Bioactivities of the Secondary Metabolites of Endophytic Fungi Isolated from Ziziphora pedicellata Pazij et Vved.
DOI:
https://doi.org/10.37134/jsml.vol13.2.10.2025Keywords:
Ziziphora pedicellata Pazij et Vved , endophytic fungi, secondary metabolites, antimicrobial, cytotoxicity, GC-MSAbstract
Endophytic fungi, which inhabit plant tissues, are renowned for their capacity to produce diverse bioactive secondary metabolites. In this study, six endophytic fungal isolates were derived from the medicinal plant Ziziphora pedicellata Pazij et Vved., native to Uzbekistan, and their secondary metabolites were evaluated for antimicrobial and cytotoxic properties. Three fungal isolates exhibiting antibacterial activity were identified through ITS gene sequencing. Ethyl acetate extracts of Alternaria doliconidium, Preussia africana, and Alternaria alternata exhibited strong antibacterial activities against Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa with an inhibition zone of between 15.43 ± 0.20 mm and 24.4 ± 0.36 mm. Furthermore, P. africana and A. alternata extracts showed cytotoxicity against HeLa, HEp-2, HBL-100, and CCRF-CEM. Gas chromatography-mass spectrometry (GC-MS) analysis of A. doliconidium, P. africana, and A. alternata extracts revealed 30, 23, and 44 compounds, respectively. These findings underscore the importance of endophytic fungi from medicinal plants as sustainable sources of novel bioactive compounds with promising therapeutic applications. The sustainability of bioactive compound production by endophytes offers a promising path toward eco-friendly and economically viable solutions for pharmaceuticals and agricultural practices.
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References
Abduraimov OS, Li W, Shomurodov HF, Feng Y. (2023). The main medicinal plants in arid regions of Uzbekistan and their traditional use in folk medicine. Plants, 12(16), 2950. doi:10.3390/plants12162950
Abdullaeva Y, Mardonova G, Eshboev F, Cardinale M, Egamberdieva D. (2024). Harnessing chickpea bacterial endophytes for improved plant health and fitness. AIMS Microbiology, 10(3), 489-506. doi: 10.3934/microbiol.2024024
Ali N, Rampazzo R de CP, Costa ADT, Krieger MA. (2017). Current nucleic acid extraction methods and their implications to point-of-care diagnostics. BioMed Research International, 1-13. doi:10.1155/2017/9306564
Ameen F, Stephenson SL, AlNadhari S, Yassin MA. (2021). Isolation, identification and bioactivity analysis of an endophytic fungus isolated from Aloe vera collected from Asir desert, Saudi Arabia. Bioprocess and Biosystems Engineering, 44(6), 1063-1070. doi:10.1007/s00449-020-02507-1
Ameli MM, Ameli MM, Pourmahdian A. (2022). The inhibitory role of stigmasterol on tumor growth by inducing apoptosis in Balb/c mouse with spontaneous breast tumor (SMMT). BMC Pharmacology and Toxicology, 23, 42. doi:10.1186/s40360-022-00578-2
Ashoka GB, Shivanna MB. (2022). Metabolite profiling, in vitro and in silico assessment of antibacterial and anticancer activities of Alternaria alternata endophytic in Jatropha heynei. Archives of Microbiology, 205, 61. doi:10.1007/s00203-022-03388-6
Azimova SS, Umarova GD, Petrova OS. (1984). On the nature of thyroid hormone receptors: Translocation of thyroid hormones through plasma membranes. Biokhimiya, 49(8), 1350-1356
DeMers M. (2022). Alternaria alternata as endophyte and pathogen. Microbiology, 168(3), 001153. doi:10.1099/mic.0.001153
Digra S, Nonzom S. (2023). An insight into endophytic antimicrobial compounds: an updated analysis. Plant Biotechnology Reports, 14, 1-31. doi:10.1007/s11816-023-00824-x
Dinglasan JLN, Otani H, Doering DT, Udwary D, Mouncey UN. (2025). Microbial secondary metabolites: advancements to accelerate discovery towards application. Nature Reviews Microbiology, 23, 338-354. doi:10.1038/s41579-024-01141-y
Chen YK, Kuo YH, Chiang BH, Lo JM, Sheen LY. (2009). Cytotoxic activities of 9,11-dehydroergosterol peroxide and ergosterol peroxide from the fermentation mycelia of ganoderma lucidum cultivated in the medium containing leguminous plants on Hep 3B cells. Journal of Agricultural and Food Chemistry, 57, 5713-5719. doi:10.1021/jf900581h
Ebadi M, Ebadi A. (2024). Genetic diversity and population structure of Alternaria alternata: An endophytic fungus isolated from various hosts. Fungal Biology, 128, 2305-2310. doi:10.1016/j.funbio.2024.11.005
Egamberdieva D, Eshboev F, Shukurov O, Alaylar B, Arora N. (2023). Bacterial bioprotectants: biocontrol traits and induced resistance to phytopathogens. Microbiology Research, 14(2), 689-703. doi:10.3390/microbiolres14020049
Egamberdieva D, Mamadalieva N, Khojimatov O, Tiezzi A. (2013). Medicinal plants from Chatkal Biosphere Reserve used for folk medicine in Uzbekistan. Medicinal and Aromatic Plant Science and Biotechnology, 7(1), 56-64.
Eram D, Arthikala M-K, Melappa G, Santoyo G. (2018). Alternaria species: endophytic fungi as alternative sources of bioactive compounds. Italian Journal of Mycology, 47, 40-54. doi:10.6092/issn.2531-7342/8468
Eshbakova KA, Zakirova RP, Khasanova KI, Bobakulov KM, Aisa HA, Sagdullaev SS, Nosov AM. (2019). Phenylpropanoids from callus tissue of Ajuga turkestanica. Chemistry of Natural Compounds, 55(1), 28-31. doi:10.1007/s10600-019-02608-8
Eshboev F, Egamberdieva D. (2024). Medicinal plant-associated endophytic fungi: metabolites and bioactivity. In: D. Egamberdieva, J.A. Parray and K. Davranov (eds) Plant Endophytes and Secondary Metabolites. Elsevier, p. 95-104.
Eshboev F, Karakozova M, Abdurakhmanov J, Bobakulov K, Dolimov K, Abdurashidov A, Baymirzaev A, Makhnyov A, Terenteva E, Sasmakov S, Piyakina G, Egamberdieva D, Nazarov P, Azimova S. (2023). Antimicrobial and cytotoxic activities of the secondary metabolites of endophytic fungi isolated from the medicinal plant Hyssopus officinalis. Antibiotics, 12(7), 1201. doi:10.3390/antibiotics12071201
Eshboev F, Mamadalieva N, Nazarov PA, Hussain H, Katanaev V, Egamberdieva D, Azimova S. (2024). Antimicrobial action mechanisms of natural compounds isolated from endophytic microorganisms. Antibiotics, 13(3), 271. doi:10.3390/antibiotics13030271
Fang JY, Lin YK, Wang PW, Alalaiwe A, Yang YC, Yang SC. (2019). The droplet-size effect of squalene@cetylpyridinium chloride nanoemulsions on antimicrobial potency against planktonic and biofilm MRSA. International Journal of Nanomedicine, 9(14), 8133-8147. doi:10.2147/ijn.s221663
Ghaffari F, Ebadi M, Mollaei S. (2023). Isolation and molecular identification of endophytic fungi associated with Ziziphora tenuior L. and their biological potential. South African Journal of Botany, 161, 358-364. doi:10.1016/j.sajb.2023.08.024
Gao W, Chai C, He Y, Li F, Hao X, Cao F, Gu L, Liu J, Hu Z, Zhang Y. (2019). Periconiastone A, an antibacterial ergosterol with a pentacyclo[8.7.0.01,5.02,14.010,15]heptadecane system from Periconia sp. TJ403-rc01. Organic Letters, 21(20), 8469-8472. doi:10.1021/acs.orglett.9b03270
Hashem AH, Attia MS, Kandil EK, Fawzi MM, Abdelrahman AS, Khader MS, Khodaira MA, Emam AE, Goma MA, Abdelaziz AM. (2023). Correction to: Bioactive compounds and biomedical applications of endophytic fungi: a recent review. Microbial Cell Factories, 22(1), 122. doi:10.1186/s12934-023-02131-0
Jia M, Chen L, Xin HL, Zheng CJ, Rahman K, Han T, Qin LP. (2016). A friendly relationship between endophytic fungi and medicinal plants: A systematic review. Frontiers in Microbiology, 7, 906. doi:10.3389/fmicb.2016.00906
Khan AL, Waqas M, Asaf S, Kamran M, Shahzad R, Bilal S, Khan MA, Kang SM, Kim YH, Yun BW. (2017). Plant growth-promoting endophyte Sphingomonas sp. LK11 alleviates salinity stress in Solanum pimpinellifolium. Environmental and Experimental Botany, 133, 58-69. doi:10.1016/j.envexpbot.2016.09.009
Kousar R, Naeem M, Jamaludin MI, Arshad A, Shamsuri AN, Ansari N, Akhtar S, Hazafa A, Uddin J, Khan A, Al-Harrasi A. (2022). Exploring the anticancer activities of novel bioactive compounds derived from endophytic fungi: mechanisms of action, current challenges and future perspectives. American Journal of Cancer Research, 12(7), 2897-2919.
Lestari S, Kurnia D, Mayanti T, Heliawati L. (2024). Antimicrobial activities of stigmasterol from Piper crocatum in vitro and in silico. Journal of Chemistry, 2935516, 1-11. doi:10.1155/2024/2935516
Li JF, Jiang HB, Jeewon R, Hongsanan S, Bhat DJ, Tang SM, Lumyong S, Mortimer PE, Xu JC, Camporesi E, Bulgakov TS, Zhao GJ, Suwannarach N, Phookamsak R. (2023). Alternaria: update on species limits, evolution, multi-locus phylogeny, and classification. Studies Fungi, 8, 1-61.
Li WY, Liu Y, Lin YT, Liu YC, Guo K, Li XN, Luo SH, Li SH. (2020). Antibacterial harziane diterpenoids from a fungal symbiont Trichoderma atroviride isolated from Colquhounia coccinea var. mollis. Phytochemistry, 170, 112198. doi:10.1016/j.phytochem.2019.112198
Mamadalieva NZ, Akramov DK, Ovidi E, Tiezzi A, Nahar L, Azimova SS, Sarker SD. (2017). Aromatic medicinal plants of the Lamiaceae family from Uzbekistan: Ethnopharmacology, essential oils composition, and biological activities. Medicines, 4(1), 8. doi:10.3390/medicines4010008
Mamadalieva NZ, Sharopov FS, Satyal P, Azimova SS, Wink M. (2016). Chemical composition of the essential oils of some central Asian Nepeta species (Lamiaceae) by GLC-MS. Natural Product Communications, 11(12), 1891-1893. doi:10.1177/1934578x1601101229
Mamadalieva NZ, Youssef FS, Ashour ML, Akramov DK, Sasmakov SA, Ramazonov NS, Azimova SS. (2021). A comparative study on chemical composition and antimicrobial activity of essential oils from three Phlomis species from Uzbekistan. Natural Product Research, 35(4), 696-701. doi:10.1080/14786419.2019.1591400
Mapperson RR, Kotiw M, Davis RA, Dearnaley JDW. (2014). The diversity and antimicrobial activity of Preussia sp. endophytes isolated from Australian dry rainforests. Current Microbiol, 68, 30-37. doi:10.1007/s00284-013-0415-5
Morais OTCD, Silva FEF, Santiago GMP, Pinto F, Pessoa ODL, Fonseca AM, Paulo CLR, Santos HS, Marinho MM, Santos JL, Moura TF, Freitas PR, Araújo ACJ, Almeida RS, Tintino SR, Coutinho HDM. (2025). Molecular docking and antibacterial activity of campesterol derivatives against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa multiresistant strains. Chemistry and Biodiversity, 22(1), e202401073. doi:10.1002/cbdv.202401073
Nagaraja A, Jalageri MD, Puttaiahgowda YM, Reddy KR, Raghu AV. (2019). A review on various maleic anhydride antimicrobial polymers. Journal of Microbiological Methods, 163, 105650. doi:10.1016/j.mimet.2019.105650
Niks M, Otto M. (1990). Towards an optimized MTT assay. Journal of Immunological Methods, 130(1), 149-151. doi:10.1016/0022-1759(90)90309-j
Nurunnabi TR, Sarwar S, Sabrin F, Alam F, Nahar L, Sohrab H, Sarker SD, Rahman SMM, Billah M. (2020). Molecular identification and antimicrobial activity of endophytic fungi isolated from Heritiera fomes (Buch. -Ham), a mangrove plant of the Sundarbans. Beni-Suef University Journal of Basic and Applied Sciences, 9(1), 88 doi:10.1186/s43088-020
O’Callaghan Y, Kenny O, O’Connell NM, Maguire AR, McCarthy FO, O'Brien NM. (2013). Synthesis and assessment of the relative toxicity of the oxidised derivatives of campesterol and dihydrobrassicasterol in U937 and HepG2 cells. Biochimie, 95(3), 496-503. doi:10.1016/j.biochi.2012.04.019
Salleh WMNHWS, Ahmad F, Khong HY, Zulkifli RM, Sarker SD. (2016). Madangones A and B: Two new neolignans from the stem bark of Beilschmiedia madang and their bioactivities. Phytochemistry Letters, 15, 168-173. doi:10.1016/j.phytol.2016.01.004
Salleh WMNHWS, Ahmad F, Khong HY. (2015). Chemical constituents from Piper caninum and antibacterial activity. Journal of Applied Pharmaceutical Science, 5(6), 20-25. doi:10.7324/JAPS.2015.50604
Seddouk L, Jamai L, Tazi K, Ettayebi M, Alaoui-Mhamdi M, Aleya L, Janati-Idrissi A. (2022). Isolation and characterization of a mesophilic cellulolytic endophyte Preussia africana from Juniperus oxycedrus. Environmental Science and Pollution Research, 29, 45589-45600. doi: 10.1007/s11356-022-19151-9
Singh D, Thapa S, Mahawar H, Kumar D, Geat N, Singh SK. (2022). Prospecting potential of endophytes for modulation of biosynthesis of therapeutic bioactive secondary metabolites and plant growth promotion of medicinal and aromatic plants. Antonie Van Leeuwenhoek, 115(6), 699-730. doi:10.1007/s10482-022-01736-6
Shurigin V, Davranov K, Wirth S, Egamberdieva D, Bellingrath-Kimura SD. (2018). Medicinal plants with phytotoxic activity harbour endophytic bacteria with plant growth inhibitory properties. Environmental Sustainability, 1, 209-215. doi:10.1007/s42398-018-0020-4
Shweta S, Gurumurthy BR, Ravikanth G, Ramanan US, Shivanna MB. (2013). Endophytic fungi from Miquelia dentata Bedd., produce the anticancer alkaloid, camptothecine. Phytomedicine, 20, 337-342. doi:10.1016/j.phymed.2012.11.015
Sundarraj S, Thangam R, Sreevani V, Kaveri K, Gunasekaran P, Achiraman S, Kannan S. (2012). γ-Sitosterol from Acacia nilotica L. induces G2/M cell cycle arrest and apoptosis through c-Myc suppression in MCF-7 and A549 cells. Journal of Ethnopharmacology, 141(3), 803-809. doi:10.1016/j.jep.2012.03.014
Tamura K, Stecher G, Kumar S. (2021). MEGA11: Molecular evolutionary genetics analysis version 11. Molecular Biology and Evolution, 38(7), 3022-3027. doi:10.1093/molbev/msab120
Tiwari P, Bae H. (2022). Endophytic fungi: Key insights, emerging prospects, and challenges in natural product drug discovery. Microorganisms, 10(2), 360. doi:10.3390/microorganisms10020360
Toppo P, Jangir P, Mehra N, Kapoor R, Mathur P. (2024). Bioprospecting of endophytic fungi from medicinal plant Anisomeles indica L. for their diverse role in agricultural and industrial sectors. Scientific Reports, 14(1), 588. doi:10.1038/s41598-023
Usman M, Shah IH, Sabir IA, Malik MS, Rehman Abdul, Murtaza G, Azam M, Rahman S ur, Rehman Asad, Ashraf GA. (2024). Synergistic partnerships of endophytic fungi for bioactive compound production and biotic stress management in medicinal plants. Plant Stress, 11(100425), 100425. doi:10.1016/j.stress.2024.100425
Wen J, Okyere SK, Wang S, Wang J, Xie L, Ran Y, Hu Y. (2022). Endophytic fungi: An effective alternative source of plant-derived bioactive compounds for pharmacological studies. Journal of Fungi, 8(2), 205. doi:10.3390/jof8020205
Xu M, Li X, Ye Q, Gong F, He X. (2024). Occurrence of dark septate endophytes in Phragmites australis in the Baiyang Lake and their resistance to Cd stress. Pedosphere, 34, 484-496. doi:10.1016/j.pedsph.2023.07.009
Ye HT, Luo SQ, Yang ZN, Wang Y-S, Ding Q, Wang KF, Yang SX, Wang Y. (2021). Endophytic fungi stimulate the concentration of medicinal secondary metabolites in Houttuynia cordata Thunb. Plant Signaling & Behavior, 16(9), 1929731. doi:10.1080/15592324.2021.1929731
Zhang Y, Zhang D, Li W, Li Y, Zhang C, Guan K, Pan B. (2020). Characteristics and utilization of plant diversity and resources in Central Asia. Regional Sustainability, 1(1), 1-10. doi:10.1016/j.regsus.2020.08.001
Zhao S, Li J, Liu J, Xiao S, Yang S, Mei J, Ren M, Wu S, Zhang H, Yang X. (2022). Secondary metabolites of Alternaria: A comprehensive review of chemical diversity and pharmacological properties. Frontiers in Microbiology, 13, 1085666. doi:10.3389/fmicb.2022.1085666
Zimowska B, Bielecka M, Abramczyk B, Nicoletti R. (2020). Bioactive products from endophytic fungi of sages (Salvia spp.). Agriculture, 10(11), 543. doi:10.3390/agriculture10110543
Ziyadullaev M, Karimov R, Abdurazakhov A, Parmanov A, Sasmakov S, Abdurakhmanov J, Eshboev F, Azimova S. (2023). Synthesis of 6-substituted 3(H)-quinazolin-4-ones and their antimicrobial activity. Pharmaceutical Chemistry Journal, 57, 373-377. doi:10.1007/s11094-023-02892-3
Zubek S, Nobis M, Błaszkowski J, Mleczko P, Nowak A. (2011). Fungal root endophyte associations of plants endemic to the Pamir Alay Mountains of Central Asia. Symbiosis, 54(3), 139-149. doi:10.1007/s13199-011-0137-z
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Copyright (c) 2025 Kamila Mardieva, Farkhod Eshboev, Jaloliddin Abdurakhmanov, Akhror Abdurashidov, Asadali Baymirzaev, Mukaddas Umarova, Umida Khamidova, Elvira Yusupova, Zilola Kabirova, Sherali Kuziev, Feruzbek Khasanov, Octavio Calvo-Gomez, Dilfuza Egamberdieva, Shamansur Sagdullaev, Shakhnoz Azimova
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