1.
Sources and Summary
Salvia sclarea (of the family Lamiaceae; the Mint family), more commonly referred to as Clary Sage, is an aromatic herb. It is used highly in the perfume industry as the main bioactive, (-)-Sclareol, can be synthesized into Ambrox (an aromatic found from naturally in Ambergris, but is rare from its natural source).[1]
It is sometimes drunk as a tea in Turkey, where it is known as misk sage tea.[2]
Clary sage also has usage as an insect repellant.[3]
1.1
Composition
- The labdane type diterpene (-)-Sclareol, at 0.002-0.026% essential oil but can be up to 1.5% with solid/liquid extraction.[4] The isomer 13-episclareol also exists, with both being biosynthesized from geranylgeranyl diphosphate.[1][5] Sclareol oxide has also been detected[6]
- Manool and 13-epimanool (as well as the latter's oxide), structurally similar to Sclareol[6]
- Salviatrienes A and B at 4.5% and 1% of the folded essential oil[6]
- E,E-α-farnesene[6]
- Salvipisone[7]
- Aethiopinone[7]
- α-eudesmol, δ-cadinene, and δ-amorphene (aromatics)[6]
The seeds of Clary sage have a 17.66+/-0.11% protein content and 27.24+/-1.32% essential oil content with 5.23+/-0.04% ash content.[2] The fatty acid composition is mostly α-linoleic acid (C18:3 n3) at 52.1+/-0.04% of fatty acids and oleic acid (C18:1 n9) at 22.05+/-0.01%.[2]
2.
Neurology
2.1
Neuroprotection
The antioxidant potential of Clary Sage in vitro is thought to exert neuroprotective effects, although it underperformed relative to other species of Salvia in protecting neuronal cells from DNA damage.[8]
2.2
Depression
The essential oil of Clary Sage, following either intraperitoneal injection (0.05-0.2mL essential oil per kg bodyweight) or inhalation (1mL essential oil in warm water to release the aroma) to rats, showed anti-depressant actions in a Forced Swim Test model with a potency greater than that of Anthemis nobilis (Chamomile), Rosmarinus officinalis (Rosemary), and Lavandula angustifolia (Lavender) and comparable to the active controls of Imipramine (30mg/kg) and fluoxetine (1.8mg/kg); this anti-depressant effect was blocked with dopamine antagonists and buspirone, a serotonin receptor (5-HT1A) antagonist.[9] When serum corticosteroids were measured (to assess the stress response), there was no significant effect of Clary Sage.[9]
Appears to have anti-depressant effects in rats, and this has been noted with the aroma of Clary Sage
2.3
Pain
In 61 college-aged females with higher than average menstrual pain (6-10 on a VAS rating scale), an abdominal massage with 2 drops of Lavandula officinalis (Lavender) to one drop Clary Sage and one drop Rosa centifolia (Rose oil) was compared to placebo aromatherapy (almond oil, same method of appplication and volume of 5cc) and control (no aromatherapy). It was noted that aromatherapy was associated with an average reduction in pain from 7 (0-10 rating scale) down to 5 and then 3 on days 1 and 2, respectively; control failed to reduce pain, and placebo aromatherapy appears to work in some persons to a lesser extent than combination therapy (herb intervention still significantly greater than the placebo group).[10] The authors noted that although heavier flows appears to be correlated with greater pain,[11] that there were no significant difference between groups.[10] A similar application method with a similar aromatherapy (Rose switched for Origanum majorana; Marjoram) noted that in persons with diagnosed primary dysmenorrhea given aromatherapy (placebo given synthestic scents; different molecules) that the herbal aromatherapy group experienced significantly greater pain relief associated with menstrual symptoms.[12]
The latter study noted that the majority or aromatics were five molecules; linalyl acetate (36.84%), linalool (22.53%), eucalyptol (17.21%), β-caryophyllene (2.69%), and α‐terpineol (3.29%). It is thought that these aromatics are likely to mediated the anaglesic effects noted.[12]
Combination therapy with at least Clary Sage and Lavender appears to be effective in reducing menstrual pain (no indiciation if this extends to pain in general or just menstrual pain), but currently no studies use Clary Sage in isolation and thus its efficacy in isolation cannot be determined
3.
Cardiovascular Health
3.1
Blood Pressure
One study using Salvia Sclarea essential oil vapors (aromatherapy) in females with urinary incontinence undergoing urodynamic assessment noted that inhalation of Salvia Sclarea for 60 minutes was associated with a drop in systolic blood pressure relative to plcebo (almond oil), a drop in diastolic relative to Lavender scent but not placebo, and a decrease in respiratory rate relative to placebo.[13] The drop in diastolic, which was not statistically significant relative to placebo, was because Lavender trended to increase blood pressure slightly.[13]
At least one study to support Clary Sage reducing blood pressure via aromatherapy
4.
Interactions with Cancer Metabolism
4.1
Immunological Interactions
CD4+CD25+ T-cells are produced in the thymus[14] or in the periphery via conversion from other T-cells[15] and express Foxp3+ to positively influence development and function.[16] CD4+CD25+ may accumulate at the site of tumors[17] where they suppress the activity of cytotoxic T-cells[18]
In mice bearing breast tumors who were then given an injection of isolated Sclareol (7.85mcg daily) directly into the tumor noted that the tumor did not grow in volume, while control experienced a standard growth rate; this was associated with an increase in IFN-γ with a concomitant decrease in IL-4 and reduced levels of the CD4+CD25+Foxp3+ Treg (T regulatory) immune cell.[19] The suppression of CD4+CD25+Foxp3+ Treg cell concentration is thought to preserve T-cell mediated cytotoxicity towards tumor cells, and was as effective as the active control of Cyclophosphamide.[19]
May have mechanisms to preserve T-cell cytotoxicity towards tumor cells via reducing the levels of a suppressive T-cell
4.3
Leukemia
Sclareol has been noted to induce apoptosis in B and T lymphocytic tumor cells with an IC50 below 20µg/mL via apoptotic means.[22] This general cytotoxcity appears to extend to most cancer cell lines testes, and one study using CCRF-CEM leukemic cells as well as normal immune cells (resting and PMA activated PMBCs) noted that free sclareol did not show any therapeutic index (GI50 between 33.1-35µM) while liposomal sclaerol had a GI50 of less than 15µM on leukemic cells and over 100µM on normal cells.[20]
References
- ^Günnewich N, Higashi Y, Feng X, Choi KB, Schmidt J, Kutchan TMA diterpene synthase from the clary sage Salvia sclarea catalyzes the cyclization of geranylgeranyl diphosphate to (8R)-hydroxy-copalyl diphosphatePhytochemistry.(2012 Sep 5)
- ^Yalcin H, Ozturk I, Tulukcu E, Sagdic OEffect of γ-irradiation on bioactivity, fatty acid compositions and volatile compounds of clary sage seed (Salvia sclarea L.)J Food Sci.(2011 Sep)
- ^Conti B, Benelli G, Leonardi M, Afifi FU, Cervelli C, Profeti R, Pistelli L, Canale ARepellent effect of Salvia dorisiana, S. longifolia, and S. sclarea (Lamiaceae) essential oils against the mosquito Aedes albopictus Skuse (Diptera: Culicidae)Parasitol Res.(2012 Jul)
- ^Caissard JC, Olivier T, Delbecque C, Palle S, Garry PP, Audran A, Valot N, Moja S, Nicolé F, Magnard JL, Legrand S, Baudino S, Jullien FExtracellular localization of the diterpene sclareol in clary sage (Salvia sclarea L., Lamiaceae)PLoS One.(2012)
- ^Caniard A, Zerbe P, Legrand S, Cohade A, Valot N, Magnard JL, Bohlmann J, Legendre LDiscovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufactureBMC Plant Biol.(2012 Jul 26)
- ^Laville R, Castel C, Filippi JJ, Delbecque C, Audran A, Garry PP, Legendre L, Fernandez XAmphilectane diterpenes from Salvia sclarea: biosynthetic considerationsJ Nat Prod.(2012 Feb 24)
- ^Walencka E, Rozalska S, Wysokinska H, Rozalski M, Kuzma L, Rozalska BSalvipisone and aethiopinone from Salvia sclarea hairy roots modulate staphylococcal antibiotic resistance and express anti-biofilm activityPlanta Med.(2007 Jun)
- ^Asadi S, Ahmadiani A, Esmaeili MA, Sonboli A, Ansari N, Khodagholi FIn vitro antioxidant activities and an investigation of neuroprotection by six Salvia species from Iran: a comparative studyFood Chem Toxicol.(2010 May)
- ^Seol GH, Shim HS, Kim PJ, Moon HK, Lee KH, Shim I, Suh SH, Min SSAntidepressant-like effect of Salvia sclarea is explained by modulation of dopamine activities in ratsJ Ethnopharmacol.(2010 Jul 6)
- ^Han SH, Hur MH, Buckle J, Choi J, Lee MSEffect of aromatherapy on symptoms of dysmenorrhea in college students: A randomized placebo-controlled clinical trialJ Altern Complement Med.(2006 Jul-Aug)
- ^Sundell G, Milsom I, Andersch BFactors influencing the prevalence and severity of dysmenorrhoea in young womenBr J Obstet Gynaecol.(1990 Jul)
- ^Ou MC, Hsu TF, Lai AC, Lin YT, Lin CCPain relief assessment by aromatic essential oil massage on outpatients with primary dysmenorrhea: a randomized, double-blind clinical trialJ Obstet Gynaecol Res.(2012 May)
- ^Seol GH, Lee YH, Kang P, You JH, Park M, Min SSRandomized Controlled Trial for Salvia sclarea or Lavandula angustifolia: Differential Effects on Blood Pressure in Female Patients with Urinary Incontinence Undergoing Urodynamic ExaminationJ Altern Complement Med.(2013 Jan 29)
- ^Mahvi DM, Henry MB, Albertini MR, Weber S, Meredith K, Schalch H, Rakhmilevich A, Hank J, Sondel PIntratumoral injection of IL-12 plasmid DNA--results of a phase I/IB clinical trialCancer Gene Ther.(2007 Aug)
- ^Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda MImmunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseasesJ Immunol.(1995 Aug 1)
- ^Hori S, Nomura T, Sakaguchi SControl of regulatory T cell development by the transcription factor Foxp3Science.(2003 Feb 14)
- ^Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DAInduction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patientsJ Clin Invest.(1996 Jul 1)
- ^Woo EY, Chu CS, Goletz TJ, Schlienger K, Yeh H, Coukos G, Rubin SC, Kaiser LR, June CHRegulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancerCancer Res.(2001 Jun 15)
- ^Noori S, Hassan ZM, Mohammadi M, Habibi Z, Sohrabi N, Bayanolhagh SSclareol modulates the Treg intra-tumoral infiltrated cell and inhibits tumor growth in vivoCell Immunol.(2010)
- ^Hatziantoniou S, Dimas K, Georgopoulos A, Sotiriadou N, Demetzos CCytotoxic and antitumor activity of liposome-incorporated sclareol against cancer cell lines and human colon cancer xenograftsPharmacol Res.(2006 Jan)
- ^Dimas K, Hatziantoniou S, Tseleni S, Khan H, Georgopoulos A, Alevizopoulos K, Wyche JH, Pantazis P, Demetzos CSclareol induces apoptosis in human HCT116 colon cancer cells in vitro and suppression of HCT116 tumor growth in immunodeficient miceApoptosis.(2007 Apr)
- ^Dimas K, Kokkinopoulos D, Demetzos C, Vaos B, Marselos M, Malamas M, Tzavaras TThe effect of sclareol on growth and cell cycle progression of human leukemic cell linesLeuk Res.(1999 Mar)