Cytotoxic Flavonoids from the Aerial Parts of Stachys lavandulifolia Vahl

Abstract

Background: Stachys lavandulifolia Vahl is a herbaceous plant distributed in the west and south western Asia. Despite of the wide medicinal uses, there are some reports on toxicity potential of this plant. In present study we attempted to evaluate the toxicity and to characterize the cytotoxic principles of S. lavandulifolia. Methods: Brine shrimp lethality test (BSLT) was used to evaluate the general toxicity of the extracts and essential oil obtained from the aerial parts of S. lavandulifolia. Phytochemical constituents of the active extract were investigated using various chromatographic and spectroscopic methods. GC and GC-MS were also used to analyze the plant essential oil. GC and GC-MS were used to analyze the plant essential oil. Cytotoxic activities of the isolated compounds were also evaluated using MTT assay method. Results: In brine shrimp lethality test (BSLT), chloroform extract and the plant essential oil exhibited the most toxicity against Artemia salina larvae (LD50: 121.8±5.6 and 127.6±14.7 µg ml-1, respectively). GC and GC-MS analyses of essential oil led to the characterization of forty compounds of which α-bisabolol (23.85%) and thymol (17.88%) were identified as the main constituents. Nine flavonoids, Pachypodol (1), chrysosplenetin (2), kumatakenin (3), velutin (4), penduletin (5), viscosine (6), chrysoeriol (7), hydroxygenkwanin (8) and apigenin (9) were isolated from the chloroform extract of S. lavandulifolia. Among the isolated compounds, chrysosplenetin (2), a polymethoxylated flavonoid, was found as the most toxic compound toward MDA-MB-23 and HT-29 cells, with IC50 values of 88.23 and 116.50 µg ml-1, respectively. Furthermore, chrysosplenetin (2), kumatakenin (3) and viscosine (6) with selectivity indices of 2.70, 2.59 and 3.33, respectively, showed higher preferential toxicity against MDA-MB-23 cells in comparison with tamoxifen (SI:2.45). Conclusion: This study reports methoxylated flavonoids as compounds which could be involved in toxicity of S. lavandulifolia. The results of MTT assay also suggest some of these compounds as appropriate candidates for anti-cancer drug development research.

Genus Stachys: A Review of Traditional Uses, Phytochemistry and Bioactivity

“…In Iran, several species are applied as traditional therapeutic agents in various conditions, including S. acerosa [ 31 ], S. fruticulosa [ 32 ], S. byzantina (known in Farsi as “lamb’s ear” or “lamb’s tongue” or “sonbolehe noghrehi” or “zabanehe bare”) [ 33 , 34 , 35 ], S. inflata (local names; ′′poulk′′ or “Ghol-e-Argavan”) [ 31 , 36 , 37 ], S. lavandulifolia (known as “Chaaye Koohi”) [ 12 , 13 , 31 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ], S. pilifera [ 31 , 45 ], S. schtschegleevii [ 32 , 34 , 46 ], S. sylvatica [ 47 ] and S. turcomanica [ 34 ]. Of considerable interest, S. sylvatica (common name “hedge woundwort”) is recommended for the treatment of women with polycystic ovary syndrome (PCOS) [ 47 ].…”

“…Regarding the cytotoxicity, the specific extract didn′t demonstrate any activity in K562, SH-SY5Y and Caco-2 cell lines, even at the highest concentrations (1.0 mg/mL). The cytotoxic activity of extracts and isolated flavonoids from the aerial parts of S. lavandulifolia were studied by Delnavazi et al (2018) through the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay [ 13 ]. The dichloromethane extract showed the highest cytotoxic activity in brine shrimp lethality test (BSLT) (LD 50 = 121.8 ± 5.6 μg/mL), while as a positive control was used podophyllotoxin (LD 50 = 3.1 ± 0.6 μg/mL).…”

“…Many species of the genus are extensively used in traditional medicine of several countries, having various names. For instance, the species S. recta , known as yellow woundwort, is called as “erba della paura” (=“herb that keeps away fear”) in Italy, attributing to the anxiolytic properties of its herbal tea, while S. lavandulifolia Vahl is called as “Chaaye Koohi” in Iran [ 11 , 12 , 13 ]. In addition, herbal preparations of Stachys spp.…”

Flavone Glycosides from the Aerial Parts of Stachys lavandulifolia Vahl

“…14,15 There are some reports in the literature on phytochemical constituents of various extracts of S. lavandulifolia in literature. [16][17][18][19][20] Four phenylethanoid glycosides including lavandulifoliosides A and B, verbascoside, and leucosceptoside A, together with one iridoid glycoside named 5-allosyloxy-aucubin have been isolated from the aerial parts of S. lavandulifolia by Delazar et al. 16 In another study, acetyl-and butyryl-Cholinesterase and tyrosinase inhibitory activity of different extracts of S. lavandulifolia were assessed and monomelittoside, melittoside, stachysolone and arbutin were isolated and reported as its major compounds.…”

“…17 Recently, Delnavazi et al reported the isolation of eight methoxylated flavonoids from chloroform extract of this species, of which chrysosplenetin, kumatakenin and viscosine were found to have higher preferential toxicity against MDA-MB-23 cells in comparison with tamoxifen. 18 The present study was an attempt to more investigate phytochemical constituents of this medicinal species, specially its flavonoid glycosides content using various chromatographic and spectroscopic methods.…”