Sage

Scientific Name(s): Salvia officinalis L. Family: Lamiaceae (mint)

Common Name(s): Sage , culinary sage , Dalmatian sage , garden sage , kitchen sage , true sage , meadow sage

Uses

Dried sage leaf is used as a culinary spice and as a source of sage oil. Sage extracts are being investigated for their potential in memory enhancement and Alzheimer disease; however, clinical trials are lacking. Anti-inflammatory and antimicrobial properties have been identified, as well as potential effects in diabetes and gastric ulcers.

Dosing

Dried sage leaf has been investigated in memory studies at doses of 300 and 600 mg. Ethanolic extract 333 mg has been studied in Alzheimer disease. Typical dosage has been described as 4 to 6 g/day of the leaf.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

There were no clinically important adverse reactions reported by healthy patients in 2 clinical trials; however, effects were similar to those reported with cholinesterase inhibitors. Cheilitis, stomatitis, dry mouth, and local irritation have been reported.

Toxicology

Data are limited. Thujone and camphor constituents are toxic.

Botany

At least 95 species and many varieties exist within the sage genus Salvia . This small, evergreen perennial plant can grow up to 1 m, and its short woody stems branch extensively. The plant is native to the Mediterranean region and grows throughout much of the world. Its violet-blue flowers bloom from June through September. This plant should not be confused with red sage or desert brush sage, which are unrelated. 1 , 2 , 3 , 4

History

The name Salvia derives from the Latin salvere , meaning to cure . Traditionally, sage and its oil have been used to treat a wide range of illnesses. Ethanolic tinctures and decoctions have been used to treat inflammation of the oral cavity and GI tract; sage has been used as a tonic and antispasmodic.

The plant has been used topically as an antiseptic and astringent and to manage excessive sweating. Sage tea has been ingested for the treatment of dysmenorrhea, diarrhea, gastritis, tonsillitis, and sore throat. The dried leaves have been smoked to treat asthma.

Dried sage leaf is used as a culinary spice and as a source of sage oil, which is obtained by steam distillation. Sage oil is used as a fragrance in soaps and perfumes. Sage is used as a food flavoring, and its aroma is said to suppress the odor of fish. Sage oleoresin is also used in the culinary industry. 2 , 4 , 5

Chemistry

S. officinalis contains 1% to 2.8% essential oil, along with flavones, phenolic acids, phenylpropanoid glycosides (eg, martynoside), triterpenoids, and diterpenes, including phenolic, quinoidal, and rearranged abietane and apianane derivatives. The plant's compounds include salvigenin, lupeol, beta-sitosterol, stigmasterol, physcion, carnosol, rosmadial, rosmanol, epirosmanol, isorosmanol, columbaridione, atuntzensin A, miltirone, carnosic acid, and 12-O-methyl carnosic acid. 4 , 6 , 7 , 8 , 9

Monoturpenes have been identified using gas chromatography and other techniques, with alpha- and beta-thujones accounting for about one-half of the oil's composition. 10 , 11 , 12 Capillary electrophoresis has been used to identify the polyphenols, 13 , 14 while high performance liquid chromatography and nuclear magnetic resonance techniques have been applied to cold water extracts in identifying polysaccharides. 15 , 16

Salvia lavandulaefolia (Spanish sage) and S. officinalis have similar compositions except that S. officinalis has a much higher concentration of thujone, which is toxic in large doses. 17 S. lavandulaefolia also contains variable amounts of camphor, cineol, limonene, camphene, and pinene. Sage oil is often adulterated by the addition of thujone derived from the leaves of Juniperus virginiana (red cedar). 4 , 12 , 18 , 19

Uses and Pharmacology

Trials in human subjects are limited.

CNS effects

Improved memory retention has been demonstrated in animal studies, 20 as well as in clinical studies. In 1 study, mood and cognitive performance were improved in young healthy volunteers given 300 and 600 mg of dried S. officinalis leaf. An anxiolytic effect was also observed. 21 In another study, ethanolic leaf extract increased memory and attention in older healthy volunteers (mean, 72.95 years of age) at lower dosages (333 mg extract), but had no effect at higher dosages. 22 Adverse reactions were similar to those reported with cholinesterase inhibitors. 23

Limited studies have evaluated the efficacy of sage extracts in Alzheimer disease. 17 , 23 , 24 While the results are promising, some methodological issues remain, and larger, long-term trials are needed before a definitive role for sage in the management of Alzheimer disease can be seen. 17 Similar results have been obtained in studies using other Salvia species, including S. lavandulaefolia and Salvia miltiorrhiza , as well as rosmarinic acid alone. 17 , 18 , 25 , 26 , 27 , 28 , 29

Other effects
Anti-inflammatory activity

Proinflammatory cytokines were suppressed in in vitro experiments with human leukocytes 30 and in induced colitis in mice. 31 No histological changes were apparent. 31 The chloroform extracts, in particular ursolic acid, of S. officinalis leaves showed strong anti-inflammatory properties after topical application. Ursolic acid exhibited dose-dependent inhibition of croton oil-induced ear edema in mice. The anti-inflammatory effect of ursolic acid was 2-fold more potent than that of indomethacin. 26 , 32

Antimicrobial activity

In vitro antimicrobial activity has been demonstrated by both the aqueous extracts of sage leaves and the essential oil. A wide antibacterial spectrum has been suggested, while activity against fungi is uncertain. 11 , 33 , 34 , 35 Interest centers on activity against vancomycin-resistant enterococci, 36 herpes simplex and corona viruses, 10 , 37 and HIV. 38 , 39

Antioxidant activity

Aqueous extracts of sage, sage tea, and volatile and phenolic sage compounds have been used in experiments demonstrating the antioxidant potential of sage and other related species. Oxygen radical absorbance capacity assay and electron spin resonance techniques have been used in assay and in vitro experiments. In vivo markers, such as glutathione levels, have been used in rats. Inhibition of lipid peroxidation and increasing food oil stability have been demonstrated, but clinical applications are lacking. 11 , 28 , 30 , 40 , 41 , 42 , 43 , 44 , 45 , 46

Cancer

Sage essential oil and its constituent monoterpenes were effective in protecting against ultraviolet-induced mutations in bacterial studies. 47

Diabetes

Studies in animals have shown effects of methanol leaf extracts and sage tea on fasting plasma glucose levels, but not on glucose tolerance tests or insulin. 48 , 49 Sage essential oil had no effect on serum glucose. 48 Other Salvia species have also been evaluated for effects on serum glucose. 50

GI activity

There is some evidence that sage oil may exert a centrally-mediated, antisecretory action; the carminative effect is likely caused by the irritating effects of the volatile oil. 3 A hydroethanolic extract was protective against ethanol-induced gastric lesions in rats. 51

Dosage

Dried sage leaf has been investigated in memory studies at doses of 300 and 600 mg. 17 Ethanolic extract 333 mg has been studied in Alzheimer disease. 22 , 24 Typical dosage has been described as 4 to 6 g/day of the leaf.

Pregnancy/Lactation

Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented. Interactions with cholinergic drugs, such as pilocarpine and scopolamine, is expected based on studies evaluating the effect of sage extracts in Alzheimer disease. 20 , 23

Adverse Reactions

Reported adverse reactions from the ingestion of sage include cheilitis, stomatitis, dry mouth, and local irritation. 5 There were no clinically important adverse reactions reported by healthy patients in 2 clinical trials 18 , 24 ; however, effects were similar to those reported with cholinesterase inhibitors. 23 Increases in blood pressure were reported in a trial evaluating S. lavandulaefolia essential oil in 2 patients with preexisting hypertension. 29

Toxicology

Doses of more than 200 nL/mL essential oil are hepatotoxic, 40 and at concentrations of 120 mcg/mL, decreased cell viability was found. 43 The intraperitoneal lethal dose in rats of a methanolic extract of sage leaves was calculated at 4,000 mg/kg. 20 Constituents thujone and camphor are recognized as neurotoxic, 40 while rosmarinic acid, carnosic acid, and carnosol were not genotoxic at dosages used in experiments. 27 , 30

Bibliography

1. Salvia officinalis L. USDA, NRCS. 2007. The PLANTS Database ( http://plants.usda.gov , July 2009). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
2. Chevallier A. The Encyclopedia of Medicinal Plants . New York, NY: DK Publishing; 1996 .
3. Blumenthal M, Goldberg A, Brinckmann J, eds. Herbal Medicine: Expanded Commission E Monographs . Newton, MA: Integrative Medicine Communications; 2000 .
4. Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics . New York, NY: Wiley; 1980 .
5. Duke, JA. CRC Handbook of Medicinal Herbs . Boca Raton, FL: CRC Press; 1985 .
6. Capek P, Hribalova V, Svandova E, Ebringergova A, Sasinkova V, Masarova J. Characterization of immunomodulatory polysaccharides from Salvia officinalis L. Int J Biol Macromol . 2003;33(1-3):113-119.
7. Hohmann J, Redei D, Mathe I, Blunden G. Phenylpropanoid glycosides and diterpenoids from Salvia officinalis . Biochem Syst Ecol . 2003;31(4):427-429.
8. Miura K, Kikuzaki H, Nakatani N. Apianane terpenoids from Salvia officinalis . Phytochemistry . 2001;58(8):1171-1175.
9. Ninomiya K, Matsuda H, Shimoda H, et al. Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett . 2004;14(8):1943-1946.
10. Loizzo MR, Saab AM, Tundis R, et al. Phytochemical analysis and in vitro antiviral activities of the essential oils of seven Lebanon species. Chem Biodivers . 2008;5(3):461-470.
11. Bozin B, Mimica-Dukic N, Samojlik I, Jovin E. Antimicrobial and antioxidant properties of rosemary and sage ( Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. J Agric Food Chem . 2007;55(19):7879-7885.
12. Raal A, Orav A, Arak E. Composition of the essential oil of Salvia officinalis L. from various European countries. Nat Prod Res . 2007;21(5):406-411.
13. Ben Hameda A, Gajdoová D, Havel J. Analysis of Salvia officinalis plant extracts by capillary electrophoresis. J Sep Sci . 2006;29(8):1188-1192.
14. Fecka I, Turek S. Determination of water-soluble polyphenolic compounds in commercial herbal teas from Lamiaceae: peppermint, melissa, and sage. J Agric Food Chem . 2007;55(26):10908-10917.
15. Capek P. An arabinogalactan containing 3-O-methyl-D-galactose residues isolated from the aerial parts of Salvia officinalis L. Carbohydr Res . 2008;343(8):1390-1393.
16. Capek P, Hríbalová V. Water-soluble polysaccharides from Salvia officinalis L. possessing immunomodulatory activity. Phytochemistry . 2004;65(13):1983-1992.
17. Kennedy DO, Scholey AB. The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm Des . 2006;12(35):4613-4623.
18. Tildesley NT, Kennedy DO, Perry EK, et al. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behav . 2003;75(3):669-674.
19. Savelev S, Okello E, Perry NS, Wilkins RM, Perry EK. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behav . 2003;75(3):661-668.
20. Eidi M, Eidi A, Bahar M. Effects of Salvia officinalis L. (sage) leaves on memory retention and its interaction with the cholinergic system in rats. Nutrition . 2006;22(3):321-326.
21. Kennedy DO, Pace S, Haskell C, Okello EJ, Milne A, Scholey AB. Effects of cholinesterase inhibiting sage ( Salvia officinalis ) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology . 2006;31(4):845-852.
22. Scholey AB, Tildesley NT, Ballard CG, et al. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology (Berl) . 2008;198(1):127-139.
23. Akhondzadeh S, Abbasi SH. Herbal medicine in the treatment of Alzheimer's disease. Am J Alzheimers Dis Other Demen . 2006;21(2):113-118.
24. Akhondzadeh S, Noroozian M, Mohammadi M, Ohadinia S, Jamshidi A, Khani M. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther . 2003;28(1):53-59.
25. Tildesley NT, Kennedy DO, Perry EK, Ballard CG, Wesnes KA, Scholey AB. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiol Behav . 2005;83(5):699-709.
26. Imanshahidi M, Hosseinzadeh H. The pharmacological effects of Salvia species on the central nervous system. Phytother Res . 2006;20(6):427-437.
27. Pereira P, Tysca D, Oliveira P, da Silva Brum LF, Picada JN, Ardenghi P. Neurobehavioral and genotoxic aspects of rosmarinic acid. Pharmacol Res . 2005;52(3):199-203.
28. Orhan I, Aslan M. Appraisal of scopolamine-induced antiamnesic effect in mice and in vitro antiacetylcholinesterase and antioxidant activities of some traditionally used Lamiaceae plants. J Ethnopharmacol . 2009;122(2):327-332.
29. Perry NS, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav . 2003;75(3):651-659.
30. Poeckel D, Greiner C, Verhoff M, et al. Carnosic acid and carnosol potently inhibit human 5-lipoxygenase and suppress pro-inflammatory responses of stimulated human polymorphonuclear leukocytes. Biochem Pharmacol . 2008;76(1):91-97.
31. Juhás S, Cikos S, Czikková S, et al. Effects of borneol and thymoquinone on TNBS-induced colitis in mice. Folia Biol (Praha) . 2008;54(1):1-7.
32. Baricevic D, Sosa S, Della Loggia R, et al. Topical anti-inflammatory activity of Salvia officinalis L. leaves: the relevance of ursolic acid. J Ethnopharmacol . 2001;75(2-3):125-132.
33. Hayouni el A, Chraief I, Abedrabba M, et al. Tunisian Salvia officinalis L. and Schinus molle L. essential oils: their chemical compositions and their preservative effects against Salmonella inoculated in minced beef meat. Int J Food Microbiol . 2008;125(3):242-251.
34. Pozzatti P, Scheid LA, Spader TB, Atayde ML, Santurio JM, Alves SH. In vitro activity of essential oils extracted from plants used as spices against fluconazole-resistant and fluconazole-susceptible Candida spp. Can J Microbiol . 2008;54(11):950-956.
35. Weckesser S, Engel K, Simon-Haarhaus B, Wittmer A, Pelz K, Schempp CM. Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance. Phytomedicine . 2007;14(7-8):508-516.
36. Horiuchi K, Shiota S, Hatano T, Yoshida T, Kuroda T, Tsuchiya T. Antimicrobial activity of oleanolic acid from Salvia officinali s and related compounds on vancomycin-resistant enterococci (VRE). Biol Pharm Bull . 2007;30(6):1147-1149.
37. Schnitzler P, Nolkemper S, Stintzing FC, Reichling J. Comparative in vitro study on the anti-herpetic effect of phytochemically characterized aqueous and ethanolic extracts of Salvia officinalis grown at two different locations. Phytomedicine . 2008;15(1-2):62-70.
38. Geuenich S, Goffinet C, Venzke S, et al. Aqueous extracts from peppermint, sage and lemon balm leaves display potent anti-HIV-1 activity by increasing the virion density. Retrovirology . 2008;5:27.
39. Bailly F, Queffelec C, Mbemba G, Mouscadet JF, Cotelle P. Synthesis and HIV-1 integrase inhibitory activities of caffeic acid dimers derived from Salvia officinalis . Bioorg Med Chem Lett . 2005;15(22):5053-5056.
40. Lima CF, Carvalho F, Fernandes E, et al. Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes. Toxicol In Vitro . 2004;18(4):457-465.
41. Lima CF, Andrade PB, Seabra RM, Fernandes-Ferreira M, Pereira-Wilson C. The drinking of a Salvia officinalis infusion improves liver antioxidant status in mice and rats. J Ethnopharmacol . 2005;97(2):383-389.
42. Lima CF, Valentao PC, Andrade PB, Seabra RM, Fernandes-Ferreira M, Pereira-Wilson C. Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage. Chem Biol Interact . 2007;167(2):107-115.
43. Aherne SA, Kerry JP, O'Brien NM. Effects of plant extracts on antioxidant status and oxidant-induced stress in Caco-2 cells. Br J Nutr . 2007;97(2):321-328.
44. Oboh G, Henle T. Antioxidant and inhibitory effects of aqueous extracts of Salvia officinalis leaves on pro-oxidant-induced lipid peroxidation in brain and liver in vitro. J Med Food . 2009;12(1):77-84.
45. Celik I, Isik I. Determination of chemopreventive role of Foeniculum vulgare and Salvia officinalis infusion on trichloroacetic acid-induced increased serum marker enzymes lipid peroxidation and antioxidative defense systems in rats. Nat Prod Res . 2008;22(1):66-75.
46. Capek P, Machová E, Turjan J. Scavenging and antioxidant activities of immunomodulating polysaccharides isolated from Salvia officinalis L. Int J Biol Macromol . 2009;44(1):75-80.
47. Vukovic-Gacic B, Nikcevic S, Beric-Bjedov T, Knezevic-Vukcevic J, Simic D. Antimutagenic effect of essential oil of sage ( Salvia officinalis L.) and its monoterpenes against UV-induced mutations in Escherichia coli and Saccharomyces cerevisiae . Food Chem Toxicol . 2006;44(10):1730-1738.
48. Eidi M, Eidi A, Zamanizadeh H. Effect of Salvia officinalis L. leaves on serum glucose and insulin in healthy and streptozotocin-induced diabetic rats. J Ethnopharmacol . 2005;100(3):310-313.
49. Lima CF, Azevedo MF, Araujo R, Fernandes-Ferreira M, Pereira-Wilson C. Metformin-like effect of Salvia officinalis (common sage): is it useful in diabetes prevention? Br J Nutr . 2006;96(2):326-333.
50. Loizzo MR, Saab AM, Tundis R, et al. In vitro inhibitory activities of plants used in Lebanon traditional medicine against angiotensin converting enzyme (ACE) and digestive enzymes related to diabetes. J Ethnopharmacol . 2008;119(1):109-116.
51. Mayer B, Baggio CH, Freitas CS, et al. Gastroprotective constituents of Salvia officinalis L. Fitoterapia . 2009;80(7):421-426.

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