Characterization of essential oils and biological activities of Etlingera spp. from different agroecology in Southeast Sulawesi, Indonesia
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Abstract. Tee SA, Alam S, Sastyarina Y, Yodha AWM, Reymon, Setiawan MA, Musdalipah. 2025. Characterization of essential oils and biological activities of Etlingera spp. from different agroecology in Southeast Sulawesi, Indonesia. Biodiversitas 26: 1653-1665. Genus Etlingera, a part of Zingiberaceae, shows potential due to secondary metabolites influenced by agroecological factors, enhancing its therapeutic uses. The study aimed to characterize essential oils and biological activities of Etlingera elatior, Etlingera rubroloba, and Etlingera calophrys rhizomes collected from South Konawe, Wakatobi, and Muna District. Gas Chromatography-Mass Spectrometry (GC-MS) profiled the essential oils, while phenolic (TPC) and flavonoid (TFC) concentrations were determined using Folin-Ciocalteu and aluminum chloride methods. Antioxidant activity was assessed using DPPH and ABTS assays, and toxicity testing was performed on shrimp larvae. The research found that multiple species grow in areas with annual rainfall ranging from 1,800-2,100 mm/year, temperatures of 23-30°C, humidity levels of 78-84%, topography of 9-72 masl, and pH of 4.9-6.5. The essential oil content includes fatty acids (20.1-42.48%), phenolic (6.28-29.52%), and terpenoid (1.24-2.39). The IC50 of antioxidant activity (ABTS) for E. elatior, E. rubroloba, and E. calophrys were 1.3 mg/mL, 1.5 mg/mL, and 1.1 mg/mL, compared to vitamin C at 2.23 mg/mL. The DPPH assay IC50 values were 2.09 mg/mL, 2.17 mg/mL, and 2.42 mg/mL, compared to vitamin C at 2.78 mg/mL, respectively. TPC values were 113.63 mgGAE/g, 26.56 mgGAE/g and 143.00 mgGAE/g, respectively. TFC values were 62.03 mgQE/g, 21.07 mgQE/g, and 34.51 mgQE/g, respectively. Toxic LC50 values for extracts were 6.98 mg/L, 18.72 mg/L, and 120.86 mg/L compared to the positive control at 3.24 mg/L. The Structural Equation Models (SEM) approach demonstrates the direct and indirect influence of climatic and soil factors on secondary metabolites and biological activity of the genus Etlingera. In conclusion, the genus Etlingera is a promising source of antioxidants and anticancer agents. It is recommended for cultivation in suitable locations in Southeast Sulawesi, instilling hope and optimism about the future of this research.
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Ahmad R, Sahidin I, Taher M, Low C, Noor NM, Sillapachaiyaporn C, Chuchawankul S, Sarachana T, Tencomnao T, Iskandar F, Rajab NF, Baharum SN. 2018. Polygonumins A, a newly isolated compound from the stem of Polygonum minus Huds with potential medicinal activities. Sci Rep 8 (1): 4202. DOI: 10.1038/s41598-018-22485-5.
Al Bashera M, Mosaddik A, Batiha GE-S, Alqarni M, Islam MA, Zouganelis GD, Alexiou A, Zahan R. 2021. In vivo and in vitro evaluation of preventive activity of inflammation and free radical scavenging potential of plant extracts from oldenlandia corymbosa l. Appl Sci 11 (19): 9073. DOI: 10.3390/app11199073.
Alam S, Purwanto BH, Hanudin E, Putra ETS. 2020. Soil diversity influences on oil palm productivity in ultramafic ecosystems, Southeast Sulawesi, Indonesia. Biodiversitas 21 (11): 5521-5530. DOI: 10.13057/biodiv/d211161.
Aswan M, Arafah N, Sahidin I, Imran, Suryani, Ngkoimani LO. 2020. Composition chemistry and distribution to quality of essential oil from rhizome E. elatior and E. calophyris by Gas Chromatography-Mass Spectrometry (GC-MS). IOP Conf Ser: Mat Sci Eng 797: 012018. DOI: 10.1088/1757-899X/797/1/012018.
Barbosa GB, Nueva MCY. 2019. Antioxidant activity and phenolic content of Hornstedtia conoidea (Zingiberaceae). Asian J Biol Life Sci 8 (1): 01-07. DOI: 10.5530/ajbls.2019.8.1.
Chan EWC, Lim YY, Wong SK. 2011. Phytochemistry and pharmacological properties of Etlingera elatior: A review. Pharmacogn J 3 (22): 6-10. DOI: 10.5530/pj.2011.22.2.
Chaouqi S, Moratalla-López N, Alonso GL, Lorenzo C, Zouahri A, Asserar N, Haidar EM, Guedira T. 2023. Effect of soil composition on secondary metabolites of Moroccan Saffron (Crocus sativus L.). Plants 12 (4): 711. DOI: 10.3390/plants12040711.
Cornara L, Malaspina P, Betuzzi F, Di Gristina E, D’Arrigo M, Ingegneri M, Trombetta D, Smeriglio A. 2023. The influence of pedo-climatic conditions on the micromorphological, phytochemical features, and biological properties of leaves of Saponaria sicula Raf. Intl J Mol Sci 24 (14): 11693. DOI: 10.3390/ijms241411693.
Cornara L, Mandrone M, Smeriglio A. 2024. Biotic and abiotic stressors in plant metabolism. Intl J Mol Sci 25 (1): 121. DOI: 10.3390/ijms25010121.
Dash B, Sahoo A, Ray A, Jena S, Nayak S. 2020. Identification of chemical constituents of Zingiber zerumbet rhizome extract using GC/MS. J Biol Active Prod Nat 10 (5): 411-417. DOI: 10.1080/22311866.2020.1821775.
David B, Wolfender J-L, Dias DA. 2015. The pharmaceutical industry and natural products: Historical status and new trends. Phytochem Rev 14: 299-315. DOI: 10.1007/s11101-014-9367-z.
Daula A, Basher M. 2019. Genus Etlingera - a review on chemical composition and antimicrobial activity of essential oils. J Med Plants Res 13 (7): 135-156. DOI: 10.5897/jmpr2019.6740.
de Boer H, Newman M, Poulsen AD, Droop AJ, Fér T, Hi?n LTT, Hlavatá K, Lamxay V, Richardson JE, Steffen K, Leong-Škorni?ková J. 2018. Convergent morphology in alpinieae (Zingiberaceae): Recircumscribing amomum as a monophyletic genus. Taxon 67 (1): 6-36. DOI: 10.12705/671.2.
Du Y, Fu X, Chu Y, Wu P, Liu Y, Ma L, Tian H, Zhu B. 2022. Biosynthesis and the roles of plant sterols in development and stress responses. Intl J Mol Sci 23 (4): 2332. DOI: 10.3390/ijms23042332.
Effendi KN, Fauziah N, Wicaksono R, Erminawati, Arsil P, Naufalin R. 2019. Analysis of bioactive components and phytochemical of powders stem and leaves of kecombrang (Etlingera elatior). IOP Conf Ser: Earth Environ Sci 406: 012003. DOI: 10.1088/1755-1315/406/1/012003.
Elgamal AM, Ahmed RF, Abd-ElGawad AM, El Gendy AE-NG, Elshamy AI, Nassar MI. 2021. Chemical profiles, anticancer, and anti-aging activities of essential oils of Pluchea dioscoridis (L.) dc. and Erigeron bonariensis L. Plants 10 (4): 667. DOI: 10.3390/plants10040667.
Erwin E, Pusparohmana WR, Sari IP, Hairani R, Usman U. 2020. Phytochemical and antioxidant activity evaluation of the bark of Tampoi (Baccaurea macrocarpa). F1000Res 7: 1977. DOI: 10.12688/f1000research.16643.2.
Fauziah F, Maulinasari M, Harnelly E, Ismail YS, Fitri L. 2022. Toxicity test of rose periwinkle (Catharanthus roseus) leaves endophytic bacteria using Brine Shrimp Lethality Test (BSLT) method. Biodiversitas 23 (1): 171-177. DOI: 10.13057/biodiv/d230122.
Fisher P, Freyre R, Gómez C, Pearson B, Sanchez-Jones T, Steed S, Laughlin W, Hochmuth R, Wasielewski J, Lieurance D, Harmon C, Paret M, Osborne L, Athearn K, Sargent S, Zhang M, Flores S, Nelson C, Retana-Cordero M, Tello N. 2023. Ginger, galangal, and turmeric production in Florida. EDIS 4: 1-9. DOI: 10.32473/edis-ep638-2023.
Fonmboh DJ, Abah ER, Fokunang TE, Herve B, Teke GN, Rose NM, Borgia NN, Fokunang LB, Andrew BN, Kaba N, Bathelemy N, Ntungwen FC. 2020. An overview of methods of extraction, isolation and characterization of natural medicinal plant products in improved traditional medicine research. Asian J Res Med Pharm Sci 9 (2): 31-57. DOI: 10.9734/ajrimps/2020/v9i230152.
Fristiohady A, Wahyuni W, Yusuf MI, Malik F, Purnama LOMJ, Bafadal M, Leorita M, Jabar A, Malaka MH, Sahidin I. 2020. Hepatoprotective activity of Etlingera elatior (Jack) R.M. Smith extract against ccl4-induced hepatic toxicity in male wistar rats. Res J Pharm Technol 13 (10): 4685-4690. DOI: 10.5958/0974-360X.2020.00807.0.
Hamsidi R, Karmilah, Daud NS, Malaka MH, Yodha AWM, Musdalipah, Arfan, Sahidin I. 2024. Chemotaxonomy in the Etlingera genus from Sulawesi, Indonesia: Design and molecular docking of antioxidant marker. Biodiversitas 25: 449-457. DOI: 10.13057/biodiv/d250202.
Huang L, Zhu X, Zhou S, Cheng Z, Shi K, Zhang C, Shao H. 2021. Phthalic acid esters: Natural sources and biological activities. Toxins 13 (7): 495. DOI: 10.3390/toxins13070495.
Ilyas YM, Sahidin I, Jabbar A, Yodha AWM, Diantini A, Pradipta IS, Amalia R, Febrianti RM, Hadisaputri YE, Ghozali M, Julaeha E. 2023. Effect of immunomodulating extract and some isolates from Etlingera rubroloba A.D. Poulsen fruits on diabetic patients with tuberculosis. Molecules 28: 2401. DOI: 10.3390/molecules28052401.
Imran, Wahyuni, Fristiohady A, Leorita M, Malaka MH, Ilyas YM, Musadar, Rahmatika NS, Darmawan A, Fajriah S, Yodha AWM, Sahidin I. 2022. Radical scavenger and antidiabetic potencies of Etlingera elatior fruits growing in South East Sulawesi-Indonesia. Res J Pharm Technol 15 (5): 2141-2146. DOI: 10.52711/0974-360X.2022.00355.
Ivanovic M, Makoter K, Razboršek MI. 2021. Comparative study of chemical composition and antioxidant activity of essential oils and crude extracts of four characteristic Zingiberaceae herbs. Plants 10 (3): 501. DOI: 10.3390/plants10030501.
Jabbar A, Ilyas YM, Wahyuni, Hamzah H, Windarsih A, Pratiwi SUT, Rohman A. 2024. LC-MS analysis, antioxidant and anti-inflamatory activity, isolation of secondary metabolite of ethanol extract stem of Etlingera rubroloba AD Poulsen. Case Stud Chem Environ Eng 10: 100780. DOI: 10.1016/j.cscee.2024.100780.
Jabbar A, Wahyuono S, Sahidin I, Puspitasari I. 2021. Free radical scavenging activity of methanol extract and compounds isolated from stems of Etlingera rubroloba A.D Poulsen. Intl J Pharm Res 13 (1): 1099-1105. DOI: 10.31838/ijpr/2021.13.01.179.
Jan R, Asaf S, Numan M, Lubna, Kim K-M. 2021. Plant secondary metabolite biosynthesis and transcriptional regulation in response to biotic and abiotic stress conditions. Agronomy 11 (5): 968. DOI: 10.3390/agronomy11050968.
Juwita T, Puspitasari IM, Levita J. 2018. Torch ginger (Etlingera elatior): A review on its botanical aspects, phytoconstituents and pharmacological activities. Pak J Biol Sci 21 (4): 151-165. DOI: 10.3923/pjbs.2018.151.165.
Karimi A, Krähmer A, Herwig N, Schulz H, Hadian J, Meiners T. 2020. Variation of secondary metabolite profile of Zataria multiflora Boiss. populations linked to geographic, climatic, and edaphic factors. Front Plant Sci 11: 969. DOI: 10.3389/fpls.2020.00969.
Karmilah K, Hamsidi R, Daud NS, Malaka MH, Yodha AWM, Musdalipah M, Sahidin S. 2024. Antioxidant and anti-inflammatory activities of diarylheptanoid from Etlingera calophrys fruit. Molekul 19 (3): 604-613. DOI: 10.20884/1.jm.2024.19.3.12413.
Laftouhi A, Eloutassi N, Ech-Chihbi E, Rais Z, Abdellaoui A, Taleb A, Beniken M, Nafidi H-A, Salamatullah AM, Bourhia M, Taleb M. 2023. The impact of environmental stress on the secondary metabolites and the chemical compositions of the essential oils from some medicinal plants used as food supplements. Sustainability 15 (10): 7842. DOI: 10.3390/su15107842.
Li T, Liang J, Chen X, Wang H, Zhang S, Pu Y, Xu X, Li H, Xu J, Wu X, Liu X. 2021. The interacting roles and relative importance of climate, topography, soil properties and mineralogical composition on soil potassium variations at a national scale in China. Catena 196: 104875. DOI: 10.1016/j.catena.2020.104875.
Lianah L, Khasanah RAN, Pranatami DA, Krisantini K. 2021. Phytochemical screening and cytotoxic evaluation of Bauhinia scandens leaf extracts using HeLa and T47D cell lines. Biodiversitas 22 (2): 913-919. DOI: 10.13057/biodiv/d220247.
Loying R, Gogoi R, Lal M. 2021. Chemical composition, biological activities and cytotoxic effects of volatile oils extracted from leaves and rhizomes of Etlingera elatior (Jack) R.M. Sm. as a potential plant for industrial value. J Environ Biol 42: 544-551. DOI: 10.22438/eb/42/2(SI)/SI-284.
Mahdavi B, Yaacob WA, Din LB. 2017. Chemical composition, antioxidant, and antibacterial activity of essential oils from Etlingera sayapensis A.D. Poulsen & Ibrahim. Asian Pacific J Trop Med 10 (8): 819-826. DOI: 10.1016/j.apjtm.2017.08.006.
Megawati, Baari MJ, Sabandar CW. 2021. Uji toksisitas ekstrak metanol Etlingera calophrys dengan metode Brine Shrimp Lethality Test (BSLT). BioWallacea 8 (2): 144-153. [Indonesian]
Molyneux P. 2004. The use of the stable free radical Diphenylpicryl-hydrazyl (DPPH) for estimating antioxidant activity. Songklanakarin J Sci Technol 26 (2): 211-219.
Mosa KA, Ali MA, Ramamoorthy K, Ismail A. 2022. Exploring the relationship between plant secondary metabolites and macronutrient homeostasis. In: Kumar V, Srivastava AK, Suprasanna P (eds). Academic Press, London, UK. DOI: 10.1016/B978-0-12-822916-3.00007-X.
Musdalipah M, Karmilah K, Tee SA, Nurhikma E, Fauziah Y, Fristiohady A, Sahidin I, Yodha AWM. 2021b. Meistera chinensis fruit properties: Chemical compound, antioxidant, antimicrobial, and antifungal activity. IOP Conf Ser: Earth Environ Sci 755: 012014. DOI: 10.1088/1755-1315/755/1/012014.
Musdalipah M, Karmilah K, Tee SA, Yodha AMW, Sahidin I, Fristiohady A. 2021a. In vitro antioxidant assay and qualitative phytochemical estimation of Meistera chinensis from Southeast Sulawesi. J Phys: Conf Ser 1763: 012093. DOI: 10.1088/1742-6596/1763/1/012093.
Musdalipah M, Sahidin S, Muhidin M, Fristiohady A. 2024. Bioactive compound profiling and biological potential of Walay rhizome (Zingiberaceae) from Southeast Sulawesi: GC-MS and LC-MS analysis. Trop J Nat Prod Res 8 (12): 9686-9694. DOI: 10.26538/tjnpr/v8i12.49.
Musdalipah M, Tee SA, Karmilah K, Sahidin S, Fristiohady A, Yodha AWM. 2021c. Total phenolic and flavonoid content, antioxidant, and toxicity test with BSLT of Meistera chinensis fruit fraction from Southeast Sulawesi. Borneo J Pharm 4 (1): 6-15. DOI: 10.33084/bjop.v4i1.1686.
Musdalipah M, Yodha AMW, Karmilah K, Tee SA, Reymon R, Daud NS, Setiawan MA, Badia E, Agustini A. 2022. Toksisitas akut dan lethal dose (LD50) ekstrak buah Walay (Meistera chinensis) asal Sulawesi Tenggara terhadap Mencit (Mus musculus). Pharmacoscript 4 (2): 186-200. [Indonesian]
Nugroho Y, Soendjoto MA, Suyanto, Matatula J, Alam S, Wirabuana PYAP. 2022. Traditional medicinal plants and their utilization by local communities around Lambung Mangkurat Education Forests, South Kalimantan, Indonesia. Biodiversitas 23 (1): 306-314. DOI: 10.13057/biodiv/d230137.
Oforma CC, Udourioh GA, Ojinnaka CM. 2020. Characterization of essential oils and fatty acids composition of stored Ginger (Zingiber officinale Roscoe). J Appl Sci Environ Manag 23 (12): 2231. DOI: 10.4314/jasem.v23i12.22.
Pant P, Pandey S, Dall'Acqua S. 2021. The influence of environmental conditions on secondary metabolites in medicinal plants: A literature review. Chem Biodivers 18: e2100345. DOI: 10.1002/cbdv.202100345.
Qaderi MM, Martel AB, Strugnell CA. 2023. Environmental factors regulate plant secondary metabolites. Plants 12 (3): 447. DOI: 10.3390/plants12030447.
Radha, Kumar M, Puri S, Pundir A, Bangar SP, Changan S, Choudhary P, Parameswari E, Alhariri A, Samota MK, Damale RD, Singh S, Berwal MK, Dhumal S, Bhoite AG, Senapathy M, Sharma A, Bhushan B, Mekhemar M. 2021. Evaluation of nutritional, phytochemical, and mineral composition of selected medicinal plants for therapeutic uses from Cold Desert of Western Himalaya. Plants 10 (7): 1429. DOI: 10.3390/plants10071429.
Sahidin I, Wahyuni, Malaka MH, Fristiohady A, Saleh A, Marianti A. 2019a. Antibacterial and radical scavenger activities of extract and compounds of Wualae (Etlingera elatior) stems from Southeast Sulawesi. IOP Conf Ser: Mater Sci Eng 546: 062027. DOI: 10.1088/1757-899X/546/6/062027.
Sahidin I, Wahyuni, Malaka MH, Jabbar A, Imran, Manggau MA. 2018. Evaluation of antiradical scavenger activity of extract and compounds from Etlingera calophrys stems. Asian J Pharmac Clin Res 11 (2): 238-241. DOI: 10.22159/ajpcr.2018.v11i2.22535.
Sahidin S, Salsabila S, Wahyuni W, Fristiohady A, Imran I. 2019b. Potensi antibakteri ekstrak metanol dan senyawa aromatik dari buah Wualae (Etlingera elatior). Jurnal Kimia Valensi 5 (1): 1-7. DOI: 10.15408/jkv.v5i1.8658. [Indonesian]
Scott JS, Young RSE, Quek L-E et al. 2024. Cis-vaccenic acid is a key product of stearoyl-CoA desaturase 1 and a critical oncogenic factor in prostate cancer. Biorxiv 2024: 1-32. DOI: 10.1101/2024.03.28.587238.
Sharifi-Rad M, Varoni EM, Salehi B, Sharifi-Rad J, Matthews KR, Ayatollahi SA, Kobarfard F, Ibrahim SA, Mnayer D, Zakaria ZA, Sharifi-Rad M, Yousaf Z, Iriti M, Basile A, Rigano D. 2017. Plants of the genus Zingiber as a source of bioactive phytochemicals: From tradition to pharmacy. Molecules 22 (12): 2145. DOI: 10.3390/molecules22122145.
Subaryanti S, Sulistyaningsih YC, Iswantini D, Triadiati T. 2021. Essential oil components, metabolite profiles, and idioblast cell densities in galangal (Kaempferia galanga L.) at different agroecology. Agrivita J Agric Sci 43 (2): 245-261. DOI: 10.17503/agrivita.v43i2.2631.
Supriya GS, Bhoomika HR, Ganapathi M, Nataraj SK, Ravi CS. 2020. Effect of different media and nutrients on growth and yield of ginger (Zingiber officinale Rosc.) in soilless culture under protected structure. J Pharmacogn Phytochem 9 (6): 2004-2007.
Tee S, Musdalipah M, Karmilah K, Sahidin I, Fristiohady A, Yodha AWM. 2021. Phytochemical and toxicity assay of Meistera chinensis fruit extract: The endemic plant of Southeast Sulawesi. In: International Seminar on Promoting Local Resources for Sustainable Agriculture and Development (ISPLRSAD 2020). Atlantis Press, Dordrecht. DOI: 10.2991/absr.k.210609.059.
Wahyuni W, Diantini A, Ghozali M, Subarnas A, Julaeha E, Amalia R, Fristiohady A, Sundowo A, Fajriah S, Hadisaputri YE, Febrianti RM, Azzahra F, Yodha AWM, Sahidin I. 2022. In-vitro anticancer activity of chemical constituents from Etlingera alba Poulsen against triple negative breast cancer and in silico approaches towards Matrix metalloproteinase-1 inhibition. Indones J Sci Technol 7 (2): 251-278. DOI: 10.17509/ijost.v7i2.50547.
Wahyuni W, Diantini A, Ghozali M, Subarnas A, Julaeha E, Amalia R, Sahidin I. 2021b. Cytotoxic and antimigration activity of Etlingera alba (A.D.) Poulsen rhizome. Adv Pharmacol Pharm Sci 2021: 6597402. DOI: 10.1155/2021/6597402.
Wahyuni, Diantini A, Ghozali M, Subarnas A, Julaeha E, Amalia R, Sahidin I. 2021a. Phytochemical screening, toxicity activity and antioxidant capacity of ethanolic extract of Etlingera alba rhizome. Pak J Biol Sci 24 (7): 807-814. DOI: 10.3923/pjbs.2021.807.814.
Whangsomnuek N, Mungmai L, Mengamphan K, Amornlerdpison D. 2019. Bioactive compounds of aqueous extracts of flower and leaf of Etlingera elatior (Jack) R.M.sm. for cosmetic application. Maejo Intl J Sci Technol 13 (3): 196-208.
Wirabuana PYAP, Alam S, Matatula J, Harahap MM, Nugroho Y, Idris F, Meinata A, Sekar DA. 2021. The growth, aboveground biomass, crown development, and leaf characteristics of three Eucalyptus species at initial stage of planting in Jepara, Indonesia. Biodiversitas 22 (5): 2859-2869. DOI: 10.13057/biodiv/d220550.
Yaz?c? A. 2024. The strain-dependent antimicrobial and antibiofilm effect of Cis and Trans - Vaccenic acid against Pseudomonas aeruginosa. Cumhuriyet Sci J 45 (1): 1-7.
Yodha AWM, Badia E, Musdalipah M, Setiawan MA, Daud NS, Fusvita A, Fristiohady A, Sahidin S. 2023. Essential oils of Alpinia monopleura and their antibacterial and antioxidant activity. Molekul 18 (1): 80-88. DOI: 10.20884/1.jm.2023.18.1.6265
Yücel Ç, Karatoprak G?, Aç?kara OB, Akkol EK, Barak TH, Sobarzo-Sánchez E, Aschner M, Shirooie S. 2022. Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations. Front Pharmacol 13: 902551. DOI: 10.3389/fphar.2022.902551.
Zargoosh Z, Ghavam M, Bacchetta G, Tavili A. 2019. Effects of ecological factors on the antioxidant potential and total phenol content of Scrophularia striata Boiss. Sci Rep 9 (1): 16021. DOI: 10.1038/s41598-019-52605-8.
Zubair MS, Khairunisa SQ, Widodo A, Nasronudin, Pitopang R. 2021. Antiviral screening on Alpinia eremochlamys, Etlingera flexuosa, and Etlingera acanthoides extracts against HIV-infected MT-4 cells. Heliyon 7 (4): e06710. DOI: 10.1016/j.heliyon.2021.e06710.