Salvia verticillata (L.)-Biological Activity, Chemical Profile, and Future Perspectives.

Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist ß-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer's disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.

Phytochemical Profile and Evaluation of the Antioxidant, Cyto-Genotoxic, and Antigenotoxic Potential of Salvia verticillata Hydromethanolic Extract.

This study comprises the phytochemical characterization, the evaluation of the total phenolic content (TPC) and antioxidant activity (AA), and the investigation of the cyto-genotoxic and antigenotoxic potential of hydromethanolic extract derived from Salvia verticillata L. leaves. HPLC-DAD-ESI-MS and HPLC-DAD were used for the characterization of the extract and determination of the major ingredients. Afterwards, the TPC and AA were determined. The cytotoxic and genotoxic effect of the extract on cultured human lymphocytes at concentrations of 10, 25, and 50 µg mL-1 was investigated via the Cytokinesis Block MicroNucleus (CBMN) assay. Moreover, its antigenotoxic potential against the mutagenic agent mitomycin C (MMC) was assessed using the same assay. The hydromethanolic extract comprises numerous metabolites, with rosmarinic acid being the major compound. It had a high value of TPC and exerted significant AA as shown by the results of the Ferric Reducing Antioxidant Power (FRAP) and Radical Scavenging Activity by DPPH• assays. A dose-dependent cytotoxic potential was recorded, with the highest dose (50 µg mL-1) exhibiting statistically significant cytotoxicity. None of the tested concentrations induced significant micronuclei (MN) frequencies, indicating a lack of genotoxicity. All tested concentrations reduced the MMC-mediated genotoxic effects, with the two lowest showing statistically significant antigenotoxic potential.

Integrative effects of phytohormones in the phenolic acids production in Salvia verticillata L. under multi-walled carbon nanotubes and methyl jasmonate elicitation.

Salvia verticillata L. is a well-known herb rich in rosmarinic acid (RA) and with therapeutic values. To better understand the possible roles of phytohormones in the production of phenolic acids in S. verticillata, in this work, we investigated some physiological and biochemical responses of the species to methyl jasmonate (MJ) and multi-walled carbon nanotubes (MWCNTs) as two effective elicitors. The leaves were sprayed with aqueous solutions containing 100 mg L-1 MWCNTs and 100 µM MJ and then harvested during interval times of exposure up to 96 h. The level of abscisic acid, as the first effective phytohormone, was altered in the leaves in response to MJ and MWCNTs elicitation (2.26- and 3.06-fold more than the control, respectively), followed by significant increases (P ˂ 0.05) detected in jasmonic acid and salicylic acid contents up to 8 h after exposure. Obtained data revealed that simultaneously with changes in phytohormone profiles, significant (P ˂ 0.05) rises were observed in the content of H2O2 (8.85- and 9.74-folds of control), and the amount of lipid peroxidation (10.18- and 17.01-folds of control) during the initial times after exposure to MJ and MWCNTs, respectively. Later, the content of phenolic acids increased in the elicited leaves due to changes in the transcription levels of key enzymes involved in their biosynthesis pathways, so 2.71- and 11.52-fold enhances observed in the RA content of the leaves after exposure to MJ and MWCNTs, respectively. It is reasonable to conclude that putative linkages between changes in some phytohormone pools lead to the accumulation of phenolic acids in the leaves of S. verticillata under elicitation. Overall, the current findings help us improve our understanding of the signal transduction pathways of the applied stimuli that led to enhanced secondary metabolite production in medicinal plants.

In vitro Antimicrobial Activity of Some Extracts of Salvia spp Harvested from the Oltenia Flora Using Different Solvents.

In this study, the antimicrobial activity of three Salvia spp. (S. glutinosa, S. splendens, S. verticillata) extracts prepared with different solvents was assessed using the diffusion method and the quantification of the minimum inhibitory concentration for each extract on S. aureus, E. coli and C. albicans standard strains. The results showed that the extracts of the three Salvia spp. are suppressing the growth of the bacteria tested with variable potency. Among the different solvent extracts, n-butanolic extracts of all the three species of Salvia spp. revealed the most important antibacterial activity against S. aureus and E. coli. S. splendens extracts proved to be the most efficient on C. albicans regardless of the solvent used.

Increased phenylpropanoids production in UV-B irradiated Salvia verticillata as a consequence of altered genes expression in young leaves.

Ultraviolet-B (UV-B) radiation as an environmental potential elicitor induces the synthesis of plant secondary metabolites. The effects of UV-B radiation on photosynthetic pigments and dry weight, biochemical and molecular features of old and young leaves of Salvia verticillata were investigated. Plants were exposed to 10.97 kJ m-2 day-1 of biologically effective UV-B radiation for up to 10 days. The sampling process was performed in four steps: 1, 5, 10, and 13 days (recovery time) after the start of irradiation. As a result of plant investment in primary and secondary metabolism, the production of phenolic compounds increased, while chlorophyll levels and leaf dry weight (%) declined. Under long-term UV-B exposure, young leaves exhibited the most significant reduction in chlorophyll a and b content and leaf dry weight. The highest level of total phenol (1.34-fold) and flavonoid concentration (2-fold) relative to the control was observed on the 5th day and recovery time, respectively. Young leaves demonstrated the highest amount of phenolic acids in recovery time. Young leaves on the 5th day of the experiment exerted the highest level of antioxidant activity when compared to the control. A positive correlation was observed between antioxidant activity and the amount of phenolic compounds. Regarding the expression of phenylpropanoid pathway genes, UV-B enhanced the expression of phenylalanine ammonia-lyase, tyrosine aminotransferase, and rosmarinic acid synthase with the highest level in young leaves on the 10th day. Overall, young leaves of S. verticillata indicated higher sensitivity to UV-B radiation and developed more tangible reactions to such radiation.

Impacts of foliar exposure to multi-walled carbon nanotubes on physiological and molecular traits of Salvia verticillata L., as a medicinal plant.

Owing to the growing applications of the multi-walled carbon nanotubes (MWCNTs) in the communications and energy industries, they have attracted increasing attention for their effects on the environment and plants. Therefore, we investigated the impact of foliar exposure to MWCNTs on the oxidative stress responses in the Salvia verticillata as a medicinal plant. Furthermore, we evaluated the possible correlations between gene expression and activity of the key enzymes in the phenolic acids biosynthesis pathways and their accumulation in the treated leaves. The leaves of two-month-old plants were sprayed with different concentrations (0-1000 mg L-1) of MWCNTs. Raman's data and Transmission Electron Microscopy images have confirmed the absorption of MWCNTs via epidermal cells layer into the parenchymal cells of the exposed leaves. The results showed that exposure to MWCNTs led to a decrease in the photosynthetic pigments and increases in the oxidative stress indices (enzymatic and non-enzymatic antioxidants) in the leaves with a dose-dependent manner. The content of rosmarinic acid as a main phenolic acid was increased in the MWCNTs-exposed leaves to 50 and 1000 mg L-1, nearly four times relative to the control. Unlike with other examined enzymes, a positive correlation was deduced between the activity and gene expression patterns of the rosmarinic acid synthase with the rosmarinic acid accumulation in the treatments. Overall, MWCNTs at the low concentrations could promote the production of the pharmaceutical metabolites by the changes in the ROS generation. However, at the higher concentrations, MWCNTs were toxic and induced the oxidative damages in S. verticillata.

Salvia verticillata: Linking glandular trichomes, volatiles and pollinators.

Plants have developed a plethora of signals to interact with other organisms, finally building up a sophisticate language for communication. In this context, we investigated Salvia verticillata L. (Lamiaceae), with the primary goal to link secondary metabolites and actual biotic relationships. We specifically analysed the volatile organic compounds (VOC) spontaneously emitted by leaves and flowers and determined the composition of the essential oils obtained from the aerial parts across 2015 and 2016. We merged information of chemical analyses to a micromorphological investigation on the glandular indumentum and to focal observations on the pollinator assemblage. The VOC profiles were highly variable, with the floral bouquet being the most complex. Flowers and leaves showed 37 and 20 exclusive compounds, dominated by 1,8-cineole (10.4%) and germacrene D (38.4%), respectively. Sesquiterpene hydrocarbons prevailed (83.3% leaves; 73.7% flowers) and 19 common compounds were detected. The oil profiles proved to be consistent across the two years: sesquiterpene hydrocarbons invariably dominated, with germacrene D, bicyclogermacrene and ß-caryophyllene as main compounds. The whole plant epidermis is thickly covered by two types of glandular hairs: peltates and small capitates, both responsible for the synthesis of terpenes, finally resulting in the VOC emission and in the essential oil production. S. verticillata attracted mainly bees belonging to two functional groups: medium-sized and large bees, notwithstanding the small size of its flowers. At the site, Apis mellifera and different Bombus species were recorded, mainly interested in feeding on nectar. The literature survey on the isolated volatile compounds confirmed the hypotheses on the seduction strategies towards Apoidea.

Evaluation of the lifespan extension effects of several Turkish medicinal plants in Caenorhabditis elegans.

Research on longevity is important to both prolong lifespan and support healthy aging. Natural products are widely being utilized and used as new resources for drug molecules. Caenorhabditis elegans is an advantageous organism for longevity research and age-related diseases. In this study, we tested a number of plant extracts for their effects on C. elegans longevity. In lifespan assays, agesynchronized wild-type C. elegans specimens were treated with different concentrations of plant extracts. Plant extracts were prepared as either infusions or decoctions, similar to their traditional utilization. Hedera helix L. (Araliaceae) extended lifespan in worms in a concentration-dependent manner. The mean survival rates in the H. helix-treated groups were significantly higher, by 23.7% when applied at 1000 µg/mL, 16% when applied at 500 µg/mL, and 16% when applied at 250 µg/mL, compared to the control group. HPLC analysis identified chlorogenic acid as the major component of H. helix. Salvia verticillata L. (Lamiaceae) and Myrtus communis L. (Myrtaceae) treatments resulted in median lifespan extension. Maximum lifespan was extended in worms by Rubus sanctus Schreb. (Rosaceae) treatment. This study provided the first evidence demonstrating the possible lifespan-extending effects of a group of Turkish medicinal plants in an in vivo model, C. elegans.

Effect-Directed Analysis for the Antioxidant Compound in Salvia verticillata.

Salvia genus is one of the largest genera of the Lamiaceae family. Its species have been used for a wide variety of disorders in the local traditional medicine systems. Therefore, the genus has been the subject of several phytochemical and biological studies. The aim of the study was to identify the major antioxidant compound(s) from the methanol extract of Salvia verticillata using activity-guided fractionation. The crude extract showed strong antioxidant activities in DPPH and ß-carotene/linoleic acid tests. The ethyl acetate fraction also exhibited a potent free radical scavenging activity compared to the other fractions. Further fractionation and purification of the ethyl acetate fraction using chromatography methods yielded a compound with high antioxidant capacity. The isolated active compound was determined as chrysoeriol. It showed a dose-dependent free radical scavenging activity with an IC50 (DPPH scavenging) value of 93.32 (80.23 - 108.57) mM.

Effects of Hydroalcoholic Extract from Salvia verticillata on Pharmacological Models of Seizure, Anxiety and Depression in Mice.

Salvia verticillata is one of the salvia species which possesses remarkable antioxidant activity. In the present study, we investigated the possible effects of hydro-alcoholic extract from Salvia verticillata plant (SVE) in various models of anxiety, depression and seizure in mice. Mice were randomly divided into control (saline), SVE-treated and standard treatment groups. The SVE-treated groups received oral administration of various doses of SVE. As a standard treatment, diazepam and imipramine were used orally for anxiety/seizure and depression tests, respectively. The results of the study revealed that the plant extract produced significant anticonvulsant activity in maximal electroshock and pentylenetetrazol induced seizure models. Moreover, in forced swim test and tail suspension test of depression, SVE produced significant antidepressant effect in mice compared to control group. However, SVE did not show any effects on anxiety-like behavior of mice in elevated plus maze and light-dark tests. These results suggest potential therapeutic effects of the plant extract in seizure and depression.