Investigations on the anti-ulcerogenic activity of Sideritis caesarea H. Duman, Aytaç & Başer

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Abstract

Ethnopharmacological relevance

Aerial parts of Sideritis caesarea H. Duman, Aytaç & Başer are used for complaints such as stomach-aches, and intestinal spasms as traditional medicine in Kayseri, Turkey.

Aim of study

To investigate the anti-ulcerogenic activity by using bioassay guided fractionation technique (BAGF) and to identify the compound(s) that are responsible for anti-ulcerogenic activity through ethanol-induced anti-ulcerogenic activity model in vivo.

Materials and methods

Liquid-liquid partition and then different chromatographic techniques were utilized for the BAGF of the ethanol (80%) extract of the aerial parts of Sideritis caesarea. Ethanol-induced gastric ulcer method on rats was employed for the determination of the anti-ulcerogenic activity, and the ulcer index was also calculated for anti-ulcerogenic activity detection.

Results

The ethanol (80%) extract of S. caesarea showed statistically potent anti-ulcerogenic activity (95.9% ulcer inhibition, p < 0.001). Among the liquid-liquid fractions, strongest anti-ulcerogenic activity was observed with the ethyl acetate fraction (91.4% inhibition, p < 0.001) and therefore BAGF studies were proceeded with the ethyl acetate fraction. Two anti-ulcerogenic flavonoids {4′-O-methylhypolaetin-7-O-[6‴-O-acetyl-β-D-allopyranosyl-(1→2)]-6″-O-acetyl-β-D-glucopyranoside and isoscutellarein-7-O-[6‴-O-acetyl-β-D-allopyranosyl-(1→2)]-6″-O-acetyl-β-D-glucopyranoside} were isolated from this fraction together with a sesquiterpene glycoside [(2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-β-D-glucopyranoside] and two additional flavonoids {4′-O-methylhypolaetin-7-O-[6‴-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside and isoscutellarein-7-O-[6‴-O-acetyl-β-D-allopyranosyl-(1→2)]-β-D-glucopyranoside}.

Conclusions

Traditional use of S. caesarea in the treatment of stomach-aches was supported by this study and four flavonoids were isolated by using BAGF method and two of them were determined to have significant anti-ulcerogenic activity. Additionally, (2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-β-D-glucopyranoside was obtained from a Sideritis genus for the first time.

Introduction

Lamiaceae family, distributed nearly worldwide, includes powerful aromatic herbs which have been in use for culinary, medicinal purposes and especially in making beverages, herbal teas, since ancient times (Fecka and Turek, 2007). Various species of the genera Salvia, Thymus, Stachys, Lavandula, Origanum, Marrubium, Satureja and Sideritis are commonly used to make herbal teas in Turkey and around (Dirmenci et al., 2018; Gürbüz et al., 2019; Tuzlacı, 2011). Among them, Sideritis species stand out with their excellent flavour and fragrance profile and a long running history of recreational and medicinal uses. A large number of studies on the members of this genus were conducted due to widespread use of its species especially in circum-Mediterranean countries (Sağır et al., 2017).

Sideritis genus is distributed in a quite wide region with more than 150 species, especially dwell in Mediterranean basin (Duman et al., 2005). According to "Flora of Turkey and the East Aegean Islands" and "Türkiye Bitkileri Listesi/Damarlı Bitkiler (The List of Plants of Turkey/Vascular Plants)", 45 Sideritis species grow wild in Turkey (Davis et al., 1988; Güner et al., 2012). Different species of Sideritis are known as "Mountain grass"; "Mountain tea", "Ironwort", "Té amarillo", "Te de monte" etc. in some European countries (González-Burgos et al., 2011; Pardo-de-Santayana et al., 2005; Todorova and Trendafilova, 2014). Traditionally, plants of genus Sideritis have been reported to be used for disorders like bronchitis, bronchial asthma, pulmonary emphysema, angina pectoris, common cold, flu, hypertension, circulatory disorders, worms in the eyes, eye infections, urinary system infections, gastrointestinal disorders including diarrhoea and peptic ulcer, anaemia, wounds, backache, rheumatism and cataract. Additionally, they are used as appetizer, analgesic, sedative, expectorant, anti-tussive, diuretic, anti-pyretic, aphrodisiac, hypoglycaemic, digestive, carminative, anti-spasmodic, anti-inflammatory, anti-microbial, anti-convulsant, disinfectant, diaphoretic, etc. (Agelet and Valles, 2001; Basile et al., 2006; Belda et al., 2013; González-Burgos et al., 2011; González-Burgos et al., 2009; Hanlidou et al., 2004; Hernandez-Perez et al., 2004; Ivancheva and Stantcheva, 2000; Karousou and Deirmentzoglou, 2011; Lentini, 2000; Leporatti and Impieri, 2007; Pardo-de-Santayana et al., 2005; Pieroni et al., 2005; Raja et al., 1997; Rivera and Obón, 1995; Todorova and Trendafilova, 2014). In Anatolia, Sideritis species are generally known as "Adaçayı", "Dağ Çayı" and are used for abdominal pain, digestion problems, stomach disorders, bronchitis, cough, common cold, sore throat and flu among local people (Ahmet Sargın, 2015; Akalın and Alpınar, 1994; Altundağ and Öztürk, 2011; Baytop, 1999; Bulut and Tuzlacı, 2013; Gürdal and Kültür, 2013; Güzel et al., 2015; Kargıoğlu et al., 2008; Kültür, 2007; Özdemir and Alpınar, 2015; Polat and Satıl, 2012; Sargın et al., 2013, 2015a, 2015b; Tetik et al., 2013; Yeşilada et al., 1995).

Since the Sideritis caesarea H. Duman, Aytaç & Başer was firstly defined in 1998 and is also an endemic species, ethnobotanical data on this plant is limited. During the ethnobotanical research in the district of Pınarbaşı (Kayseri, Turkey), conducted by our research group, decoction of S. caesarea was recorded to be used as a calming herbal tea and a folk remedy for stomach-aches and intestinal spasms (Gençler Özkan and Koyuncu, 2005). Based on this ethnobotanical data, anti-ulcerogenic activity of S. caesarea was investigated in our previous screening study, and statistically significant anti-ulcerogenic activity was observed (95.8% ulcer inhibition, p < 0.001) by ethanol-induced ulcerogenesis model in rats (Gürbüz et al., 2005).

In the present study, by using bioassay guided fractionation technique (BAGF), identification of the fraction(s)/compound(s) of the S. caesarea responsible for the anti-ulcerogenic activity was aimed. The quantitative determination of two anti-ulcerogenic flavonoids isolated from the bioactive fraction in the ethanol extract (80%) was carried out by HPLC analysis as well.

Section snippets

Plant material

Flowering aerial parts of Sideritis caesarea H. Duman, Aytaç & Başer (Dağ çayı) were collected from Kayseri, the district of Sarız, Dayıoluk village, the slopes in the east of the village N: 38° 21′ 01″, E: 26° 30′ 57″ July 07, 2014 and were dried under shade at room temperature. Voucher specimens were identified by Prof. Dr. Ayşe Mine GENÇLER ÖZKAN (botanist) and prepared herbarium specimens are stored in Gazi University Faculty of Pharmacy Herbarium (GUE-3232). The plant name was checked with

Results and discussion

S. caesarea was revealed to be used as folk medicine in the treatment of stomach-aches and intestinal spasms in Pınarbaşı-Kayseri, Turkey (Gençler Özkan and Koyuncu, 2005). Previous anti-ulcerogenic activity screening studies, have noted the potent anti-ulcerogenic activity of decoction of the aerial parts of S. caesarea at 960 mg/kg (the extract obtained 5 g aerial parts/kg) dose in ethanol-induced ulcerogenesis on rats (Gürbüz et al., 2005). In this study, it was attempted to determine the

Conclusion

In this study, four flavonoids were isolated from S. caesarea, a folk medicine, by using BAGF method, and two of the compounds were determined to have significant anti-ulcerogenic activity. Although these compounds are not new substances; their anti-ulcerogenic activities have been determined for the first time in this study, whereas the other flavonoids are also obtained from the fractions possessing anti-ulcerogenic activity. (2E,6E

Acknowledgements

This study was financially supported by “The Scientific and Technological Research Council of Turkey-TUBITAK” (project number: TBAG-112S581).

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