International Journal of Advanced Life Sciences (IJALS) ISSN 2277 – 758X

Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE

Evaluate the effect of oral administration of Salvia officinalis extract on albino rats' fetuses during gestation period Abdel-Wahab El-Ghareeb, Eman Youssri Salah EL-Din, Amel Ramadan Omar* and Shaimaa Elsayed Atallah Department of Zoology, Faculty of Science, Cairo University, Egypt E-mail : [email protected] Abstract Experimental studies on the toxicity of the sage are scarce despite its use in traditional medicine. So, this research is conducted to evaluate the toxicity of sage extract during the gestation period in female rats. 30 virgin female pregnant rats were divided into control and treated groups, 15 rats in each group. The treated group was received 500mg/kg rat of sage diluted in saline, from the 5th to 20thday of pregnancy. The control group received saline water at the same time. The gravid uteri of the pregnant dams were removed and its fetuses were extracted, then the fetal liver and kidney were stained with haematoxylin and eosin (H&E). The light microscopic examination of the fetal liver showed several hemorrhagic sites, rupture of endothelial cells lining the central vein with dilatation in the central vein and accumulation of the red blood cells and macrophages. Also, an increased in Corresponding Author the number of erythroblasts and megakaryocytes are observed. Examination Amel R. Omar of the fetal kidney maternally treated with sage indicated that glomeruli Department of Zoology, appeared shrunken, swollen with wide, narrow capsular spaces respectively. Faculty of Science, Cairo The convoluted tubules show some abnormal changes in its histological University, Egypt E-mail : [email protected] organization; Nuclei of its epithelial cells are pykcnotic with condensation in Article History chromatin material. In addition, nuclei and cytoplasm of cells, which form the Received on 25 May, 2016; proximal and distal tubules show degeneration and necrosis on it. Saliva Received in revised form officinal is should be considered as a drug and handled with precaution. Care 14 July 2016; Accepted must be taken to control the amount of plant extract taken by man. 19 August, 2016 Keywords : Kidney, liver, Rattus norvegicus, histology and Salvia officinalis

Introduction The herb under investigation is sage (Salvia officinalis) The scientific word “herb” is derived from the of family : Lamiaceae. Common sage (Salvia officinalis) Latin word herba meaning “grass”. This term has been is widely distributed in the northern coastal region referring to plants of which the leaves, stems, or fruits of the Mediterranean and grows wild in the calcareous are used in several purposes such as food, for mountains of northern and central Spain, southern medicines, or for their fragrance or taste. Herbal France, and the western part of the Balkan Peninsula. medicine “herbology” refers to society and traditional Common sage is cultivated in the countries of the medicinal practice depends on the utilization of plants Balkan Peninsula, throughout the Mediterranean and its extracts for the therapy of patient. There are region, and in the United States. In fact its name Salvia many ways in which herbs can be administered, the officinalis related to its medicinal characters. Salvia most common of which is in the form of a liquid that is stems from the Latin word salvere, which means to drunk by the patient - either an herbal tea or a (possibly save or to care. Also, the term officinalis is medical. diluted) plant extract (Bashar and Omar, 2011). This species of Salvia is familiar by woody stems and

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Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE blue and purple flowers. It is the most economically phenolcarboxylic acids (chlorogenic, caffeic, rosmarinic) important species of the S. officinalis group and, along contents of indigenous sage (Salvia officinalis L.) was with S. fruticosa (Rivera et al., 1994), has a very long investigated in different times of the year (Gîrd et al., tradition as a medicinal and aromatic herb with a 2014). wide range of applications. Sage tea has been Research proves that aqueous extracts of traditionally used as a therapy for digestive and S. officinalis has antiproliferative effects on two tumor circulation disturbances, bronchitis, cough, asthma, cell lines. Also, it has cytotoxic and cytogenetic effects angina, mouth and throat inflammations, depression, on tumor cell lines (Al-Barazanjy et al., 2013). excessive sweating, skin diseases, and many other This current research is an attempt to review the diseases (Rami and Li, 2011; Walch et al., 2011; usage of S. officinalis extract by pregnant albino rats Khan et al., 2011). Salvia essential oils have been used and to discuss some of the implications arising from as a therapy in a wide range of diseases like those it in the kidney and liver tissues. The main aim of of the nervous system, heart and blood circulation, the study is to alert healthcare professionals to the fact respiratory system, digestive system, and metabolic that herbal medicine products are not entirely free of and endocrine diseases. In addition, sage essential oil risks for pregnant women. has been shown to have carminative, antispasmodic, Materials and Methods antiseptic, and astringent properties (Loizzo et al., 2007 Sample Collection and extraction and Radulescu et al., 2004). A good quality, sage (Salvia officinalis) were 28 components were identified for S. officinalis purchased from spice dealer. Aqueous extract of Salvia (Hamdipour et al., 2014). By analyzed samples of leaves was prepared as follows: Amount of 50 g of S. officinalis, the major components, with different the powdered plant was suspended in 200 ml of concentrations, are: 1,8-cineole, camphor, borneol, distilled water and stirred by magnetic stirrer overnight bornyl acetate, camphene, α- and β-thujone, linalool, α- at 45°C, then was filtered once through gauze and once and β-caryophyllene, α-humulene, α- and β-pinene, through filter paper. Filtrate extract was gently poured viridiflorol, pimaradiene, salvianolic acid, rosmarinic into pre-weighed glass Petri dishes and left at 37°C acid, carnosolic acid, ursolic acid, etc. (Croteau et al., for 48 - 72 hours. The crude dried extract, then was 1981 and Khan et al., 2011). Studies have shown placed in labeled, tightly sealed plastic tubes and stored that some biological properties of the essential oil of at -20°C until used (Al-Barazanjy et al., 2013). Salvia depend on camphor, 1,8-cineole, α-thujone, and Animal Housing β-thujone (Radulescu et al., 2004). The essential oil of sage contains about 20% camphor, and as the leaves Virgin female and male albino rats, Rattus expand, the camphor content also increases (Avato norvegicus, weighing about 170-180g were used in et al., 2005). In a study, the most powerful scavenging the present investigation. The animals were obtained compounds were reported to be α-thujone and β- from the animal house of the Faculty of Veterinary thujone, bornyl acetate, camphor, menthone, and 1,8- Medicine, Giza, Egypt. Before starting the experiment, cineol in the essential oil (Hussain et al., 2011). Several animals were allowed to acclimatize for at least 7 days. studies deal with phytochemical analysis of Salvia Pregnancy was established by housing females in the officinalis; changes in total phenolic, flavonoids and pro-estrous and estrous stages with healthy, fertile

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Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE males over night; 12-h light/dark cycle (2:1) under embedded in paraffin wax at 56 degree in hot air oven. controlled environmental condition of temperature (25 Paraffin bees wax tissue blocks were prepared for ± 2ºC), humidity (60 ± 20%) and given feed and water sectioning at 5 µm thicknesses using Reichert microtome. ad libitum. The next morning, females with a positive The obtained tissue sections were mounted on glass vaginal plug or vaginal smears were considered slides, deparaffinized, stained with haematoxylin pregnant, and the day of detection was defined as the (Ehrlich) and counterstained by eosin for routine first day of pregnancy or gestation (McClain and examination, then examination was done through the Becker, 1975). Experimental protocols and procedures light electric microscope (Banchroft and Stevens, 1996). used in this study were approved by the Cairo Results University, Faculty of Science, and Institutional Animal Fetal liver of untreated group Care and Use Committee (IACUC) (Egypt) (CUFS /S The liver of embryos of the control group displayed /9/15). The animals were handled according to the the histological features of the normal liver (Fig.-1). Guide for the Care and Use of Laboratory Animals, 8th Edition (2011 National Academies Press). Histopathological Changes of liver tissue of fetus Experimental design and Animal treatment The liver of this group showed a marked loss of the lobular architecture and disorganization of the Pregnant rats were allocated into two groups (15 hepatic strands. By examination of the liver of the fetus per group). The control group received saline water maternally treated with sage revealed congestion of and the experimental groups received 500 mg/kg rat the blood vessels and blood sinusoid, through which of sage diluted in saline; according to Eidi et al. (2005), blood escape, causing several hemorrhagic sites (Fig.- the LD (50) of the methanolic extract of the Sage 2), also rupture of endothelial cells (EN) lining the is measured (4000 mg/kg). The herb was administered central vein is recorded with dilation in the central vein orally by gavage from day 5 up to 20 of pregnancy, (CV) with accumulation of the red blood cells and defined as the critical period for the structural macrophages (Fig.-3). Severe degeneration of hepatic development span of the embryonic stage for rats tissue is recorded; sign of degeneration was observed (WHO, 2001). The dams were euthanized with sodium by the presence of numerous vacuoles in the cytoplasm pentobarbital. Cesarean sections were performed on of hepatocytes (H) and nuclear material of it (Fig.-4). the pregnant rats. The gravid uteri of the pregnant An Increased in number of erythroblasts (EC) and rats were removed and its contents extracted (fetuses megakaryocytic (MG) are observed (Fig.-4). with its corresponding liver and kidney). Fetal kidney of untreated group Histopathological studies The embryonic kidney of the control group Fetal biopsy of the liver, kidney and kidney of displays the histological features of the normal renal the control and treated groups were firstly fixed for tissue (Fig.-5). histological investigation by light microscopy using; 10% formaline solution for 24 hrs. Washing was Histopathological Changes of renal tissue of fetus done in running water to remove excess fixative Examination of the embryonic kidney of maternally then dehydration using serial ascending series of orally administrated sage reveals that, glomeruli appeared ethyl alcohol. Specimens were cleared in xylene and shrunken, swollen with wide, narrow capsular spaces

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Fig.-1: A Photomicrograph of a section of liver of a fetus from control mother. Showing normal liver tissue, the central vein with its intact endothelial lining (CV). The hepatic lobules that can be only distinguished by their central veins, hepatocytes (H) and blood sinusoids (Si).

Fig.-2: A Photomicrograph showing fetus treated liver, megakaryocyte (MG) and hemorrhagic sites (asters), central vein and endothelial cells (EN). Fig.- 3: A Photomicrograph showing fetus treated liver with degeneration in the endothelia lining the central vein, hepatocytes (H), erythrocytes (EC). Fig.- 4: A Photomicrographshowing fetus treated liver, hepatocytes, megakaryocyte and erythrocytes. Fig.- 5: Photomicrograph of a section of kidney of a fetus from control mother. Showing a part of the cortical region containing, a glomeruli (G) within Bowman's capsule (BC) and both proximal (x) and distal (D) tubules. Fig.-6: showing fetus treated kidney, decrease and increase in capsular space of Bowman’s capsule due to swollen and shrinkage in glomeruli respectively, nacrosis (asters) in the proximal (PT) and distal tubule (DT), glomeruli (G), capsular space (CS), Bowman's capsule (BC). Fig.-7: Showing fetus treated kidney with pyknosis (P) to cells of distal and proximal tubules. Fig-8: Showing fetus treated kidney with degeneration of glomeruli of Bowman's capsule (arrow) and necrosis (asters). All photos have been stained with H&E stain. (CS) respectively (Fig.-6). The convoluted tubules showed degeneration and necrosis on it. Also, an showed some abnormal changes in its histological evidence of degeneration in glomeruli (G) of Bowman’s organization; Nuclei of its epithelial cells were capsule (BC) was recorded (Fig.-8). pykcnotic (P) with condensation in chromatin material Discussion (Fig.-7). In addition, nuclei and cytoplasm of cells, Since the sage plant is widely used in traditional which form the proximal (PT) and distal tubules (DT) medicine, and regarded as safe by the U.S. Food

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Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE and Drug Administration and is approved for food use The growth of tumor cell lines has shown a as a spice or seasoning, any unreasonable utilization significant decrease. This significant decrease may be could lead to many complications caused by the well- due to the effect of different phytochemical compounds known toxicity of the essential oil components of sage found in S. officinalis, particularly triterpinoids as (Millet et al., 1981; Geller et al., 1984; Hooser, 1990; indicated by Al-Barazanjy et al. (2013), Slamenova Leushner, 1997). et al. (2004) and Amirghofran et al. (2010) who found European Medicines Agency (2009) listed that that different species of Salvia show inhibitory effects the safety of sage during pregnancy has not been on tumor cell lines. The aqueous and methanolic established, thus the use of it during pregnancy is not extracts of Salvia triloba have a time dependent effect recommended. So, the current study was focused on the on RD tumor cell line as found by Ibrahim and Aqel long term use of Salvia officinalis during pregnancy to (2010). The cytotoxicity of the plant extract could evaluate its effect on the fetal tissues. be due to presence of triterpinoids compounds in the The present study has been observed that the extracts. impact of S. officinalis on rats during pregnancy Salvinal isolated compound from aqueous causing many disorders on the fetal hepatic and renal extracts of Salvia miltiorrhizae, showed inhibitory tissues, but the plant sage were analyzed to twenty activity against tumor cell growth (IC50 range, 4-17 μm) eight components (Hamdipour et al., 2014), to observe and induced apoptosis in human cancer cells. By using which of the sage components may be teratogenic. flow cytometry analysis, salvinal treatment resulted Sage modulated antioxidant pathways to in a concentration-dependent accumulation of cells in minimize stress by scavenging free radicals (Luvone the G2 /M phase by inhibited tubulin polymerization et al., 2006; Elida et al., 2010), inhibiting lipid peroxi- in a concentration-dependent manneras recorded by dation (Ozkan et al., 2010). The active constitutes of Chang et al. (2004). sage polyphenols, especially, phenolic and rosmarinic Plant derived alkaloid flavopereirine, utilized acid have antioxidant effects, thus protecting membrane in the form of a purified plant extract, selectively lipids of fatty acids and phospholipids from oxidative destroyed cancer cells. This selectivity of this stress (Lima et al., 2005; Nour et al., 2010; Kianbakht anticancer agent could be due to the difference in et al., 2011). Also, Lima et al. (2007) who found that membrane properties between cancer and normal cells sage officinalis contain some phenolic compound reported by Beljanski (2000). This effect may be due and the most abundant ones are Rosmarinic acid to antioxidant activity and suppression of metabolic and Luteolin-7-glucoside, which are characterized by a activation, which could be mechanisms through which significant protection ability against cell death in sage or some of its components act as desmutagen. The the HepG2 normal cell line. The methanol crude antioxidant effect of S. officinalis was recorded by extracts of six Salvia species were examined and the Patenkovic et al. (2009) and Dizaye (2010). extracts were characterized by its antitumor character The ability of S. officinalis extracts to reduce in vitro (Tepe, 2008 and Askun et al., 2009). There was a significant increase in proliferation of normal the mitotic index (M.I) value can be traced to its cell line; Murine fibroblast (L20B) as recorded by chemical constituents such as taninnes that have the Al-Barazanjy et al. (2013). ability to block cell cycle progression Al-Barazanjy

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Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE et al. (2013). The study of Patenkovic et al. (2009) inflammation were recorded after death. Ingestion of and Grzegorczyk and Wysokinska (2008) explained three tablets of sage leaves per day by a 22-year-old the effect of different extracts of S. officinalis on M.I young man resulted in epileptic convulsions, muscle attributed to the antioxidant effects of terpenoids, cramps and respiratory disorders (European Pharma- which enhanced the cell death. In bone marrow cells of copoeia, 1971), and implicated in abortion during mice, reduction in the M.I exposed a mitodepressive pregnancy (Newall et al., 1996). Furthermore, Valnet ability of the extract of Sage on division Modallal et al. (1990) recommended that this plant should not be (2008). consumed while lactation period because of its harmful Thujone as a one constitutes of sage is a effects on infants. monoterpene that occurs mainly as a mixture of alpha Conclusion and beta diastereoisomers, it lowers cholesterol and Saliva officinalis should be considered as a drug triglyceride levels (Kee et al., 2009 and EL-Kholy and handled with precaution. Care must be taken to et al., 2010). Any unreasonable utilization could lead control the amount of plant extract taken by man. to many complications caused by the well-known Acknowledgements toxicity of the essential oil components of sage We are grateful to Cairo University, Zoology (Hooser, 1990 and Leushner, 1997). Mainly, such Department, and Faculty of Science for their toxic effect has been attributed to terpenic ketones; collaboration. the thujone and camphor components of the oil References (Millet et al., 1981). Also, inflammatory properties to Al-Barazanjy, R.K., Dizaye, K. and AL-Asadye, A.A. the oil extract are mainly due to the cineole component 2013. Cytotoxic and cytogenetic effects of Salvia (Santos and Rao, 1997). Other side effects to the oils officinalis on different tumor cell lines. Middle are hypoglycemic and spasmolytic effects (Perfumi East Journal of Internal Medicine., 6(4): 15 - 25. et al., 1991), epileptic reactions (Arnold, 1988 and Amirghofran, Z., Bahmani, M., Azadmehr, A., Javidnia, Kbayssi, 1993), loss of equilibrium, tachycardia, K., Ramazani, M. and Ziaei, A. 2010. Effect of permanent brain damage (Arnold, 1988; Newall et al., Salvia mirzayanii on immune system and induction 1996) and other problems related to the nervous of apoptosis in peripheral blood lymphocytes. system (Elisabetsky et al., 1995). In animal studies, Natural Product Res. In Press. thujone as a one compound of sage extract inhibits Arnold, W.N. 1988. Vincent Van Gogh and thujone the gamma-aminobutyric acid A (GABAA) receptor connection. JAMA., 260 (20): 3042 - 3044. in the brain causing excitation and convulsions in a dose-dependent manner, there is some unclear data of Aşkun, T., Tumen, G., Satil, F. and Ates, M. 2009. carcinogenicity in rats (Pelkonen et al., 2013). Also, at Characterization of the phenolic composition dose-related pharmacotoxic symptoms were noted and antimicrobial activities of Turkish medicinal in mice upon injection of each of the four oil extracts. plants. Pharmaceutical Biology., 47 (7): 563-571. Farhat et al. (2001) recorded state of impaired coordi- Avato, P., Fortunato, I., Ruta, C.D. and Elia, R. 2005. nation of movement and epileptogenic symptoms prior Glandular hairs and essential oils in micro mice death. Highly vascularized skin and peritoneum propagated plants of Salvia officinalis L. Plant layers, dark blood clots on the heart, and intestinal Sci., 169: 29-36.

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Bancroft, J.D. and Stevens, A. 1996. The haematoxylin absence of significant serum chemistry and and eosin. Theory and practice of histological genomic changes. Oxid. Med. Cell Longev., 3(2): techniques, 4th Eds, Ch 6, pp. 99–112. Churchill 129-144. Livingstone, London, New York & Tokyo. Elisabetsky, E., Marschner, J., Souza, D.O. 1995. Bashar, S. and Omar, S. 2011. Greco-Arab and Islamic Effect of linalool on glutamatergic system in the Herbal Medicine: Traditional System, Ethics, rat cerebral cortex. Neurochemical Research., Safety, Efficacy, and Regulatory Issues (John 20(4): 461- 465. Wiley and sons), pp. 552. 47421 - 1. EL-Kholy, W.M., EL-Habibi, E.M. and Mousa, A.T. Beljanski, M. 2000. The anticancer agent PB-100, 2010. Oxidative stress in brains of rats intoxicated selectively active on malignant cells, inhibits with aluminum and the neuromodulating effect multiplication of sixteen malignant cell lines, of different forms of sage. J. of Am. Sci., 6 (12) : even multidrug resistant. Genet. Mol. Biol., 1283 - 1297. 23(1): 29-33. European Medicines Agency London, 12 November Chang, J-Y., Chang, C.Y., Kuo, C-C., Chen, L-T., 2009. Doc. Ref.: EMA/HMPC/331653/2008. Wein, Y.S. and Kuo, Y-H. 2004. Salvinal, a European Pharmacopoeia. 1971. vol. II, European novel microtubule inhibitor isolated from Salvia Treaty Series No. 50, Maisonneuve, S.A. miltiorrhizae bunge (Danshen), with antimitotic Publishers, France. activity in multidrug-sensitive and-resistant human Farhat, G.N., Affara, N.I. and Gali-Muhtasib, H.U. tumor cells. Mol. Pharmacol., 65(1): 77 - 84. 2001. Seasonal changes in the composition of Croteau, R., Felton, M., Karp, F. and Kjonaas, R.1981. the essential oil extract of East Mediterranean Relationship of Camphor Biosynthesis to Leaf sage (Salvia libanotica) and its toxicity in mice. Development in Sage (Salvia officinalis). Plant Toxicon. pp. 1601-1605. Physiol., 67 : 820 - 824. Geller, R.J., Spyker, D.A., Garretson, L.K. and Rogol, Dizaye, K. 2010. Allevation of Cisplatininduced A.D. 1984. Camphor toxicity: development of a nephrotoxicity in albino rats by aqueous extract triage strategy. Veterinary and Human Toxicology., of Salvia officinalis. Proceeding of the CB 26 (2): 8 - 10. medical treatment symposium, spiez laboratory, Gîrd, C.E., Nencu, I., Costea, T., Duţu, L.E., Popescu, Switzerland (CBMTS VIII). M.L. and Ciupitu, N. 2014. Quantitative analysis Eidi, M., Eidi, A. and Zamanzadeh, H. 2005. Effect of phenolic compounds from Salvia officinalis L. of Salvia officinalis L. leaves on serum glucose leaves. Farmacia., 62 (4): 649 - 657. and insulin in healthy and streptozotocin-induced Grzegorczyk, I. and Wysokinska, H. 2008. Liquid diabetic rats. J. Ethnopharmacol., 100: 310-313. shoot culture of Salvia officinalis L. for micro- Elida, B., Daniel, Z., Payal, P., Vishal, J., Tejas, L., propagation and production of antioxidant Inna, K., Sidney, J. and Sidhartha, D. 2010. A compounds; Effect of triacontanol. Acta. Societatis novel dietary supplement containing multiple Botanicorum., 77(2): 99 - 104. phytochemicals and vitamins elevates hepato- Hamidpour, R., Hamidpour, S., Hamidpour, M. and renal and cardiac antioxidant enzymes in the Shahlan, M. 2014. Chemistry, pharmacology and

Int. j. Adv. Lif. Sci., Available online on at www. Int. J. Adv. Lif. Sci., Available online on at www. ijals.com Page 313 International Journal of Advanced Life Sciences (IJALS) ISSN 2277 – 758X

Abdel-Wahab El-Ghareeb et al., IJALS, Volume (9) Issue (3) August - 2016. RESEARCH ARTICLE

medicinal property of S. officinalis (sage) to Lima, C.F., Valentao, P.C.R., Andrade, P.B., Seabra, prevent and cure illnesses such as obesity, diabetes, R.M., Fernandes-Ferreira, M. and Pereira Wilson, depression, dementia, lupus, autism, heart disease C. 2007. Water and methanolic extracts of Salvia

and cancer. J. Tradit. Complement Med., 4: 82 -88. officinalis protect HepG2 cells from t-BHP Hooser, S.B. 1990. Toxicology of selected pesticides, induced oxidative damage. Chem. Biol. Interact., drugs, and chemicals. D-limonene, linalool, and 167(2): 107 - 15. crude Citrus oil extracts. Veterinary Clinics of Lima, C.F., Andrade, P.B., Seabra, R.M., Fernandes- North America - Small Animal Practice., 20, 383 Ferreira, M. and Pereira, W.C. 2005. The drinking - 385. of a Salvia officinalis infusion improves liver Hussain, A., Anwar, F., Iqbal, T. and Bhatti, I. antioxidant status in mice and rats. J. Ethno- 2011. Antioxidant attributes of four Lamiaceae pharmacol., 97(2): 383 - 389. essential oils. Pak. J. Bot., 43: 1315 - 1321. Loizzo, M.R., Tundis, R., Menichini, F., Saab, A.M. Ibrahim, A. and Aqel, A.A. 2010. Effect of Salvia triloba and Statti, G.A. 2007. Cytotoxic activity of L.f. extracts on neoplastic cell lines. Jordan essential oils from labiatae and lauraceae families Journal of Biological Sciences., 3(2): 69-76. against in vitro human tumor models. Anticancer Kbayssi, H. 1993. Encyclopedia of Weeds and Res., 27: 3293 - 3299. Medicinal Plants. Scientific Books, Beirut, Luvone, T., DeFilippis, D., Esposito, G., D'Amico, Lebanon. p. 271. A. and Izzo, A.A. 2006. The spice sage and its Kee, E., Livengood, M., Carter, E., Mckenna, M. and active ingredient rosmarinic acid protect PC12 Cafiero, M. 2009. Aromatic interactions in the cells from amyloid-beta peptide induced neuro- binding of ligands to HMGCoA reductase. J. of toxicity. J. Pharmacol. Exp. Ther., 317 (3): 1143 Physics. and Chem. of Solids., 113(44) : 14810 - - 1149. 14815. Mc Clain, R.M. and Becker, B.A. 1975.Teratogenicity, Khan, A., Najeeb-ur- Rahman, Alkharfy, K. and foetal toxicity and placental transfer of lead Gilani, A. 2011. Antidiarrheal and antispasmodic nitrate in rats. Toxicol. Appl. Pharmacol., 931: 72 activities of Salvia officinalis are mediated - 82. through activation of K+ channels. J. Bangladesh Millet, Y., Jouglard, J., Steinmetz, M.D., Tognetti, P. Pharmacol. Soci., 6:111-116. and Arditti, J. 1981. Toxicity of some essential Kianbakht, S., Abasi, B., Perham, M. and Hashem, plant oils: clinical and experimental study. Clin. F. 2011. Antihyperlipidemic effects of Salvia Toxicol., 18 (12): 1485 - 1498. officinalis L. leaf extract in patients with hyper- Modallal, N., Abderrahman, S. and Papini, A. 2008. lipidemia: A randomized double-blind placebo- Cytogenetic effect of Arum maculatum extract on controlled clinical trial. Phytother. Res., 25(12): the bone marrow. CaryologiaA., 61(4): 383 - 87. 1849 - 1953. Newall, C.A., Anderson, L.A. and Phillipson, J.D. Leushner, J. 1997. Reproductive toxicity studies of 1996. Herbal Medicine, A Guide for Health- D-camphor in rats and rabbits. Arzneimittel- Care Professionals. The Pharmaceutical Press, forschung., 47(2): 124 - 128. London. pp. 231- 232.

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Nour, W., Al-Haj, B., Talal, A., Aburjai, O., Taha, N. Santos, F.A. and Rao, V.S., 1997. Mast cell and Ahmad, M. 2010. Thujone corrects cholesterol involvement in the rat paw oedema response to and triglyceride profiles in diabetic rat model. 1,8-cineole, the main constituent of Eucalyptus Natural Product Res., 25(12):1180 - 1184. and Rosemary oils. European Journal of Ozkan, G., Sagdic, O., Gokturk, S., Unal, O. and Pharmacology., 331 (2-3): 253 - 258. Albayrak, S. 2010. Study on chemical composition Slamenova, D., Masterova, I., Labaj, J., Horvathova, and biological activities of essential oil and E., Kubala, P., Jakubikova, J. and Wsolova, L. extract from Salvia pisidica. Food Science and 2004. Cytotoxic and DNA-damaging effects of Technology., 43: 186 - 190. diterpenoid quinones from the roots of Salvia Patenkovic, A., Stamenkovic-Radak, M., Banjanac, officinalis L. on colonic and hepatic human cells T. and Andjelkovic, M. 2009. Antimutagenic cultured in vitro. Basic Clin. Pharmacol Toxicol., effect of sage tea in the wing spot test of 94(6): 282 - 90. Drosophila melanogaster. Food. Chem. Toxicol., Tepe, B. 2008. Antioxidant potentials and rosmarinic 47(1): 180 - 83. acid levels of the methanolic extracts of Salvia Pelkonen, O., Abass, K.and Wiesner, J. 2013. Thujone virgata (Jacq), Salvia staminea (Montbret & and thujone - containing herbal medicinal and Aucher ex Bentham) and Salvia verbenaca (L.) botanical products: Toxicological assessment. from Turkey. Bioresource Technology., 99: 1584 Regulatory Toxicology and Pharmacology., 65 - 1588. (1): 100 - 107. Valnet, J. 1990. Aromatherapie, Maloine. S.A. Publishers, Perfumi, M., Arnold, N. and Tacconi, R. 1991. Paris, pp. 338 - 343. Hypoglycemic activity of Salvia fruticosa Mill. Walch, S.G., Kuballa, T., Stuhlinger, W. and from Cyprus. Journal of Ethnopharmacology., Lachenmeier, D.W. 2011. Determination of the 34 (2-3) : 135 - 140. biologically active flavour substances thujone Radulescu, V., Chiliment, S. and Oprea, E.2004. and camphor in foods and medicines containing Capillary gas chromatography-mass spectrometry sage (Salvia officinalis L.). Chem. Cent. J. 5: 5- of volatile and semi-volatile compounds of Salvia 44. officinalis. J. Chromatogr A., 1027 : 121-126. WHO (World Health Organization). 2001. Principles Rami, K. and Li, Z. 2011. Antimicrobial activity of for evaluating health risks to reproduction essential oil of Salvia officinalis L. collected in associated with exposure to chemicals. Environ- Syria. Afr. J. Biotech., 10: 8397-8402. mental Health Criteria., 225: 1 - 187. Rivera, D., Obon, C. and Cano, F. 1994. The botany, history and traditional uses of three-lobed sage (Salvia fruticosa Miller). Economic Botany., 48 (2): 190 - 195.

Corresponding Author : Amel R. Omar, Department of Zoology, Faculty of Science, Cairo University, Egypt, E-mail : [email protected] © 2016, IJALS. All Rights Reserved.

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