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.

Potential renoprotective effects of silymarin against vancomycin-induced nephrotoxicity in rats.

Silymarin (SLY), a flavonoid complex isolated from the seeds of Silybum marianum (Asteraceae), has antioxidant, anti-apoptotic, anti-inflammatory, and anti-lipid peroxidative effects. Vancomycin (VA), used for treating serious infections, has been associated with nephrotoxicity, which limits its use. Therefore, this study aimed to investigate the potential renoprotective effects of SLY on VA-induced nephrotoxicity using renal, apoptotic (caspase-3, caspase-8, and caspase-9 enzyme activities), and oxidative stress [nitric oxide (NO) and malondialdehyde (MDA)] markers; serum blood urea nitrogen (BUN) and creatinine levels; and histopathological examination. A total of 49 male Wistar albino rats were used (n = 7): control [saline, intraperitoneally (i.p.)], dimethyl sulfoxide (i.p.), VA [400 mg/(kg-day), i.p.], SLY100 [100 mg/(kg-day), i.p.], VA + SLY50 [50 mg/(kg-day), i.p.], VA + SLY100 [100 mg/(kg-day), i.p.], and VA + SLY200 [200 mg/(kg-day), i.p.]. SLY was administered once daily for 8 days. One day after the first treatment of SLY, VA administration was started and continued for 7 days. The levels of serum creatinine and BUN were evaluated using ELISA, caspase enzyme activities and levels of MDA and NO in the kidney tissues were evaluated by the colorimetric methods. The serum BUN, creatinine, NO, MDA levels, and caspase activities were significantly higher in VA group than in control (p < 0.05). However, caspase activities were significantly lower in VA + SLY200 than in VA (p < 0.05). The MDA, serum BUN, and creatinine levels were significantly lower in VA + SLY (50, 100, and 200) groups than in VA group (p < 0.05). VA + SLY200 was found to be the most effective group based on the caspase activities; MDA, NO, serum BUN, creatinine levels; and histopathological findings.

Potential protective effects of naringenin against vancomycin-induced nephrotoxicity via reduction on apoptotic and oxidative stress markers in rats.

Vancomycin (VCM), a glycopeptide antibiotic, is a drug widely used in severe infections. However, VCM induce notable nephrotoxic side effects. Naringenin (NAR) is a natural of flavonoid and are known as strongly antioxidant, nefroprotective, antiapoptotic, and anti-inflammatory. The purpose of this study was to determine the potential protective effects of NAR against VCM-induced nephrotoxicity by measuring apoptotic and oxidative stress markers and evaluating histopathological alterations in rats. For this purpose, we used male Wistar albino rats that divided into seven groups: (i) Control [saline, intraperitoneally (i.p.)], (ii) carboxymethyl cellulose (0.5% CMC, orally), (iii) VCM (400 mg/kg, i.p.), (iv) NAR100 (100 mg/kg, orally), (v) VCM + NAR25 (25 mg/kg, orally), (vi) VCM + NAR50 (50 mg/kg, orally), and (vii) VCM + NAR100 (100 mg/kg, orally) groups. VCM administration was started one day after the first treatment of NAR and continued across 7-day. Caspase-3, -8, and-9 activities and malondialdehyde (MDA) and nitric oxide (NO) levels were measured by colorimetric methods in the kidney tissues, creatinine, and blood urea nitrogen (BUN) levels were analyzed based on ELISA in serum. Caspase-3 and -8 activities, NO levels, serum creatinine and BUN levels were significantly higher in VCM group in comparison with VCM + NAR (25, 50, and 100) groups (p < 0.05). Caspase-9 activity and MDA were significantly higher in VCM group compared to VCM + NAR (25 and 50) groups (p < 0.05). Histopathological alterations in VCM group were significantly diminished by administration of NAR, especially NAR 25. In conclusion, NAR 25 and 50 mg have more potent protective effects on VCM-induced nephrotoxicity compared to NAR 100 mg.

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.

Wound Healing Effect of Kaempferol in Diabetic and Nondiabetic Rats.

BACKGROUND: Flavonoids have previously been suggested to play a role in wound healing. To date, however, limited information is available on the wound healing effect of kaempferol (KM), which belongs to the class of flavonoids. The objective of this study was to determine the wound healing effects of KM. MATERIALS AND METHODS: The wound healing effects of KM with two different concentrations (0.5% and 1% [weight/weight, w/w]) were evaluated in incisional and excisional wound models on diabetic and nondiabetic rats by macroscopic, biomechanical, biochemical, and histopathological analyses. Diabetes was induced by streptozotocin. The KM ointments were prepared using a mixture of glycol stearate:propylene glycol:liquid paraffin (3:6:1); 0.5 g of the ointments were topically applied on the wounded areas once a day for 7 and 14 d. On days 0, 7, and 14, wounds were photographed, and macroscopic examination of the wounds was performed. After 7 and 14 d, hydroxyproline levels, biomechanical analysis, and histopathological parameters (reepithelialization, thickness of granulation tissue, angiogenesis, presence of inflammation, deposition of collagen, presence of fibrosis, degree of dermal inflammation, and number of mast cells) were assessed. RESULTS: The best wound healing effect was observed in the diabetic excisional and nondiabetic incisional wounds (92.12% and 94.17%, respectively) treated with 1% (w/w) KM ointment for 14 d according to macroscopic examination. The nondiabetic excisional (14th day) and incisional (7th day) wounds treated with 1% (w/w) KM ointment showed statistically higher levels of hydroxyproline than the control groups (2.84 and 2.07 µg/mg, respectively, P < 0.01). Reepithelialization scores of KM-treated diabetic and nondiabetic excisional wounds on both 7 and 14 d (P < 0.05 and P < 0.01) and incisional wounds on the day 14 (P < 0.05) were significantly higher than controls. The maximum tensile strength was observed in nondiabetic and diabetic groups (0.92 and 0.82 g/s, respectively) treated with 0.5% (w/w) KM ointment on day 14. CONCLUSIONS: Thus, KM appears to be an effective topical wound healing agent in the treatment of both nondiabetic and diabetic wounds.

Effects of Equisetum arvense Ointment on Dermal Wound Healing in Rats .

UNLABELLED: The aim of this study was to evaluate the effectiveness of Equisetum arvense ointment on dermal wound healing in rats. METHODS: The authors studied a total of 56 wounds in four groups of rats. Each wound measured 15 mm x 15 mm. The first group did not receive treatment while the second group was treated with a 1:1 mixture of Vaseline and lanolin ointment. Equisetum arvense ointment doses of 5% and 10% were used in the third and fourth groups. The rats were observed at days 7 and 14 post wounding. The state of the wound healing was evaluated using wound closure ratio and histopathologic studies. RESULTS: Equisetum arvense 5% and 10% groups and the Vaseline-lanolin group had a statistically significant higher wound closure ratio than the control group (P &0.05). Equisetum arvense ointment groups had a 95.26% and 99.96% wound closure ratio (P & 0.05) and higher dermal and epidermal regeneration, angiogenesis, and granulation tissue thickness after 14 days as compared to the other groups (P & 0.05). P. Equisetum arvense ointment exhibits significant wound healing activity in rats. Further clinical and experimental studies are needed to confirm these results. .