Sage
Salvia officinalis L. Family: Lamiaceae (mint)
Sage , culinary sage , Dalmatian sage , garden sage , kitchen sage , true sage , meadow sage
 
Clinical Overview
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
 
Administration & 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
 
References
 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

16. Capek P, Hríbalová V. Water-soluble polysaccharides from Salvia officinalis L. possessing immunomodulatory activity. Phytochemistry . 2004;65(13):1983-1992.  PubMed

 

17. Kennedy DO, Scholey AB. The psychopharmacology of European herbs with cognition-enhancing properties. Curr Pharm Des . 2006;12(35):4613-4623.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

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.  PubMed

 

51. Mayer B, Baggio CH, Freitas CS, et al. Gastroprotective constituents of Salvia officinalis L. Fitoterapia . 2009;80(7):421-426.  PubMed