Increased oxidative stress in diabetic wound areas impairs wound healing. Quercetin exhibits significant antioxidant properties. We investigated the effects of topical quercetin on antioxidant status in diabetic wound areas and its effect on wound healing in rats. A 2 cm(2) cutaneous wound was produced on the back of streptozotocin induced diabetic and normal rats. Rats were divided into three groups of 20: normal healthy control group, diabetic group and quercetin treated diabetic group. The control and diabetic groups were treated topically with ointment base once daily for 21 days. The quercetin treated diabetic rats were treated similarly with ointment containing quercetin. The quercetin treated diabetic group exhibited increased levels of catalase, glutathione peroxidase, superoxide dismutase and total thiols compared to the diabetic group. Nitrite levels in the diabetic group were decreased significantly on day 3 compared to the healthy control group. Malondialdehyde levels were decreased in the quercetin treated diabetic group compared to the diabetic group. The expression of proliferating cell nuclear antigen) (PCNA) was greater in the quercetin treated diabetic group on day 7 compared to healthy control and diabetic groups. Formation of granulation tissue and the quality of healed tissue was improved in the quercetin treated diabetic group compared to the diabetic group. Quercetin improves antioxidant status in wounds of diabetic rats and stimulates the proliferation phase, which accelerates wound healing.

Development of novel drugs or formulations to accelerate the wound healing process is the need of current era. Quercetin (Q), a bioflavonoid, at 0.3% concentration has showed some wound healing potential in our preliminary studies. The present study was aimed to explore the wound healing potential of 0.3% quercetin formulated in 3 different vehicles, that is, dimethyl sulfoxide (DMSO; 10%), ointment base, and corn oil. Ninety experimentally wounded rats were grouped in 6 groups. The 0.3% quercetin mixed with DMSO, ointment base, and corn oil was topically applied once daily for 21 days on the wounds of groups 2, 4, and 6, respectively. DMSO, ointment base, and corn oil alone was applied similarly in groups 1, 3, and 5, respectively. Gross evaluation and wound contraction results revealed accelerated wound closure in all quercetin-treated groups. The mRNA expressions of vascular endothelial growth factor, transforming growth factor-β1, and interluekin-10 were markedly upregulated in healing tissues of quercetin-treated groups. Tumor necrosis factor-α mRNA expression and protein levels were lowered by quercetin treatment. Quercetin-treated groups also showed increased activities of SOD (superoxide dismutase) and catalase, and levels of total thiols in wound tissues on day 7. Levels of superoxide anion radicals and malondialdehyde were markedly lower in quercetin-treated groups. Histologically, wound sections of quercetin-treated groups showed early dominance of fibroblasts, increased blood vessels, marked collagen deposition, and regenerated epithelial layer. The significant effects were more pronounced in ointment + Q group among all the quercetin-treated groups. In conclusion, 0.3% quercetin mixed in ointment base produced the fastest and better wound healing in rats.

The objective of this study is to determine the subchronic toxicity of thiamethoxam and ameliorative effect of quercetin on oxidative stress and antioxidant parameters in testes of male rats. Subchronic oral exposure of male rats to thiamethoxam, quercetin and their combination on oxidative stress and antioxidant parameters in testes was studied. In this study, 96 adult male rats were divided in 6 groups each comprises of 8 rats for 60 and 90 days treatment schedule. Rats in group I were kept as control and received 2% gum Acacia. Rats in groups II, III, IV, V, VI were administered with lower dose of TMX (105 mg/kg b.wt.), higher dose of TMX (210 mg/kg b.wt.), quercetin (50 mg/kg), lower dose of TMX (105 mg/kg) + Qu (50 mg/kg) and higher dose of TMX (210 mg/kg b.wt.) + Qu (50mg/kg), respectively. Rats from each group were sacrificed on 61 and 91 days of experiment. In view of this, effect of subchronic oral toxicity of thiamethoxam and amelioration potential of quercetin was studied on various parameters viz. oxidative and nitrosative stress indices and antioxidant parameters in testes. The histopathological alterations in tissues of testes of animals in various treatment groups of 60 and 90 days treatment were studied. The levels of protein carbonyl and nitric oxide in testes were increased significantly (p ≤ 0.05) in thiamethoxam treated groups as compared to control and quercetin groups, in 60 and 90 days treatment schedules, indicating oxidative stress, whereas tissue protein showed opposite trend due to protein catabolism induced by thiamethoxam. There was significant increase in the level of tissue protein and decrease in oxidative stress biomarkers described above when TMX was administered with quercetin indicating ameliorative effect of quercetin. The levels of GPx and GSH testes were significantly (p ≤ 0.05) lower in TMX treated groups as compared to control, but there was significant restoration of these parameters to normal when TMX was administered along with quercetin indicating amelioration by quercetin. The levels of protein carbonyl content and nitrite in testes increased significantly (p ≤ 0.05) whereas tissue protein showed opposite trend due to protein catabolism induced by thiamethoxam indicating oxidative stress. Increased concentration of GPx and GSH level was also observed in this study indicating amelioration by quercetin. Quercetin co-treatment with thiamethoxam groups did not produce improvement in histopathological changes manifested

Purpose: There is an urgent need of effective drug/formulation to speed up the healing process in diabetic wounds. In our earlier studies, quercetin has accelerated the healing of nondiabetic wounds. So, we investigated the wound-healing potentials of quercetin in diabetic rats. Materials and methods: A square-shaped cutaneous wound (approximate to 400 mm(2)) was created on the back of nondiabetic and diabetic rats. They were divided into three groups, viz. healthy control (nondiabetic), diabetic control and diabetic-treated group. Ointment base was topically applied for 21 days in healthy and diabetic control groups. Quercetin (0.3%) ointment was similarly applied in third group. Effects of quercetin on repair and regenerations of diabetic wounds in terms of wound closure, inflammation, angiogenesis, fibroblast proliferation, collagen synthesis, epithelialization, axonal regeneration etc was studied. Results: Quercetin accelerated the wound closure and increased the expressions of IL-10, VEGF and TGF-beta(1) in granulation/healing tissue of diabetic wound. However, quercetin decreased the expression of TNF-alpha, IL-1 beta, and MMP-9. Histopathological evaluation revealed amelioration of persistence of inflammatory cells by quercetin in diabetic wounds. There was good quality of granulation tissue, marked fibroblast proliferation, well organized collagen deposition, early regeneration of epithelial layer etc. in the quercetin treated diabetic wounds in comparison to diabetic control group. Results of immunohistochemistry showed more angiogenesis, faster phenotypic switching of fibroblast to myofibroblasts and increased GAP-43 positive nerve fibers in quercetin-treated diabetic wounds. Conclusion: Quercetin ointment at 0.3% w/w concentration modulates cytokines, growth factors and protease, thereby improved repair and regenerations of cutaneous diabetic wounds in rats.

Studies on subchronic toxicity of thiamethoxam and its amelioration by quercetin on oxidative stress and antioxidant parameters in male rats were conducted. Ninety six (96) adult male rats were divided in 6 groups for 60 and 90 days study, each comprising of 8 rats. Group I was kept as control and received 2% gum acacia. Groups II, III, IV, V, VI were administered with lower dose of TMX (2.5% MTD), higher dose of TMX (5.0% MTD), quercetin (50mg/kg), lower dose of TMX (2.5% MTD) + Qu (50mg/kg) and higher dose of TMX (5.0% MTD) + Qu (50mg/kg), respectively. Oxidative stress parameters such as lipid peroxidation (MDA) and protein carbonyl content (PCC) was seen to have increased and antioxidant parameters such as superoxide dismutase (SOD) and total thiols decreased significantly. Quercetin in this study exhibited amelioration effect by reversing the effect of thiamethoxam on these parameters investigated.

Dimethyl sulfoxide (DMSO) is one of the commonly used vehicles to dissolve water insoluble drugs, including used for wound healing purposes, for different experiments. The present study was aimed to investigate the gross effects and histopathological changes produced by topical DMSO on granulation tissue at wound site. Open excision cutaneous wounds were created on the back of ten male rats and equally divided into two groups. Distilled water and DMSO (10 %) were topically applied once daily for 21 days on wounds of Group I (control group) and Group II, respectively. Grossly, wounds revealed that DMSO facilitated wound closure on day 7 and 12. On day 21, the wound was still not closed in DMSO treated group in comparison to control group. The H & E stained sections of control group showed formation of complete, immature and thin epithelial layer, collagen deposition and infiltration of abundant number of mononuclear cells. Sections of DMSO treated group showed blood vessels, scattered infiltration of inflammatory cells, collagen fibers and partially formed epithelial layer. Semi-quantitative score for inflammatory cells and epithelialization was significantly lower in DMSO treated group. Picrosirius red stained sections showed dominance of orange-red (thicker) collagen fibers in control group and yellow-green (thinner) collagen fibers in DMSO treated group. DMSO treated group showed higher and lower thin collagen and thick collagen fiber fraction, respectively in comparison to control group. Thus, it might be concluded that DMSO facilitates wound closure during the early stages and delays the wound closure during at later stages of wound healing.

Abstract Quercetin on wounds could be favorable for healing based on its variety of biological effects. Eighty wounded rats were divided into four groups i.e. dimethyl sulfoxide, 0.03% quercetin, 0.1% quercetin, and 0.3% quercetin-treated. Different treatments were topically applied for 20 days. Quercetin (0.3%) caused the fastest wound closure and markedly improved the oxidative stress. Quercetin treatment increased the expressions of IL-10, VEGF, TGF-β1, CD31, α-SMA, PCNA, and GAP-43, and decreased the expressions of TNF-α. Early infiltration of inflammatory cells and formation of good quality granulation tissue dominated by fibroblast proliferation, angiogenesis, and collagen deposition in quercetin treated groups was also evident. All these effects were more pronounced at 0.3% quercetin concentration. The earliest regeneration of epithelial layer was also observed in 0.3% quercetin-treated wounds. In conclusion, 0.3% quercetin accelerates wound healing efficiently by modulating antioxidant system of wound, cytokines, growth factors, other proteins and cells involved in healing.

Quercetin has role in angiogenesis and proliferation of epithelial cells and fibroblasts. So, it was hypothesized that exogenous application of quercetin could be beneficial in wound healing. In present study, experimentally-wounded male rats were equally divided into four groups. Quercetin as a 0.1, 1.0 and 10.0% concentration (w/v) solution was topically applied on the wounds of group 2, 3 and 4, respectively, once daily for 16days. However, dimethyl sulfoxide (DMSO; 75%) alone was applied topically in group 1. Gross evaluation of wound revealed that topical application of 0.1% quercetin caused fastest wound closure, as compared to other treatments in our study. The reduction in wound area and increased wound contraction were fastest in 0.1% quercetin group during the entire study. Histopathologically, the granulation tissue was of better quality and showed appropriate proliferation of fibroblasts in 0.1% quercetin-treated group in comparison to other groups. There was significant collagen deposition, which was better arranged and compacted in 0.1% quercetin-treated group. The 0.1% quercetin-treated group also showed regenerated epithelium layer, which was lacking in other groups. Histological score was significantly higher in 0.1% quercetin-treated group, as compared to DMSO and 10% quercetin-treated groups. Overall, there were no significant differences between the different treatment groups for the values of superoxide dismutase, total thiols, superoxide anion radicals, malondialdehyde levels and total proteins. Only the catalase value was significantly decreased in DMSO-treated group, as compared to 0.1% quercetin treated group. In conclusion, quercetin at 0.1% concentration has pronounced pro-healing potential in male rats.