Bioassay-guided isolation studies on Scutellaria salviifolia Benth.

Scutellaria salviifolia Benth. (Lamiaceae) is an endemic plant of Turkey [1]. Previous studies of this genus have reported the isolation of flavonoids, iridoid glucosides, phenylethanoid glycosides, diterpenoids, triterpenoids, alkaloids and essential oils. Species and their active principles possess antioxidant, antitumor, antiangiogenesis, hepatoprotective, anticonvulsant, antibacterial, and antiviral activities [2]. Free radicals are one of the key factors that cause several disorders, including cancer. For these reason, investigations on the anticancer activity related with antioxidant compounds are getting very important [3]. On the other hand, recent discoveries found liver X receptors (LXRs) could regulate tumor growth in a variety of cancer cell lines [4]. In the present study, we aimed to isolate active compounds of S. salviifolia on the basis of free radical scavenging capacity against DPPH, NO and SO radicals, cytotoxic activity against HEp-2 cell line, and LXRs ligand activity using a LXRα luciferase reporter assay. Aqueous extract of S. salviifolia showed potent SO radical scavenging (IC₅₀ 159 µg/mL), LXRα agonistic (nearly equivalent to activity of 10 nM T0901317, positive control, at 100 µg/mL) and cytotoxic (IC₅₀ 250 µg/mL) activities. The extract was subjected to polyamide column chromatography to afford five main fractions (Frs. A-E). Phenolic compounds-rich fractions (Frs. D, E) also showed significant activities in the both test systems with the IC₅₀ ranges of 20 – 202 µg/mL for radicals, 116 and 33 µg/mL for Hep-2 cell line, respectively. Repeated column chromatografies of the Frs. D and E resulted in the isolation of four phenolic compounds in pure form. Structures of the isolated compounds were identified as 3,5-dihydroxyphenyl-6'-O-E-p-coumaroyl-β-glucopyranoside (1), hispidulin (2), luteolin-4'-O-β-glucopyranoside (3), and apigenin-5-O-β-glucopyranoside (4) by means of 1D- and 2D-NMR data. Studies on active constituents are still in progress.

Acknowledgements: This study was supported by The Scientific and Technological Research Council of Turkey (Program No: 2211-C) and Hacettepe University BAB (Project No: 014-D08 301 001). The authors are grateful to Prof. Dr. Toshiaki Makino and Dr. Ishiuchi Kan'ichiro (Nagoya City University, Faculty of Pharmaceutical Sciences, Nagoya, Japan) for recording NMR spectra.

Keywords: Scutellaria salviifolia, free radical scavenging, cytotoxic activity, phenolic compounds.

References:

[1] Davis PH. Flora of Turkey and East Aegean Islands. Volume 7. Edinburg: University Press, 1982, 78 – 100.

[2] Shang X, He X, He X, Li M, Zhang R, Fan P, Zhang Q, Jia Z. The genus Scutellaria an ethnopharmacological and phytochemical review. J Ethnopharmacol 2010, 128: 279 – 313.

[3] Harput US, Genc Y, Saracoglu I. Cytotoxic and antioxidative activities of Plantago lagopus L. and characterization of its bioactive compounds. Food Chem Toxicol 2012, 50: 1554 – 1559.

[4] Zhang W, Jiang H, Zhang J, Zhang Y, Liu A, Zhao Y, Zhu X, Lin Z, Yuan X. Liver X receptor activation induces apoptosis of melanoma cell through caspase pathway. Cancer Cell Int 2014, 14: 16.