Bio-guided bioactive profiling and HPLC-DAD fingerprinting of Ukrainian saffron (Crocus sativus stigmas): moving from correlation toward causation

Olha Mykhailenko; Vilma Petrikaitė; Michal Korinek; Mohamed El-Shazly; Bing-Hung Chen; Chia-Hung Yen; Chung-Fan Hsieh; Ivan Bezruk; Asta Dabrišiūtė; Liudas Ivanauskas; Victoriya Georgiyants; Tsong-Long Hwang

doi:10.1186/s12906-021-03374-3

Bio-guided bioactive profiling and HPLC-DAD fingerprinting of Ukrainian saffron (Crocus sativus stigmas): moving from correlation toward causation

BMC Complement Med Ther. 2021 Jul 21;21(1):203. doi: 10.1186/s12906-021-03374-3.

Authors

Olha Mykhailenko^#¹, Vilma Petrikaitė^#^{2

3}, Michal Korinek^{4

5

6

7}, Mohamed El-Shazly^{8

9}, Bing-Hung Chen^{10

11}, Chia-Hung Yen¹², Chung-Fan Hsieh¹³, Ivan Bezruk¹, Asta Dabrišiūtė², Liudas Ivanauskas¹⁴, Victoriya Georgiyants¹, Tsong-Long Hwang^{15

16

17

18}

Affiliations

¹ Department of Pharmaceutical Chemistry, National University of Pharmacy of Ministry of Health of Ukraine, 4-Valentinivska st, Kharkiv, 61168, Ukraine.
² Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences, Sukilėlių pr. 13, LT-50162, Kaunas, Lithuania.
³ Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio al. 7, LT-10257, Vilnius, Lithuania.
⁴ Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. michalk@kmu.edu.tw.
⁵ Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan. michalk@kmu.edu.tw.
⁶ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. michalk@kmu.edu.tw.
⁷ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33302, Taiwan. michalk@kmu.edu.tw.
⁸ Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Organization of African Unity Street, Abassia, Cairo, 11566, Egypt.
⁹ Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, 11835, Egypt.
¹⁰ Department of Biotechnology, College of Life Science, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
¹¹ The Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan.
¹² Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
¹³ Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.
¹⁴ Lithuanian University of Health Sciences, Department of Analytical and Toxicological Chemistry, A. Mickevičiaus g. 9, 44307, Kaunas, LT, Lithuania.
¹⁵ Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan. htl@mail.cgu.edu.tw.
¹⁶ Research Center for Chinese Herbal Medicine, Research Center for Food and Cosmetic Safety, and Graduate Institute of Health Industry Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, 33302, Taiwan. htl@mail.cgu.edu.tw.
¹⁷ Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan. htl@mail.cgu.edu.tw.
¹⁸ Department of Chemical Engineering, Ming Chi University of Technology, New Taipei City, 24301, Taiwan. htl@mail.cgu.edu.tw.

^# Contributed equally.

Abstract

Background: Saffron or stigmas of Crocus sativus L. is one of the most valuable food products with interesting health-promoting properties. C. sativus has been widely used as a coloring and flavoring agent. Stigmas secondary metabolites showed potent cytotoxic effects in previous reports.

Methods: The present study investigated the chemical composition and the cytotoxic effect of Ukrainian saffron crude extracts and individual compounds against melanoma IGR39, triple-negative breast cancer MDA-MB-231, and glioblastoma U-87 cell lines in vitro using MTT assay. Several bioactivity in vitro assays were performed. The chemical profile of the water and hydroethanolic (70%, v/v) crude extracts of saffron stigmas was elucidated by HPLC-DAD analysis.

Results: Seven compounds were identified including crocin, picrocrocin, safranal, rutin, apigenin, caffeic acid, ferulic acid. Crocin, picrocrocin, safranal, rutin, and apigenin were the major active constituents of Ukrainian C. sativus stigmas. The hydroethanolic extract significantly reduced the viability of MDA-MB-231 and IGR39 cells and the effect was more potent in comparison with the water extract. However, the water extract was almost 5.6 times more active against the U-87 cell line (EC₅₀ of the water extract against U-87 was 0.15 ± 0.02 mg/mL, and EC₅₀ of the hydroethanolic extract was 0.83 ± 0.03 mg/mL). The pure compounds, apigenin, and caffeic acid also showed high cytotoxic activity against breast cancer, melanoma, and glioblastoma cell lines. The screening of the biological activities of stigmas water extract (up to 100 μg/mL) including anti-allergic, anti-virus, anti-neuraminidase, and anti-inflammatory effects revealed its inhibitory activity against neuraminidase enzyme by 41%.

Conclusions: The presented results revealed the qualitative and quantitative chemical composition and biological activity of Crocus sativus stigmas from Ukraine as a source of natural anticancer and neuraminidase inhibitory agents. The results of the extracts' bioactivity suggested future potential applications of saffron as a natural remedy against several cancers.

Keywords: Crocus sativus; Crude extract; Cytotoxic activity; HPLC; Stigmas.

MeSH terms

Breast Neoplasms / drug therapy
Cell Line / drug effects
Chromatography, High Pressure Liquid
Crocus / chemistry*
Crocus / metabolism
Crocus / toxicity*
Female
Glioblastoma / drug therapy
Humans
In Vitro Techniques
Melanoma / drug therapy
Phytochemicals / pharmacology*
Plant Extracts / pharmacology*
Tetrazolium Salts

Substances

Phytochemicals
Plant Extracts
Tetrazolium Salts