Wound healing activity of Salvia huberi ethanolic extract in streptozocin-induced diabetic rats.

Objective: The aim of this study was to examine the in vivo wound healing potential of Salvia huberi Hedge (endemic to Turkey) on excision and incision wound models in diabetic rats. Method: Male Wistar albino rats, 3-4 months old and weighing 180-240g were used. The animals were randomly divided into five groups including Control, Vehicle and Fito reference, and two different concentrations (0.5% and 1% weight/weight (w/w)) of ethanol extract of Salvia huberi were investigated in both wound models on streptozocin-induced diabetic rats using macroscopic, biomechanical, biochemical, histopathological, genotoxic and gene expression methods over both seven and 14 days. Fito cream (Tripharma Drug Industry and Trade Inc., Turkey) was used as the reference drug. Results: A total of 60 rats were used in this study. Salvia huberi ointments at 0.5% and 1% (w/w) concentrations and Fito cream showed 99.3%, 99.4% and 99.1% contraction for excision wounds, and 99.9%, 97.0% and 99% contraction for incision wounds, respectively. In Salvia huberi ointments and Fito cream groups, re-epithelialisation increased dramatically by both day 7 and day 14 (p<0.05). By day 14, low hydroxyproline and malondialdehyde (MDA) levels, and high glutathione (GSH) levels were observed in the Salvia huberi ointment groups. After two application periods, damaged cell percent and genetic damage index values and micronucleus frequency of Salvia huberi ointment treatment groups were lower than Control and Vehicle groups (p<0.001). A growth factor expression reached a high level by day 7 in the Control group; in Salvia huberi-treated groups it was decreased. Conclusion: The study showed that application of Salvia huberi ointments ameliorated the healing process in diabetic rats with excisional and incisional wounds and may serve as a potent healing agent.

Biochemical, Histopathologic, and Genotoxic Effects of Ethanol Extract of Salvia hypargeia (Fisch. & Mey.) on Incisional and Excisional Wounded Diabetic Rats.

Purpose: Nonhealing wounds are a serious problem of diabetic patients. Salvia species are traditionally used for the treatment of wounds. The aim of the study was to investigate the effects of ointment prepared with ethanol extract obtained from the aerial parts of Salvia hypargeia, an endemic plant from Turkey, on diabetic rat incisional and excisional skin wounds. Materials and Methods: Male Wistar albino rats (n: 60) were divided into five groups. Diabetes was induced and two concentrations (0.5% and 1%) of the extract were used for ointments and applied on wounds for 7 and 14 days. Fito cream was chosen as a reference drug. Results: In excisional wounds, healing ratios of 0.5% (63.4% and 99.3%) and 1% (65.5% and 99.9%) S. hypargeia groups were higher compared to control (35.9% and 75.1%), and in incisional wounds, healing ratios of 0.5% (78.1% and 98.5%) and 1% (84.4% and 99.4%) S. hypargeia groups were higher compared to control (30.5% and 72.9%) (p < .01). Hydroxyproline (0.31 ± 0.3 and 0.34 ± 0.2) levels were lower and GSH (10.7 ± 3.1 and 7.6 ± 0.9) levels were higher in 0.5% and 1% S. hypargeia groups on the 14th day (p < .01). Histopathological results revealed re-epithelialization and formation of granulation tissue in all S. hypargeia groups. Genotoxicologic results indicated, GDI, DCP values, and MN frequency of 0.5% and 1% S. hypargeia groups did not reach to significant levels both on the 7 and 14 days. Conclusions: S. hypargeia may have a potential for therapeutic use in treatment and management of diabetic wounds with a successful topical application.

Wound healing properties, antimicrobial and antioxidant activities of Salvia kronenburgii Rech. f. and Salvia euphratica Montbret, Aucher & Rech. f. var. euphratica on excision and incision wound models in diabetic rats.

Diabetic patients suffer from persistent and non-healing wounds. Salvia species are traditionally used for the treatment of wounds and colds. The aims of the present study were to evaluate the in vivo wound healing potential, in vitro antimicrobial and antioxidant activities, and total phenolic and flavonoid contents of the aerial parts of two endemic taxa, Salvia kronenburgii Rech. f. (SK) and Salvia euphratica Montbret, Aucher & Rech. f. var. euphratica (SE). Two different concentrations (0.5% and 1% (w/w)) of ethanol extracts were investigated in incision and excision wound models on Streptozotocin-induced diabetic rats using biomechanical, biochemical, histopathological, macroscopic, and genotoxic methods for 7 and 14 days. Antimicrobial activity was evaluated against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Acinetobacter baumannii, Aeromonas hydrophila, Mycobacterium tuberculosis, Candida glabrata, Candida parapsilosis, and Candida tropicalis using the broth microdilution and the resazurin microtiter assay plate methods. Fito®, Ampicillin, Ethambutol, Isoniazid, and Fluconazole were used as reference drugs. Antioxidant capacities and total phenolic and flavonoid contents of both extracts were detected using DPPH free radical scavenging assay, Folin-Ciocalteu, and Al(NO3)3 methods, respectively. SK ointment at 0.5% and 1% (w/w) concentrations and SE ointment at 1% (w/w) concentration showed 99.9%, 99.5%, and 99.7% contraction, respectively for excision wounds, and SK and SE ointments at 1% (w/w) concentration showed 99.4% and 99.2% contraction for incision wounds while Fito® showed 98.9% and 98.5% contraction, respectively. Increased re-epithelialization (P < 0.01 and P < 0.001), angiogenesis, and decreased dermal inflammation (P < 0.001) were determined for SK and SE ointments at both 7 and 14 days. SE ointment on day 7 and SK ointment on day 14 reduced oxidative damage to DNA when compared to control (P < 0.01 and P < 0.001). Both tested plants had greater antibacterial activity against A. baumannii (62.5 µg/mL MIC value) and SE had greater antimycobacterial activity against M. tuberculosis (0.24 µg/mL MIC value) when compared to reference drugs Ampicillin, Isoniazid, and Ethambutol (125, 0.97, and 1.95 µg/mL MIC values, respectively). Antioxidant capacities, total phenolic and flavonoid contents of SE and SK were 87.08%, 76.21 µg GAE/mg, 43.43 µg QE/mg and 72.17%, 41.81 µg GAE/mg, 33.62 µg QE/mg, respectively. SK and SE had strong wound healing effects while SK found to be more effective than SE at both 7 and 14 days.