SAGE LEAF Labiatae

Salviae officinalis folium

Synonyms: Common or Dalmatian sage leaf. lactone structures, such as rosmanol, epirosmanol,
7-methoxyrosmanol and galdosol, which have
Definition been identified in sage leaf [11,13] and/or sage
Sage Leaf consists of the dried leaves of Salvia oleoresin [12].
officinalis L. Safficinolide and sageone [14], methyl carnosate,
the lactone sagequinone methide A [11], and other
Monographs on (common or Dalmatian) sage related diterpenes [11] have also been isolated.
leaf from Salvia officinalis L. and three-lobed Some of these compounds may be artefacts formed
sage leaf from Salvia fructicosa Mill. [S. triloba during extraction and isolation.
L. fil.] appear in the European Pharmacopoeia.  Triterpenes Pentacyclic triterpene acids, mainly
Certain other well-known Salvia species, such as ursolic acid (up to 3.5%) and oleanolic acid (up to
S. lavandulaefolia (or lavandulifolia) Vahl (Span- 0.4%), and the triterpene alcohols α- and β-amyrin
ish sage) and S. sclarea L. (clary sage) are used (0.18% and 0.10% respectively) [15].
primarily for their essential oils.  Flavonoids, ca. 1.1% [16], principally flavones
and their glycosides including: luteolin, its 7-gluco-
side, 7-glucuronide, 3′-glucuronide and 7-methyl
CONSTITUENTS ether; 6-hydroxyluteolin, its 7-glucoside and 7-

 Essential oil
oil, up to 3% [1] (Ph. Eur. min. 1.5%
V/m for whole dried leaf, 1.0% V/m for cut dried
CH3
leaf), of very variable composition depending on
the source, time of harvesting and other factors.
O
The principal components are monoterpenoids
such as α-thujone (10-60%), β-thujone (4-36%),
camphor (5-20%) and 1,8-cineole (2-15%), tog-
ether with sesquiterpenes such as α-humulene,
β-caryophyllene and viridiflorol [1-3]. H3C CH3
 Hydroxycinnamic acid derivatives, about 3.5%,
principally the caffeic acid dimer rosmarinic acid α-Thujone
(up to 3.3%) [4]. Caffeic acid trimers (melitric acid
A, methyl melitrate A, sagecoumarin and salvia-
nolic acid K) [5,6] and a tetramer (sagerinic acid) O
[6] have also been isolated. OH
HO
Collectively, these and similar compounds are O H
sometimes described as “tannins” or “Labiatae
HO
tannins” since they may be adsorbed by hide HO OH
powder to some extent in methods for the deter-
mination of tannins in herbal drugs (e.g. Ph. Eur. O

method 2.8.14). However, they are not genuine

tannins in the sense of condensed tannins (pro-
Rosmarinic acid
anthocyanidins) or hydrolysable tannins (gallo- and
ellagitannins).
Other hydroxycinnamic compounds present OH CH3
include 6-feruloyl-glucose [7] and a polyalcohol
HO
derivative of it [8], three hydroxycinnamic esters CH3
of disaccharides, e.g. 1-caffeoyl-(6′-apiosyl)- HOOC
glucoside [9] and free caffeic acid [8].
 Phenolic diterpenes Carnosic acid, a tricyclic
diterpene, occurs in the fresh leaf [10] and to
some extent in the dried leaf [11] and certain
H
types of extract [12]. However, carnosic acid is
H3C CH3
fairly unstable and readily auto-oxidises to form
lactones (see the diagram in the Rosemary Leaf
monograph), especially the bitter-tasting lactone Carnosic acid
carnosol (0.35%) [10]. In turn, carnosol can degrade
further to produce other phenolic diterpenes with

Sage leaf 1 or 1 339

9 September 2005
Sage Leaf

glucuronide; 6-methoxyluteolin and its 7-methyl diazepine antagonist. Activity-guided analysis

ether; apigenin, its 7-glucoside and 7-methyl ether revealed five benzodiazepine receptor-active
(= genkwanin); 6-methoxyapigenin (= hispidulin) constituents, of which three are flavones and two
and its 7-methyl ether (cirsimaritin); vicenin-2 (= diterpenes. Compared to diazepam (IC50: 0.05 µM)
apigenin 6,8-di-C-glucoside)
C-glucoside) [13,17-19] and 5-
C the diterpene galdosol (IC50: 0.8 µM) and the flavone
methoxysalvigenin [20]. hispidulin (IC50: 1.3 µM) were the most active;
 Phenolic glycosides, a diverse range including, 7-methoxyrosmanol (IC50: 7.2 µM) also exhibited
in addition to the glycosides mentioned under strong affinity, while apigenin (IC50: 30 µM) and
Hydroxycinnamic acid derivatives and Flavonoids, cirsimaritin (IC50: 350 µM) were considerably less
picein (4-hydroxyacetophenone glucoside), 4- active [13].
hydroxyacetophenone 4-(6′-apiosyl)-glucoside, cis-
and trans-p-coumaric acid 4-(2′-apiosyl)-glucoside, Other activities
isolariciresinol 3-glucoside, 1-hydroxypinoresinol Sage oil has strong antimicrobial properties,
1-glucoside and others [7,8,19]. attributed principally to the presence of thujones.
 Polysaccharides Crude fractions rich in water- Inhibitory activity of the oil against Gram-positive
soluble arabinogalactans and also high-MW pectin and Gram-negative bacteria and against a range
and glucuronoxylan-related polysaccharides have of fungi has been demonstrated [29,30]. Antiviral
been isolated from aerial parts of sage [21,22]. activity (against vesicular stomatitis virus) was
 Other constituents include small amounts exhibited by a methanolic extract from sage aerial
of benzoic acid derivatives (p-hydroxybenzoic, parts and two phenolic diterpene constituents
gentisic, syringic and other acids) [8,23] and phyto- (safficinolide and sageone) [14].
sterols (β-sitosterol and stigmasterol, 0.001%)
[15,18]. Sage oil had only a relatively weak spasmolytic
effect on isolated guinea pig tracheal and ileal
Published Assay Methods smooth muscle in comparison with oils from other
Rosmarinic acid by HPLC [24]. Phenolic diterpenes Labiatae such as melissa leaf or thyme [31].
and rosmarinic acid by HPLC [25].
An 80%-ethanolic extract from sage leaf exhib-
ited dose-dependent cholinesterase-inhibiting
PHARMACOLOGY activity. It was a more selective inhibitor of
butyrylcholinesterase (IC50: 0.054 mg/ml) than of
In vitro acetylcholinesterase (IC50: 0.365 mg/ml) [32].

Antioxidant activity It has recently been shown that water-soluble

Sage leaf extracts exhibit strong antioxidant activity, polysaccharides isolated from aerial parts of sage
largely attributable to various phenolic constituents possess immunomodulatory activity [21,22].
including phenolic diterpenes such as carnosol [8]
and hydroxycinnamic acid derivatives, notably In vivo
rosmarinic acid [4]. Topically applied chloroform extracts from sage leaf
(obtained from four different plant populations)
In a carotene bleaching test, the antioxidative dose-dependently inhibited croton oil-induced ear
activity of a dry acetone extract (15:1) from sage oedema in mice with an ID50 corresponding to dried
leaf was found to be 101-116% of that of the leaf at 2-4 mg/cm2. Almost 50% of the extract proved
synthetic antioxidant butylated hydroxytoluene to be ursolic acid which, as an isolated compound,
(BHT) [26]. exhibited strong anti-inflammatory activity in the
same test with an ID50 of 0.14 µMoles/cm2, almost
Lipid peroxidation in both enzyme-dependent twice as potent as indometacin with an ID50 of 0.26
and enzyme-independent test systems were µMoles/cm2 [33].
inhibited more effectively by a dry 50%-methan-
olic extract from aerial parts of sage leaf than by Pharmacological studies in humans
α-tocopheryl acid succinate (as a positive control). In a double-blind, placebo-controlled, crossover
The antioxidant activity was attributed mainly to study, 30 healthy young volunteers (17 males, 13
phenolic compounds, rosmarinic acid being the females; mean age 24 years) were given, on three
main contributor due to its high concentration in separate days at 7-day intervals in accordance
the extract [27,28]. with a randomized scheme, different single-dose
treatments in identical opaque capsules: 300 mg or
Affinity to human benzodiazepine receptors 600 mg of dried sage leaf, or placebo. On each test
A methanolic extract from sage leaf showed day, pre-dose and at 1 hour and 4 hours post-dose,
affinity to human brain benzodiazepine receptors each participant underwent mood assessment,
(from post-mortem frontal cortex) by competitive requiring completion of Bond-Lader mood scales
displacement of 3H-flumazenil, a specific benzo- and the State Trait Anxiety Inventory (STAI) before

340
 Sage Leaf

and after a 20-minute performance on the Defin- THERAPEUTICS

ed Intensity Stress Simulator (DISS) computerized
multitasking battery. The last comprised a set of Actions
four cognitive and psychomotor tasks presented Antioxidant [4,26-28], anti-inflammatory [33],
concurrently on a split (quartered) screen layout, antimicrobial [29,30], carminative [36,37], weakly
to which responses had to be made with an spasmolytic [31,37], astringent [36-39], antihidrotic
external mouse, giving attention simultaneously (inhibits perspiration) [37-40]. Considered to be a
to all four tasks while monitoring the cumulative stimulant and tonic to the digestion and nervous
score (reflecting accuracy and speed of response) system [36,39].
in the centre of the screen. The DISS engenders Recent human studies have demonstrated bene-
increases in self-ratings of negative mood, arousal ficial effects of sage leaf on cognitive performance
and stress-related physiological responses. and mood in healthy young volunteers [32] and
Both doses of sage leaf led to post-dose improved cognitive function in elderly patients with mild to
ratings of mood before performing on the DISS, moderate Alzheimer’s disease [34].
with the lower dose reducing anxiety and the
higher dose increasing ‘alertness’, ‘calmness’ and Indications
‘contentedness’ on the Bond-Lader scales. How- None adequately substantiated by pharmacolog-
ever, the lower dose reduced alertness on the DISS ical or clinical studies.
and, as a result of performing on the DISS, the
previously reduced anxiety effect of this dose was Uses based on experience or tradition
abolished. After the higher dose, task performance Internal: Digestive disorders such as dyspepsia,
on the DISS battery improved at both post-dose flatulence, poor digestion and bloating [37-40];
sessions, but after the lower dose task performance to reduce excessive perspiration [37-40,42], e.g.
decreased. The results indicated that single doses of in the menopause [39,42]. Also taken as a gentle,
sage leaf can improve cognitive performance and stimulating tonic [39].
mood in healthy young participants, although the Topical (as a gargle or mouthwash): Inflammations
lower dose (300 mg) appeared to fall somewhat of the mouth or throat mucosa, such as pharyngitis,
below the level required for beneficial effects. It is tonsillitis, stomatitis, gingivitis and glossitis [36-
possible that inhibition of cholinesterases by sage 40].
leaf (demonstrated only in vitro) could be involved
in the mechanism causing these effects [32]. Contraindications
Sage leaf should not be taken during pregnancy
or lactation (except in amounts present as a
CLINICAL STUDIES flavouring in foods) [35,42]. Epileptics are also
advised to avoid it due to the convulsant potential
In a randomized, double-blind, placebo-controlled of thujones [40].
study, patients aged 65-80 years of age with a
diagnosis of mild to moderate dementia and Side effects
probable Alzheimer’s disease were treated for 16 None reported.
weeks with 60 drops/day of either a sage leaf liquid
extract (1:1, 45% ethanol; n = 15) or a placebo Interactions with other drugs
liquid (n = 15). Compared with the placebo group, None known.
patients in the sage leaf group experienced sig-
nificant benefits in cognitive function by the end Dosage
of treatment, as indicated by improved scores in Internal daily dose: 3-6 of dried leaf, usually as an
the Clinical Dementia Rating (CDR; p<0.003) infusion [37,38]; liquid extract 1:1 in 45% ethanol,
and the Alzheimer’s Disease Assessment Scale 2-6 ml [34,37].
(ADAS-Cog; p = 0.03). Within the limitations of a For topical use in mouthwashes and gargles: 2.5 g of
fairly small number of patients and short period dried leaf to 100 ml of water as an infusion [38].
of follow-up, the results suggested efficacy of the
sage leaf extract in the management of mild to
moderate Alzheimer’s disease [34]. SAFETY
Several open studies, carried out mainly in the 1930s The amount of sage leaf consumed as a culinary
on patients or healthy volunteers but including a herb in food presents no hazard, but a degree
larger 1989 study (unpublished) on 80 patients of caution is necessary with larger amounts due
with idiopathic hyperhidrosis (the secretion of an to the presence of thujones and camphor in the
abnormally large amount of sweat), supported the essential oil. Recommended dosages should not
longstanding belief that sage leaf aqueous extracts be exceeded or taken over prolonged periods, and
have anti-hyperhidrotic activity [35]. sage leaf preparations should be avoided during

341
Sage Leaf

pregnancy and lactation [43]. The pure essential 4. Lamaison JL, Petitjean-Freytet C, Duband F and Carnat AP.
oil should never be used [44]. Rosmarinic acid content and antioxidant activity in French
Lamiaceae. Fitoterapia 1991, 62, 166-171.
5. Lu Y, Foo LY and Wong H. Sagecoumarin, a novel caffeic
In a randomized clinical study, 15 elderly patients acid trimer from Salvia officinalis. Phytochemistry 1999,
treated with 60 drops/day of a sage leaf liquid 52, 1149-1152.
extract (1:1, 45% ethanol) for 16 weeks experienced 6. Lu Y and Foo LY. Rosmarinic acid derivatives from Salvia
officinalis. Phytochemistry 1999, 51, 91-94.
slightly more mild gastrointestinal complaints than 7. Wang M, Li J, Rangarajan M, Shao Y, LaVoie EJ, Huang
those receiving placebo, but the differences were T-C and Ho C-T. Antioxidative Phenolic Compounds from
not statistically significant [34]. Sage (Salvia officinalis). J. Agric. Food Chem. 1998, 46,
4869-4873.
8. Wang M, Kikuzaki H, Zhu N, Sang S, Nakatani N and
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to be 2.6 g/kg [45]. α-Thujone, which is more tox- glycosides from sage (Salvia
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while 60 mg/kg causes a tonic convulsion leading to 10. Brieskorn CH. Salbei - seine Inhaltsstoffe und sein thera-
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by conversion to less toxic metabolites [46]. 1477.
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Sage Leaf

Dosage Mode of administration

Unless otherwise prescribed: Cut drug for infusions; alcoholic extracts and distillates
Internal Daily dose: 4-6 g of the drug; 0.1-0.3 g of for gargles, rinses and other topical applications, as
essential oil; 2.5-7.5 g of tincture (in accordance with well as for internal use; also as pressed juice from the
Erg. DAB 6); 1.5-3 g of fluid extract (in accordance with fresh plant.
Erg. DAB 6).
Gargles and rinses 2.5 g of the drug or 2-3 drops of Actions
essential oil to 100 ml of water as an infusion, or 5 g of Antibacterial, fungistatic, virustatic, astringent, promotes
alcoholic extract to a glass of water. secretion and inhibits perspiration.

344