Clary sage

• 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]

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]

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-HT_1A) 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

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

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

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

HCT116 tumor-bearing mice appear to have reduced tumor size in response to injections of Sclareol (following liposomal incorporation, 1100mg/kg over 5 days with 50% dosing decrements),^[20] and suppression of HCT116 tumors has been noted elsewhere in immunodeficient mice.^[21]

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]