İlkay ERDOĞAN ORHAN, Didem DELİORMAN ORHAN, Nilüfer ORHAN, Mustafa ASLAN, Hasya Nazlı EKİN

Evaluation of enzyme inhibitory and antioxidant activity of some Lamiaceae plants

Lamiaceae is one of the most widespread families in Turkey. The aim of this study was to determine antialzheimer, antidiabetic, antioxidant and antiobesity activities of ethanol extracts of Lamium purpureum var. purpureum, Origanum onites, Salvia sclarea, S. virgata and Thymus zygioides var. lycaonius. Acetylcholinesterase, butyrylcholinesterase, α-amylase, α-glucosidase, and pancreatic lipase inhibitory activities were tested for the determination of the activity of these extracts. Furthermore, total antioxidant, ferric-reducing antioxidant power, metalchelating and N,N-dimethyl-p-phenylendiamine radical scavenging assays were utilized to screen antioxidant activity. Total phenolic content of the extracts were also calculated. Among the tested extracts, T. zygioides var. lycaonius aerial part extract (85.28 ± 0.89 %) showed the highest inhibitory activity against α-glucosidase. The inhibitory activities of all extracts against α-amylase were lower than 50 %. S. sclarea leaf extract indicated remarkable butyrylcholinesterase inhibition (51.76 ± 1.04 %), but all of the plant extracts were inactive against acetylcholinesterase. The Salvia species showed the highest total antioxidant activity. S. sclarea flower (1.34 ± 0.08) and leaf (1.34 ± 0.08) extracts showed the highest ferric-reducing antioxidant power activities. Our findings indicated that O. onites, S. sclarea, S. virgata, and T. zygioides var. lycaonius extracts showed valuable inhibitory activity and emerged as the sources of possible α-glucosidase inhibitors for future studies

PDF

___

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014; 37 Suppl 1: 8190. [CrossRef]
Muriach M, Flores-Bellver M, Romero FJ, Barcia JM. Diabetes and the brain: oxidative stress, inflammation, and autophagy. Oxid Med Cell Longev. 2014; 2014: 102158. [CrossRef]
You Q, Chen F, Wang X, Jiang YM, Lin SY. Anti-diabetic activities of phenolic compounds in muscadine against alpha-glucosidase and pancreatic lipase. LWT-Food Sci Technol. 2012; 46(1): 164-168. [CrossRef]
Racette SB, Deusinger SS, Deusinger RH. Obesity: overview of prevalence, etiology, and treatment. Phys Ther. 2003; 83(3): 276-288. [CrossRef]
Buchholz T, Melzig MF. Polyphenolic compounds as pancreatic lipase inhibitors. Planta Med. 2015; 81(10): 771-783. [CrossRef]
Kim GN, Shin MR, Shin SH, Lee AR, Lee JY, Seo BI, Kim MY, Kim TH, Noh JS, Rhee MH, Roh SS. Study of antiobesity effect through inhibition of pancreatic lipase activity of Diospyros kaki fruit and Citrus unshiu peel. Biomed Res Int. 2016; 2016: 1723042. [CrossRef]
Saedi E, Gheini MR, Faiz F, Arami MA. Diabetes mellitus and cognitive impairments. World J Diabetes. 2016; 7(17): 412-422. [CrossRef]
Profenno LA, Porsteinsson AP, Faraone SV. Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biol Psychiatry. 2010; 67(6): 505-512. [CrossRef]
Greig NH, Utsuki T, Yu Q, Zhu X, Holloway HW, Perry T, Lee B, Ingram DK, Lahiri DK. A new therapeutic target in Alzheimer's disease treatment: Attention to butyrylcholinesterase. Curr Med Res Opin. 2001; 17(3): 159-165. [CrossRef]
Davis PH. Flora of Turkey and the East Aegean Islands, Edinburgh University Press, Edinburgh, 1965.
Gurdal B, Kultur S. An ethnobotanical study of medicinal plants in Marmaris (Mugla, Turkey). J Ethnopharmacol. 2013; 146(1): 113-126. [CrossRef]
Karaman Ö, Elgin Cebe G. Diyabet ve Türkiye’de antidiyabetik olarak kullanılan bitkiler. J Fac Pharm Ankara. 40(3): 47-61. [CrossRef]
Honda G, Yeşilada E, Tabata M, Sezik E, Fujita T, Takeda Y, Takaishi Y, Tanaka T. Traditional medicine in Turkey VI. Folk medicine in West Anatolia: Afyon, Kütahya, Denizli, Muğla, Aydin provinces. J Ethnopharmacol. 1996; 53(2): 75-87. [CrossRef]
Perry NS, Houghton PJ, Theobald A, Jenner P, Perry EK. In-vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol. 2000; 52(7): 895-902. [CrossRef]
Mehran MM, Norasfard MR, Abedinzade M, Khanaki K. Lamium album or Urtica dioica? Which is more effective in decreasing serum glucose, lipid and hepatic enzymes in streptozotocin induced diabetic rats: A comparative study. Afr J Tradit Complement Altern Med. 2015; 12(5): 84-88. [CrossRef]
Çam ME, Yildiz S, Ertaş B, Acar AE, Taşkın T. Antidiabetic effects of Salvia triloba and Thymus praecox subsp. skorpilii var. skorpilii in a rat model of streptozotocin/nicotinamide-induced diabetes. Marmara Pharm J. 2017; 21(4): 818-827. [CrossRef]
Şenol FS, Orhan I, Celep F, Kahraman A, Doğan M, Yilmaz G, Şener B. Survey of 55 Turkish Salvia taxa for their acetylcholinesterase inhibitory and antioxidant activities. Food Chem. 2010; 120(1): 34-43. [CrossRef]
Kindl M, Blažeković B, Bucar F, Vladimir-Knežević S. Antioxidant and anticholinesterase potential of six Thymus species. Evid Based Complement Alternat Med. 2015; 2015: 1-10. [CrossRef]
Chung YK, Heo HJ, Kim EK, Kim HK, Huh TL, Lim Y, Kim SK, Shin DH. Inhibitory effect of ursolic acid purified from Origanum majorana L. on the acetylcholinesterase. Mol Cells. 2001; 11(2): 137-143
Iauk L, Acquaviva R, Mastrojeni S, Amodeo A, Pugliese M, Ragusa M, Loizzo MR, Menichini F, Tundis R. Antibacterial, antioxidant and hypoglycaemic effects of Thymus capitatus (L.) Hoffmanns. et Link leaves' fractions. J Enzyme Inhib Med Chem. 2014; 30(3): 360-365. [CrossRef]
Kabbaoui ME, Chda A, Mejrhit N, Azdad O, Farah A, Aarab L, Bencheikh R, Tazi A. Antidiabetic effect of Thymus satureioides aqueous extract in streptozotocin-induced diabetic rats. Int J Pharm Pharm Sci. 2016; 8(9): 140-145. [CrossRef]
Ekoh SN, Akubugwo EI, Ude VC, Edwin N. Anti-hyperglycemic and anti-hyperlipidemic effect of spices (Thymus vulgaris, Murraya koenigii, Ocimum gratissimum and Piper guineense) in alloxan-induced diabetic rats. Int J Biosci. 2014; 4(2): 179-187. [CrossRef]
Perez Gutierrez RM Inhibition of advanced glycation end-product formation by Origanum majorana in vitro and in streptozotocin-induced diabetic rats. Evid Based Complement Alternat Med. 2012; 2012:598638. [CrossRef]
Vujicic M, Nikolic I, Kontogianni VG, Saksida T, Charisiadis P, Vasic B, Stosic-Grujicic S, Gerothanassis IP, Tzakos AG, Stojanovic I. Ethyl acetate extract of Origanum vulgare L. ssp. hirtum prevents streptozotocin-induced diabetes in C57BL/6 mice. J Food Sci. 2016; 81(7): H1846-H1853. [CrossRef]
Huang M, Wang P, Xu S, Xu W, Xu W, Chu K, Lu J. Biological activities of salvianolic acid B from Salvia miltiorrhiza on type 2 diabetes induced by high-fat diet and streptozotocin. Pharm Biol. 2015; 53(7): 1058-1065. [CrossRef]
Perfumi M, Arnold N, Tacconi R. Hypoglycemic activity of Salvia fruticosa Mill. from Cyprus. J Ethnopharmacol. 1991; 34(2-3): 135-140. [CrossRef]
Jimenez J, Risco S, Ruiz T, Zarzuelo A. Hypoglycemic activity of Salvia lavandulifolia. Planta Med. 1986; 52(04): 260262.
Kianbakht S, Dabaghian FH. Improved glycemic control and lipid profile in hyperlipidemic type 2 diabetic patients consuming Salvia officinalis L. leaf extract: A randomized placebo. Controlled clinical trial. Complement Ther Med. 2013; 21(5): 441-446. [CrossRef]
Eidi A, Eidi M. Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats. Diabetes Metab Syndr: Clin Res Rev. 2009; 3(1): 40-44. [CrossRef]
Vuksan V, Jenkins AL, Dias AG, Lee AS, Jovanovski E, Rogovik AL, Hanna A. Reduction in postprandial glucose excursion and prolongation of satiety: possible explanation of the long-term effects of whole grain Salba (Salvia hispanica L.). Eur J Clin Nutr. 2010; 64(4): 436-438. [CrossRef]
Nickavar B, Abolhasani L. Bioactivity-guided separation of an α-amylase inhibitor flavonoid from Salvia virgata. Iran J Pharm Res. 2013; 12(1): 57-61.
Khan T, Zahid M, Asim M, Shahzad ul H, Iqbal Z, Choudhary MI, Ahmad VU. Pharmacological activities of crude acetone extract and purified constituents of Salvia moorcraftiana Wall. Phytomedicine. 2002; 9(8): 749-752. [CrossRef]
Flores-Bocanegra L, Gonzalez-Andrade M, Bye R, Linares E, Mata R. α-Glucosidase inhibitors from Salvia circinata. J Nat Prod. 2017; 80(5): 1584-1593. [CrossRef]
Asghari B, Salehi P, Sonboli A, Nejad Ebrahimi S. Flavonoids from Salvia chloroleuca with α-amylsae and αglucosidase inhibitory effect. Iran J Pharm Res. 2015; 14(2): 609-615.
Bisio A, De Mieri M, Milella L, Schito AM, Parricchi A, Russo D, Alfei S, Lapillo M, Tuccinardi T, Hamburger M, De Tommasi N. Antibacterial and hypoglycemic diterpenoids from Salvia chamaedryoides. J Nat Prod. 2017; 80(2): 503514. [CrossRef]
Colombo G, Carai MM, Loi B, Zaru A, Riva A, Cabri W, Morazzoni P. Hypoglycemic effects of a standardized extract of Salvia miltiorrhiza roots in rats. Pharmacogn Mag. 2015; 11(44): S545–S549. [CrossRef]
Huang M, Xie Y, Chen L, Chu K, Wu S, Lu J, Chen X, Wang Y, Lai X. Antidiabetic effect of the total polyphenolic acids fraction from Salvia miltiorrhiza bunge in diabetic rats. Phytother Res. 2012; 26(6): 944-948. [CrossRef]
Cai H, Lian L, Wang YU, Yu Y, Liu WEI. Protective effects of Salvia miltiorrhiza injection against learning and memory impairments in streptozotocin-induced diabetic rats. Exp Ther Med. 2014; 8(4): 1127-1130. [CrossRef]
Hasanein P, Felehgari Z, Emamjomeh A. Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms. Neurosci Lett. 2016; 622: 72-77. [CrossRef]
Kleinschnitz C, Yu HY, Zhang ZL, Chen J, Pei A, Hua F, Qian X, He J, Liu CF, Xu X. Carvacrol, a food-additive, provides neuroprotection on focal cerebral ischemia/reperfusion injury in mice. PloS One. 2012; 7(3): 1-8. [CrossRef]
Topçu G, Öztürk M, Kuşman M, Barla Demirkoz AA, Kolak U, Ulubelen A. Terpenoids, essential oil composition and fatty acids profile, and biological activities of Anatolian Salvia fruticosa Mill. Turk J Chem. 2013; 37: 619-632. [CrossRef]
Orhan I, Kartal M, Kan Y, Sener B. Activity of essential oils and individual components against acetyl- and butyrylcholinesterase. Z Naturforsch C. 2008; 63(7-8): 547-553. [CrossRef]
Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961; 7: 88-95. [CrossRef]
Ali H, Houghton PJ, Soumyanath A. α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J Ethnopharmacol. 2006; 107(3): 449-455. [CrossRef]
Lam SH, Chen JM, Kang CJ, Chen CH, Lee SS. α-Glucosidase inhibitors from the seeds of Syagrus romanzoffiana. Phytochemistry. 2008; 69(5): 1173-1178. [CrossRef]
Lee YM, Kim YS, Lee Y, Kim J, Sun H, Kim JH, Kim JS. Inhibitory activities of pancreatic lipase and phosphodiesterase from Korean medicinal plant extracts. Phytother Res. 2012; 26(5): 778-782. [CrossRef]
Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem. 1999; 269(2): 337-341. [CrossRef]
Schlesier K, Harwat M, Bohm V, Bitsch R. Assessment of antioxidant activity by using different in vitro methods. Free Radic Res. 2002; 36(2): 177-187. [CrossRef]
Chua MT, Tung YT, Chang ST. Antioxidant activities of ethanolic extracts from the twigs of Cinnamomum osmophloeum. Bioresour Technol. 2008; 99(6): 1918-1925. [CrossRef]
Oyaizu M. Studies on products of browning reaction. Jpn J Nutr Diet. 1986; 44(6): 307-315. [CrossRef]
Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J Enol Vitic. 1965; 16(3): 144-158.