Combination Effect of Extracts and Pure Compounds of Endophytic Fungi Isolated from Sungkai (Peronema canescens) Leaves on Antioxidant Activity
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Keywords:
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Antioxidant, Combination Effect, Endophytic Fungi Extract, Pure Compound, Sungkai
Abstract
Endophytic fungi extracts have various biological and pharmacological activities as natural antioxidants which have the potential to be developed in the pharmaceutical. Drugs made from natural substances frequently work best when they are present in large quantities. This may result in unfavorable side effects from using more of one substance at a time. This limitation can be overcome by using a combination of the extracts/pure compounds that allow synergistic interactions with strong antioxidant properties at fairly low concentrations. The purpose of this research was to determine the combined effect of endophytic fungi extracts and its pure compounds on their antioxidant activity. This research was initiated by rejuvenating eight selected endophytic fungal isolates from Sungkai leaves and morphological characterization was carried out. Each fungus was cultivated in PDB medium for 4 weeks under statistical conditions. Ethyl acetate was used to extract the endophytic fungi’s liquid culture, which was then evaporated. Each endophytic fungal extract (PD1-PD8) and their five pure compounds were tested for antioxidant activity by the DPPH method. Then a combination of two and three extracts was carried out with a ratio of 1:1. The results show that the interaction of the mixture of endophytic fungi extracts and their pure compounds can be classified as synergistic (combined effect of the extracts > individual effects), additive (combined effect of the extracts = individual effect), and nothing is antagonistic (combined effect of the extracts < individual effects). The best combination in this study was PD4+PD5+PD6 (1:1:1) which could be used as a formula for further research into in vivo immunostimulant tests. Another conclusion from this research is that the pure compounds contained in the extracts have lower antioxidant activity than the extracts and do not have a synergistic effect on the combination.
References
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Nutmakul, T. and S. Chewchinda (2023). Synergistic Effect of Trikatuk, a Traditional Thai Formulation, on Antioxidant and Alpha-glucosidase Inhibitory Activities. Heliyon, 9(1); 13063
Oktiansyah, R., E. Elfita, H. Widjajanti, A. Setiawan, P. L. Hariani, and N. Hidayati (2023a). Endophytic Fungi Isolated from the Root Bark of Sungkai (Peronema canescens) as Antibacterial and Antioxidant. Journal of Medical Pharmaceutical and Allied Sciences, 12(2320); 8–15
Oktiansyah, R., E. Elfita, H. Widjajanti, A. Setiawan, M. Mardiyanto, and S. S. A. Nasution (2023b). Antioxidant and Antibacterial Activity of Endophytic Fungi Isolated from the Leaves of Sungkai (Peronema canescens). Tropical Journal of Natural Product Research, 7(3); 82–97
Oktiansyah, R., H. Widjajanti, A. Setiawan, S. S. A. Nasution, Mardiyanto, and Elfita (2023). Antibacterial and Antioxidant Activity of Endophytic Fungi Extract Isolated from Leaves of Sungkai (Peronema canescens). Science and Technology Indonesia, 8(2); 170–177
Pezzani, R., B. Salehi, S. Vitalini, M. Iriti, F. A. Zuñiga, J. Sharifi-Rad, M. Martorell, and N. Martins (2019). Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective. Medicina, 55(4); 110
Pitt, J. I. and A. D. Hocking (2009). Fungi and Food Spoilage, volume 519. Springer
Rahardhian, M. R. R., Y. Susilawati, A. Sumiwi, M. Muktiwardoyo, and Muchtaridi (2022). A Review of Sungkai (Peronema canescens): Traditional Usage, Phytoconstituent, and Pharmacological Activities. International Journal of Applied Pharmaceutics, 14(5); 15–23
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Sari, M. T., H. Widjajanti, F. Ferlinahayati, H. Hermansyah, R. Oktiansyah, and E. Elfita (2023). Secondary Metabolite of Endophytic fungi Daldinia eschscholtzii from the Leaves Syzygium polyanthum. Science and Technology Indonesia,, 8(4); 560–569
Septiana, E., Y. Yadi, and P. Simanjuntak (2020). Antioxidant Activity of Endophytic Fungi Isolated from Turmeric Flowers. Biosaintifika: Journal of Biology & Biology Education, 12(2); 268–273
Sharma, K., S. Guleria, V. K. Razdan, and V. Babu (2020). Synergistic Antioxidant and Antimicrobial Activities of Essential Oils of Some Selected Medicinal Plants in Combination and with Synthetic Compounds. Industrial Crops and Products, 154; 112569
Sitarek, P., A. Merecz-Sadowska, T. Kowalczyk, J. Wieczfinska, R. Zajdel, and T. Śliwiński (2020). Potential Synergistic Action of Bioactive Compounds from Plant Extracts against Skin Infecting Microorganisms. International Journal of Molecular Sciences, 21(14); 5105
Sonam, K. S. and S. Guleria (2017). Synergistic Antioxidant Activity of Natural Products. Annals of Pharmacology and Pharmaceutics, 2(8); 1086
Srisuksomwong, P., L. Kaenhin, and L. Mungmai (2023). Collagenase and Tyrosinase Inhibitory Activities and Stability of Facial Cream Formulation Containing Cashew Leaf Extract. Cosmetics, 10(1); 17
Tiwari, P. and H. Bae (2022). Endophytic Fungi: Key Insights, Emerging Prospects, and Challenges in Natural Product Drug Discovery. Microorganisms, 10(2); 360
Vaou, N., E. Stavropoulou, C. Voidarou, Z. Tsakris, G. Rozos, C. Tsigalou, and E. Bezirtzoglou (2022). Interactions between Medical Plant-derived Bioactive Compounds: Focus on Antimicrobial Combination Effects. Antibiotics, 11(8); 1014
Walsh, T. J., R. T. Hayden, and D. H. Larone (2018). Larone’s Medically Important Fungi: A Guide to Identification. John Wiley & Sons
Watanabe, T. (1993). Pictorial Atlas of Soil and Seed Fungi. CRC Press
Widjajanti, H., E. Nurnawati, E. D. Zahwa, et al. (2022). Optimization of Antibacterial Production of Endophytic Fungi with Various Sources of C, N, and pH using The Response Surface Methodology. Science and Technology Indonesia, 7(2); 149–157
Zhou, X., S. W. Seto, D. Chang, H. Kiat, V. Razmovski Naumovski, K. Chan, and A. Bensoussan (2016). Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research. Frontiers in Pharmacology, 7; 201
Zihad, S., M. T. Hasan, M. S. Sultana, S. Nath, L. Nahar, M. A. Rashid, S. J. Uddin, S. D. Sarker, and J. A. Shilpi (2022). Isolation and Characterization of Antibacterial Compounds from Aspergillus Fumigatus: An Endophytic Fungus from a Mangrove Plant of the Sundarbans. Evidence-Based Complementary and Alternative Medicine, 2022
Zulkefli, N., C. N. M. Che Zahari, N. H. Sayuti, A. A. Kamarudin, N. Saad, H. S. Hamezah, H. Bunawan, S. N. Baharum, A. Mediani, and Q. U. Ahmed (2023). Flavonoids As Potential Wound healing Molecules: Emphasis on Pathways Perspective. International Journal of Molecular Sciences, 24(5); 4607
Atanasov, A. G., S. B. Zotchev, V. M. Dirsch, and C. T. Supuran (2021). Natural Products in Drug Discovery: Advances and Opportunities. Nature reviews Drug discovery, 20(3); 200–216
Basavegowda, N. and K. H. Baek (2021). Synergistic Antioxidant and Antibacterial Advantages of Essential Oils for Food Packaging Applications. Biomolecules, 11(9); 1267
Ben Mrid, R., N. Bouchmaa, W. Ouedrhiri, A. Ennoury, Z. ZouaouI, I. Kabach, M. Nhiri, and R. El Fatimy (2022). Synergistic Antioxidant Effects of Natural Compounds on H2O2-induced Cytotoxicity of Human Monocytes. Frontiers in Pharmacology, 13; 830323
Chan, W. J. J., J. Adiwidjaja, A. J. McLachlan, A. V. Boddy, and J. E. Harnett (2023). Interactions between Natural Products and Cancer Treatments: Underlying Mechanisms and Clinical Importance. Cancer Chemotherapy and Pharmacology, 91(2); 103–119
Choudhury, A. (2022). Potential Role of Bioactive Phytochemicals in Combination Therapies against Antimicrobial Activity. Journal of Pharmacopuncture, 25(2); 79
Dai, C., J. Lin, H. Li, Z. Shen, Y. Wang, T. Velkov, and J. Shen (2022). The Natural Product Curcumin As an Antibacterial Agent: Current Achievements and Problems. Antioxidants, 11(3); 459
Dillasamola, D., Y. Aldi, H. Kurniawan, and I. M. Jalius (2021). Immunomodulator Effect Test of Sungkai Leaves (Peronema canescsens Jack.) Ethanol Extract Using Carbon Clearance Method. 2nd International Conference on Contemporary Science and Clinical Pharmacy 2021, 40; 1–6
Ebrahimi, B., S. Baroutian, J. Li, B. Zhang, T. Ying, and J. Lu (2023). Combination of Marine Bioactive Compounds and Extracts for the Prevention and Treatment of Chronic Diseases. Frontiers in Nutrition, 9; 1047026
El Sayed, A. S., M. T. El Sayed, A. M. Rady, N. Zein, G. Enan, A. Shindia, S. El Hefnawy, M. Sitohy, and B. Sitohy (2020). Exploiting the Biosynthetic Potency of Taxol from Fungal Endophytes of Conifers Plants; Genome Mining and Metabolic Manipulation. Molecules, 25(13); 3000
Elfita, R. Oktiansyah, Mardiyanto, H. Widjajanti, A. Setiawan, and S. S. A. Nasution (2023). Bioactive Compounds of Endophytic Fungi Lasiodiplodia theobromae Isolated from The Leaves of Sungkai (Peronema canescens). Biointerface Research in Applied Chemistry, 13(6); 50–57
Elfita, R. Oktiansyah, M. Mardiyanto, H. Widjajanti, and A. Setiawan (2022). Antibacterial and Antioxidant Activity of Endophytic Fungi Isolated from Peronema canescens Leaves. Biodiversitas Journal of Biological Diversity, 23(9); 4783–4792
Falakdin, P., D. Dastan, and S. Pourmoslemi (2023). Combined Antimicrobial Activity of Extracts from Quercus infectoria Galls and Scrophularia striata Aerial Parts for an Anticariogenic Herbal Mouthwash. Journal of Pharmacopuncture, 26(1); 44
Fazly Bazzaz, B. S., S. Darvishi Fork, R. Ahmadi, and B. Khameneh (2021). Deep Insights into Urinary Tract Infections and Effective Natural Remedies. African Journal of Urology, 27(1); 1–13
Gakuubi, M. M., M. Munusamy, Z. X. Liang, and S. B. Ng (2021). Fungal Endophytes: A Promising Frontier for Discovery of Novel Bioactive Compounds. Journal of Fungi, 7(10); 786
Gupta, A., V. Meshram, M. Gupta, S. Goyal, K. A. Qureshi, M. Jaremko, and K. K. Shukla (2023). Fungal Endophytes: Microfactories of Novel Bioactive Compounds with Therapeutic Interventions; A Comprehensive Review on the Biotechnological Developments in the Field of Fungal Endophytic Biology Over the Last Decade. Biomolecules, 13(7); 1038
Ialongo, D., V. Tudino, M. Arpacioglu, A. Messore, E. Patacchini, R. Costi, R. Di Santo, and V. N. Madia (2023). Synergistic Effects of Caffeine in Combination with Conventional Drugs: Perspectives of a Drug That Never Ages. Pharmaceuticals, 16(5); 730
Komariah, M., S. Amirah, S. Maulana, M. F. Abdurrahman, K. Ibrahim, H. Platini, J. A. J. M. N. Lele, K. Kohar, L. Rahayuwati, and M. K. Z. H. Firdaus (2023). The Efficacy of Herbs as Complementary and Alternative Therapy in Recovery and Clinical Outcome Among People with COVID-19: A Systematic Review, Meta-Analysis, and Meta-Regression. Therapeutics and Clinical Risk Management, 19; 611–627
Liu, Z. H., D. M. Wang, S. F. Fan, D. W. Li, and Z. W. Luo (2016). Synergistic Effects and Related Bioactive Mechanism of Potentilla Fruticosa L. Leaves Combined with Ginkgo Biloba Extracts Studied with Microbial Test System (mts). BMC Complementary and Alternative Medicine, 16(1); 1–14
Murugaiyan, J., P. A. Kumar, G. S. Rao, K. Iskandar, S. Hawser, J. P. Hays, Y. Mohsen, S. Adukkadukkam, W. A. Awuah, and R. A. M. Jose (2022). Progress in Alternative Strategies to Combat Antimicrobial Resistance: Focus on Antibiotics. Antibiotics, 11(2); 200
Nguyen, T. L. A. and D. Bhattacharya (2022). Antimicrobial Activity of Quercetin: An Approach to Its Mechanistic Principle. Molecules, 27(8); 2494
Nutmakul, T. and S. Chewchinda (2023). Synergistic Effect of Trikatuk, a Traditional Thai Formulation, on Antioxidant and Alpha-glucosidase Inhibitory Activities. Heliyon, 9(1); 13063
Oktiansyah, R., E. Elfita, H. Widjajanti, A. Setiawan, P. L. Hariani, and N. Hidayati (2023a). Endophytic Fungi Isolated from the Root Bark of Sungkai (Peronema canescens) as Antibacterial and Antioxidant. Journal of Medical Pharmaceutical and Allied Sciences, 12(2320); 8–15
Oktiansyah, R., E. Elfita, H. Widjajanti, A. Setiawan, M. Mardiyanto, and S. S. A. Nasution (2023b). Antioxidant and Antibacterial Activity of Endophytic Fungi Isolated from the Leaves of Sungkai (Peronema canescens). Tropical Journal of Natural Product Research, 7(3); 82–97
Oktiansyah, R., H. Widjajanti, A. Setiawan, S. S. A. Nasution, Mardiyanto, and Elfita (2023). Antibacterial and Antioxidant Activity of Endophytic Fungi Extract Isolated from Leaves of Sungkai (Peronema canescens). Science and Technology Indonesia, 8(2); 170–177
Pezzani, R., B. Salehi, S. Vitalini, M. Iriti, F. A. Zuñiga, J. Sharifi-Rad, M. Martorell, and N. Martins (2019). Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective. Medicina, 55(4); 110
Pitt, J. I. and A. D. Hocking (2009). Fungi and Food Spoilage, volume 519. Springer
Rahardhian, M. R. R., Y. Susilawati, A. Sumiwi, M. Muktiwardoyo, and Muchtaridi (2022). A Review of Sungkai (Peronema canescens): Traditional Usage, Phytoconstituent, and Pharmacological Activities. International Journal of Applied Pharmaceutics, 14(5); 15–23
Ranjutha, V., Y. Chen, L. A. Al Keridis, M. Patel, N. Alshammari, M. Adnan, S. Sahreen, S. C. Gopinath, and S. Sasidharan (2023). Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence. Antibiotics, 12(3); 477
Santra, H. K. and D. Banerjee (2022). Bioactivity Study and Metabolic Profiling of Colletotrichum Alatae LCS1, an Endophyte of Club Moss Lycopodium Clavatum L. PloS one, 17(4); e0267302
Sari, M. T., H. Widjajanti, F. Ferlinahayati, H. Hermansyah, R. Oktiansyah, and E. Elfita (2023). Secondary Metabolite of Endophytic fungi Daldinia eschscholtzii from the Leaves Syzygium polyanthum. Science and Technology Indonesia,, 8(4); 560–569
Septiana, E., Y. Yadi, and P. Simanjuntak (2020). Antioxidant Activity of Endophytic Fungi Isolated from Turmeric Flowers. Biosaintifika: Journal of Biology & Biology Education, 12(2); 268–273
Sharma, K., S. Guleria, V. K. Razdan, and V. Babu (2020). Synergistic Antioxidant and Antimicrobial Activities of Essential Oils of Some Selected Medicinal Plants in Combination and with Synthetic Compounds. Industrial Crops and Products, 154; 112569
Sitarek, P., A. Merecz-Sadowska, T. Kowalczyk, J. Wieczfinska, R. Zajdel, and T. Śliwiński (2020). Potential Synergistic Action of Bioactive Compounds from Plant Extracts against Skin Infecting Microorganisms. International Journal of Molecular Sciences, 21(14); 5105
Sonam, K. S. and S. Guleria (2017). Synergistic Antioxidant Activity of Natural Products. Annals of Pharmacology and Pharmaceutics, 2(8); 1086
Srisuksomwong, P., L. Kaenhin, and L. Mungmai (2023). Collagenase and Tyrosinase Inhibitory Activities and Stability of Facial Cream Formulation Containing Cashew Leaf Extract. Cosmetics, 10(1); 17
Tiwari, P. and H. Bae (2022). Endophytic Fungi: Key Insights, Emerging Prospects, and Challenges in Natural Product Drug Discovery. Microorganisms, 10(2); 360
Vaou, N., E. Stavropoulou, C. Voidarou, Z. Tsakris, G. Rozos, C. Tsigalou, and E. Bezirtzoglou (2022). Interactions between Medical Plant-derived Bioactive Compounds: Focus on Antimicrobial Combination Effects. Antibiotics, 11(8); 1014
Walsh, T. J., R. T. Hayden, and D. H. Larone (2018). Larone’s Medically Important Fungi: A Guide to Identification. John Wiley & Sons
Watanabe, T. (1993). Pictorial Atlas of Soil and Seed Fungi. CRC Press
Widjajanti, H., E. Nurnawati, E. D. Zahwa, et al. (2022). Optimization of Antibacterial Production of Endophytic Fungi with Various Sources of C, N, and pH using The Response Surface Methodology. Science and Technology Indonesia, 7(2); 149–157
Zhou, X., S. W. Seto, D. Chang, H. Kiat, V. Razmovski Naumovski, K. Chan, and A. Bensoussan (2016). Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research. Frontiers in Pharmacology, 7; 201
Zihad, S., M. T. Hasan, M. S. Sultana, S. Nath, L. Nahar, M. A. Rashid, S. J. Uddin, S. D. Sarker, and J. A. Shilpi (2022). Isolation and Characterization of Antibacterial Compounds from Aspergillus Fumigatus: An Endophytic Fungus from a Mangrove Plant of the Sundarbans. Evidence-Based Complementary and Alternative Medicine, 2022
Zulkefli, N., C. N. M. Che Zahari, N. H. Sayuti, A. A. Kamarudin, N. Saad, H. S. Hamezah, H. Bunawan, S. N. Baharum, A. Mediani, and Q. U. Ahmed (2023). Flavonoids As Potential Wound healing Molecules: Emphasis on Pathways Perspective. International Journal of Molecular Sciences, 24(5); 4607
Authors
Elfita, Oktiansyah, R., Mardiyanto, Setiawan, A., & Widjajanti, H. (2024). Combination Effect of Extracts and Pure Compounds of Endophytic Fungi Isolated from Sungkai (Peronema canescens) Leaves on Antioxidant Activity. Science and Technology Indonesia, 9(1), 69–76. https://doi.org/10.26554/sti.2024.9.1.69-76
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