Background: Diabetes is a dangerous metabolic disorder that is becoming more common worldwide. In the present research, we aimed to analyze the chemical composition, in silico molecular docking, and evaluate the biological features of Salvia mirzayanii. Materials and Methods: The constituents found in the aqueous extract of S. mirzayanii leaves were identified using gas chromatography–mass spectrometry (GC-MS). The major compounds of S. mirzayanii extract were subjected to molecular docking analysis. Screening for potential antioxidant abilities was conducted using radical scavenging assays. Alpha-amylase and α-glucosidase inhibitory kinetic studies were performed to evaluate the in vitro antihyperglycemic potential of S. mirzayanii. The in vivo function of S. mirzayanii extract was evaluated by examining the gene expression of phosphoenolpyruvate carboxykinase (PEPCK), glucose 6-phosphatase (G6Pase), and glucose transporter-4 (GLUT4) in diabetic rats. Results: The major compounds in aqueous extract of S. mirzayanii were 1, 8-cineole (51. 6 + 2. 7%), linalool acetate (22. 0 + 1. 9%), a-terpinyl acetate (9. 3 + 0. 7%), and aromadendrene (5. 6 + 0. 6). In silico studies indicated that 1, 8-cineole was a more potent inhibitor of α-amylase and α-glucosidase enzymes. The liquid extract of S. mirzayanii showed considerable radical scavenging activity against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and effective inhibition of α-amylase (IC50 = 0. 01 ± 0. 02) and α-glucosidase (IC50 = 0. 11 ± 0. 01). The highest antihyperglycemic activity was observed with a 600 mg/kg dose of the plant’s aqueous extract. Conclusions: Altogether, our findings show the possibility of applying the aqueous extract of S. mirzayani leaves as a potential therapeutic compound.

Salvia mirzayanii Rech. & Esfand is an Iranian endemic plant belonging to the Lamiaceae family which has many pharmacological effects including antioxidant, anti-cholinesterase, antimicrobial, anticancer, anti-inflammatory and enhancing cognition and memory. It is considered as an endemic species of Iran, that is in danger of extinction. The bulks aromatic plants come from wild populations whose essential oils compositions as well as their biological properties are severely affected by the geographical location Therefore, the aim of the present study is to provide more information on the variation of essential oil composition of S. mirzayanii collected from four different geographical regions. The aerial parts of four populations of S. mirzayanii were collected from different natural habitats of Fars province in southwest of Iran. Chemical composition of S. mirzayanii were isolated by hydrodistillation using clevenger type apparatus and analyzed by GC-FID and GC/MS. The major compounds in four populations were α-terpinyl acetate, Eudesm-7(11)-en-4-ol, bicyclogermacrene, δ-cadinene and 1,8-Cineole in four populations. Polyphenolics content were identified by HPLC analysis. Predominant phenolic constituents in all extracts were chlorogenic acid, vaniline and rosmarinic acid, p-cumaric acid, trans-ferulic acid and quercetin. The DPPH radical inhibition was measured by using a micro-plate reader. The best antioxidant activity was related to ecotype3 with 1281.48 μg/mL and the highest amount of total phenol is related to ecotype1 and ecotype4.

Objectives: As some species of the Salvia family have been shown to exert antidepressant-like activity, the aim of this study was to investigate the antidepressant effects of the aqueous and hydroalcoholic extracts of Salvia mirzayanii and Salvia macrosiphon, two endemic species of salvia in Iran. Methods: In total, 148 eight-week-old male albino mice (25-35 g) were used to carry out the forced swimming test. The effects of different doses of the aqueous (100-1800 mg/kg) and hydroalcoholic extracts (75-900 mg/kg) of Salvia mirzayanii and Salvia macrosiphon on immobility, climbing, and swimming behaviors were examined. Fluoxetine and imipramine were used as control drugs. The effects of extracts on locomotor activity were also evaluated. Results: High doses of the aqueous extracts of both plants and hydroalcoholic extract of Salvia mirzayanii produced a significant reduction in immobilityandincrease inswimmingcomparedto the control group. The hydroalcoholic extract of Salvia macrosiphon did not show any significant effect on immobility and swimming. Only some doses of hydroalcoholic extract of Salvia mirzayanii and aqueous extract of Salvia macrosiphon showed a significant increase in climbing behavior. The aqueous and hydroalcoholic extract of both plants caused a decrease in spontaneous activity. Conclusions: The findings of this study indicated that the aqueous and hydroalcoholic extracts of Salvia mirzayanii and the aqueous extract of Salvia macrosiphon had antidepressant-like activity. In addition, the hydroalcoholic extract of Salvia mirzayanii and the aqueous extracts of Salvia macrosiphon were more effective fractions of these plants. These endemic Iranian Salvia species may have potential therapeutic effects for depression.

Aerial parts of Salvia Mirzayanii was extracted with methanol. Methanol extract was suspended in water and defatted with petroleum ether. The defatted part was then partitioned between ethyl acetate and water. The ethyl acetate partition was chromatographed on a silica gel column to afford several fractions. Lymphocyte proliferation inhibitory assay of the resulted fractions was compared in-vitro and the fraction with more immunosuppressive activity was subjected to more purification to yield three methoxylated flavones: 5, 7-dihydroxy, 6, 4’ – dimethoxyflavone(1), 5-hydroxy, 6, 7, 3’ , 4’ – tetramethoxyflavone(2) and 5, 3’-dihydroxy, 6, 7, 4’ – trimethoxyflavone (3). Compounds 2 and 3 potently suppressed the proliferation of human blood lymphocytes with IC50 values of 1. 3 ± 0. 04 μ g/mL and 1. 3 ± 0. 21 μ g/mL in comparison with prednisolone as one of the lymphocyte suppressor drugs (IC50=1. 45 ± 0. 6 μ g/mL). In phagocyte chemiluminescence assay, compounds 1 and 3 in peripheral mononuclear cells (PMNCs) exerted suppressive moderate activity against ROS with IC50 of 55. 3 ± 0. 4 and 36. 2 ± 0. 7 μ g/mL, respectively, while compound 2 showed weak activity with IC50 values more than 100 μ g/mL. In conclusion, compounds 2 and 3 have a similar suppressive effect more than compound 1 on PHA-activated lymphocyte proliferation, which might be because of their C-3’ oxidation pattern of ring B. It is indicated that the presence of 3’-OH or 3’-OMe in flavone ring B, caused more antiproliferation activity than 3’-H. Oxidative burst assay showed more activity for compound 1 which is less methoxylated than others. It also showed more activity for compounds 3 than 2, which differ only in 3’-OH instead of 3’-OMe.