Compendium of the most significant studies with reference to properties, intake, effects.

Ovidi E, Laghezza Masci V, Zambelli M, Tiezzi A, Vitalini S, Garzoli S. Laurus nobilis, Salvia sclarea and Salvia officinalis Essential Oils and Hydrolates: Evaluation of Liquid and Vapor Phase Chemical Composition and Biological Activities. Plants (Basel). 2021 Apr 6;10(4):707. doi: 10.3390/plants10040707. 

Abstract. Laurus nobilis, Salvia officinalis and Salvia sclarea essential oils (EOs) and hydrolates (HYs) were investigated to define their chemical compositions and biological properties. Gas-chromatography/Mass-spectrometry (GC/MS) and Headspace-GC/MS (HS-GC/MS) techniques were used to characterize the liquid and vapor phase chemical composition of EOs and HYs. 1,8-Cineole (42.2%, 33.5%) and α-pinene (16.7%, 39.0%) were the main compounds of L. nobilis EO; 1,8-cineole (30.3%, 48.4%) and camphor (17.1%, 8.7%) were for S. officinalis EO; linalyl acetate (62.6%, 30.1%) and linalool (11.1%, 28.9%) were for S. sclarea EO for the liquid and vapor phase, respectively. Chemical profile of HYs was characterized by 1,8-cineole (65.1%, 61.4%) as a main constituent of L. nobilis and S. officinalis HYs, while linalool (89.5%) was the main constituent of S. sclarea HY. The antioxidant activity of EOs and HYs was carried out by DPPH and ABTS assays and antimicrobial properties were also investigated by microdilution and the disc diffusion method for liquid and vapor phase against five different bacterial strains such as Escherichia coli ATCC 25922, Pseudomonas fluorescens ATCC 13525 and Acinetobacter bohemicus DSM 102855 among Gram-negative and Bacillus cereus ATCC 10876 and Kocuria marina DSM 16420 among Gram-positive. L. nobilis and S. officinalis EOs demonstrated considerable antibacterial activity, while S. sclarea EO proved to be less effective. Agar diffusion method and vapor phase test showed the EOs activity with the biggest halo inhibition diameters against A. bohemicus and B. cereus. A remarkably high antioxidant activity was determined for L. nobilis showing low EC50 values and also for S. sclarea; good EO results were obtained in both of the used assays. S. officinalis EC50 values were slightly higher to which corresponds to a lower antioxidant activity. Concerning the HYs, the EC50 values for L. nobilis, S. officinalis and S. sclarea were remarkably high corresponding to an extremely low antioxidant activity, as also obtained by expressing the values in Trolox equivalent antioxidant capacity (TEAC).

Zhussupova A, Zhumaliyeva G, Ogay V, Issabekova A, Ross SA, Zhusupova GE. Immunomodulatory Effects of Plant Extracts from Salvia deserta Schang. and Salvia sclarea L. Plants (Basel). 2022 Oct 12;11(20):2690. doi: 10.3390/plants11202690. 

Abstract. Medicines, their safety, effectiveness and quality are indispensable factors of national security, important on a global scale. The COVID-19 pandemic has once again emphasized the importance of improving the immune response of the body in the face of severe viral infections. Plants from the Salvia L. genus have long been used in traditional medicine for treatment of inflammatory processes, parasitic diseases, bacterial and viral infections. The aim of the current study was to evaluate the immunomodulatory effects of plant extracts LS-1, LS-2 from Salvia deserta Schang. and LS-3, LS-4 from Salvia sclarea L. plants growing in southern Kazakhstan by conventional and ultrasonic-assisted extraction, respectively. The cytotoxic effects of the named sage extracts on neonatal human dermal fibroblasts (HDFn) were evaluated using the MTT assay. Immunomodulatory effects of the studied extracts were compared by examining their influence on pro-inflammatory cytokine secretion and phagocytic activity of murine immune cells. Depending on the physiological state of the innate immune cells, sage extracts LS-2 and LS-3 had either a stimulating effect on inactivated macrophages or suppressed cytokine-producing activity in LPS-activated macrophages. The greatest increase in TNF-α secretion was found after treatment of spleen T lymphocytes with sage extract LS-2, obtained by ultrasonic-assisted extraction.

Mervić M, Bival Štefan M, Kindl M, Blažeković B, Marijan M, Vladimir-Knežević S. Comparative Antioxidant, Anti-Acetylcholinesterase and Anti-α-Glucosidase Activities of Mediterranean Salvia Species. Plants (Basel). 2022 Feb 25;11(5):625. doi: 10.3390/plants11050625. 

Abstract. Salvia species have a cosmopolitan distribution and comprise several well-known plants valuable for pharmaceutical and food industries due to their recognized medicinal, food flavouring, and preservative properties. The present study aimed to evaluate and compare the biological activities of seven wild-growing Salvia species from the Mediterranean area (S. fruticosa, S. glutinosa, S. nemorosa, S. officinalis, S. pratensis, S. sclarea, S. verticillata). All studied ethanolic leaf extracts exhibited significant DPPH and NO radical scavenging ability, lipid peroxidation inhibition, and reducing power, as well as moderate iron-chelating properties. Together with S. officinalis and S. fruticosa, S. verticillata showed anti-acetylcholinesterase activity, while S. glutinosa was also found to possess the ability to inhibit α-glucosidase. Total flavonoid (0.37-0.90%), phenolic acid (3.55-12.44%), tannin (1.22-2.60%), and anthocyanin contents (0.03-0.08%) were determined in Salvia leaves. Rosmarinic acid was the predominant hydroxycinnamic acid in all studied sage plants, ranging from 9400 to 38,800 μg/g. The correlation study showed a strong relationship between biological activities and contents of total phenolic acids, total tannins, and rosmarinic acid, indicating their significant contribution to the efficiency of tested Salvia species. Our results highlighted Mediterranean sage plants as rich sources of potent antioxidant, neuroprotective, and hypoglycemic agents which are worthy of further research.

Yalcin H, Ozturk I, Tulukcu E, Sagdic O. Effect of γ-irradiation on bioactivity, fatty acid compositions and volatile compounds of clary sage seed (Salvia sclarea L.). J Food Sci. 2011 Sep;76(7):C1056-61. doi: 10.1111/j.1750-3841.2011.02331.x. 

Abstract. Clary sage seeds (Salvia sclarea L.) were obtained from plants cultivated, and 2.5, 4.0, 5.5, and 7.0 kGy doses of γ-irradiation were applied to the clary sage seeds. They were then analyzed for their protein, ash, oil and dry matter contents, and fatty acid composition. Additionally, the total phenolic contents, antiradical, antioxidant activities, and volatile compounds of the clary sage seed extract were determined. There was no significant difference in protein content. However, the moisture, oil, and ash contents of the samples were affected by irradiation. While the 7 kGy dose had a positive effect on the total phenolic content and antiradical activity of the sage seed extract, all doses have negative effects on the antioxidant activity of the sage seed. The main fatty acid of the sage seed was remarkably found as α-linolenic acid. The four irradiation levels caused significant differences in fatty acid composition by affecting all fatty acids except palmitic, palmitoleic, and eicosenoic acids. The dominant volatile compounds of control sage seed were found as β-pinene (18.81%) and limonene (15.60%). Higher doses of the irradiation decreased volatile components of sage seed. Clary sage seed including high omega-3 can be irradiated with low doses (≤ 2.5 kGy) of γ-irradiation....© 2011 Institute of Food Technologists®

Chalvin C, Drevensek S, Chollet C, Gilard F, Šolić EM, Dron M, Bendahmane A, Boualem A, Cornille A. Study of the genetic and phenotypic variation among wild and cultivated clary sages provides interesting avenues for breeding programs of a perfume, medicinal and aromatic plant. PLoS One. 2021 Jul 21;16(7):e0248954. doi: 10.1371/journal.pone.0248954. 

Abstract. A road-map of the genetic and phenotypic diversities in both crops and their wild related species can help identifying valuable genetic resources for further crop breeding. The clary sage (Salvia sclarea L.), a perfume, medicinal and aromatic plant, is used for sclareol production and ornamental purposes. Despite its wide use in the field of cosmetics, the phenotypic and genetic diversity of wild and cultivated clary sages remains to be explored. We characterized the genetic and phenotypic variation of a collection of six wild S. sclarea populations from Croatia, sampled along an altitudinal gradient, and, of populations of three S. sclarea cultivars. We showed low level of genetic diversity for the two S. sclarea traditional cultivars used for essential oil production and for ornamental purposes, respectively. In contrast, a recent cultivar resulting from new breeding methods, which involve hybridizations among several genotypes rather than traditional recurrent selection and self-crosses over time, showed high genetic diversity. We also observed a marked phenotypic differentiation for the ornamental clary sage compared with other cultivated and wild clary sages. Instead, the two cultivars used for essential oil production, a traditional and a recent one, respectively, were not phenotypically differentiated from the wild Croatian populations. Our results also featured some wild populations with high sclareol content and early-flowering phenotypes as good candidates for future breeding programs. This study opens up perspectives for basic research aiming at understanding the impact of breeding methods on clary sage evolution, and highlights interesting avenues for clary breeding programs.

Caniard A, Zerbe P, Legrand S, Cohade A, Valot N, Magnard JL, Bohlmann J, Legendre L. Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture. BMC Plant Biol. 2012 Jul 26;12:119. doi: 10.1186/1471-2229-12-119.

Abstract. Background: Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species....Conclusions: SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They represent two of the first characterized hydroxylating diTPSs in angiosperms and generate the dihydroxylated labdane sclareol without requirement for additional enzymatic oxidation by activities such as cytochrome P450 monoxygenases. Yeast-based production of sclareol by co-expresssion of SsLPPS and SsSS was efficient enough to warrant the development and use of such technology for the biotechnological production of scareol and other oxygenated diterpenes.

Gad HA, Mamadalieva RZ, Khalil N, Zengin G, Najar B, Khojimatov OK, Al Musayeib NM, Ashour ML, Mamadalieva NZ. GC-MS Chemical Profiling, Biological Investigation of Three Salvia Species Growing in Uzbekistan. Molecules. 2022 Aug 23;27(17):5365. doi: 10.3390/molecules27175365. 

Abstract. Salvia is a potentially valuable aromatic herb that has been used since ancient times. The present work studied the chemical profile of three Salvia species essential oils (EO): S. officinalis, S. virgata and S. sclarea, as well as assessing their antioxidant and enzyme inhibitory activities. A total of 144 compounds were detected by GC-MS analysis, representing 91.1, 84.7 and 78.1% in S. officinalis, S. virgata and S. sclarea EOs, respectively. The major constituents were cis-thujone, 2,4-hexadienal and 9-octadecenoic acid, respectively. The principal component analysis (PCA) score plot revealed significant discrimination between the three species. The antioxidant activity of the EOs was evaluated using in vitro assays. Only S. virgata EO showed antioxidant activity in the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay (26.6 ± 1.60 mg Trolox equivalent (TE)/g oil). Moreover, this oil exhibited the highest antioxidant activity in 2,2-azino bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric-reducing antioxidant capacity (CUPRAC) and ferric-reducing power (FRAP) assays in comparison with the other two EOs (190.1 ± 2.04 vs. 275.2 ± 8.50 and 155.9 ± 1.33 mg TE/g oil, respectively). However, S. virgata oil did not show any effect in the chelating ability assay, while in the PBD assay, S. officinalis had the best antioxidant activity (26.4 ± 0.16 mmol TE/g oil). Enzyme inhibitory effect of the EOs was assessed against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, α-glucosidase and α-amylase. AChE enzyme was more sensitive to S. officinalis EO (4.2 ± 0.01 mg galantamine equivalent (GALAE)/g oil), rather than S. virgata EO, which was ineffective. However, S. virgata had the highest BChE effect (12.1 ± 0.16 mg GALAE/g oil). All studied oils showed good tyrosinase inhibitory activity, ranging between 66.1 ± 0.61 and 128.4 ± 4.35 mg kojic acid equivalent (KAE)/g oil). Moreover, the EOs did not exhibit any glucosidase inhibition and were weak or inefficient on amylase enzyme. Partial least squares regression (PLS-R) models showed that there is an excellent correlation between the antioxidant activity and the volatile profile when being compared to that of enzyme inhibitory activity. Thus, the studied Salvia essential oils are interesting candidates that could be used in drug discovery for the management of Alzheimer's and hyperpigmentation conditions.