Mehmet Evren OKUR, Ayşe Esra KARADAĞ, Nihal KARAKAŞ, Fatih DEMİRCİ, Rabia YILMAZ

In vitro cytotoxicity evaluation of Marrubium vulgare L. methanol extract

Marrubium vulgare L. (Lamiaceae) is a herbal drug used for centuries for many diseases. In this present study the plant material was acquired from commercial sources in pharma grade (PhEur 8.0) quality. The methanol extract of the aerial parts was evaluated for its in vitro cytotoxic activity by measuring the percentage of viable cells (U87 LN229 and T98G glioblastoma multiforme cell lines) using a luminescence system, and the antioxidant activities by ABTS and DPPH radical scavenging spectrophotometrically. As a result, the methanol extract of M. vulgare showed 48.97 ± 0.82 mg of GA/g corresponding to the total phenolic amounts, and moderate antioxidant activity (1.33 and 2.08) by ABTS• and DPPH• assays. To the best of knowledge, after evaluation of the cytotoxicity on M. vulgare treated U87 (IC50:270.3 μM), LN229 (IC50:343.9 μM) and T98G (336.6 μM) glioblastoma multiforme (GBM) cell lines, significant cytotoxic activities with 69.9% (p= 0.0081) and 71% cell viability (p= 0.0028) was observed in M. vulgare treated U87 and LN229 GBM cell lines, respectively. Overall, further in vitro and in vivo bioactivity studies based on phytochemistry on various M. vulgare preparations are worthwhile in order to discover bioactive secondary metabolites.

PDF

___

Meyre-Silva C, Cechinel-Filho V. A review of the chemical and pharmacological aspects of the genus Marrubium. Curr Pharm Des. 2010; 16(31): 3503-3518. [CrossRef]
Paula de Oliveira A, Santin JR, Lemos M, Junior LCK, Couto AG, Bittencourt CMS, Filho VC, Faloni de Andrde S. Gastroprotective activity of methanol extract and marrubiin obtained from leaves of Marrubium vulgare L. (Lamiaceae). J Pharm Pharmacol. 2011; 63(9): 1230–1237. [CrossRef]
Yousefi K, Fathiazad F, Soraya H, Rameshrad M, Maleki-Dizaji N, Garjani A. Marrubium vulgare L. methanolic extract inhibits inflammatory response and prevents cardiomyocyte fibrosis in isoproterenol-induced acute myocardial infarction in rats. Bioimpacts. 2014; 4(1): 21–27. [CrossRef]
Bardai S El, Lyoussi B, Wibo M, Morel N. Pharmacological evidence of hypotensive activity of Marrubium vulgare and Foeniculum vulgare in spontaneously hypertensive rat. Clin Exp Hypertens. 2001; 23(4): 329–343. [CrossRef]
Rigano D, Aviello G, Bruno M, Formisano C, Rosselli S, Capasso R, Senatore F, Izzo AA, Borrelli F. Antispasmodic effects and structure−activity relationships of labdane diterpenoids from Marrubium globosum ssp. libanoticum. J Nat Prod. 2009; 72(8): 1477–1481. [CrossRef]
Herrera-Arellano A, Aguilar-Santamaría L, García-Hernández B, Nicasio-Torres P, Tortoriello J. Clinical trial of Cecropia obtusifolia and Marrubium vulgare leaf extracts on blood glucose and serum lipids in type 2 diabetics. Phytomedicine. 2004; 11(7–8): 561–566. [CrossRef]
Berrougui H, Isabelle M, Cherki M, Khalil A. Marrubium vulgare extract inhibits human-LDL oxidation and enhances HDL-mediated cholesterol efflux in THP-1 macrophage. Life Sci. 2006; 80(2): 105–112. [CrossRef]
Nawwar MAM, El-Mousallamy AMD, Barakat HH, Buddrus J, Linscheid M. Flavonoid lactates from leaves of Marrubium vulgare. Phytochemistry. 1989; 28(11):3201–3206. [CrossRef]
Rodrigues CA, Savi AOS, Schlemper V, Reynaud F, Cechinel-Filho V. An improved extraction of marrubiim from Marrubium vulgare. Chromatographia. 1998; 47(7–8): 449–450. [CrossRef]
Knoss W, Zapp J. Accumulation of furanic labdane diterpenes in Marrubium vulgare and Leonurus cardiaca. Planta Med. 1998; 64(4): 357–361. [CrossRef]
Stoyanov GS, Dzhenkov D, Ghenev P, Iliev B, Enchev Y, Tonchev AB. Cell biology of glioblastoma multiforme: From basic science to diagnosis and treatment. Med Oncol. 2018; 35(3): 27. [CrossRef]
Kanu OO, Mehta A, Di C, Lin N, Bortoff K, Bigner DD, Yan H, Adamson DC. Glioblastoma multiforme: A review of therapeutic targets, Expert Rev. Anticancer Ther. 2009; 13(6): 701-718. [CrossRef]
Alphandéry E. Glioblastoma treatments: An account of recent industrial developments. Front Pharmacol. 2018; 9: 879. [CrossRef]
Ferreira J, Ramos AA, Almeida T, Azqueta A, Rocha E. Drug resistance in glioblastoma and cytotoxicity of seaweed compounds, alone and in combination with anticancer drugs: A mini review. Phytomedicine. 2018; 48: 84–93. [CrossRef]
Erukainure OL, Ashraf N, Naqvi AS, Zaruwa MZ, Muhammad A, Odusote AD, Elemo GN. Fatty acids rich extract from Clerodendrum volubile suppresses cell migration; abates oxidative stress; and regulates cell cycle progression in glioblastoma multiforme (U87 MG) cells. Front Pharmacol. 2018; 9: 251. [CrossRef]
Desai V, Bhushan A. Natural bioactive compounds: Alternative approach to the treatment of glioblastoma multiforme. Biomed Res Int. 2017; 2017: 1–10. [CrossRef]
Halliwell B, Gutteridge JM. Free radicals in biology and medicine. fifth ed., Oxford University Press, USA 2015.
Bouterfas K, Mehdadi Z, Elaoufi MM, Latreche A, Benchiha W. Antioxidant activity and total phenolic and flavonoids content variations of leaves extracts of white Horehound (Marrubium vulgare Linné) from three geographical origins. Ann Pharm Fr. 2016; 74(6): 453-462. [CrossRef]
Amri B, Martino E, Vitulo F, Corana F, Kaâb LBB, Rui M, Rossi D, Mori M, Rossi S, Collina S. Marrubium vulgare L. Leave extract: Phytochemical composition, antioxidant and wound healing properties. Molecules. 2017; 22(11): 1851. [CrossRef]
Brahmi N, Scognamiglio M, Pacifico S, Mekhoukhe A, Madani K, Fiorentino A, Monaco P. 1H NMR based metabolic profiling of eleven Algerian aromatic plants and evaluation of their antioxidant and cytotoxic properties. Food Res Int. 2015; 76: 334-341. [CrossRef]
El Euch SK, Cieśla Ł, Bouzouita N. Free Radical scavenging fingerprints of selected aromatic and medicinal tunisian plants assessed by means of TLC-DPPH test and ımage processing. J AOAC Int. 2014; 97(5): 1291-1298. [CrossRef]
Okur ME, Ozbek H, Çiçek Polat D, Yılmaz S, Arslan R. Hypoglycemic activity of Capparis ovata desf. var. palaestina zoh. methanol extract. Braz J Pharm Sci. 2018; 54(3): 1–9. [CrossRef]
Zarai Z, Kadri A, Chobba IB, Mansour RB, Bekir A, Mejdoub H, Gharsallah N. The in-vitro evaluation of antibacterial, antifungal and cytotoxic properties of Marrubium vulgare L. essential oil grown in Tunisia. Lipids Health Dis. 2011; 10(161): 1-8. [CrossRef]
Hamedeyazdan S, Fathiazad F, Sharifi S, Nazemiyeh H. Antiproliferative activity of Marrubium persicum extract in the MCF-7 human breast cancer cell line. Asian Pac J Cancer Prev. 2012; 13: 5843-5848. [CrossRef]
Lodhi S, Vadnere GP, Sharma VK, Usman R. Marrubium vulgare L.: A review on phytochemical and pharmacological aspects. J Intercult Ethnopharmacol. 2017; 6(4): 429-452. [CrossRef]
Yamaguchi K, Ligget JL, Kım NC, Baek SJ. Anti-proliferative effect of horehound leaf and wild cherry bark extracts on human colorectal cancer cells. Oncol Rep. 2006; 15(1): 275-281. [CrossRef]
Paunovic V, Kosic M, Djordjevic S, Zugic A, Djalinac N, Gasic U, Trajkovic V, Harhaji-Trajkovic J. Marrubium vulgare ethanolic extract induces proliferation block, apoptosis, and cytoprotective autophagy in cancer cells in vitro. Cell Mol Biol. 2016; 62(11): 107-113.
Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958; 181(4617): 1199.
Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999; 26(9–10): 1231–1237. [CrossRef]
Okur ME, Ayla Ş, Çiçek Polat D, Günal MY, Yoltaş A, Biçeroğlu Ö. Novel insight into wound healing properties of methanol extract of Capparis ovata Desf. var. palaestina Zohary fruits. J Pharm Pharmacol. 2018; 70: 1401–1413. [CrossRef]
Okur ME, Çiçek Polat D, Ozbek H, Yılmaz S, Yoltaş A, Arslan R. Evaluation of the antidiabetic property of Capparis ovata desf. Var. Paleastina zoh. Extracts using in vivo and in vitro approaches. Endocrine Metab Immune Disord Drug Targets. 2018; 18: 489–501. [CrossRef]
Spanos GA, Wrolstad RE. Influence of processing and storage on the phenolic composition of Thompson Seedless grape juice. J Agric Food Chem. 1990; 38(7): 1565–1571. [CrossRef]