:
antioxidant, antibacterial, brine shrimps, cytotoxicity, phytochemical, Ziziphus nummulariaAbstract
In modern medicine, synthetic drugs are predominant, yet they often pose health hazards. So, there is a need to find natural alternatives. Ziziphus nummularia (Burm. F.) Wight & Arn., belongs to family Rhamnaceae, is well known for its traditional value such as its fruits have been used as natural appetizer and orally consumed around the world. This study investigated the phytochemical composition and bioactivity of crude and fractionated extracts from the stem bark of Ziziphus nummularia. Crude extracts were prepared using cold maceration, followed by partitioning based on polarity into n-hexane, chloroform, and ethyl acetate fractions. These extracts were subjected to phytochemical analysis and evaluated for antioxidant, antibacterial, and cytotoxic activities. The crude methanolic extract exhibited the highest antioxidant activity, with IC50 values of 136.49 μg/mL in DPPH and 78.9 μg/mL in ABTS assays. Antibacterial tests using the agar well diffusion method revealed that the methanolic extract, ethyl acetate, and chloroform fractions demonstrated broad-spectrum antibacterial activity against E. coli, K. pneumoniae, S. aureus, and S. epidermidis, with inhibition zones ranging from 0 to 8.43 ± 0.23 mm at 400 mg/mL. The brine shrimp lethality assay indicated significant cytotoxicity in the methanolic, ethyl acetate, and chloroform extracts, compared to the negligible effect of the n-hexane fraction. These findings highlight the potential of Z. nummularia as a source of bioactive compounds with therapeutic applications against infectious diseases, toxins, and oxidative stress. Further isolation of pure compounds and animal trials are recommended to explore its potential in drug discovery.
References
Abdallah R, Shaito AA, Badran A, Baydoun S, Sobeh M, Ouchari W, ... Baydoun E (2024). Fractionation and phytochemical composition of an ethanolic extract of Ziziphus nummularia leaves: antioxidant and anticancerous properties in human triple negative breast cancer cells. Frontiers in Pharmacology 15:1331843. https://doi.org/10.3389/fphar.2024.1331843
Ads EN, Rajendrasozhan S, Hassan SI, Sharawy SMS, Humaidi JR (2017). Phytochemical, antimicrobial and cytotoxic evaluation of Ziziphus spina-christi (L.) stem bark. Biomedical Research 28(15):6646-6653.
Afzal T, Bibi Y, Ishaque M, Masood S, Qayyum A, Nisa S, ... Chung G (2022). Pharmacological properties and preliminary phytochemical analysis of Pseudocaryopteris foetida (D. Don) PD Cantino leaves. Saudi Journal of Biological Sciences 29(2):1185-1190. https://doi.org/10.1016/j.sjbs.2021.09.048
Aggarwal B, Sharma P, Lamba H (2018). Ethanobotanical, phytochemical and pharmacological properties of Zizyphus nummularia (Burm. F.): A review. International Journal of Phytomedicine 10:137-147. http://dx.doi.org/10.5138/09750185.2265
Aggarwal B, Sharma P, Lamba HS (2020). Gas chromatography–mass spectrometry characterization of bioactive compounds from Ziziphus nummularia (Burm. F.) stem bark with promising in vitro antiplasmodial activity. Journal of Pharmacy and Bioallied Sciences 12(1):42-47. https://doi.org/10.4103%2Fjpbs.JPBS_41_18
Ahmed E, Arshad M, Bibi Y, Ahmed MS (2018). Phytochemical and antioxidant potential of crude methanolic extract and fractions of Celtis eriocarpa Decne. leaves from lesser Himalaya Region of Pakistan. Pakistan Journal of Botany 50(1):279-285.
Ajanal M, Gundkalle MB, Nayak SU (2012). Estimation of total alkaloid in Chitrakadivati by UV-spectrophotometer. Ancient Science of Life 31(4):198-201. https://doi.org/10.4103%2F0257-7941.107361
Akbari S, Abdurahman NH, Yunus RM, Alara OR, Abayomi OO (2019). Extraction, characterization and antioxidant activity of fenugreek (Trigonella-foenum graecum) seed oil. Materials Science for Energy Technologies 2(2):349-355. https://doi.org/10.1016/j.mset.2018.12.001
Alghamdi MD, Nazreen S, Ali NM, Amna T (2022). ZnO nanocomposites of Juniperus procera and Dodonaea viscosa extracts as antiproliferative and antimicrobial agents. Nanomaterials 12(4):664. https://doi.org/10.3390/nano12040664
Anusmitha KM, Aruna M, Job JT, Narayanankutty A, Benil PB, Rajagopal R, Alfarhan A, Barcelo D (2022). Phytochemical analysis, antioxidant, anti-inflammatory, anti-genotoxic, and anticancer activities of different Ocimum plant extracts prepared by ultrasound-assisted method. Physiological and Molecular Plant Pathology 117:101746. https://doi.org/10.1016%2Fj.pmpp.2021.101746
Ashraf A, Sarfraz RA, Anwar F, Shahid SA, Alkharfy KM (2015). Chemical composition and biological activities of leaves of Ziziphus mauritiana L. native to Pakistan. Pakistan Journal of Botany 47(1):367-376.
Beg MA, Teotia U, Farooq S (2016). In vitro antibacterial and anticancer activity of Ziziphus. Journal of Medicinal Plants Studies 4(5):230-233.
Bibi Y, Naeem J, Zahara K, Arshad M, Qayyum A (2018). In vitro antimicrobial assessment of selected plant extracts from Pakistan. Iranian Journal of Science and Technology, Transactions A: Science 42:267-272. http://dx.doi.org/10.1007/s40995-018-0498-8
Bibi Y, Nisa S, Zia M, Waheed A, Ahmed S, Chaudhary MF (2012). In vitro cytotoxic activity of Aesculus indica against breast adenocarcinoma cell line (MCF-7) and phytochemical analysis. Pakistan Journal of Pharmaceutical Sciences 25(1):183-187.
Cao J, Chen C, Wang Y, Chen X, Chen Z, ... Luo X (2016). Influence of autologous dendritic cells on cytokine‑induced killer cell proliferation, cell phenotype and antitumor activity in vitro. Oncology Letters 12(3):2033-2037. https://doi.org/10.3892/ol.2016.4839
Das K, Gezici S (2018). Secondary plant metabolites, their separation and identification, and role in human disease prevention. Annals of Phytomedicine 7:13-24. http://dx.doi.org/10.21276/ap.2018.7.2.3
Dubey K, Dubey R, Gupta R, Gupta A (2017). Anti-diabetic potential of aqueous, methanolic and saponin extract of leaves of Ziziphus nummlaria Linn. Journal of Drug Delivery and Therapeutics 7(7):173-174. https://doi.org/10.22270/jddt.v7i7.1625
Elsyana V, Bintang M, Priosoeryanto BP (2016). Cytotoxicity and antiproliferative activity assay of clove mistletoe (Dendrophthoe pentandra (L.) Miq.) leaves extracts. Advances in Pharmacological and Pharmaceutical Sciences, 2016. https://doi.org/10.1155/2016/3242698
Fernández-Poyatos MDP, Zengin G, Salazar-Mendías C, Ruiz-Medina A, Sinan KI, Llorent-Martínez EJ (2020). Study on three Sarcocapnos species as potential sources of bioactive compounds: relation between phenolic content and bioactivity by multivariate Analysis. Journal of Analytical Methods in Chemistry 8885169. https://doi.org/10.1155%2F2020%2F8885169
Ghasham AA, Al Muzaini M, Qureshi KA, Elhassan GO, Khan RA, Farhana SA, … Abdallah WE (2017). Phytochemical screening, antioxidant and antimicrobial activities of methanolic extract of Ziziphus mauritiana Lam. leaves collected from Unaizah, Saudi Arabia. International Journal of Pharmaceutical Research & Allied Sciences 6(3).
Gul R, Jan SU, Faridullah S, Sherani S, Jahan N (2017). Preliminary phytochemical screening, quantitative analysis of alkaloids, and antioxidant activity of crude plant extracts from Ephedra intermedia indigenous to Balochistan. The Scientific World Journal 5873648. https://doi.org/10.1155/2017/5873648
Hu B, Das P, Lv X, Shi M, Aa J, Wang K, ... Wu X (2022). Effects of 'healthy' fecal microbiota transplantation against the deterioration of depression in fawn-hooded rats. mSystems 7(3):e21822. https://doi.org/10.1128/msystems.00218-22
Huang A, Zhou W (2023). Mn-based cGAS-STING activation for tumor therapy. Chinese Journal of Cancer Research 35(1):19-43. https://doi.org/10.21147/j.issn.1000-9604.2023.01.04
Huang B, Gui M, An H, Shen J, Ye F, Ni Z, ... Lin J (2023). Babao Dan alleviates gut immune and microbiota disorders while impacting the TLR4/MyD88/NF-кB pathway to attenuate 5-Fluorouracil-induced intestinal injury. Biomedicine & Pharmacotherapy 166:115387. https://doi.org/10.1016/j.biopha.2023.115387
Huang R, Chen H, Liang J, Li Y, Yang J, Luo C, ... Xie X (2021). Dual role of reactive oxygen species and their application in cancer therapy. Journal of Cancer 12(18):5543. https://doi.org/10.7150%2Fjca.54699
Imran S, Bibi Y, Munawar T, Yousaf AM, Hasnain M (2023). A panoramic review on ethnomedicinal, therapeutic, phytochemical, and advance attributes, of the genus Ziziphus Mill., native to Pakistan. Ethnobotany Research and Applications 25:1-32. http://dx.doi.org/10.32859/era.25.67.1-31
Indriaty I, Ginting B, Hasballah K (2022). Assessment cytotoxic assay of Rhizophora plants mangrove using brine shrimp (Artemia salina L) model. In: IOP Conference Series: Earth and Environmental Science 951(1):012070. IOP Publishing. http://dx.doi.org/10.1088/1755-1315/951/1/012070
Irawan C, Elya B, Hanafi M, Saputri FC (2023). Cytotoxicity by brine shrimp lethality test and potential Rhinachantus nasutus (L.) Kurz stem bark ethanol extract as anti-inflammatory and antimicrobial. Egyptian Journal of Chemistry 66(12):321-326. https://doi.org/10.21608/ejchem.2023.187779.7462
Ishaque M, Bibi Y, Ayoubi SA, Masood S, Nisa S, Qayyum A (2021). Iriflophenone-3-C-β-d glucopyranoside from Dryopteris ramosa (Hope) C. Chr. with promising future as natural antibiotic for gastrointestinal tract infections. Antibiotics 10(9):1128. https://doi.org/10.3390/antibiotics10091128
Jaleel F, Sohu ASS, Akhtar M, Irshad K, Irshad MB, Mehboob S (2020). Green synthesized nano particles based inspection of ethano-medicinal flora of Cholistan Desert, Pakistan. IOP Conference Series: Materials Science and Engineering 993(1):012116. https://doi.org/10.1088/1757-899X/993/1/012116
Ji X, Guo J, Tian J, Ma K, Liu Y (2023). Research progress on degradation methods and product properties of plant polysaccharides. Journal of Light Industry 38(3):55-62. https://doi.org/10.12187/2023.03.007
Khalil MS, Shakeel M, Gulfam N, Ahmad SU, Aziz A, Ahmad J, … Khandaker MU (2022). Fabrication of silver nanoparticles from Ziziphus nummularia fruit extract: effect on hair growth rate and activity against selected bacterial and fungal strains. Journal of Nanomaterials 1-14. https://doi.org/10.1155/2022/3164951
Khan AQ, Rashid K, AlAmodi AA, Agha MV, Akhtar S, Hakeem I, ... Uddin S (2021). Reactive oxygen species (ROS) in cancer pathogenesis and therapy: An update on the role of ROS in anticancer action of benzophenanthridine alkaloids. Biomedicine & Pharmacotherapy 143:112142. https://doi.org/10.1016/j.biopha.2021.112142
Khan MN, Haq FU, Rahman S, Ali A, Musharraf SG (2020). Metabolite distribution and correlation studies of Ziziphus jujuba and Ziziphus nummularia using LC-ESI-MS/MS. Journal of Pharmaceutical and Biomedical Analysis 178:112918. https://doi.org/10.1016/j.jpba.2019.112918
Kumar S, Garg VK, Sharma PK (2010). A review of Ziziphus nummularia. Pharmacology Online 2:565-574.
Kurek M, Benaida-Debbache N, Elez Garofulić I, Galić K, Avallone S, Voilley A, Waché Y (2022). Antioxidants and bioactive compounds in food: Critical review of issues and prospects. Antioxidants 11(4):742. https://doi.org/10.3390/antiox11040742
Lou Z, Gong YQ, Zhou X, Hu GH (2018). Low expression of miR‑199 in hepatocellular carcinoma contributes to tumor cell hyper‑proliferation by negatively suppressing XBP1. Oncology Letters 16(5):6531-6539. https://doi.org/10.3892/ol.2018.9476
Mao X, Chen Y, Lu X, Jin S, Jiang P, Deng Z, … Kang S (2023). Tissue resident memory T cells are enriched and dysfunctional in effusion of patients with malignant tumor. Journal of Cancer 14(7):1223-1231. https://doi.org/10.7150/jca.83615
Meshginfar N, Sadeghi Mahoonak A, Hosseinian F, Ghorbani M, Tsopmo A (2018). Production of antioxidant peptide fractions from a by-product of tomato processing: Mass spectrometry identification of peptides and stability to gastrointestinal digestion. Journal of Food Science and Technology 55:3498-3507. https://doi.org/10.1007%2Fs13197-018-3274-z
Mohammed HA, Al-Omar MS, Mohammed SA, Alhowail AH, Eldeeb HM, Sajid MS, … Khan RA (2021). Phytochemical analysis, pharmacological and safety evaluations of halophytic plant, Salsola cyclophylla. Molecules 26(8):2384. https://doi.org/10.3390/molecules26082384
Nembo EN, Hescheler J, Nguemo F (2020). Stem cells in natural product and medicinal plant drug discovery—An overview of new screening approaches. Biomedicine & Pharmacotherapy 131:110730. https://doi.org/10.1016/j.biopha.2020.110730
Nigussie D, Davey G, Legesse BA, Fekadu A, Makonnen E (2021). Antibacterial activity of methanol extracts of the leaves of three medicinal plants against selected bacteria isolated from wounds of lymphoedema patients. BMC Complementary Medicine and Therapies 21:1-10. https://doi.org/10.1186/s12906-020-03183-0
Niu M, Guo H, Shang J, Meng X (2023). Structural characterization and immunomodulatory activity of a mannose-rich polysaccharide isolated from Bifidobacterium breve H4–2. Journal of Agricultural and Food Chemistry 71(49):19791-19803. https://doi.org/10.1021/acs.jafc.3c04916
Noreen H, Semmar N, Farman M, McCullagh JS (2017). Measurement of total phenolic content and antioxidant activity of aerial parts of medicinal plant Coronopus didymus. Asian Pacific Journal of Tropical Medicine 10(8):792-801. https://doi.org/10.1016/j.apjtm.2017.07.024
Nwidu LL, Elmorsy E, Thornton J, Wijamunige B, Wijesekara A, Tarbox R, Warren A, Carter WG (2017). Anti-acetylcholinesterase activity and antioxidant properties of extracts and fractions of Carpolobia lutea. Pharmaceutical Biology 55(1):1875-1883. https://doi.org/10.1080%2F13880209.2017.1339283
Oikeh EI, Oviasogie FE, Omoregie ES (2020). Quantitative phytochemical analysis and antimicrobial activities of fresh and dry ethanol extracts of Citrus sinensis (L.) Osbeck (sweet Orange) peels. Clinical Phytoscience 6(1):1-6. https://doi.org/10.1186/s40816-020-00193-w
Padalia H, Chanda S (2021). Synthesis of silver nanoparticles using Ziziphus nummularia leaf extract and evaluation of their antimicrobial, antioxidant, cytotoxic and genotoxic potential (4-in-1 system). Artificial Cells, Nanomedicine, and Biotechnology 49(1):354-366. https://doi.org/10.1080/21691401.2021.1903478
Pandey A, Singh R, Radhamani J, Bhandari DC (2010). Exploring the potential of Ziziphus nummularia (Burm. f.) Wight et Arn. from drier regions of India. Genetic Resources and Crop Evolution 57:929-936. http://dx.doi.org/10.1007/s10722-010-9566-4
Rauf A, Ali J, Khan H, Mubarak MS, Patel S (2016). Emerging CAM Ziziphus nummularia with in vivo sedative-hypnotic, antipyretic and analgesic attributes. 3 Biotech 6:1-10. https://doi.org/10.1007%2Fs13205-015-0322-5
Ray SD, Das N, Ray S (2021). A multi-pronged approach to assessing inflammatory inhibitory activity of a new cyclic alkaloid compound from root bark of Ziziphus Nummularia (Aubrev.). Research Square. https://doi.org/10.21203/rs.3.rs-1134126/v1
Shah RB, Modi HA, Srivastava A (2018). Medicinal plant’s potential activity against skin disease-causing bacteria and their phytochemical assessment. International Journal of Pharmaceutical & Biological Archives 9(3):85-92.
Sharaf MH, Abdelaziz AM, Kalaba MH, Radwan AA, Hashem AH (2022). Antimicrobial, antioxidant, cytotoxic activities and phytochemical analysis of fungal endophytes isolated from Ocimum basilicum. Applied Biochemistry and Biotechnology 1-19. https://doi.org/10.1007/s12010-021-03702-w
Sharma S, Chakraborty D (2021). Traditional medicinal plants used by tribal communities in Tonk district, Rajasthan. Plant Science Today 8(1):225-228. http://dx.doi.org/10.14719/pst.2021.8.1.1077
Sharma SK, Singh J, Maherchandani S, Kashyap SK (2012). Antibacterial activity of Ziziphus nummularia and Prosopis cineraria leaves extracts against Staphylococcus aureus and Escherichia coli. Veterinary Practitioner 13(1):46-48.
Song Y, Li X, Nie S, Hu Z, Zhou D, Sun D, ... Wang S (2023). Extracellular vesicles released by glioma cells are decorated by annexin A2 allowing for cellular uptake via heparan sulfate. Cancer Gene Therapy 30(8):1156-1166. https://doi.org/10.1038/s41417-023-00627-w
Sonia S, Singh SK (2019). Phytoconstituents of Ziziphus nummularia (Burm. f.) Wight & Arn. leaves extracts using GC-MS spectroscopy. Research and Review Journal of Life Science 9:109-118.
Soukand R, Kalle R, Pieroni A (2022). Homogenisation of biocultural diversity: Plant ethnomedicine and its diachronic change in Setomaa and Võromaa, Estonia, in the last century. Biology 11(2):192. https://doi.org/10.3390/biology11020192
Thirumurugan K, Shihabudeen MS, Hansi PD (2010). Antimicrobial activity and phytochemical analysis of selected Indian folk medicinal plants. Steroids 1(7):430-434.
Uddin N, Ali N, Uddin Z, Nazir N, Zahoor M, Rashid U, … Liu M (2020). Evaluation of cholinesterase inhibitory potential of different genotypes of Ziziphus nummularia, their HPLC-UV, and molecular docking analysis. Molecules 25(21):5011. https://doi.org/10.3390/molecules25215011
Uddin N, Muhammad N, Nisar M, Aisha Ali N, Ullah R, Ali EA, … Zeb A (2022). Distribution of polyphenolic compounds, antioxidant potential, and free amino acids in Ziziphus fruits extract; a study for determining the influence of wider geography. Food Science & Nutrition 10(5):1414-1430. https://doi.org/10.1002%2Ffsn3.2726
Ullah I, Ullah I, Ali M, Durrani F, Khan SU, Hussain D, … Bahadur S (2023). Quantitative study of medicinal plants and biological activities of two common species used by inhabitants of district Bannu, Pakistan. Acta Ecologica Sinica 43(2):271-287. http://dx.doi.org/10.1016/j.chnaes.2021.08.006
Wei S, Sun T, Du J, Zhang B, Xiang D, ... Li W (2018). Xanthohumol, a prenylated flavonoid from Hops, exerts anticancer effects against gastric cancer in vitro. Oncology Reports 40(6):3213-3222. https://doi.org/10.3892/or.2018.6723
Yadav SM, Sharma VK, Sharma PK, Sharma J (2022). Pharmacognostical, phytochemical, antimicrobial and hepatoprotective screening of some plants of family Rhamnaceae. International Journal of Health Sciences III:4890-4911. https://dx.doi.org/10.53730/ijhs.v6nS3.6985
Yan J, Liu D, Wang J, You W, Yang W, Yan S, ... He W (2024). Rewiring chaperone-mediated autophagy in cancer by a prion-like chemical inducer of proximity to counteract adaptive immune resistance. Drug Resistance Updates 73:101037. https://doi.org/10.1016/j.drup.2023.101037
Zahara K, Bibi Y, Qayyum A, Nisa S (2019). Investigation of antimicrobial and antioxidant properties of Bidens biternata. Iranian Journal of Science and Technology, Transactions A: Science 43:725-734. http://dx.doi.org/10.1007/s40995-018-0564-2
Zhou L, Xie M, Yang F, Liu J (2020). Antioxidant activity of high purity blueberry anthocyanins and the effects on human intestinal microbiota. Lwt 117:108621. http://dx.doi.org/10.1016/j.lwt.2019.108621
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