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Apoptosis and antioxidant mechanisms are pathways for the treatment of endometriosis (Endo). Rutin (Rtn) is an antioxidant flavonol that induces apoptosis. This study, for first time, was conducted to evaluate the effects of rutin on Endo through apoptosis and antioxidant mechanisms. The experimental Endo was induced in 24 rats and then the animals were subdivided into Endo-sole, 3000 and 6000 µg/kg rutin (Rtn-3000 and Rtn-6000) and vitamin C groups. After 4 weeks, the expression of Bcl2, Bax, anti Pro Caspase-9, cleaved Caspase-9, pro PARP, pro Cleaved PARP, Pro PARP, pro mTOR and mTOR were assessed by western blotting technique. The protein concentrations of malondialdehyde (MDA), total antioxidant capacity, and super oxide dismutase and gutathione peroxidase were also evaluated. TUNEL staining was also used for the detection of apoptosis. Caspase-9 and concentration of antioxidants were higher in the treated groups compared to Endo-sole group (P P

Kaolinite nanocomposites (NCs) could be utilized as agents for wound healing owing to their efficiency and low toxicity. The present study was conducted to synthesize a novel silver/kaolinite NCs (Ag/Kaol NCs) and investigate their chitosan derivation (Ag/Kaol/Chit NCs) using oak extract. XRD, SEM, EDX, FT-IR, and DLS were employed for the investigation of structural and physio-chemical properties of the synthesized NCs. The obtained results revealed that synthesized Ag/Kaol NCs were mesoporous and spherical with sizes ranging from 7–11 nm. They also demonstrated successful synthesis between silver and kaolinite using the extract. Cytotoxicity and in vitro antibacterial activity were also investigated. The clinical effects of ointments containing the NCs for improving wound healing were studied on the wound area, total bacterial count, histological parameters, and protein expression of some genes. Nanocomposites were safe up to 0.50 mg/mL. The results of in vivo and in vitro antibacterial activity showed that Ag/Kaol NCs, were of antibacterial activity ( ${P} ). The results of antioxidant activity indicated that Ag/Kaol NCs have antioxidant structures. Our findings concerning molecular mechanism implied that Ag/Kaol/Chit increased the expression of Wnt/ $\beta $ -catenin and collagen ( ${P} ). In sum, Ag/Kaol/Chit showed antibacterial activity and improved wound healing by decreasing the inflammation and promoting the proliferative phase. The novel NCs showed wound healing properties by decreasing inflammation and total bacterial count and increasing proliferative phase. The application of Ag/Kaol/Chit was suggested as a green agent for improving infected wound healing.

PubMedID: 31760838 Context:Cinnamomum verum J. Presl. (Lauraceae) has a high number of polyphenols with insulin-like activity, increases glucose utilization in animal muscle, and might be beneficial for diabetic patients. Objective: This study evaluated the effectiveness of an ointment prepared from Cinnamomum verum hydroethanolic extract on wound healing in diabetic mice. Materials and methods: A total of 54 male BALB/c mice were divided into three groups: (1) diabetic non-treated group mice that were treated with soft yellow paraffin, (2 and 3) mice that were treated with 5 and 10% C. verum. Two circular full-thickness excisional wounds were created in each mouse, and the trial lasted for 16 d following induction of the wound. Further evaluation was made on the wound contraction ratio, histopathology parameters and mRNA levels of cyclin D1, insulin-like growth factor 1 (IGF-1), glucose transporter-1 (GLUT-1), total antioxidant capacity, and malondialdehyde of granulation tissue contents. HPLC apparatus was utilized to identify the compounds. Results: The HPLC data for cinnamon hydroethanolic extract identified cinnamaldehyde (11.26%) and 2-hydroxyl cinnamaldehyde (6.7%) as the major components. A significant increase was observed in wound contraction ratio, fibroblast proliferation, collagen deposition, re-epithelialization and keratin biosynthesis in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05). The expression level of cyclin D1, IGF1, GLUT 1 and antioxidant capacity increased in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05). Conclusions: Topical administration of C. verum accelerated wound healing and can possibly be employed in treating the wounds of diabetic patients. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Despite the use of essential oils for wound healing, their application is compromised due to their hydrophobic and volatile nature. This study was conducted to evaluate the efficiency of peppermint essential oil (PEO) loaded into nanostructured lipid carriers (PEO-NLC) on In-vitro antibacterial activity and In-vivo infected wound healing in mice model. The PEO-NLC was prepared using hot melt homogenization technique. Then, the morphology and size of PEO-NLC were determined by using Zeta potential (ZP) and Scanning Electron Microscopy (SEM) analyses. For in vitro study, PEO and PEO-NLC were tested for antibacterial activities against Escherichia coli, Salmonella typhimurium, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Bacillus anthracis, Staphylococcus pneumonia, and Listeria monocytogenes Species. In order to perform an in vivo study, two full-thickness wounds with the size of 5 mm were induced in each mouse and inoculated with Pseudomonas aeruginosa and Staphylococcus aureus. The animals were divided into four groups as control, Mupirocin®, PEO, and PEO-NLC. Wound contraction, bacterial count, histological examinations, and molecular analyses were performed on these mice. Particle size analyses showed that all the fabricated PEO-NLC were in the range from 40 to 250 nm with narrow PDI∼0.4. The ZP value of the all fabricated PEO-NLC was found to be -10 to -15mv. SEM analysis indicated that the particles had a smooth surface, spherical and uniformly distributed around. In vitro analysis showed that PEO and PEO-NLC have similar antibacterial activities against S. epidermidis, S. aureus, L. monocytogenes, E. coli, and P. aeruginosa species. In vivo analysis showed that wound contraction rate, fibroblast infiltration, collagen deposition, and re-epithelialization were increased in PEO and PEO-NLC-treated animals compared to the control group. Also, it indicated positive effects on the FGF-2 and EGF mRNA levels expressions. Our results suggest the efficacy of PEO-NLC in order to treat an infected wound model and can provide an appropriate strategy for producing topical formulations.

In the present study, new-layered inorganic/organic hybrid of silver/talc nanocomposites (Ag/Tlc-NPs) and its chitosan-capped derivative (Ag/Tlc/Csn NCs) were biochemically synthesized utilizing Lawsonia inermis L. extract. The silver nanoparticles (Ag NPs) were synthesized employing green method on the exterior surface layer of talc mineral as a solid substrate. The negatively charged surface layer of talc might function as templates and can attract the chitosan cations from a solution to yield a layered hybrid structure, whose inorganic phase is formed by Si-O-Ag bonds. Our results revealed that Ag NPs were formed on the exterior surface of talc with a diameter with size of 124–215 nm. In addition, cytotoxicity, in vitro antibacterial activity, and clinical effects of wound-healing ointments containing talc were investigated. The results implied the successful synthesis of Ag/Tlc/Csn NCs using the extract. The structures were safe up to 0.50 mg/mL. In vitro studies confirmed antioxidant and antibacterial properties of Ag/Tlc/Csn NCs. In sum, our findings showed that the ointments improve wound healing process by inducing an anti-inflammatory M2 phenotype and bFGF, CD206, collagen1A, and IL-10 production that causes fibroblast migration and wound closure through influencing M2 macrophage. Ag/Tlc/Csn is suggested to be taken into consideration as a medical combination for improving infected wound healing and as a promising agent for clinical administration.

The preparation of ointments from natural compounds is essential for accelerating infected wounds. This study investigated the effects of topical uses of gold nanoparticles (Au)/perlite (Au/Perl) nanocomposites (NCs) by the help of Urtica dioica extract and its chitosan-capped derivative (Chit) on methicillin-resistant Staphylococcus aureus (MRSA)-infected wound healing in a mouse model. Furthermore, Au/Perl/Chit nanocomposite was prepared using protonated chitosan solution. The physicochemical properties of the as-synthesized nanocomposites were also investigated. The effects of Au/Perl/Chit NC were assessed by antibacterial, histopathological parameters as well as molecular evaluations. Then, they were compared with synthetic agent of mupirocin. The results revealed that Au/Perl NC was mesoporous and spherical in a range of 13–15 nm. Topical administration of Au/Perl/Chit ointment accelerated wound healing by reducing bacteria colonization and wound rate enhancing collagen biosynthesis and re-epithelialization, the expressions of IL-10, PI3K, AKT, bFGF, and COL1A genes, which is in agreement with the obtained results for mupirocin. In conclusion, the results strongly demonstrated that administration of ointments prepared from Au/Perl and Au/Perl/Chit nanocomposites stimulates MRSA-infected wound healing by decreasing the length of healing time and regulating PI3K/AKT/bFGF signaling pathway and is a promising candidate in stimulating MRSA-infected wound regeneration.

This study was conducted to design and evaluate a wound dressing based on a polycaprolactone (PCL) nanofiber coated with gamma oryzanol (GO) and chitosan (CS) in mice model. All the dressings were prepared by electrospinning method, and their morphology and physical properties were investigated. The mice were divided into five groups and treated with I) PCL-sole (PCL), III) PCL-mupirocin (PCL-M), IV) PCL-GO, IV) PCL-CS, and V) PCL-CS-GO. Wound area, total bacterial count, histopathological parameters, and expressions of IL-1β, TNF-α, IL-10, MMP-9, EGF, and VEGF were assessed. The fibers were randomly distributed in PCL group, but loading CS and GO increased the complexity and placing on the dressings. PCLs loaded with GO and CS showed lower viscosity, surface tension, and fiber diameter and higher conductivity and water contact angle compared to unloaded PCLs (P

The present study was conducted to develop a simple and novel synthesis process, one-step Salvia officinalis extract-assisted biosynthesis route to synthesize ZnO/Magnetite-based nanocomposites (ZnO/Mgt-NCs). Characterization of the physicochemical properties of the ZnO/Mgt-NCs was performed using XRD, FESEM, EDX, TEM, FT-IR, and DLS techniques. Furthermore, their biomedical properties for antibacterial properties and wound healing activity were assessed. According to the TEM and FESEM image, the synthesized spherical Fe3O4 nanoparticles on the surface of quartz were formed ranging from about 13–14 nm. In addition, based on the EDX spectra, the elemental analysis showed the presence of Zinc, Oxygen, and Iron elements in the as-synthesized ZnO/Mgt-NCs. Biomedical studies confirmed that ZnO/Mgt-NCs had antibacterial properties and demonstrated antibacterial activity against Streptococcus pyogenes and Pseudomonas aeruginosa. It also revealed infected wound healing activity by decreasing the total bacterial tissue on top of improving granulation tissue, collagen density and epithelization. Therefore, the new Magnetite-based ZnO/Mgt-NCs has greater potential to cure wounds efficiently.

This study aims to evaluate the effects of topical sole and co-administration of Platelet-rich plasma (PRP) and chitosan on the infected burn wounds model by Candida albicans in Wistar rats. A circle partial thickness contact burn wound model occurred via brass a size of 8mm diameter between the shoulders and after that, 50μl of a suspension containing C. albicans yeast (5×107) colony forming unit was poured on the surface of the wound. The experimental groups included Control, Clotrimazole, PRP and Chitosan+PRP that received any agent, Clotrimazole®, PRP and Chitosan+PRP to treat the wound, respectively. To assess the healing rate, wound size rate, tissue yeast count (TYC) and immunohistochemical staining for heat shock protein 70 (HSP70), HSP 90 and proliferating cell nuclear antigen (PCNA) were conducted. Moreover, enzymatic activity of glutathione peroxidase (GPx), superoxide dismutase (SOD) and malondialdehyde (MDA) rate were evaluated. The results demonstrated that the co-administration of Chitosan+PRP drastically (P

The present study was conducted to evaluate the in vitro antibacterial activity and wound healing effects of caraway essential oil (CEO) loaded into nanostructured lipid carriers (CEO-NLCs). Zeta size (ZS), zeta potential (ZP) and scanning electron microscopy (SEM) techniques were employed in order to investigate the size and morphology of CEO-NLCs. According to the obtained results, the particle size was 40 nm-250 nm with narrow PDI∼0.23. The ZP value of all the CEO-NLCs was -11.7. The findings of SEM analysis showed a smooth-surfaced, spherical and uniform distribution of the particles. The results of In vitro studies indicated the antibacterial activity of the CEO-NLCs groups against Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa compared to blank and DMSO. Topical administration of the CEO-NLCs decreased the inflammatory phase whereas it increased granulation tissue formation. Seemingly, the CEO-NLCs can be used for the treatment of the infected excision wounds in the clinical condition.

Background: Salvia officinalis L. (Lamiaceae) is known to have antibacterial properties possibly conducive to the healing process of infected wounds. Purpose: The present study aimed to evaluate the effects of an ointment containing Salvia officinalis essential oil (SOO) on an infected wound model. Methods: Essential oil hydrodistillated from the dried leaves of the plant was analyzed by GC-FID and GC–MS. After creating two full-thickness cutaneous wounds, mice were classified into four groups, control, and animals treated with 2 % mupirocin® (standard positive drug), and 2 % and 4 % (w/w) of SOO. In order to evaluate the effects of SOO on the wound healing phases, the expression levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), cyclin-D1, Bcl-2, fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factors (VEGF) were analyzed using qRT-PCR. Immunohistochemistry analysis, tissue total antioxidant capacity (TAC) and malondialdehyde (MDA) were further assessed in all groups. Results: Concerning essential oil, the main compounds were found to be cis-thujone (26.8 %), camphor (16.4 %), trans-thujone (14.1 %) and 1,8-cineole (10.8 %). Our findings showed that the topical application of SOO was able to shorten the inflammatory phase and accelerate the cellular proliferation, re-vascularization, collagen deposition and re-epithelialization in comparison to the control group (p

Nanostructured lipid carriers are used for protecting essential oils against environmental factors and also for increasing antimicrobial capability. Gels prepared from Mentha pulegium essential oil (MPO)-loaded into nanostructured lipid carriers (MPO-NLCs) might hasten the infected wound healing process. This study evaluates in-vitro antibacterial activity of MPO-NLCs and in-vivo wound healing activity of MPO-NLCs in BALB/c mice model. To evaluate the effect of MPO-NLCs on wound healing, wound contraction, tissue bacterial count, histological and molecular parameters were assessed at 3, 7 and 14 days after creating wound. MPO-NLCs showed the most antibacterial activity against positive bacteria of Staphylococcus epidermidis, Staphylococcus aureus and Listeria monocytogenes and also negative bacteria of Escherichia coli and Pseudomonas aeruginosa (P

Medicinal plants are conventionally used for wound healing, but their action mechanisms are still unknown. The present study evaluated the effect of topical administration of ointment containing dill (Anethum graveolens) essential oil (DEO) in the management of apoptosis and cell proliferation during MRSA-infected experimentally induced wound healing process in BALB/c mice model. The GC-FID and GC-MS techniques were used to analyze chemical composition of the essential oil. The mice were randomly divided into four treatment groups including negative control (sham), 2% and 4% DEO and mupirocin®-treated animals. The full-thickness excisional wounds were inoculated by 5 × 107 colony-forming units of MRSA. In order to assess the effect of different concentrations of DEO on wounds infection, wound area, bacterial count, histopathological, immunohistochemical and RT-PCR analysis were evaluated. The GC-MS analysis identified α-phellandrene (47.3%), p-cymene (18.5%) and carvone (14.1%) as the main compounds of the essential oil tested here. Administration of DEO prevented bacterial growth and also reduced wound area in comparison to the control group. Topical administration of DEO significantly reduced the inflammatory phase and accelerated re-epithelialization, angiogenesis, fibroblast and collagen deposition. Moreover, the DEO-treated animals exhibited higher expressions of Bcl-2, p53 caspase-3, VEGF and FGF-2 in comparison to the control and mupirocin®-treated groups (P

The repair of peripheral nerve injuries is still one of the most challenging tasks and concerns in neurosurgery, plastic and orthopedic surgery. Effect of acetyl-L-carnitine (ALC) loaded chitosan conduit as an in situ delivery system of ALC in bridging the defects was studied using a rat sciatic nerve regeneration model. A 10-mm sciatic nerve defect was bridged using a chitosan conduit (CHIT/ALC) filled with 10 μL ALC (100 ng/mL). In control group (CHIT), the conduit was filled with the same volume of the phosphate buffered solution. The regenerated fibers were studied 4, 8, 12 and 16 weeks after surgery. The functional and electrophysiological studies confirmed faster recovery of the regenerated axons in ALC treated than control group (P

This study is aimed to analyse the cross-link between cyclin D1, cdk-4, p21, PCNA and DNA damage during different periods of reperfusion following experimental torsion in rats. Thirty mature male Wistar rats (N = 6) were used. Following 4 hr from torsion induction, the reperfusion was induced. Animals were subdivided into groups, including 4 hr torsion-induced (T1), 1 hr post-reperfusion (T2), 2 hr post-reperfusion (T3), 4 hr post-reperfusion (T4) and 8 hr post-reperfusion (T5) groups. The seminiferous tubules differentiation (TDI) and spermatogenesis indices were evaluated. The expressions of cyclin D1, cdk-4, p21and PCNA were analysed using Reverse Transcriptase-PCR (RT-PCR). Moreover, the cyclin D1+ , cdk-4+ , p21+ and PCNA+ cell numbers/mm2 of tissue were assessed through immunohistochemical staining. The testicular DNA fragmentation was analysed using TUNEL assay and DNA ladder test. Observations demonstrated that reperfusion significantly increased (p < 0.05) up-regulated the expressions of cyclin D1, cdk-4 and PCNA. The animals in T5 group showed diminished expression of p21 and represented diminished DNA fragmentation versus T1 group. In conclusion, minimum 8 hr post-reperfusion is needed to re-initiate necessary expressions of cyclin D1, cdk-4 and PCNA to restore cell cycling machinery and ameliorate torsion-induced DNA damage.

In Iranian traditional therapy folk, the Pistacia is used for treatment of wound inflammation. Here in the present study, the In vivo effect of Pistacia atlantica hulls ointment (PAO) on the wound healing process was assessed. Excision and incision wounds were induced in rats. Three different doses of PAO were administrated. Following 3, 7, 14 and 21 days, the tissue samples were obtained and skin irritation ratio, hydroxyproline content, as well as immune cells, fibroblasts, fibrocytes distribution and collagen density were analyzed. Moreover, the cellular RNA damage examined using epi-fluorescent microscope. Hydroethanolic extract of PAO significantly (P

Nowadays, borage flowers and leaves are used medicinally for wound healing because of plant constituents, gamma-linolenic acid, alpha linolenic acid and delta-6-fatty acid. The aim of of the present study was to evaluate the ability of borage extract ointment wound healing process. Under surgical anaesthesia, excisional wounds were made on back of 30 rats by punching. Rats were divided into 3 groups of borage 1.5% ointment, eucerin-vaseline, and control. All the rats were treated with topical ointments daily for 21 days. Histopathological examination was performed on the 3rd, 7th, 14th, and 21st days and the wound healing was assessed. The results showed that wound size of the test groups were reduced early as compared to control group. The significant results of histopathological evaluation were obtained with borage, when compared to the other groups as well as to the control and the placebo. Present study demonstrated that borage extract was capable of promoting wound healing process. Key words: Borage, herbal extract, histopathological study, rat, wound healing.