TY - JOUR

T1 - Chromones and coumarins from Saposhnikovia divaricata (Turcz.) Schischk. Growing in Buryatia and Mongolia and their cytotoxicity

AU - Urbagarova, Bayarma M.

AU - Shults, Elvira E.

AU - Taraskin, Vasilii V.

AU - Radnaeva, Larisa D.

AU - Petrova, Tatyana N.

AU - Rybalova, Tatyana V.

AU - Frolova, Tatyana S.

AU - Pokrovskii, Andrey G.

AU - Ganbaatar, Jamsranjav

N1 - Funding Information: The authors are grateful to Dr. Oleg A. Anenkhonov, Institute of General and Experimental Biology SB RAS, Ulan-Ude, Republic of Buryatia, Russia, for the help in plant identification and and geographical consultations; also our thank goes to Dr. Victor V. Chepinoga, V.B. Sochava Institute of Geography SB RAS, Irkutsk, Russia, for the photo of Saposhnikovia divaricata. Authors would like to acknowledge the Multi-Access Chemical Service Center SB RAS for spectral and analytical measurements. This work was performed under partial financial support from the Russian Foundation for Basic Research (Projects No 17-33-50176 and 19-53-44003) and Project № МК-501.2019.4 of the RF President Grant for government support of young Russian scientists. Publisher Copyright: © 2019

PY - 2020/10/28

Y1 - 2020/10/28

N2 - Ethnopharmacological relevance: Saposhnikovia divaricata (family Apiaceae) a traditional medicinal plant distributed in many provinces of China, is well known for the pharmaceutical value and has been used for rheumatic arthritis, and anxiety in children. Antiviral, antioxidant and antiproliferative activities were also mentioned. The application of this plant are recorded in the Chinese Medicine (CM) classical text the Shen Nong's Materia Medica (Shen Nong Ben Cao Jing). In this monograph S. divaricata (syn Radix Ledebouriella divaricata) is graded as a premium-grade herb, with their broad-spectrum of therapeutic applications for the treatment of cough, common cold, arthralgia, as well as in rheumatic disorders. Aim of the study: To isolate and identify chemical constituents (chromones and coumarins) from S. divaricata, collected in Buryatia and Mongolia and to study their in vitro anticancer activity against MEL-8, U-937, DU-145, MDA-MB-231 and ВТ-474 cell lines. Materials and methods: An 40% aqueous ethanol extract of the roots of S. divaricata was prepared and further successively fractionated by extraction with petroleum ether, diethyl ether, tert-butyl methyl ether and ethyl acetate. The obtained extracts were subjected to a series of chromatographic separations on silica gel for isolation of individual compounds. Isolated compounds were tested for their cytotoxicity with respect to model cancer cell lines using the conventional MTT assays. Results: Total of 15 individual compounds: coumarins scopoletin 2, bergapten 3, isoimperatorin 4, marmesin 5, (+)-decursinol 9, (−)-praeruptorin B 10, oxypeucedanin hydrate 11, chromones: hamaudol 6, cimifugin 7, 5-О-methylvisamminol 8, chromone glycosides: prim-O-glucosylcimifugin 12, sec-O-glucosylhamaudol 13, 4′-O-β-D-glucopyranosyl-5-О-methylvisamminol 14, 4′-O-β-D-glucopyranosylvisamminol (15) and also polyyne compound panaxinol 1 were isolated and characterized. The structure of dihydropyranocoumarin 10 was confirmed by X-ray diffraction analyses. HPLC-UV method was used for determination of the content of most abundant chromones 7, 12 and 14 in the roots of S. divaricata, collected in Mongolia. Compounds 3–11 and 13, 14 were evaluated for their cytotoxicity with respect to model cancer cell lines. All the compounds were non-toxic in the hemolysis test. Conclusion: This report about the phytochemical profiles of S. divaricata growing in Mongolia and Buryatia led to the identification of 14 compounds including coumarins and chromones. The available coumarins and chromones may serve as new leads for the discovery of anticancer drugs.

AB - Ethnopharmacological relevance: Saposhnikovia divaricata (family Apiaceae) a traditional medicinal plant distributed in many provinces of China, is well known for the pharmaceutical value and has been used for rheumatic arthritis, and anxiety in children. Antiviral, antioxidant and antiproliferative activities were also mentioned. The application of this plant are recorded in the Chinese Medicine (CM) classical text the Shen Nong's Materia Medica (Shen Nong Ben Cao Jing). In this monograph S. divaricata (syn Radix Ledebouriella divaricata) is graded as a premium-grade herb, with their broad-spectrum of therapeutic applications for the treatment of cough, common cold, arthralgia, as well as in rheumatic disorders. Aim of the study: To isolate and identify chemical constituents (chromones and coumarins) from S. divaricata, collected in Buryatia and Mongolia and to study their in vitro anticancer activity against MEL-8, U-937, DU-145, MDA-MB-231 and ВТ-474 cell lines. Materials and methods: An 40% aqueous ethanol extract of the roots of S. divaricata was prepared and further successively fractionated by extraction with petroleum ether, diethyl ether, tert-butyl methyl ether and ethyl acetate. The obtained extracts were subjected to a series of chromatographic separations on silica gel for isolation of individual compounds. Isolated compounds were tested for their cytotoxicity with respect to model cancer cell lines using the conventional MTT assays. Results: Total of 15 individual compounds: coumarins scopoletin 2, bergapten 3, isoimperatorin 4, marmesin 5, (+)-decursinol 9, (−)-praeruptorin B 10, oxypeucedanin hydrate 11, chromones: hamaudol 6, cimifugin 7, 5-О-methylvisamminol 8, chromone glycosides: prim-O-glucosylcimifugin 12, sec-O-glucosylhamaudol 13, 4′-O-β-D-glucopyranosyl-5-О-methylvisamminol 14, 4′-O-β-D-glucopyranosylvisamminol (15) and also polyyne compound panaxinol 1 were isolated and characterized. The structure of dihydropyranocoumarin 10 was confirmed by X-ray diffraction analyses. HPLC-UV method was used for determination of the content of most abundant chromones 7, 12 and 14 in the roots of S. divaricata, collected in Mongolia. Compounds 3–11 and 13, 14 were evaluated for their cytotoxicity with respect to model cancer cell lines. All the compounds were non-toxic in the hemolysis test. Conclusion: This report about the phytochemical profiles of S. divaricata growing in Mongolia and Buryatia led to the identification of 14 compounds including coumarins and chromones. The available coumarins and chromones may serve as new leads for the discovery of anticancer drugs.

KW - Chromones

KW - Coumarins

KW - Cytotoxicity

KW - Liquid chromatography

KW - Pyranocoumarins

KW - Saposhnikovia divaricata

KW - PEROXIDE PRESOAKING PRIOR

KW - APOPTOSIS

KW - RADIX

KW - PYRANOCOUMARINS

KW - PERFORMANCE LIQUID-CHROMATOGRAPHY

KW - ARREST

KW - PRETREATMENT

KW - INHIBITOR

KW - CONSTITUENTS

KW - EXTRACT

UR - http://www.scopus.com/inward/record.url?scp=85085075869&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2019.112517

DO - 10.1016/j.jep.2019.112517

M3 - Article

C2 - 31931162

AN - SCOPUS:85085075869

VL - 261

SP - 112517

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

SN - 0378-8741

M1 - 112517

ER -