pharmjournalРазработка и регистрация лекарственных средствDrug development & registration2305-20662658-5049LLC «CPHA»10.33380/2305-2066-2023-12-3-89-95pharmjournal-1546Research ArticleМЕТОДЫ АНАЛИЗА ЛЕКАРСТВЕННЫХ СРЕДСТВANALYTICAL METHODSСостав и содержание гидролизуемых таннинов в листьях фейхоа, Acca sellowianaComposition and Content of Hydrolysable Tannins in Feijoa Leaves, Acca sellowianahttps://orcid.org/0000-0003-4642-651XКрольТ. А.KrolT. A.

117216, Москва, ул. Грина, д. 7

7/1, Greena str., Moscow, 117216

tatianakroll1@gmail.comhttps://orcid.org/0000-0002-1228-0594БалеевД. Н.BaleevD. N.

117216, Москва, ул. Грина, д. 7

7/1, Greena str., Moscow, 117216

https://orcid.org/0000-0002-8383-9965ОсиповВ. И.OssipovV. I.

117216, Москва, ул. Грина, д. 7

7/1, Greena str., Moscow, 117216

Федеральное государственное бюджетное научное учреждение «Всероссийский научно-исследовательский институт лекарственных и ароматических растений» (ФГБНУ ВИЛАР)РоссияAll-Russian Scientific Research Institute of Medicinal and Aromatic PlantsRussian Federation2023300820231238995Copyright © Кроль Т.А., Балеев Д.Н., Осипов В.И., 20232023Кроль Т.А., Балеев Д.Н., Осипов В.И.Krol T.A., Baleev D.N., Ossipov V.I.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmjournal.ru/jour/article/view/1546Введение

Введение. Растение Acca sellowiana, или фейхоа, принадлежит к семейству Myrtaceae и представляет собой вечнозеленый кустарник или небольшое дерево высотой 4–6 метров. Фитохимический состав наиболее подробно изучен у плодов A. sellowiana. Показано, что они наиболее богаты фенольными кислотами, гидролизуемыми и конденсированными таннинами, стероидными сапонинами и флавоноидами. Известно, что гидролизуемые таннины обладают высокой биологической активностью.

Цель

Цель. Изучить состав и содержание гидролизуемых таннинов в листьях A. sellowiana.

Материалы и методы

Материалы и методы. Ультраэффективная жидкостная хроматография в комбинации с диодным и масс-спектрометрическим детекторами.

Результаты и обсуждение

Результаты и обсуждение. В результате анализа в экстракте из листьев A. sellowiana были обнаружены 22 фенольных соединения. Они были классифицированы как флаван-3-олы, флавоноиды и гидролизуемые таннины. Два соединения идентифицировать не удалось. Общее содержание гидролизуемых таннинов составило 44,28 мг/г или 90 % всех фенольных соединений. При этом эллаготаннины были основными фенольными соединениями экстракта. Их содержание составило 40,47 мг/г, тогда как галлоилглюкоз только 3,81 мг/г.

Заключение

Заключение. Таким образом, изучен состав и содержание гидролизуемых таннинов в листьях растений A. sellowiana, интродуцированных в оранжерейном комплексе ФГБНУ ВИЛАР. Показано, что листья накапливают в основном мономерные эллаготаннины, на долю которых приходится 92 % от общего содержания гидролизуемых таннинов. Полученные данные свидетельствуют, что листья A. sellowiana могут быть использованы в качестве сырья для получения экстрактов с высоким содержанием эллаготаннинов и разработки на их основе лекарственных препаратов.

Introduction

Introduction. Acca sellowiana, or feijoa belongs to the Myrtaceae family and it is an evergreen shrub or small tree 4–6 meters high. The phytochemical composition has been most thoroughly studied in the fruits of A. sellowiana. It has been shown that feijoa is rich in phenolic acids, hydrolysable and condensed tannins, steroidal saponins, and flavonoids. Hydrolysable tannins are known to have high biological activity.

Aim

Aim. To study the composition and content of hydrolysable tannins in the leaves of A. sellowiana.

Materials and methods

Materials and methods. Ultra-high performance liquid chromatography coupled with diode array detection and mass spectrometry.

Results and discussion

Results and discussion. The results obtained showed the presence of 22 phenolic compounds in the extract of the A. sellowiana leaves. They have been classified as flavan-3-ols, flavonoids and hydrolysable tannins. Two compounds could not be identified. The total content of hydrolysable tannins was 44,28 mg/g (90 % of the total phenolic content). At the same time, ellagitannins were the main phenolic compounds of the extract (40,47 mg/g), while the amount of galloyl-glucose was only 3,81 mg/g.

Conclusions

Conclusions. Composition and content of hydrolysable tannins in the leaves of A. sellowiana introduced in the greenhouse of VILAR have been studied. The leaves accumulate mainly monomeric ellagitannins represented 92 % of the total content of hydrolysable tannins. The data obtained indicate that the leaves of A. sellowiana can be used as a raw material for obtaining extracts with a high content of ellagitannins and developing drugs based on them.

Acca sellowianaжидкостная хроматографияфенольные соединениягидролизуемые танниныAcca sellowianaliquid chromatographyphenolic compoundshydrolysable tanninsReferencesAoyama H., Sakagami H., Hatano T. Three new flavonoids, proanthocyanidin, and accompanying phenolic constituents from Feijoa sellowiana. Bioscience, Biotechnology, and Biochemistry. 2018;82(1):31–41. DOI: 10.1080/09168451.2017.1412246.Aoyama H., Sakagami H., Hatano T. Three new flavonoids, proanthocyanidin, and accompanying phenolic constituents from Feijoa sellowiana. Bioscience, Biotechnology, and Biochemistry. 2018;82(1):31–41. DOI: 10.1080/09168451.2017.1412246.Fischer G., Parra-Coronado A. Influence of some environmental factors on the feijoa (Acca sellowiana [Berg] Burret): A review. Agronomía Colombiana. 2020;38(3):388–397. DOI: 10.15446/agron.colomb.v38n3.88982.Fischer G., Parra-Coronado A. Influence of some environmental factors on the feijoa (Acca sellowiana [Berg] Burret): A review. Agronomía Colombiana. 2020;38(3):388–397. DOI: 10.15446/agron.colomb.v38n3.88982.Tuncel N. B., Yılmaz N. Optimizing the extraction of phenolics and antioxidants from feijoa (Feijoa sellowiana, Myrtaceae). Journal of Food Science and Technology. 2015;52(1):141–150. DOI: 10.1007/s13197-013-0968-0.Tuncel N. B., Yılmaz N. Optimizing the extraction of phenolics and antioxidants from feijoa (Feijoa sellowiana, Myrtaceae). Journal of Food Science and Technology. 2015;52(1):141–150. DOI: 10.1007/s13197-013-0968-0.Omarova Z. M., Kuljan R. V. Evaluation of hybrid forms of feijoa (Feijoa sellowiana Berg) on the basis of productivity and fruit quality. Novye tehnologii. 2019;3:181–189. (In Russ.)Omarova Z. M., Kuljan R. V. Evaluation of hybrid forms of feijoa (Feijoa sellowiana Berg) on the basis of productivity and fruit quality. Novye tehnologii. 2019;3:181–189. (In Russ.)Mehrabani D., Rasekh H., Farahi M. H., Masoumi S. J., Acker J. P. Screening of feijoa (Acca Sellowiana (O. Berg) Burret) fruit effect on proliferation and apoptosis using bone marrow derived stem cells model. Electronic Journal of General Medicine. 2020;18(1):em269. DOI: 10.29333/ejgm/8458.Mehrabani D., Rasekh H., Farahi M. H., Masoumi S. J., Acker J. P. Screening of feijoa (Acca Sellowiana (O. Berg) Burret) fruit effect on proliferation and apoptosis using bone marrow derived stem cells model. Electronic Journal of General Medicine. 2020;18(1):em269. DOI: 10.29333/ejgm/8458.Kedelidze N., Nakashidze I., Baratashvili D., Lomtatidze N. Feijoa (Feijoa sellowiana Berg) and its usage in medicine. Georgian Journal of Biomedical Sciences. 2019:11.Kedelidze N., Nakashidze I., Baratashvili D., Lomtatidze N. Feijoa (Feijoa sellowiana Berg) and its usage in medicine. Georgian Journal of Biomedical Sciences. 2019:11.Mosbah H., Louati H., Boujbiha M. A., Chahdoura H., Snoussi M., Flamini G., Ascrizzi R., Bouslema A., Achour L., Selmi B. Phytochemical characterization, antioxidant, antimicrobial and pharmacological activities of Feijoa sellowiana leaves growing in Tunisia. Industrial Crops and Products. 2018;112:521–531. DOI: 10.1016/j.indcrop.2017.12.051.Mosbah H., Louati H., Boujbiha M. A., Chahdoura H., Snoussi M., Flamini G., Ascrizzi R., Bouslema A., Achour L., Selmi B. Phytochemical characterization, antioxidant, antimicrobial and pharmacological activities of Feijoa sellowiana leaves growing in Tunisia. Industrial Crops and Products. 2018;112:521–531. DOI: 10.1016/j.indcrop.2017.12.051.Dell’Olmo E., Gaglione R., Pane K., Sorbo S., Basile A., Esposito S., Arciello A. Fighting multidrug resistance with a fruit extract: anti-cancer and anti-biofilm activities of Acca sellowiana. Natural Product Research. 2021;35(10):1686–1689. DOI: 10.1080/14786419.2019.1624961.Dell’Olmo E., Gaglione R., Pane K., Sorbo S., Basile A., Esposito S., Arciello A. Fighting multidrug resistance with a fruit extract: anti-cancer and anti-biofilm activities of Acca sellowiana. Natural Product Research. 2021;35(10):1686–1689. DOI: 10.1080/14786419.2019.1624961.Motohashi N., Kawase M., Shirataki Y., Tani S., Saito S., Sakagami H., Kurihara T., Nakashima H., Wolfard K., Mucsi I., Varga A., Molnár, J. Biological activity of Feijoa peel extracts. Anticancer research. 2000;20:4323–4330.Motohashi N., Kawase M., Shirataki Y., Tani S., Saito S., Sakagami H., Kurihara T., Nakashima H., Wolfard K., Mucsi I., Varga A., Molnár, J. Biological activity of Feijoa peel extracts. Anticancer research. 2000;20:4323–4330.Ramírez F., Kallarackal J. Phenological growth stages of Feijoa [Acca sellowiana (O. Berg) Burret] according to the BBCH scale under tropical Andean conditions. Scientia Horticulturae. 2018;232:184–190. DOI: 10.1016/j.scienta.2017.12.059.Ramírez F., Kallarackal J. Phenological growth stages of Feijoa [Acca sellowiana (O. Berg) Burret] according to the BBCH scale under tropical Andean conditions. Scientia Horticulturae. 2018;232:184–190. DOI: 10.1016/j.scienta.2017.12.059.Zhu F. Chemical and biological properties of feijoa (Acca sellowiana). Trends in Food Science & Technology. 2018;81:121–131. DOI: 10.1016/j.tifs.2018.09.008.Zhu F. Chemical and biological properties of feijoa (Acca sellowiana). Trends in Food Science & Technology. 2018;81:121–131. DOI: 10.1016/j.tifs.2018.09.008.Montoro P., Serreli, G., Gil K. A., D’Urso G., Kowalczyk A., Tuberoso C. I. G. Evaluation of bioactive compounds and antioxidant capacity of edible feijoa (Acca sellowiana (O. Berg) Burret) flower extracts. Journal of Food Science and Technology. 2020;57(6):2051–2060. DOI: 10.1007/s13197-020-04239-2.Montoro P., Serreli, G., Gil K. A., D’Urso G., Kowalczyk A., Tuberoso C. I. G. Evaluation of bioactive compounds and antioxidant capacity of edible feijoa (Acca sellowiana (O. Berg) Burret) flower extracts. Journal of Food Science and Technology. 2020;57(6):2051–2060. DOI: 10.1007/s13197-020-04239-2.Aniq F. O., Elfarnini M., Abdel-hamid A. A., Blaghen M. Chemical composition of isoflavones compounds and antioxidants from Feijoa sellowiana leaves. GSC Biological and Pharmaceutical Sciences. 2019;9(1):120–124. DOI: 10.30574/gscbps.2019.9.1.0157.Aniq F. O., Elfarnini M., Abdel-hamid A. A., Blaghen M. Chemical composition of isoflavones compounds and antioxidants from Feijoa sellowiana leaves. GSC Biological and Pharmaceutical Sciences. 2019;9(1):120–124. DOI: 10.30574/gscbps.2019.9.1.0157.Cebi N., Sagdic O. Characterization of Feijoa sellowiana leaves based on volatile and phenolic compound compositions and antimicrobial properties. Food Science and Technology. 2022;42:e14221. DOI: 10.1590/fst.14221.Cebi N., Sagdic O. Characterization of Feijoa sellowiana leaves based on volatile and phenolic compound compositions and antimicrobial properties. Food Science and Technology. 2022;42:e14221. DOI: 10.1590/fst.14221.El-Shenawi S. M., Marzouk M. S., Dib R. A., Elyazed H. A., Shaffie N. M., Moharram F. A. Polyphenols and biological activities of Feijoa sellowiana leaves and twigs. Revista Latinoamericana de Química. 2008;36(3):103–120.El-Shenawi S. M., Marzouk M. S., Dib R. A., Elyazed H. A., Shaffie N. M., Moharram F. A. Polyphenols and biological activities of Feijoa sellowiana leaves and twigs. Revista Latinoamericana de Química. 2008;36(3):103–120.Kim J., Gripenberg S., Karonen M., Salminen J.-P. Seed tannin composition of tropical plants. Phytochemistry. 2021;187:112750. DOI: 10.1016/j.phytochem.2021.112750.Kim J., Gripenberg S., Karonen M., Salminen J.-P. Seed tannin composition of tropical plants. Phytochemistry. 2021;187:112750. DOI: 10.1016/j.phytochem.2021.112750.Haslam E. Vegetable tannins–Lessons of a phytochemical lifetime. Phytochemistry. 2007;68(22–24):2713–2721. DOI: 10.1016/j.phytochem.2007.09.009.Haslam E. Vegetable tannins–Lessons of a phytochemical lifetime. Phytochemistry. 2007;68(22–24):2713–2721. DOI: 10.1016/j.phytochem.2007.09.009.Baert N., Karonen M., Salminen J.-P. Isolation, characterisation and quantification of the main oligomeric macrocyclic ellagitannins in Epilobium angustifolium by ultra-high performance chromatography with diode array detection and electrospray tandem mass spectrometry. Journal of Chromatography A. 2015;1419:26–36. DOI: 10.1016/j.chroma.2015.09.050.Baert N., Karonen M., Salminen J.-P. Isolation, characterisation and quantification of the main oligomeric macrocyclic ellagitannins in Epilobium angustifolium by ultra-high performance chromatography with diode array detection and electrospray tandem mass spectrometry. Journal of Chromatography A. 2015;1419:26–36. DOI: 10.1016/j.chroma.2015.09.050.Yoshida T., Yoshimura M., Amakura Y. Chemical and biological significance of oenothein B and related ellagitannin oligomers with macrocyclic structure. Molecules. 2018;23(3):552. DOI: 10.3390/molecules23030552.Yoshida T., Yoshimura M., Amakura Y. Chemical and biological significance of oenothein B and related ellagitannin oligomers with macrocyclic structure. Molecules. 2018;23(3):552. DOI: 10.3390/molecules23030552.de Oliveira Schmidt H., Rockett F. C., Klen A. V. B., Schmidt L., Rodrigues E., Tischer B., Augusti P. R., de Oliveira V. R., da Silva V. L., Flôres S. H., de O. Rios A. New insights into the phenolic compounds and antioxidant capacity of feijoa and cherry fruits cultivated in Brazil. Food Research International. 2020;136:109564. DOI: 10.1016/j.foodres.2020.109564.de Oliveira Schmidt H., Rockett F. C., Klen A. V. B., Schmidt L., Rodrigues E., Tischer B., Augusti P. R., de Oliveira V. R., da Silva V. L., Flôres S. H., de O. Rios A. New insights into the phenolic compounds and antioxidant capacity of feijoa and cherry fruits cultivated in Brazil. Food Research International. 2020;136:109564. DOI: 10.1016/j.foodres.2020.109564.Mosbah H., Chahdoura H., Adouni K., Kamoun J., Boujbiha M. A., Gonzalez-Paramas A. M., Santos-Buelga C., Ciudad-Mulero M., Morales P., Fernández-Ruiz V., Achour L., Selmi B. Nutritional properties, identification of phenolic compounds, and enzyme inhibitory activities of Feijoa sellowiana leaves. Journal of Food Biochemistry. 2019;43(11):e13012. DOI: 10.1111/jfbc.13012.Mosbah H., Chahdoura H., Adouni K., Kamoun J., Boujbiha M. A., Gonzalez-Paramas A. M., Santos-Buelga C., Ciudad-Mulero M., Morales P., Fernández-Ruiz V., Achour L., Selmi B. Nutritional properties, identification of phenolic compounds, and enzyme inhibitory activities of Feijoa sellowiana leaves. Journal of Food Biochemistry. 2019;43(11):e13012. DOI: 10.1111/jfbc.13012.Díaz-de-Cerio E., Arráez-Román D., Segura-Carretero A., Ferranti P., Nicoletti R., Perrotta G. M., Gómez-Caravaca A. M. Establishment of pressurized-liquid extraction by response surface methodology approach coupled to HPLC-DAD-TOF-MS for the determination of phenolic compounds of myrtle leaves. Analytical and Bioanalytical Chemistry. 2018;410(15):3547–3557. DOI: 10.1007/s00216-018-0914-0.Díaz-de-Cerio E., Arráez-Román D., Segura-Carretero A., Ferranti P., Nicoletti R., Perrotta G. M., Gómez-Caravaca A. M. Establishment of pressurized-liquid extraction by response surface methodology approach coupled to HPLC-DAD-TOF-MS for the determination of phenolic compounds of myrtle leaves. Analytical and Bioanalytical Chemistry. 2018;410(15):3547–3557. DOI: 10.1007/s00216-018-0914-0.Engström M. T., Palijarvi M., Salminen J. P. Rapid fingerprint analysis of plant extracts for ellagitannins, gallic acid, and quinic acid derivatives and quercetin-, kaempferol- and myricetin-based flavonol glycosides by UPLC-QqQ-MS/MS. Journal of Agricultural and Food Chemistry. 2015;63(16):4068–4079.Engström M. T., Palijarvi M., Salminen J. P. Rapid fingerprint analysis of plant extracts for ellagitannins, gallic acid, and quinic acid derivatives and quercetin-, kaempferol- and myricetin-based flavonol glycosides by UPLC-QqQ-MS/MS. Journal of Agricultural and Food Chemistry. 2015;63(16):4068–4079.Vivas N., Laguerre M., de Boissel I. P., de Gaulejac N. V., Nonier M.-F. Conformational interpretation of vescalagin and castalagin physicochemical properties. Journal of agricultural and food chemistry. 2004;52(7):2073–2078. DOI: 10.1021/jf030460m.Vivas N., Laguerre M., de Boissel I. P., de Gaulejac N. V., Nonier M.-F. Conformational interpretation of vescalagin and castalagin physicochemical properties. Journal of agricultural and food chemistry. 2004;52(7):2073–2078. DOI: 10.1021/jf030460m.Wakamori S., Matsumoto S., Kusuki R., Ikeuchi K., Yamada H. Total synthesis of casuarinin. Organic Letters. 2020;22(9):3392–3396. DOI: 10.1021/acs.orglett.0c00876.Wakamori S., Matsumoto S., Kusuki R., Ikeuchi K., Yamada H. Total synthesis of casuarinin. Organic Letters. 2020;22(9):3392–3396. DOI: 10.1021/acs.orglett.0c00876.Santos L. S., Alves Filho E. G., Ribeiro P. R. V., Zocolo G. J., Silva S. M., de Lucena E. M. P., Alves R. E., de Brito E. S. Chemotaxonomic evaluation of different species from the Myrtaceae family by UPLC-qToF/MS-MS coupled to supervised classification based on genus. Biochemical Systematics and Ecology. 2020;90:104028. DOI: 10.1016/j.bse.2020.104028.Santos L. S., Alves Filho E. G., Ribeiro P. R. V., Zocolo G. J., Silva S. M., de Lucena E. M. P., Alves R. E., de Brito E. S. Chemotaxonomic evaluation of different species from the Myrtaceae family by UPLC-qToF/MS-MS coupled to supervised classification based on genus. Biochemical Systematics and Ecology. 2020;90:104028. DOI: 10.1016/j.bse.2020.104028.Araújo A. R., Araújo A. C., Reis R. L., Pires R. A. Vescalagin and castalagin present bactericidal activity toward methicillin-resistant bacteria. ACS biomaterials science & engineering. 2021;7(3):1022–1030. DOI: 10.1021/acsbiomatrials.0c01698.Araújo A. R., Araújo A. C., Reis R. L., Pires R. A. Vescalagin and castalagin present bactericidal activity toward methicillin-resistant bacteria. ACS biomaterials science & engineering. 2021;7(3):1022–1030. DOI: 10.1021/acsbiomatrials.0c01698.Quideau S., Varadinova T., Karagiozova D., Jourdes M., Pardon P., Baudry C., Genova P., Diakov T., Petrova R. Main structural and stereochemical aspects of the antiherpetic activity of nonahydroxyterphenoyl-containing C-glycosidic ellagitannins. Chemistry & biodiversity. 2004;1(2):247–258. DOI: 10.1002/cbdv.200490021.Quideau S., Varadinova T., Karagiozova D., Jourdes M., Pardon P., Baudry C., Genova P., Diakov T., Petrova R. Main structural and stereochemical aspects of the antiherpetic activity of nonahydroxyterphenoyl-containing C-glycosidic ellagitannins. Chemistry & biodiversity. 2004;1(2):247–258. DOI: 10.1002/cbdv.200490021.Kato E., Uenishi Y., Inagaki Y., Kurokawa M., Kawabata J. Isolation of rugosin A, B and related compounds as dipeptidyl peptidase-IV inhibitors from rose bud extract powder. Bioscience, Biotechnology, and Biochemistry. 2016;80(11):2087–2092. DOI: 10.1080/09168451.2016.1214533.Kato E., Uenishi Y., Inagaki Y., Kurokawa M., Kawabata J. Isolation of rugosin A, B and related compounds as dipeptidyl peptidase-IV inhibitors from rose bud extract powder. Bioscience, Biotechnology, and Biochemistry. 2016;80(11):2087–2092. DOI: 10.1080/09168451.2016.1214533.Al-Sayed E., Michel H. E., Khattab M. A., El-Shazly M., Singab A. N. Protective role of casuarinin from melaleuca leucadendra against ethanol-induced gastric ulcer in rats. Planta Medica. 2020;86(01):32–44. DOI: 10.1055/a-1031-7328.Al-Sayed E., Michel H. E., Khattab M. A., El-Shazly M., Singab A. N. Protective role of casuarinin from melaleuca leucadendra against ethanol-induced gastric ulcer in rats. Planta Medica. 2020;86(01):32–44. DOI: 10.1055/a-1031-7328.Kuo P.-L., Hsu Y.-L., Lin T.-C., Lin L.-T., Chang J.-K., Lin C.-C. Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cells. Planta medica. 2005;71(3):237–243. DOI: 10.1055/s-2005-837823.Kuo P.-L., Hsu Y.-L., Lin T.-C., Lin L.-T., Chang J.-K., Lin C.-C. Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cells. Planta medica. 2005;71(3):237–243. DOI: 10.1055/s-2005-837823.Tolkachev O. N., Sheichenko O. P., Fadeeva I. I., Sheichenko V. I., Semenova T. S., Shipulina L. D., Vichkanova S. A., inventors. The method of obtaining the antiviral drug «Hyporamine». Patent RUS RU2098111C1. 10.12.1997. Available at: https://patents.google.com/patent/RU2098111C1/ru. (In Russ.)Tolkachev O. N., Sheichenko O. P., Fadeeva I. I., Sheichenko V. I., Semenova T. S., Shipulina L. D., Vichkanova S. A., inventors. The method of obtaining the antiviral drug «Hyporamine». Patent RUS RU2098111C1. 10.12.1997. Available at: https://patents.google.com/patent/RU2098111C1/ru. (In Russ.)Xiao S.-Y., Wen B.-Q., Zhuang H.-Y., Wang J.-L., Tang J., Chen H.-Z., Chen X.-X., Cao Y. Extraction and antitumor activity of pedunculagin from eucalyptus leaves. International Conference on Biomedical Engineering and Biotechnology. 2012:280–282. DOI: 10.1109/iCBEB.2012.217.Xiao S.-Y., Wen B.-Q., Zhuang H.-Y., Wang J.-L., Tang J., Chen H.-Z., Chen X.-X., Cao Y. Extraction and antitumor activity of pedunculagin from eucalyptus leaves. International Conference on Biomedical Engineering and Biotechnology. 2012:280–282. DOI: 10.1109/iCBEB.2012.217.Khalifa I., Zhu W., Nafie M. S., Dutta K., Li C. Anti-COVID-19 effects of ten structurally different hydrolysable tannins through binding with the catalytic-closed sites of COVID-19 main protease: An in-silico approach. 2020. DOI: 10.20944/preprints202003.0277.v1.Khalifa I., Zhu W., Nafie M. S., Dutta K., Li C. Anti-COVID-19 effects of ten structurally different hydrolysable tannins through binding with the catalytic-closed sites of COVID-19 main protease: An in-silico approach. 2020. DOI: 10.20944/preprints202003.0277.v1.

The authors declare that there are no conflicts of interest present.