Secondary metabolites of endophytic fungii isolated from the stem bark of Sungkai (Peronema canescens Jack.)

Year 2024, Volume: 28 Issue: 1, 89 - 109, 28.06.2025

Rian Oktiansyah Elfita Elfita , Hary Wıdjajantı , Poedji Loekitowati Hariani Nurlisa Hidayati Arum Setıawan , Salni Salni

Abstract

Infectious diseases are a global challenge today. One preventive measure is to maintain and improve humans’ immunity. Many people consume sungkai, a medicinal plant that is believed to cut down the exposure of severe covid-19 because it is related to antioxidant and antibacterial activity. This research investigated the antioxidant and antimicrobe agents of fungal endophyte extracts from the stem bark of sungkai. Endophytic fungal was isolated from the fresh tissue of the stem bark of sungkai and identified morphologically. The antioxidant of the endophytic fungi extract was tested with the DPPH, and antibacterial agent was tested by using the paper disc diffusion method. Molecular identification of endophytic fungi was done to extract that showed the most potential antioxidant and antibacterial activity. The pure compounds were isolated by chromatographic techniques. Structural determinations of the compounds were accomplished using a spectroscopic method, comprising 1D and 2D NMR. Twenty isolates of fungal endophyte were found residing in the stem bark of sungkai, specifically RB1-RB20. Isolates RB4 and RB6 showed the most potential antioxidant and antibacterial activity and were identified molecularly. The results of molecular identification showed that RB4 and RB6 were Curvularia intermedia and Colletotrichum cliviicola. Based on the spectroscopic analysis, the compounds identified from the two fungi were the different compound, specifically 3- hydroxy-4(hydroxy(4-hydroxyphenyl)methyl)-ɣ-butyrolactone (1) and 5-hydroxy-4-(hydroxymethyl)-2H-pyran-2-on (2). Compound 1 and 2 showed antibacterial and antioxidant in strong to moderate. These compounds and the endophytic fungi extract can be used as a new ingredient for medicine because it has antioxidant and antibacterial activity with further research.

Keywords

Antibacterial , antioxidant , endophytic fungi , secondary metabolites , sungkai (Peronema canescens)

References

• [1] Alagawany M, Attia YA, Farag MR, Elnesr SS, Nagadi SA, Shafi ME, Khafaga AF, Ohran H, Alaqil AA, Abd El-Hack ME. The strategy of boosting the ımmune system under the COVID-19 pandemic. Front Vet Sci. 2021 ;7:570748. https://doi.org/10.3389/fvets.2020.570748
• [2] Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe P. Enhancing immunity in viral infections, with special emphasis on COVID-19: A review. Diabetes Metab Syndr Clin Res Rev. 2020;14(1):367–382. https://doi.org/10.1016/j.dsx.2020.04.015.
• [3] Yuki K, Fujiogi M, Koutsogiannaki S. COVID-19 pathophysiology: A review. Clin Immunol. 2020;215:108427. https://doi.org/10.1016/j.clim.2020.108427.
• [4] Sifuentes-Franco S, Sánchez-Macías DC, Carrillo-Ibarra S, Rivera-Valdés JJ, Zuñiga LY, Sánchez-López VA. Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 Supplementation on Infectious Diseases. Healthcare (Basel). 2022;10(3):487.https://doi.org/10.3390/healthcare10030487
• [5] Altenburg J, De Graaff CS, Van Der Werf TS, Boersma WG. Immunomodulatory effects of macrolide antibiotics - Part 1: Biological mechanisms. Respiration. 2010;81(1):67-74. https://doi.org/10.1159/000320319
• [6] Fratta Pasini AM, Stranieri C, Cominacini L, Mozzini C. Potential role of antioxidant and anti-ınflammatory therapies to prevent severe SARS-Cov-2 complications. Antioxidants (Basel). 2021;10(2):272. https://doi.org/10.1248/bpb.b15-00698
• [7] Deledda A, Annunziata G, Tenore GC, Palmas V, Manzin A, Velluzzi F. Diet-derived antioxidants and their role in ınflammation, obesity and gut microbiota modulation. Antioxidants (Basel). 2021;10(5):708. https://doi.org/10.3390/antiox10050708
• [8] Kusaki M, Ohta Y, Inufusa H, Yamashita T, Morihara R, Nakano Y, Liu X, Shang J, Tian F, Fukui Y, Sato K, Takemoto M, Hishikawa N, Abe K. Neuroprotective effects of a novel antioxidant mixture Twendee X in mouse stroke model. J Stroke Cerebrovasc Dis. 2017;26(6):1191-1196. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.01.003
• [9] Michalska P, Mayo P, Fernández-Mendívil C, Tenti G, Duarte P, Buendia I, Ramos MT, López MG, Menéndez JC, León R. Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer's Disease. Antioxidants (Basel). 2020;9(8):650. https://doi.org/10.3390/antiox9080650
• [10] Zachary JF. Mechanisms of Microbial Infections. Pathologic Basis of Veterinary Disease. 2017:132–241.e1. https://doi.org/10.1016%2FB978-0-323-35775-3.00004-7
• [11] Elfita, Munawar, Muharni, Sudrajat MA. Identification of New Lactone Derivatives Isolated from Trichoderma sp., An Endophytic Fungus of Brotowali (Tinaspora crispa). HAYATI J Biosci. 2014;21(1):15–20. https://doi.org/10.4308/hjb.21.1.15
• [12] Andersen L, Corazon SS, Stigsdotter UK. Nature Exposure and Its Effects on Immune System Functioning: A Systematic Review. Systematic Rev. 2021;18(1416):1-48. https://doi.org/10.3390/ijerph18041416
• [13] Silveira MP, Fagundes KK, Bizuti MR, Starck E, Rossi RC, Silva DBR. Physical exercise as a tool to help the immune system against COVID-19: an integrative reviewe of the current literature. Clin Exp Med. 2021;21(1):15-28. https://doi.org/10.1007/s10238-020-00650-3
• [14] Alagawany M, Attia YA, Farag MR, Elnesr SS, Nagadi SA, Shafi ME, Khafaga AF, Ohran H, Alaqil AA, Abd El-Hack ME. The Strategy of Boosting the Immune System Under the COVID-19 Pandemic. Front Vet Sci. 2021;7(1):1-17. https://doi.org/10.3389/fvets.2020.570748
• [15] Alhazmi HA, Najmi A, Javed SA, Sultana S, Al Bratty M, Makeen HA, Meraya AM, Ahsan W, Mohan S, Taha MME, Khalid A. Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19. Front Immunol. 2021;12(1):1-24. https://doi.org/10.3389/fimmu.2021.637553
• [16] Safriani N, Rungkat FZ, Yuliana ND, Prangdimurti E. Immunomodulatory and Antioxidant Activities of Select Indonesian Vegetables, Herbs, and Spices on Human Lymphocytes. Int J Food Sci. 2021;1(1):1-12. https://doi.org/10.1155/2021/6340476
• [17] Sharifi-Rad M, Anil Kumar NV, Zucca P, Varoni EM, Dini L, Panzarini E, Rajkovic J, Tsouh Fokou PV, Azzini E, Peluso I, Prakash Mishra A, Nigam M, El Rayess Y, Beyrouthy ME, Polito L, Iriti M, Martins N, Martorell M, Docea AO, Setzer WN, Calina D, Cho WC, Sharifi-Rad J. Lifestyle, oxidative stress, and antioxidants: Back and forth in the pathophysiology of chronic diseases. Front Physiol. 2020;11:694. https://doi.org/10.3389/fphys.2020.00694.
• [18] Tan BL, Norhaizan ME, Liew WPP, Rahman HS. Antioxidant and oxidative stress: A mutual interplay in age-related diseases. Front Pharmacol. 2018;9:1162. https://doi.org/10.3389/fphar.2018.01162
• [19] Lourenço SC, Moldão-Martins M, Alves VD. Antioxidants of natural plant origins: From sources to food industry applications. Molecules. 2019;24(22):4132. https://doi.org/10.3390/molecules26061752
• [20] Jamil M, Aleem MT, Shaukat A, Khan A, Mohsin M, Rehman TU, Abbas RZ, Saleemi MK, Khatoon A, Babar W, Yan R, Li K. Medicinal Plants as an Alternative to Control Poultry Parasitic Diseases. Life (Basel). 2022 ;12(3):449. https://doi.org/10.3390/life12030449
• [21] Kaggwa B, Kyeyune H, Munanura EI, Anywar G, Lutoti S, Aber J, Bagoloire LK, Weisheit A, Tolo CU, Kamba PF, Ogwang PE. Safety and efficacy of medicinal plants used to manufacture herbal products with regulatory approval in Uganda: A cross-sectional study. Evid Based Complement Alternat Med. 2022;2022:1304839. https://doi.org/10.1155/2022/1304839.
• [22] Ibrahim A, Arifuddin M, Cahyo P W, Widayat W, Bone M. Isolation, Characterization and secondary metabolite endophytic fungal ısolate from Peronema canescens jack leaf and Coptosapelta tomentosa Val. K. Heyne Root. J Trop Pharm Chem. 2019;4(5):215–225. https://doi.org/10.25026/jtpc.v4i5.169
• [23] Dillasamola D, Aldi Y, Kurniawan H, Jalius IM. Immunomodulator effect test of Sungkai leaves ( Peronema canescsens Jack.) ethanol extract using carbon clearance method. Adv Health Sci Res 2021;40:1–6. https://doi.org/10.25026/jtpc.v4i5.169
• [24] Pindan PN, Daniel, Chairul S, Rahayu A, Magdaleni. Ujı fıtokımıa dan ujı aktıvıtas antıoksıdan ekstrak fraksı n-heksana, etıl asetat dan etanol sısa darı daun sungkaı (Peronema canescens jack.) Dengan metode dpph. Jurnal Atomik. 2021;22–7:1-12. https://doi.org/10.55522/jmpas.V12İ2.4925
• [25] Muharnı M, Ferlınahayatı F, Yohandını H, Rıyantı F, Pakpahan N. The anticholesterol activity of betulinic acid and stigmasterol isolated from the leaves of sungkai (Peronema canescens jack). İnt J Appl Pharm. 2021;13(2):198–203. https://doi.org/10.22159/ijap.2021v13i2.40372
• [26] Abeysinghe DT, Kumara KAH, Kaushalya KAD, Chandrika UG, Alwis DDDH. Phytochemical screening, total polyphenol, flavonoid content, in vitro antioxidant and antibacterial activities of Sri Lankan varieties of Murraya koenigii and Micromelum minutum leaves. Heliyon. 2021;7(7):e07449. https://doi.org/10.1016/j.heliyon.2021.e07449
• [27] Le NTM, Cuong DX, Thinh PV, Minh TN, Manh TD, Duong TH, Minh TTL, Oanh VTT. Phytochemical screening and evaluation of antioxidant properties and antimicrobial activity against Xanthomonas axonopodis of Euphorbia tirucalli extracts in Binh Thuan province, Vietnam. Molecules. 2021; 26(4):941. https://doi.org/10.3390/molecules26040941
• [28] Yahia Y, Benabderrahim MA, Tlili N, Bagues M, Nagaz K. Bioactive compounds, antioxidant and antimicrobial activities of extracts from different plant parts of two Ziziphus Mill. species. PLoS One. 2020;15(5):e0232599. https://doi.org/10.1371/journal.pone.0232599
• [29] Boy FR, Casquete R, Martínez A, Córdoba M de G, Ruíz-Moyano S, Benito MJ. Antioxidant, antihypertensive and antimicrobial properties of phenolic compounds obtained from native plants by different extraction methods. Int J Environ Res Public Health. 2021;18(5):2475. https://doi.org/10.3390/ijerph18052475
• [30] Singh A, Banerjee P, Anas M, Singh N, Qamar İ. Traditional nutritional and health practices targeting lifestyle behavioral changes in humans. J Lifestyle Med. 2020;10(2):67–73. https://doi.org/10.15280/jlm.2020.10.2.67
• [31] Okaiyeto K, Oguntibeju OO. African herbal medicines: Adverse effects and cytotoxic potentials with different therapeutic applications. Int J Environ Res Public Health. 2021;18(11): 5988. https://doi.org/10.3390/ijerph18115988
• [32] Sharma H, Rai AK, Dahiya D, Chettri R, Nigam PS. Exploring endophytes for in vitro synthesis of bioactive compounds similar to metabolites produced in vivo by host plants. AIMS Microbiol. 2021;7(2):175–199. https://doi.org/10.1007/s12639-017-0935-1
• [33] Vigneshwari A, Rakk D, Németh A, Kocsubé S, Kiss N, Csupor D, Papp T, Škrbić B, Vágvölgyi C, Szekeres A. Host metabolite producing endophytic fungi isolated from Hypericum perforatum. PLoS One. 2019;14(5):e0217060. https://doi.org/10.1371/journal.pone.0217060.
• [34] Alam B, Lǐ J, Gě Q, Khan MA, Gōng J, Mehmood S, Yuán Y, Gǒng W. Endophytic Fungi: From Symbiosis to secondary metabolite communications or vice versa? Front Plant Sci. 2021;12:791033. https://doi.org/10.3389/fpls.2021.791033
• [35] Singh A, Singh DK, Kharwar RN, White JF, Gond SK. Fungal endophytes as efficient sources of plant-derived bioactive compounds and their prospective applications in natural product drug discovery: Insights, avenues, and challenges. Microorganisms. 2021;9(1):1–42. https://doi.org/10.3390/microorganisms9010197
• [36] Castro P, Parada R, Corrial C, Mendoza L, Cotoras M. Endophytic fungi isolated from Baccharis linearis and Echinopsis chiloensis with antifungal activity against Botrytis cinerea. J Fungi (Basel) 2022; 8(2):197. https://doi.org/10.3390/jof8020197
• [37] Oktiansyah R, Elfita E, Widjajanti H, Setiawan A, Hariani PL, Hidayati N. Endophytic fungi isolated from the root bark of sungkai (Peronema canescens) as anti-bacterial and antiokxidant. J Med Pharm Allied Sci. 2023;12(2):5754–5761. https://doi.org/10.55522/jmpas.V12İ2.4925
• [38] Syarifah, Elfita, Widjajanti H, Setiawan A, Kurniawati AR. Diversity of endophytic fungi from the root bark of Syzygium zeylanicum, and the antibacterial activity of fungal extracts, and secondary metabolite. Biodiversitas. 2021;22(10):4572–4582. https://doi.org/10.13057/biodiv/d221051
• [39] Wen J, Okyere SK, Wang S, Wang J, Xie L, Ran Y, Hu Y. Endophytic Fungi: An effective alternative source of plant-derived bioactive compounds for pharmacological studies. J Fungi (Basel). 2022;8(2):205. https://doi.org/10.3390/jof8020205
• [40] Zihad SMNK, Hasan MT, Sultana MS, Nath S, Nahar L, Rashid MA, Uddin SJ, Sarker SD, Shilpi JA. Isolation and characterization of antibacterial compounds from Aspergillus fumigatus: An endophytic fungus from a mangrove plant of the Sundarbans. Evid Based Complement Alternat Med. 2022;2022:9600079. https://doi.org/10.1155/2022/9600079
• [41] Song Z, Sun YJ, Xu S, Li G, Yuan C, Zhou K. Secondary metabolites from the Endophytic fungi Fusarium decemcellulare F25 and their antifungal activities. Front Microbiol. 2023 ;14:1127971. https://doi.org/10.3389/fmicb.2023.1127971
• [42] Elfita, Oktiansyah R, Mardiyanto, Widjajanti H, Setiawan A. Antibacterial and antioxidant activity of endophytic fungi isolated from Peronema canescens leaves. Biodiversitas. 2022;23(9):4783–4892. https://doi.org/10.13057/biodiv/d230946
• [43] Widjajanti H, Muharni, Nurnawati E, Tripuspita V. The potency of endophytic fungi isolated from Hippobroma longiflora (L) G. Don as an antioxidant sources. IOP Conf Ser Earth Environ Sci. 2022;976:012045 https://doi.org/10.1088/1755-1315/976/1/012045
• [44] Tan WN, Nagarajan K, Lim V, Azizi J, Khaw KY, Tong WY, Leong CR, Chear NJ. Metabolomics analysis and antioxidant potential of endophytic Diaporthe fraxini ED2 grown in different culture media. J Fungi (Basel). 2022;8(5):519. https://doi.org/10.3390/jof8050519
• [45] Xu K, Li XQ, Zhao DL, Zhang P. Antifungal secondary metabolites produced by the fungal endophytes: Chemical diversity and potential use in the development of biopesticides. Front Microbiol. 2021;12:689527. https://doi.org/10.3389/fmicb.2021.689527
• [46] Fernando K, Reddy P, Guthridge KM, Spangenberg GC, Rochfort SJ. A metabolomic study of Epichloë endophytes for screening antifungal metabolites. Metabolites. 2022;12(1):37. https://doi.org/10.3390/metabo12010037
• [47] Tiwari P, Bae H. Endophytic Fungi: Key insights, emerging prospects, and challenges in natural product drug discovery. Microorganisms. 2022;10(2):360. https://doi.org/10.3390/microorganisms10020360
• [48] Elfita, Oktiansyah R, Mardiyanto, Widjajanti H, Setiawan A, Nasution SSA. Bioactive compound of endophytic fungi Lasiodiplidoa theobromae isolated from the leaves of Sungkai (Peronema canescens). Biodiversitas J Biol Divers 2023;23(9): 4783-4792. https://doi.org/10.13057/biodiv/d230946.
• [49] İbrahim SRM, Mohamed GA, Al Haidari RA, El-Kholy AA, Zayed MF. Potential anti-malarial agents from endophytic fungi: A review. Mini-Reviews Med Chem. 2018;18(13):11–32. https://doi.org/10.2174/1389557518666180305163151
• [50] Cui XX, Wang L, Fang HY, Zheng YG, Su CY. The cultivable endophytic fungal community of Scutellaria baicalensis: Diversity and relevance to flavonoid production by the host. Plant Signal Behav. 2022 ;17(1):2068834. https://doi.org/10.1080/15592324.2022.2068834
• [51] Deshmukh SK, Dufossé L, Chhipa H, Saxena S, Mahajan GB, Gupta MK. Fungal endophytes: A potential source of antibacterial compounds. J Fungi (Basel). 2022;8(2):164. https://doi.org/10.3390/jof8020164
• [52] Singh A, Singh DK, Kharwar RN, White JF, Gond SK. Fungal endophytes as efficient sources of plant-derived bioactive compounds and their prospective applications in natural product drug discovery: Insights, avenues, and challenges. Microorganisms. 2021;9(1):197. https://doi.org/10.3390/microorganisms9010197
• [53] Oktiansyah, R, Elfita E, Widjajanti H, Setiawan A, Mardiyanti M, Nasution SSA. Antioxidant and antibacterial activity of endophytyc fungi isolated from the leaves of Sungkai (Peronema canescens). Trop J Nat Res. 2023;7(3):2596-2604. https://doi.org/10.26538/tjnpr/v7i3.20
• [54] Walsh TJ, Hayden RT, Larone DH. Larone’s Medically Important Fungi: A Guide to Identification. 2018. https://doi.org/10.1128/9781555819880
• [55] Watanabe T. Pictorial Atlas of Soil and Seed Fungi. 2010. https://doi.org/10.1201/EBK1439804193
• [56] Abbas S, Shanbhag T, Kothare A. Applications of bromelain from pineapple waste towards acne. Saudi J Biol Sci. 2021;28(1):1001–1009. https://doi.org/10.1016/j.sjbs.2020.11.032
• [57] Ding Z, Tao T, Wang L, Zhao Y, Huang H, Zhang D, Liu M, Wang Z, Han J. Bioprospecting of novel and bioactive metabolites from endophytic fungi isolated from rubber tree Ficus elastica leaves. J Microbiol Biotechnol. 2019;29(5):731-738. https://doi.org/10.4014/jmb.1901.01015
• [58] Tamura K, Stecher G, Kumar S. MEGA11: Molecular Evolutionary Genetics Analysis Version 11. Mol Biol Evol. 2021;38(7):3022-3027. https://doi.org/10.1093/molbev/msab120
• [59] Oktiansyah R, Juliandi B, Widayati KA, Juniantito V. Neuronal cell death and mouse (Mus musculus) behaviour induced by bee venom. Trop Life Sci Res. 2018; 29(2):1–11. https://doi.org/10.21315/tlsr2018.29.2.1
• [60] Stiles CM, Datnoff LE, Rayside PA. Pythium spp. isolated from bermudagrass during overseed transitions in Florida and pathogenicity of Pythium irregulare on Poa trivialis. Plant Dis. 2007;91(10):1237–1244. https://doi.org/10.1094/PDİS-91-10-1237
• [61] Raftoyannis Y, Dick MW. Effects of inoculum density, plant age and temperature on disease severity caused by Pythiaceous fungi on several plants. Phytoparasitica. 2002;30(1):67–76. https://doi.org/10.1007/BF02983972
• [62] Jara M, Holcomb K, Wang X, Goss EM, Machado G. The potential distribution of Pythium insidiosum in the Chincoteague National Wildlife Refuge, Virginia. Front Vet Sci. 2021;8:640339. https://doi.org/10.3389/fvets.2021.640339
• [63] Oktiansyah R, Widjajanti H, Setiawan A, Nasution SSA, Mardiyanto M, Elfita E. Antibacterial and antioxidant activity of endophytic fungi extract isolated from leaves of Sungkai (Peronema canescens). Sci Technol İndones. 2023;8(2):170–177. https://doi.org/10.26554/sti.2023.8.2.170-177 1.
• [64] Zhao J, Zhou L, Wang J, Shan T, Zhong L, Liu X, Gao X. Endophytic fungi for producing bioactive compounds originally from their host plants. In book: Current Research, Technology and Education Topics in Applied Microbiology and Microbial BiotechnologyEdition: First EditionPublisher: Formatex Research Center, Badajoz, Spain. 2010. https://doi.org/10.26538/tjnpr/v7i3.20
• [65] Rashmi M, Venkateswara Sarma V. Secondary Metabolite Production by Endophytic Fungi: The Gene Clusters, Nature, and Expression. Reference Series in Phytochemistry Endophytes and Secondary Metabolites. 2019; 475-490. Springer International Publishing. https://doi.org/10.1007/978-3-319-90484-9_20
• [66] Kaaniche F, Hamed A, Abdel-Razek AS, Wibberg D, Abdissa N, El Euch IZ, Allouche N, Mellouli L, Shaaban M, Sewald N. Bioactive secondary metabolites from new endophytic fungus Curvularia. sp isolated from Rauwolfia macrophylla. PLoS One. 2019;14(6):e0217627. https://doi.org/10.1371/journal.pone.0217627
• [67] Rai N, Kumari Keshri P, Verma A, Kamble SC, Mishra P, Barik S, Kumar Singh S, Gautam V. Plant associated fungal endophytes as a source of natural bioactive compounds. Mycology. 2021;12(3):139-159. https://doi.org/10.1080/21501203.2020.1870579
• [68] Kausar F, Kim KH, Farooqi HMU, Farooqi MA, Kaleem M, Waqar R, Khalil AAK, Khuda F, Abdul Rahim CS, Hyun K, Choi KH, Mumtaz AS. Evaluation of antimicrobial and anticancer activities of selected medicinal plants of Himalayas, Pakistan. Plants (Basel). 2021 Dec 24;11(1):48. https://doi.org/10.3390/plants11010048
• [69] Adhikari A, Khan MA, Imran M, Lee KE, Kang SM, Shin JY, Joo GJ, Khan M, Yun BW, Lee IJ. The Combined ınoculation of Curvularia lunata AR11 and biochar stimulates synthetic silicon and potassium phosphate use efficiency, and mitigates salt and drought stresses in rice. Front Plant Sci. 2022;13:816858. Front Plant Sci. 2022;13(3):1–14. https://doi.org/10.3389/fpls.2022.816858
• [70] Santra HK, Banerjee D. Bioactivity study and metabolic profiling of Colletotrichum alatae LCS1, an endophyte of club moss Lycopodium clavatum L. PLoS One. 2022;17(4):1–29. https://doi.org/10.1371/journal.pone.0267302
• [71] Polak J, Grąz M, Wlizło K, Szałapata K, Kapral-Piotrowska J, Paduch R, Jarosz-Wilkołazka A. Bioactive Properties of a Novel Antibacterial Dye Obtained from Laccase-Mediated Oxidation of 8-Anilino-1-naphthalenesulfonic Acid. Molecules. 2022 ;27(2):487. https://doi.org/10.3390/molecules27020487.
• [72] Al-Mijalli SH, Assaggaf H, Qasem A, El-Shemi AG, Abdallah EM, Mrabti HN, Bouyahya A. Antioxidant, antidiabetic, and antibacterial potentials and chemical composition of Salvia officinalis and Mentha suaveolens grown wild in Morocco. Adv Pharmacol Pharm Sci. 2022;2022:2844880.https://doi.org/10.1155/2022/2844880
• [73] Songserm P, Klanrit P, Klanrit P, Phetcharaburanin J, Thanonkeo P, Apiraksakorn J, Phomphrai K, Klanrit P. Antioxidant and anticancer potential of bioactive compounds from Rhinacanthus nasutus cell suspension culture. Plants (Basel). 2022;11(15):1994. https://doi.org/10.3390/plants11151994
• [74] Shahrivari S, Alizadeh S, Ghassemi-Golezani K, Aryakia E. A comprehensive study on essential oil compositions, antioxidant, anticholinesterase and antityrosinase activities of three Iranian Artemisia species. Sci Rep. 2022;12(1):7234. https://doi.org/10.1038/s41598-022-11375-6
• [75] El-Hawary SS, Moawad AS, Bahr HS, Abdelmohsen UR, Mohammed R. Natural product diversity from the endophytic fungi of the genusAspergillus. RSC Adv. 2020;10(37):58–79. https://doi.org/10.1039/d0ra04290k
• [76] Safriani N, Rungkat FZ, Yuliana ND, Prangdimurti E. Immunomodulatory and Antioxidant Activities of Select Indonesian Vegetables, Herbs, and Spices on Human Lymphocytes. Int J Food Sci. 2021;1(1):1-12. https://doi.org/10.1155/2021/6340476
• [77] Ding Z, Tao T, Wang L, Zhao Y, Huang H, Zhang D, Liu M, Wang Z, Han J. Bioprospecting of Novel and Bioactive Metabolites from Endophytic Fungi Isolated from Rubber Tree Ficus elastica Leaves. J Microbiol Biotechnol. 2019;29(5):731-738. https://doi.org/10.4014/jmb.1901.01015
• [78] Olugbami JO, Gbadegesin MA, Odunola OA. In vitro evaluation of the antioxidant potential, pheolic and flavonoid contents of the stem bark ethanol extract of Anogeissus leiocarpus. Afr J Med Med Sci. 2014;4391):101-109. https://doi.org/10.4014/jmb.1901.01015
• [79] Lee KJ, Oh YC, Cho WY, Ma JY. Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay. Hindawi. 2015;1(1):1-13. https://doi.org/10.1155/2015/165457