Sage

Summary and Pharmaceutical Comment

The characteristic components of sage (Salvia officinalis) to which its traditional uses can be attributed are the volatile oil and tannins. The oil of a related species Salvia lavandulifolia is being investigated for symptomatic treatment of Alzheimer’s disease. However, at present, there is a lack of well-designed clinical studies investigating the reputed effects of sage. Sage oil contains high concentrations of thujone, a toxic ketone, and should not be ingested. Sage is commonly used as a culinary herb and presents no hazard when ingested in amounts normally encountered in foods. However, extracts of the herb should be used with caution and should not be ingested in large amounts or over prolonged periods.

Sage should not be used during pregnancy and lactation.

Species (Family)

*Salvia officinalis L. (Labiatae/Lamiaceae)

S. lavandulifolia Vahl

Synonym(s)

*Dalmatian Sage, Garden Sage, True Sage

Part(s) Used

Leaf

Pharmacopoeial and Other Monographs

BHP 1996(G9)

BP 2007(G84)

Complete German Commission E(G3)

ESCOP 2003(G76)

Martindale 35th edition(G85)

Ph Eur 2007(G81)

Legal Category (Licensed Products)

SGSL(G37)

Constituents

The following is compiled from several sources, including Reference 1 and General References G2, G52, G58 and G62.

Acids Phenolic – caffeic, chlorogenic, ellagic, ferulic, gallic and rosmarinic.(2)

Flavonoids 5-Methoxysalvigenin.

Terpenes Monoterpene glycosides. Diterpenes, abietanes including carnosic acid and derivatives, e.g. carnasol. Triterpenes, oleanolic acid and derivatives.

Tannins 3–8%. Hydrolysable and condensed.(2, 3)

Volatile oil 1–2.8%. Pharmacopoeial standard not less than 1.0% cut herb.(G81, G84) Major components are a- and b-thujones (35–

50%, mainly a). Others include 1,8-cineole, borneol, camphor, caryophyllene, linalyl acetate and various terpenes.(4, 5)

Figure 1 Selected constituents of sage.

It has been noted that commercial sage may be substituted with Salvia triloba.(1) In contrast to S. officinalis, the principal volatile oil component of S. triloba is 1,8-cineole, with a-thujone only accounting for 1–5%.(1) Compared with S. officinalis, the volatile oil yield of various Salvia species is lower, with lower total ketone content and higher total alcohol content.(6)

Food Use

Sage is commonly used as a culinary herb. It is listed by the

Council of Europe as a natural source of food flavouring (category N2).(G16) This category indicates that sage can be added to

foodstuffs providing the concentration of thujones (a and b) present in the final product does not exceed 0.5 mg/kg, with the exceptions of alcoholic beverages (10 mg/kg), bitters (35 mg/kg),

food containing sage (25 mg/kg) and sage stuffing (250 mg/ kg).(G16) Previously, sage has been listed as GRAS (Generally Recognised As Safe).(G65)

Herbal Use

Sage is stated to possess carminative, antispasmodic, antiseptic, astringent and antihidrotic properties. Traditionally, it has been used to treat flatulent dyspepsia, pharyngitis, uvulitis, stomatitis,

gingivitis, glossitis (internally or as a gargle/mouthwash), hyperhidrosis, and galactorrhoea.(G2, G4, G7, G32, G43, G52, G54, G64)

The herbals of Gerard, Culpeper and Hill credit sage with the ability to enhance memory.(7) The German Commission E approved internal use for dyspeptic symptoms and excessive

Figure 2 Sage (Salvia officinalis).

perspiration, and external use for inflammation of mucous membranes of mouth and throat.(G3)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Leaf 1–4 g as an infusion three times daily;(G7) 4–6 g daily. (G3)

Liquid extract 1–4 mL (1:1 in 45% alcohol) three times daily.(G7)

Gargles, rinses 2.5 g/100 mL water.(G3)

Pharmacological Actions

In vitro and animal studies

Hypotensive activity in anaesthetised cats, CNS-depressant action (prolonged barbiturate sleep) in anaesthetised mice, and an antispasmodic action in vitro (guinea-pig ileum) have been reported for a sage extract(8) and for the essential oil.(9)

Antispasmodic activity Inhibition of contractions induced by acetylcholine, histamine, serotonin and barium chloride by 60– 80% has been noted for a total sage extract, with lesser activity exhibited by a total flavonoid extract.(8) An initial spasmogenic action exhibited by low doses of sage oil has been attributed to the pinene content.(9) Antispasmodic activity in vivo (guinea-pigs) has been reported for sage oil administered intravenously, which released contraction of Oddi's sphincter induced by intravenous morphine.(5)

Anticholinesterase activity Early herbals claim that sage enhances the memory.(7) The anticholinesterase activity of several Salvia species and their constituents have been investigated in the search for new drugs for the treatment of Alzheimer's disease. The inhibition of anticholinesterase in vitro by an ethanolic extract of S. officinalis (2.5 mg/mL) was 68%, and by oils of S. officinalis and S. lavandulifolia (0.1 mg/mL) was 52% and 63%, respectively.(10) The IC50 value of S. lavandulifolia oil is reportedly 0.03 mg/mL.(11)

Figure 3 Sage – dried drug substance (leaf).

ingested. S. lavandulifolia oil has a much lower content of thujone than does S. officinalis oil.(12) In view of the toxicity of the

essential oil, sage extracts should be used with caution and not ingested in large amounts.

Drug interactions None documented. However, the potential for preparations of sage to interact with other medicines administered concurrently, particularly those with similar or opposing effects, should be considered. There is limited evidence from preclinical studies that sage has hypoglycaemic activity. Sage oil has a high content of thujones, which are convulsants.

Pregnancy and lactation Sage is contra-indicated during pregnancy. Traditionally, it is reputed to be an abortifacient and to affect the menstrual cycle.(G30) The volatile oil contains a high proportion of a- and b-thujones, which are known to be abortifacient and emmenagogic. Sage should not be used during lactation.

Preparations

Proprietary single-ingredient preparations

Austria: Salvysat. Czech Republic: Caj ze Salveje; Florsalmin; List Salveje Lekarske; Nat Salveje Lekarske; Salvejova Nat. Germany: Aperisan; Salbei Curarina; Salvysat; Sweatosan N; Viru-Salvysat. Italy: Saugella Dermoliquido.

Proprietary multi-ingredient preparations

Argentina: Acnetrol; Parodontax Fluor; Sigmafem; Sigmafen Free; Tereonsit. Australia: Feminine Herbal Complex. Austria: Cional; Dynexan; Mentopin; Paradenton. Canada: Original Herb Cough Drops. Chile: Eciclean. Czech Republic: Diabetan; Diabeticka Cajova Smes-Megadiabetin; Pulmoran; Stomatosan; Tormentan. France: Bolcitol; Gonaxine; Saugella; Tisane Hepatique de Hoerdt. Germany: Amara-Tropfen; Melissengeist; Parodontal. Israel: Baby Paste þ Chamomile; Kamilotract. Italy: Donalg; Saugella Attiva; Saugella Dermolatte; Saugella Fitothym; Saugella Salviettine; Saugella Solido ph 3.5. South Africa: Amara; Dynexan. Spain: Diabesor; Menstrunat; Natusor Farinol; Natusor Low Blood Pressure. Switzerland: Strath Gouttes pour les muqueuses; Tisane pectorale et antitussive; Wala Echinacea. Venezuela: One Drop Spray. UK: Lane's Sage and Garlic Catarrh Remedy; Menopace Plus; Napiers Echinacea Tea.

References

1Tucker AO et al. Botanical aspects of commercial sage. Econ Bot 1980; 34: 16–19.

2 Petri G et al. Tannins and other polyphenolic compounds in the genus

Salvia. Planta Med 1988: 54: 575.

3Murko D et al. Tannins of Salvia officinalis and their changes during storage. Planta Med 1974; 25: 295–300.

4Jalsenjak V et al. Microcapsules of sage oil: Essential oils content and antimicrobial activity. Pharmazie 1987; 42: 419–420.

5 Giachetti D et al. Pharmacological activity of essential oils on Oddi's sphincter. Planta Med 1988: 54: 389–392.

6Ivanic R, Savin K. A comparative analysis of essential oils from several wild species of Salvia. Planta Med 1976; 30: 25–31.

7Perry EK et al. Medicinal plants and Alzheimer's disease: integrating ethnobotanical and contemporary scientific evidence. J Alt Complement Med 1998; 4: 419–428.

8Todorov S et al. Experimental pharmacological study of three species from genus Salvia. Acta Physiol Pharmacol Bulg 1984; 10: 13–20.

9Taddei I et al. Spasmolytic activity of peppermint, sage and rosemary essences and their major constituents. Fitoterapia 1988; 59: 463–468.

10Perry N et al. European herbs with cholinergic activities: potential in dementia therapy. Int J Geriat Psychiat 1996; 11: 1063–1069.

11Perry NSL et al. In-vitro inhibition of human erythrocyte acetylcholinesterase by Salvia lavandulaefolia essential oil and constituent terpenes. J Pharm Pharmacol 2000; 52: 895–902.

12Houghton PJ. Personal communication.

13Jimenez J et al. Hypoglycaemic activity of Salvia lavandulifolia. Planta Med 1986: 52: 260–262.

14Cabo J et al. Accion hipoglucemiante de preparados fitoterapicos que contienen especies del genero salvia. Ars Pharmac 1985; 26: 239–249.

15Recio MC et al. Antimicrobial activity of selected plants employed in the Spanish Mediterranean area. Part II. Phytother Res 1989; 3: 77.

16Centini F et al. A case of sage oil poisoning. Zacchia 1987; 60: 263– 174.

17Millet Y. Experimental study of the toxic convulsant properties of commercial preparations of essences of sage and hyssop.

Electroencephal Clin Neurophysiol 1980; 49: 102P.

18Millet Y et al. Toxicity of some essential plant oils – clinical and experimental study. Clin Toxicol 1981; 18: 1485–1498.

19Opdyke DLJ. Sage oil Dalmatian. Food Cosmet Toxicol 1974; 12: 987–988.

Summary and Pharmaceutical Comment

Phytochemical studies on sarsaparilla have focused on the nature of the steroidal saponin constituents, with limited information available regarding additional constituents. No documented scientific evidence from preclinical studies was found to justify the herbal uses. Also, there is a lack of robust clinical research assessing the efficacy and safety of sarsaparilla. No toxicity data were located, although large doses may be irritant to the gastrointestinal mucosa and should, therefore, be avoided.

There are no known problems with the use of sarsaparilla during pregnancy and lactation but, as a precaution, amounts ingested should not exceed those usually found in foods.

Species (Family)

*Smilax regelii Killip & C.V. Morton (Smilacaceae)

†S. purhampuy Ruiz

Synonym(s)

*Smilax ornata Hook

†S. febrifuga Kunth, S. febrifuga var. aequatoris A. DC

Part(s) Used

Rhizome, root

516 Sarsaparilla

Pharmacopoeial and Other Monographs

BHC 1992(G6)

BHP 1996(G9)

Martindale 35th edition(G85)

Legal Category (Licensed Products)

GSL(G37)

Constituents

The following is compiled from several sources, including General Reference G6.

Saponins About 2%. Sarsasapogenin (parigenin), smilagenin, diosgenin, tigogenin, asperagenin, laxogenin from various species,(1) sarsasaponin (parillin), smilasaponin (smilacin) and sarsaparilloside.

Other constituents Caffeoylshikimic acid, ferulic acid, shikimic acid, kaempferol, quercetin, phytosterols (e.g. b-sitosterol, stigmasterol, pollinastanol), resin, starch, volatile oil (trace) and cetyl alcohol.

Food Use

Sarsaparilla is listed by the Council of Europe as a natural source of food flavouring (category N4). This category indicates that the use of sarsaparilla as a flavouring agent is recognised but that

there is insufficient information available to further classify it into categories N1, N2 or N3.(G16) Sarsaparilla has been used as a

vehicle and flavouring agent for medicaments,(G45) and is widely employed in the manufacture of non-alcoholic beverages.(G59) Previously, sarsaparilla has been listed as GRAS (Generally Recognised As Safe).

Herbal Use

Sarsaparilla is stated to possess antirheumatic, antiseptic and antipruritic properties. Traditionally, it has been used for psoriasis

S

Figure 2 Sarsaparilla (Smilax regelii).

Figure 3 Sarsaparilla – dried drug substance (root).

and other cutaneous conditions, chronic rheumatism, rheumatoid

arthritis, as an adjunct to other treatments for leprosy, and specifically for psoriasis.(G6, G7, G8, G64)

Dosage

Dosages for oral administration (adults) for traditional uses recommended in standard herbal reference texts are given below.

Dried root 1–4 g as a decoction three times daily.(G6)

Pharmacological Actions

In vitro and animal studies

Anti-inflammatory(2) and hepatoprotective(3) effects have been described following studies in rats.

Clinical studies

There is a lack of clinical research assessing the effects of sarsaparilla and rigorous randomised clinical trials are required. The following observations and uses require assessment in welldesigned clinical studies.

Improvement of appetite and digestion(4) as well as a diuretic(4, 5) action have been reported. Limited clinical data utilising extracts indicate improvement in psoriasis;(6) the extract has also been used as an adjuvant for the treatment of leprosy.(7)

Side-effects, Toxicity

None documented for sarsaparilla. However, there is a lack of clinical safety and toxicity data for sarsaparilla and further investigation of these aspects is required. Large doses of saponins are reported to cause gastrointestinal irritation resulting in

diarrhoea and vomiting. Although haemolytic activity has been documented for the saponins,(G62) they are not harmful when

taken by mouth and are only highly toxic if injected into the bloodstream.(G59)

Contra-indications, Warnings

None documented for sarsaparilla. In view of the possible irritant nature of the saponin constituents, excessive ingestion should be avoided.

Drug interactions None documented. However, the potential for preparations of sarsaparilla to interact with other medicines

administered concurrently, particularly those with similar or opposing effects, should be considered.

Pregnancy and lactation There are no known problems with the use of sarsaparilla during pregnancy and lactation. However, in view of the possible irritant nature of the saponin components, excessive ingestion (amounts greater than those found in foods) should be avoided.

Preparations

Proprietary multi-ingredient preparations

Argentina: Urinefrol. Australia: Dermaco; Herbal Cleanse; Proesten. Brazil: Elixir de Inhame; Elixir de Marinheiro. Canada: Damiana-Sarsaparilla Formula. Italy: Tisana Kelemata. Malaysia: Cleansa Plus; Total Man. UK: Gerard House Reumalex; HRI Clear Complexion; Jamaican Sarsaparilla; Napiers Skin Tablets; Skin Eruptions Mixture.

Sarsaparilla 517

References

1Sharma SC et al. Über Saponine von Smilax parvifolia Wall. Pharmazie 1980; 35: 646.

2Ageel AM et al. Experimental studies on antirheumatic crude drugs used in Saudi traditional medicine. Drugs Exp Clin Res 1989; 15: 369–

372.

3Rafatullah S et al. Hepatoprotective and safety evaluation studies on sarsaparilla. Int J Pharmacog 1991; 29: 296–301.

4Harnischfeger G, Stolze H. Smilax species – Sarsaparille. In: Bewahrte Pflanzendrogen in Wissenschaft und Medizin. Bad Homburg/ Melsungen: Notamed Verlag., 1983: 216–225.

5 Hobbs C. Sarsaparilla – a literature review. Herbalgram 1988; 17: 1, 10–15.

6Thermon FM. The treatment of psoriasis with a sarsaparilla compound. N Engl J Med 1942; 227: 128–133.

7Rollier R. Treatment of lepromatous leprosy by a combination of DDS and sarsaparilla (Smilax ornata). Int J Leprosy 1959; 27: 328–340.