Полифенолы Perilla frutescens семейства Lamiaceae, идентифицированные с помощью тандемной масс-спектрометрии

Perilla frutescens получила применение в основном как масличная культура. Семена периллы содержат 40–53 % масла, 28 % белка. Вегетационный период составляет 100–150 дней. В России периллу выращивают на Дальнем Востоке, где урожайность достигает 0.8–1.2 т/га. Это растение короткого дня, поэтому большинство форм не цветет в условиях средней полосы России. Перилла различного географического происхождения имеет свои особенные, резко отличные признаки, характеризующие две географические группы: японскую и корейско-китайскую. Эти группы различаются длиной вегетационного периода, а также по высоте растений, окраске стебля, поверхности и величине листьев, форме куста, форме и размеру соцветий, величине чашечек и цвету семян. Perilla frutescens содержит большое количество полифенольных соединений, которые являются биологически активными компонентами. Цель данной работы состояла в метаболомном исследовании экстрактов из листьев P. frutescens, полученных из коллекции Всероссийского института генетических ресурсов растений им. Н.И. Вавилова и выращенных на полях его Дальневосточной опытной станции (Приморский край, Россия). Для идентификации целевых аналитов в экстрактах использовали метод высокоэффективной жидкостной хроматографии в сочетании с ионной ловушкой. Предварительные результаты показали наличие 23 биологически активных соединений, соответствующих виду P. frutescens. В дополнение к упомянутым метаболитам, в экстрактах P. frutescens был впервые обнаружен ряд соединений. Это кумарин умбеллиферон; тритерпен сквален; стеаридоновая кислота; высокомолекулярные карбоновые кислоты: тетракозановая кислота и сальвиановая кислота C; лигнан сирингарезинол; циклобутановый лигнан сагериновая кислота и др. Широкий спектр биологически активных соединений открывает богатые возможности для создания новых лекарственных средств и биологически активных добавок на основе экстрактов периллы семейства Lamiaceae, подсемейства Lamioideae, трибы Satureji и подтрибы Perillinae.

1. Abeywickrama G., Debnath S.C., Ambigaipalan P., Shahidi F. Phenolics of selected cranberry genotypes (Vaccinium macrocarpon Ait.) and their antioxidant efficacy. J. Agric. Food Chem. 2016;64(49): 9342-9351. https://doi.org/10.1021/acs.jafc.6b04291.

2. Ahmed H.M. Ethnomedicinal, phytochemical and pharmacological investigations of Perilla frutescens (L.) Britt. Molecules. 2019;24:102. https://doi.org/10.3390/molecules24010102.

3. Azmir J., Zaidula I.S.M., Rahmana M.M., Sharif K.M., Mohamed A., Sahena F., Jahurul M.H.A., Ghafoor K., Norulaini N.A.N., Omar A.K.M. Techniques for extraction of bioactive compounds from plant materials: a review. J. Food Eng. 2013;117(4):426-436. https://doi.org/10.1016/j.jfoodeng.2013.01.014.

4. Banno N., Akihisa T., Tokuda H., Yasukawa K., Higashihara H., Ukiya M., Watanabe K., Kimura Y., Hasegawa J., Nishino H. Triterpene acids from the leaves of Perilla frutescens and their antiinflammatory and antitumor-promoting effects. Biosci. Biotechnol. Biochem. 2004;68(1):85-90. https://doi.org/10.1271/bbb.68.85.

5. Bonzanini F., Bruni R., Palla G., Serlataite N., Caligiani A. Identification and distribution of lignans in Punica granatum L. fruit endocarp, pulp, seeds, wood knots and commercial juices by GC-MS. Food Chem. 2009;117(4):745-749. https://doi.org/10.1016/j.foodchem.2009.04.057.

6. Chen W., Gong L., Guo Z., Wang W., Zhang H., Liu X., Yu S., Xiong L., Luo J. A novel integrated method for large-scale detection, identification, and quantification of widely targeted metabolites: application in the study of rice metabolomics. Mol. Plant. 2013;6(6):1769-1780. https://doi.org/10.1093/mp/sst080.

7. Chen X., Zhang S., Xuan Z., Ge D., Chen X., Zhang J., Wang Q., Wu Y., Liu B. The phenolic fraction of Mentha haplocalyx and its constituent linarin ameliorate inflammatory response through inactivation of NF-kB and MAPKs in lipopolysaccharide-induced RAW264.7 cells. Molecules. 2017;22(5):811. https://doi.org/10.3390/molecules22050811.

8. Chen X., Zhu P., Liu B., Ge D., Wei L., Xu Y. Simultaneous determination of fourteen compounds of Hedyotis diffusa Willd extract in rats by UHPLC-MS/MS method: application to pharmacokinetics and tissue distribution study. J. Pharm. Biomed. Anal. 2018;159:490-512. https://doi.org/10.1016/j.jpba.2018.07.023.

9. Cirlini M., Mena P., Tassotti M., Herrlinger K.A., Nieman K.M., Dall’Asta C., Del Rio D. Phenolic and volatile composition of a dry spearmint (Mentha spicata L.). Molecules. 2016;21(8):1007. https://doi.org/10.3390/molecules21081007.

10. Cukelj N., Jakasa I., Sarajlija H., Novotni D., Curic D. Identification and quantification of lignans in wheat bran by gas chromatography-electron capture detection. Talanta. 2011;84(1):127-132. https://doi.org/10.1016/j.talanta.2010.12.025.

11. Di Loreto A., Bosi S., Montero L., Bregola V., Marotti L., Sferrazza R.E., Dinelli G., Herrero M., Cifuentes A. Determination of phenolic compounds in ancient and modern durum wheat genotypes. Electrophoresis. 2018;39:2001-2010.

12. Dinelli G., Segura-Carretero A., Di Silvestro R., Marotti I., Arraez-Roman D., Benedettelli S., Ghiselli L., Fernandez-Gutierrez A. Profiles of phenolic compounds in modern and old common wheat varieties determined by liquid chromatography coupled with time-of-flight mass spectrometry. J. Chromatogr. A. 2011;1218(42):7670-7681. https://doi.org/10.1016/j.chroma.2011.05.065.

13. Goufo P., Singh R.K., Cortez I. A reference list of phenolic compounds (including stilbenes) in grapevine (Vitis vinifera L.) roots, woods, canes, stems, and leaves. Antioxidants. 2020;9(5):398. https://doi.org/10.3390/antiox9050398.

14. Gu L., Wu T., Wang Z. TLC bioautography-guided isolation of antioxidants from fruit of Perilla frutescens var. acuta. LWF - Food Sci. Technol. 2009;42(1):131-136. https://doi.org/10.1016/j.lwt.2008.04.006.

15. Hamed A.R., El-Hawary S.S., Ibrahim R.M., Abdelmohsen U.R., El-Halawany A.M. Identification of chemopreventive components from halophytes belonging to Aizoaceae and Cactaceae through LC/MS - bioassay guided approach. J. Chromatogr. Sci. 2021;59(7):618-626. https://doi.org/10.1093/chromsci/bmaa112.

16. Hassan W.H.B., Abdelaziz S., Al Yosef H.M. Chemical composition and biological activities of the aqueous fraction of Parkinsonea aculeata L. growing in Saudi Arabia. Arabian J. Chem. 2019;12(3): 377-387. https://doi.org/10.1016/j.arabjc.2018.08.003.

17. He Y.-K., Yao Y.-Y., Chang Y.-N. Characterization of anthocyanins in Perilla frutescens var. acuta extract by advanced UPLC-ESI-ITTOF-MSn method and their anticancer bioactivity. Molecules. 2015; 20(5):9155-9169. https://doi.org/10.3390/molecules20059155.

18. Honda G., Koezuka Y., Kamisako W., Tabata M. Isolation of sedative principles from Perilla frutescens. Chem. Pharm. Bull. 1986;34(4): 1672-1677. https://doi.org/10.1248/cpb.34.1672.

19. Hussain F., Jahan N., Rahman K., Sultana B., Jamil S. Identification of hypotensive biofunctional compounds of Coriandrum sativum and evaluation of their angiotensin-converting enzyme (ACE) inhibition potential. Oxid. Med. Cell. Longev. 2018;2018:4643736. https://doi.org/10.1155/2018/4643736.

20. Jiang R.-W., Lau K.-M., Hon P.-M., Mak T.C.W., Woo K.-S., Fung K.-P. Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Curr. Med. Chem. 2005;12(2):237-246. https://doi.org/10.2174/0929867053363397.

21. Justesen U. Negative atmospheric pressure chemical ionisation lowenergy collision activation mass spectrometry for the characterisation of flavonoids in extracts of fresh herbs. J. Chromatogr. A. 2000;902(2):369-379. https://doi.org/10.1016/s0021-9673(00)00861-x.

22. Kan S., Chen G., Han C., Chen Z., Song X., Ren M., Jiang H. Chemical constituents from the roots of Xanthium sibiricum. Nat. Prod. Res. 2011;25(13):1243-1249. https://doi.org/10.1080/14786419.2010.539182.

23. Kaufmann C.M., Grassmann J., Letzel T. HPLC method development for the online-coupling of chromatographic Perilla frutescens extract separation with xanthine oxidase enzymatic assay. J. Pharmaceut. Biomed. Analys. 2016;124:347-357. https://doi.org/10.1016/j.jpba.2016.03.011.

24. Kim S., Oh S., Noh H.B., Ji S., Lee S.H., Koo J.M., Choi C.W., Jhun H.P. In vitro antioxidant and anti-Propionibacterium acnes activities of cold water, hot water, and methanol extracts, and their respective ethyl acetate fractions, from Sanguisorba officinalis L. roots. Molecules. 2018;23(11):3001. https://doi.org/10.3390/molecules23113001.

25. Lee J.H., Park K.H., Lee M.H., Kim H.T., Seo W.D., Kim J.Y. Identification, characterization, and quantification of phenolic compounds in the antioxidant activity-containing fraction from the seeds in Korean perilla (Perilla frutescens) cultivars. Food Chem. 2013;136(2): 843-852. https://doi.org/10.1016/j.foodchem.2012.08.057.

26. Li Z.-X., Zhu H., Cai X.-P., He D.-D., Hua J.-L., Ju J.-M., Lv H., Ma L., Li W.-L. Simultaneous determination of five triterpene acids in rat plasma by liquid chromatography-mass spectrometry and its application in pharmacokinetic study after oral administration of Folium Eriobotryae effective fraction. Biomed. Chromatogr. 2015;29(12): 1791-1797. https://doi.org/10.1002/bmc.3497.

27. Longvah T., Deosthale Y.G., Kumar P.U. Nutritional and short term toxicological evaluation of Perilla seed oil. Food Chem. 2000;70(1): 13-16. https://doi.org/10.1016/S0308-8146(99)00263-0.

28. Marzouk M.M., Hussein S.R., Elkhateeb A., El-Shabrawy M., AbdelHameed E.-S.S., Kawashty S.A. Comparative study of Mentha species growing wild in Egypt: LC-ESI-MS analysis and chemosystematic significance. J. Appl. Pharm. Sci. 2018;8(8):116-122. https://doi.org/10.7324/JAPS.2018.8816.

29. Meng L., Lozano Y.F., Gaydou E.M., Li B. Antioxidant activities of polyphenols extracted from Perilla frutescens varieties. Molecules. 2009;14(1):133-140. https://doi.org/10.3390/molecules14010133.

30. Pandey R., Kumar B. HPLC-QTOF-MS/MS-based rapid screening of phenolics and triterpenic acids in leaf extracts of Ocimum species and their interspecies variation. J. Liq. Chromatogr. Relat. Technol. 2016;39(4):225-238. https://doi.org/10.1080/10826076.2016.1148048.

31. Paudel L., Wyzgovski F.J., Scheerens J.C., Chanon A.M., Reese R.N., Smiljanic D., Wesdemiotis C., Blakeslee J.J., Riedl K.M., Rinaldi P.L. Nonanthocyanin secondary metabolites of black raspberry (Rubus occidentalis L.) fruits: identification by HPLC-DAD, NMR, HPLC-ESI-MS, and ESI-MS/MS analyses. J. Agric. Food Chem. 2013;61(49):12032-12043. https://doi.org/10.1021/jf4039953.

32. Peng Y., Ye J., Kong J. Determination of phenolic compounds in Perilla frutescens L. by capillary electrophoresis with electrochemical detection. J. Agric. Food Chem. 2005;53(21):8141-8147. https://doi.org/10.1021/JF051360E.

33. Pharmacopoeia of the Eurasian Economic Union. Approved by Decision of the Board of Eurasian Economic Commission No. 100 dated August 11, 2020. http://www.eurasiancommission.org/ru/act/texnreg/deptexreg/LSMI/Documents/Фармакопея Союза 11 08.pdf

34. Razgonova M.P., Zakharenko A.M., Grudev V., Ercisli S., Golokhvast K.S. Comparative analysis of Far East Sikhotinsky Rhododendron (Rh. sichotense) and East Siberian Rhododendron (Rh. adamsii) using supercritical CO2-extraction and HPLC-MS/MS spectrometry. Molecules. 2020;25:3774. https://doi.org/10.3390/molecules25173774.

35. Sanchez-Rabaneda F., Jauregui O., Lamuela-Raventos R.M., Viladomat F., Bastida J., Codina C. Qualitative analysis of phenolic compounds in apple pomace using liquid chromatography coupled to mass spectrometry in tandem mode. Rapid Commun. Mass Spectrom. 2004;18(5):553-563. https://doi.org/10.1002/rcm.1370.

36. Sharma M., Sandhir R., Singh A., Kumar P., Mishra A., Jachak S., Singh S.P., Singh J., Roy J. Comparison analysis of phenolic compound characterization and their biosynthesis genes between two diverse bread wheat (Triticum aestivum) varieties differing for chapatti (unleavened flat bread) quality. Front. Plant Sci. 2016;7:1870. https://doi.org/10.3389/fpls.2016.01870.

37. Spinola V., Pinto J., Castilho P.C. Identification and quantification of phenolic compounds of selected fruits from Madeira Island by HPLCDAD-ESI-MSn and screening for their antioxidant activity. Food Chem. 2015;173:14-30. https://doi.org/10.1016/j.foodchem.2014.09.163.

38. Sun L., Tao S., Zhang S. Characterization and quantification of polyphenols and triterpenoids in thinned young fruits of ten pear varieties by UPLC-Q TRAP-MS/MS. Molecules. 2019;24(1):159. https://doi.org/10.3390/molecules24010159.

39. Sun S., Gao Y., Ling X., Lou H. The combination effects of phenolic compounds and fluconazole on the formation of ergosterol in Candida albicans determined by high-performance liquid chromatography/tandem mass spectrometry. Anal. Biochem. 2005;336:39-45. https://doi.org/10.1016/j.ab.2004.06.038.

40. Sut S., Zengin G., Maggi F., Malagoli M., Dall’Acqua S. Triterpene acid and phenolics from ancient apples of Friuli Venezia Giulia as nutraceutical ingredients: LC-MS study and in vitro activities. Molecules. 2019;24(6):1109. https://doi.org/10.3390/molecules24061109.

41. Toh T.H., Prior B.A., van der Merwe M.J. Quantification of plasma membrane ergosterol of Saccharomyces cerevisiae by direct-injection atmospheric pressure chemical ionization/tandem mass spectrometry. Anal. Biochem. 2001;288(1):44-51. https://doi.org/10.1006/abio.2000.4877.

42. Vallverdu-Queralt A., Jauregui O., Medina-Remon A., Lamuela-Raventos R.M. Evaluation of a method to characterize the phenolic profile of organic and conventional tomatoes. Agric. Food Chem. 2012;60(13):3373-3380. https://doi.org/10.1021/jf204702f.

43. Wang F., Li D., Han Z., Gao H., Wu L. Chemical constituents of Rhodiola rosea and inhibitory effect on UV-induced A375-S2 cell death. J. Shenyang Pharmaceut Univ. 2007;24(5):280-283.

44. Xu L.L., Xu J.J., Zhong K.R., Shang Z.P., Wang F., Wang R.F., Liu B. Analysis of non-volatile chemical constituents of Menthae Haplocalycis herba by ultra-high performance liquid chromatography-high resolution mass spectrometry. Molecules. 2017;22:1756. https://doi.org/10.3390/molecules22101756.

45. Yamazaki M., Nakajima J., Yamanashi M., Makita Y., Springob K., Awazuhara M., Saito K. Metabolomics and differential gene expression in anthocyanin chemo-varietal forms of Perilla frutescens. Phytochemistry. 2003;62(6):987-995. https://doi.org/10.1016/s0031-9422(02)00721-5.

46. Yang S.T., Wu X., Rui W., Guo J., Feng Y.F. UPLC/Q-TOF-MS analysis for identification of hydrophilic phenolics and lipophilic diterpenoids from Radix Salviae Miltiorrhizae. Acta Chromatogr. 2015;27:711-728. https://doi.org/10.1556/achrom.27.2015.4.9.

47. Zhang Z., Jia P., Zhang X., Zhang Q., Yang H., Shi H., Zhang L. LC-MS/MS determination and pharmacokinetic study of seven flavonoids in rat plasma after oral administration of Cirsium japonicum DC. extract. J. Ethnopharmacol. 2014;158:66-75. https://doi.org/10.1016/j.jep.2014.10.022.

48. Zhou X.-J., Yan L.-L., Yin P.-P., Shi L.-L., Zhang J.-H., Liu J.-H., Ma C. Structural characterisation and antioxidant activity evaluation of phenolic compounds from cold-pressed Perilla frutescens var. arguta seed flour. Food Chem. 2014;164:150-157. https://doi.org/10.1016/j.foodchem.2014.05.062.