Euodia daniellii Hemsl. Extract and Its Active Component Hesperidin Accelerate Cutaneous Wound Healing via Activation of Wnt/β-Catenin Signaling Pathway

The activation of the Wnt/β-catenin signaling pathway plays a key role in the wound-healing process through tissue regeneration. The extract of Euodia daniellii Hemsl. (E. daniellii), a member of the Rutaceae family, activates the Wnt/β-catenin signaling pathway. However, the function of E. daniellii in wound healing has not yet been elucidated. We performed a migration assay to determine the wound-healing effect of E. daniellii extract in vitro using human keratinocytes and dermal fibroblast. In addition, a mouse acute wound model was used to investigate the cutaneous wound-healing effect of E. daniellii extract in vivo and confirm the potential mechanism. E. daniellii extract enhanced the migration of human keratinocytes and dermal fibroblasts via the activation of the Wnt/β-catenin pathway. Moreover, the E. daniellii extract increased the levels of keratin 14, PCNA, collagen I, and α-SMA, with nuclei accumulation of β-catenin in vitro. E. daniellii extract also efficiently accelerated re-epithelialization and stimulated wound healing in vivo. Furthermore, we confirmed that hesperidin, one of the components of E. daniellii, efficiently accelerated the migration of human keratinocytes and dermal fibroblasts, as well as wound healing in vivo via the activation of the Wnt/β-catenin pathway. Overall, E. daniellii extract and its active component, hesperidin, have potential to be used as therapeutic agents for wound healing.     

In vitro wound healing evaluation,antioxidant and chemical profiling of Baeckea frutescens leaves ethanolic extract

Occurrence of the wound or chronic wound, which results to disability, amputation and diminish quality of life, are leading to increased healthcare expenditure around the globe. Despite effective conventional wound healing medicines, the exploration of alternative medicines are continuing process as researchers seek for the approach to reduce the cost of wound healing management. In present study, wound healing properties of ethanolic extract of Baeckea frutescens leaves were determined by evaluating their cytotoxicity, proliferation and migration rate on two types of cells, keratinocytes (HaCaT) and fibroblasts (BJ). Furthermore, the antioxidant properties of this plant were determined by DPPH scavenging, ferric reducing antioxidant power (FRAP) and total phenolics content (TPC) assays. The phytochemistry of the extract was evaluated by phytochemicals screening and liquid chromatography mass spectrometry (LCMS) analysis. Results of this study indicated Baeckea frutescens extract increased the rate of proliferation and migration on both HaCat and BJ cells within their nontoxic doses. The extract also possessed a very good antioxidant property as demonstrated with high DPPH radical scavenging, FRAP and TPC values, comparable to that of Green tea extract, a widely known antioxidant. The phytochemistry analyses and LCMS exhibited the presence saponins, flavonoids, tannins and steroids in Baeckea frutescens extract possibly responsible to their antioxidant and wound healing properties.     

Comparison of Pulsed and Continuous Wave Diode Laser at 940 nm on the Viability and Migration of Gingival Fibroblasts

Gingival fibroblasts have critical roles in oral wound healing. Photobiomodulation (PBM) has been shown to promote mucosal healing and is now recommended for managing oncotherapy-associated oral mucositis. This study examined the effects of the emission mode of a 940 nm diode laser on the viability and migration of human gingival fibroblasts. Cells were cultured in a routine growth media and treated with PBM (average power 0.1 W cm⁻², average fluence 3 J cm⁻², every 12 h for six sessions) in one continuous wave and two pulsing settings with 20% and 50% duty cycles. Cell viability was assessed using MTT, and digital imaging quantified cell migration. After 48 and 72 h, all treatment groups had significantly higher viability (n = 6, P < 0.05) compared with the control. The highest viability was seen in the pulsed (20% duty cycle) group at the 72-h time point. PBM improved fibroblast migration in all PBM-treated groups, but differences were not statistically significant (n = 2, P > 0.05). PBM treatments can promote cell viability in both continuous and pulsed modes. Further studies are needed to elucidate the optimal setting for PBM-evoked responses for its rationalized use in promoting specific phases of oral wound healing.     

The Unexplored Wound Healing Activity of Urtica dioica L. Extract: An In Vitro and In Vivo Study

Wound healing is a great challenge in many health conditions, especially in non-healing conditions. The search for new wound healing agents continues unabated, as the use of growth factors is accompanied by several limitations. Medicinal plants have been used for a long time in would healing, despite the lack of scientific evidence veryfying their efficacy. Up to now, the number of reports about medicinal plants with wound healing properties is limited. Urtica dioica L. is a well-known plant, widely used in many applications. Reports regarding its wound healing potential are scant and sparse. In this study, the effect of an Urtica dioica L. extract (containing fewer antioxidant compounds compared to methanolic or hydroalcoholic extracts) on cell proliferation, the cell cycle, and migration were examined. Additionally, antioxidant and anti-inflammatory properties were examined. Finally, in vivo experiments were carried out on full-thickness wounds on Wistar rats. It was found that the extract increases the proliferation rate of HEK-293 and HaCaT cells up to 39% and 30% after 24 h, respectively, compared to control cells. The extract was found to increase the population of cells in the G₂/M phase by almost 10%. Additionally, the extract caused a two-fold increase in the cell migration rate of both cell lines compared to control cells. Moreover, the extract was found to have anti-inflammatory properties and moderate antioxidant properties that augment its overall wound healing potential. Results from the in vivo experiments showed that wounds treated with an ointment of the extract healed in 9 days, while wounds not treated with the extract healed in 13 days. Histopathological examination of the wound tissue revealed, among other findings, that inflammation was significantly reduced compared to the control. Urtica dioica L. extract application results in faster wound healing, making the extract ideal for wound healing applications and a novel drug candidate for wound healing.     

Effect of Moringa oleifera Leaf Extract on Excision Wound Infections in Rats: Antioxidant,Antimicrobial, and Gene Expression Analysis

The present study investigated the wound healing activity of Moringa oleifera leaf extract on an infected excision wound model in rats. Infection was induced using methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. An investigation was also done to study the effect of Moringa extract on the vascular endothelial growth factor (VEGF) and transforming growth factor-beta 1 (TGF-β1) gene expression in vitro using human keratinocytes (HaCaT). The methanol extract of M. oleifera leaves was analyzed for the presence of phytochemicals by LCMS. The antimicrobial activity of the extract was also determined. Wound contraction, days for epithelization, antioxidant enzyme activities, epidermal height, angiogenesis, and collagen deposition were studied. M. oleifera showed an antimicrobial effect and significantly improved wound contraction, reduced epithelization period, increased antioxidant enzymes activity, and reduced capillary density. Effect of the extract was less in wounds infected with P. aeruginosa when compared to MRSA. The VEGF and TGF-β1 gene expression was increased by M. oleifera.     

Synthesis and Characterization of Silver Nanoparticles from Rhizophora apiculata and Studies on Their Wound Healing,Antioxidant, Anti-Inflammatory,and Cytotoxic Activity

Silver nanoparticles (AgNPs) have recently gained interest in the medical field because of their biological features. The present study aimed at screening Rhizophora apiculata secondary metabolites, quantifying their flavonoids and total phenolics content, green synthesis and characterization of R. apiculata silver nanoparticles. In addition, an assessment of in vitro cytotoxic, antioxidant, anti-inflammatory and wound healing activity of R. apiculata and its synthesized AgNPs was carried out. The powdered plant material (leaves) was subjected to Soxhlet extraction to obtain R. apiculata aqueous extract. The R. apiculata extract was used as a reducing agent in synthesizing AgNPs from silver nitrate. The synthesized AgNPs were characterized by UV-Vis, SEM-EDX, XRD, FTIR, particle size analyzer and zeta potential. Further aqueous leaf extract of R. apiculata and AgNPs was subjected for in vitro antioxidant, anti-inflammatory, wound healing and cytotoxic activity against A375 (Skin cancer), A549 (Lung cancer), and KB-3-1 (Oral cancer) cell lines. All experiments were repeated three times (n = 3), and the results were given as the mean ± SEM. The flavonoids and total phenolics content in R. apiculata extract were 44.18 ± 0.086 mg/g of quercetin and 53.24 ± 0.028 mg/g of gallic acid, respectively. SEM analysis revealed R. apiculata AgNPs with diameters ranging from 35 to 100 nm. XRD confirmed that the synthesized silver nanoparticles were crystalline in nature. The cytotoxicity cell viability assay revealed that the AgNPs were less toxic (IC₅₀ 105.5 µg/mL) compared to the R. apiculata extract (IC₅₀ 47.47 µg/mL) against the non-cancerous fibroblast L929 cell line. Antioxidant, anti-inflammatory, and cytotoxicity tests revealed that AgNPs had significantly more activity than the plant extract. The AgNPs inhibited protein denaturation by a mean percentage of 71.65%, which was equivalent to the standard anti-inflammatory medication diclofenac (94.24%). The AgNPs showed considerable cytotoxic effect, and the percentage of cell viability against skin cancer, lung cancer, and oral cancer cell lines was 31.84%, 56.09% and 22.59%, respectively. R. apiculata AgNPs demonstrated stronger cell migration and percentage of wound closure (82.79%) compared to the plant extract (75.23%). The overall results revealed that R. apiculata AgNPs exhibited potential antioxidant, anti-inflammatory, wound healing, and cytotoxic properties. In future, R. apiculata should be further explored to unmask its therapeutic potential and the mechanistic pathways of AgNPs should be studied in detail in in vivo animal models.     

Bud-Poplar-Extract-Embedded Chitosan Films as Multifunctional Wound Healing Dressing

Wounds represent a major global health challenge. Acute and chronic wounds are sensitive to bacterial infection. The wound environment facilitates the development of microbial biofilms, delays healing, and promotes chronic inflammation processes. The aim of the present work is the development of chitosan films embedded with bud poplar extract (BPE) to be used as wound dressing for avoiding biofilm formation and healing delay. Chitosan is a polymer with antimicrobial and hydrating properties used in wound dressing, while BPE has antibacterial, antioxidative, and anti-inflammatory properties. Chitosan-BPE films showed good antimicrobial and antibiofilm properties against Gram-positive bacteria and the yeast Candida albicans. BPE extract induced an immunomodulatory effect on human macrophages, increasing CD36 expression and TGFβ production during M1/M2 polarization, as observed by means of cytofluorimetric analysis and ELISA assay. Significant antioxidant activity was revealed in a cell-free test and in a human neutrophil assay. Moreover, the chitosan-BPE films induced a good regenerative effect in human fibroblasts by in vitro cell migration assay. Our results suggest that chitosan-BPE films could be considered a valid plant-based antimicrobial material for advanced dressings focused on the acceleration of wound repair.     

Formulation and characterization of a novel cutaneous wound healing ointment by silver nanoparticles containing Citrus lemon leaf: A chemobiological study

IntroductionFormulating new wound-healing ointments by natural compounds is the first research priority in the developing and developed countries. This study was intended to provide green formulation of Ag-NP ointment containing Citrus lemon leaf aqueous extract and examine its capability of healing cutaneous wounds and its antioxidant and cytotoxicity activities under in vitro and in vivo conditions.Materials and methodsDifferent techniques, including UV–Vis and FT-IR spectroscopy, were used to characterize Ag-NPs. MTT assay was used to investigate cytotoxicity property of Ag-NPs. Antioxidant activity of Ag-NPs were examined by DPPH in the presence of butylated hydroxytoluene as positive control. Parameters of cutaneous wound healing were measured both histopathologically and biochemically.ResultsClear peak at 429 nm shown by UV–Vis spectroscopy indicated formation of Ag-NPs. In FT-IR spectroscopy, presence of many antioxidant compounds provided an excellent condition to reduce silver in Ag-NPs. FE-SEM and TEM images showed spherical Ag-NPs with an average size of 25.1 nm. The synthesized silver nanoparticles had excellent cell viability on the HUVECs line and indicated this method was nontoxic. Application of Ag-NP ointment improved wound healing parameters significantly (P ≤ 0.01). Ag-NPs reduced wound areas, total cells, neutrophils and lymphocytes significantly (P ≤ 0.01) and increased wound contracture, vessels, hexosamines, hydroxyl proline, hexuronic acid, fibrocytes, fibroblasts and fibrocyte/ fibroblast ratios significantly (P ≤ 0.01).ConclusionsOnce our results are verified by clinically experimental studies, Ag-NP ointment can be used as a modern one to treat several types of wounds, especially cutaneous ones, in humans.     

Multi-targeted potential of Pittosporum senacia Putt.: HPLC-ESI-MSn analysis,in silico docking,DNA protection,antimicrobial, enzyme inhibition,anti-cancer and apoptotic activity

Pittosporum senacia (PS) Putt. (Pittosporaceae), indigenous to the Mascarene Islands, is a common ingredient in traditional medicines. However, there is currently a dearth of studies to validate some of these traditional claims. Given the broad traditional uses of PS against several diseases, we aimed to provide a comprehensive insight into the biological and chemical profile of P. senacia. The antioxidant, enzyme inhibitory activity, anticancer, and phytochemical composition of the methanolic extract of P. senacia leaf extracts were studied. The possible interaction and binding mode of the most abundant phytochemicals were studied via in silico docking experiments on tyrosinase and α-glucosidase. The mechanism behind the cytotoxic property of P. senacia extract for MDA-MB-231 was also examined using different methods including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability test checking apoptosis-associated genes, and wound healing assays. Twenty-six compounds were identified, of which caffeoylquinic acid derivatives, ferulic acid derivative, cinnamoylquinic acid derivative and two other polyphenols (oleuropeine and isoramnetin glucoside) being abundant, have been tested using in silico studies, against α-glucosidase and tyrosinase. The extract (IC₅₀ = 118.8 μg/ml) exhibited time and dose dependent anti-proliferative effect on human breast cancer cell line, MDA-MB-231. According to the expression profile of apoptosis inhibitors and apoptosis promoters genes, expression of Bax and Bak genes were significantly increased compared to Bcl-2 and Birc5 genes. Based on wound healing analysis, cell migration was inhibited after the application of the plant extract. The present findings suggested that PS might be a good candidate as sources of bioactive compounds for designing functional applications.     

Natural okra-based hydrogel for chronic diabetic wound healing

As a representative of chronic wounds, the long-term high levels of oxidative stress and blood sugar in chronic diabetic wounds lead to serious complications, making them the biggest challenge in the research on wound healing. Many edible natural biomaterials rich in terpenes, phenols, and flavonoids can act as efficient antioxidants. In this study, okra extract was selected as the main component of a wound dressing. The okra extracts obtained via different methods comprehensively maintained the bioactivity of multiple molecules. The robust antioxidant properties of okra significantly reduced intracellular reactive oxygen species production, thereby accelerating the wound healing process. The results showed that okra extracts and their hydrogel dressings increased cell migration, angiogenesis, and re-epithelization of the chronic wound area, considerably promoting wound remodeling in diabetic rats. Therefore, okra-based hydrogels are promising candidates for skin regeneration and wider tissue engineering applications.     

Effect of a topical formulation containing Calophyllum brasiliense Camb. extract on cutaneous wound healing in rats

This study evaluated the wound healing effects of topical application of an emulsion containing the HPLC-standardised extract from Calophyllum brasiliense Cambess (Clusiaceae) leaves in rats. The macroscopic analysis demonstrated that the wounds treated with the C. brasiliense emulsion healed earlier than the wounds treated with emulsion base and Dersani®. The percentage of wound healing in the group treated with the C. brasiliense emulsion was significantly higher than in the other groups at 7 and 14 days. On day 14, the animals treated with the C. brasiliense emulsion exhibited a 90.67% reduction of the wound areas. The histological evaluation revealed that on day 21, the group treated with the C. brasiliense emulsion exhibited a significant increase in fibroblasts compared with the other groups. Thus, the C. brasiliense emulsion had healing properties in the topical treatment of wounds and accelerated the healing process.     

LLLT Effects on Oral Keratinocytes in an Organotypic 3D Model

Several in vitro studies evaluated the cellular and molecular events related to interactions between phototherapy and target tissues, including oral keratinocytes and fibroblasts, providing elucidative data about phototherapy‐induced healing. However, these interactions were limited to the application of a bidimensional cell culture model of oral mucosal cells. Thus, thisstudy evaluated the use of an organotypic oral epithelium model to elucidate the morphological and phenotypic responses of cells subjected to low‐level laser therapy (LLLT). Oral keratinocytes were seeded in the ex vivo ‐produced oral mucosal equivalent (EVPOME ) model, with a porcine acellular dermal matrix. LLLT was applied by means of the LaserTABLE device (780 nm, 25 mW ) at 0.5, 1.5 and 3 J cm⁻². After three irradiations, morphology, proliferation and gene expression of growth factors were assessed. LLLT and control groups presented similar morphological features, characterized by the formation of a stratified, differentiated and keratinized epithelium. LLLT enhanced the cell proliferation and gene expression of keratinocytes (hKGF ) as well as epidermal (hEGF ) growth factors. In general, analysis of these data shows that the three‐dimensional cell culture model can be applied for phototherapy studies and that the positive effects of LLLT were confirmed by the use of an organotypic model.     

Antibacterial Effects of Commiphora gileadensis Methanolic Extract on Wound Healing

Commiphora gileadensis (CG) is a small tree distributed throughout the Middle East. It was traditionally used in perfumes in countries in this area. In Saudi Arabia, it was used to treat wounds burns and as an antidote to scorpion stings. This study aimed to evaluate the antimicrobial activity and cutaneous wound healing efficiency of the CG extracts using microbiological tests, rate of wound contraction and histopathological changes. CG plant were extracted using the methanol extraction technique; then, the methanolic extract was characterized using liquid chromatography coupled with mass spectrometry (LC–MS). Afterwards, a six-millimetre (mm) excision wound was induced in 60 male Balb/c mice. Mice were classified into two classes; each class consisted of three groups of 10 mice. In the non-infected wound class, the group I was assigned as control and received normal saline. Group II received gentamicin treatment, and group III treated with CG-methanolic extract. In the Staphylococcus aureus-infected class, group IV received normal saline, and groups V and VI were treated with gentamicin and CG-methanolic extract, respectively. The colonization of infected wounds was determined using colony-forming units (CFUs), and the percentage of wound contraction was measured in all groups. Finally, the histopathologic semi-quantitative determination of wound healing was evaluated by inflammatory cell infiltration, the presence of collagen fibres and granulation tissue, and the grade of re-epithelization. Composition analysis of the methanolic extract confirmed the presence of a high amount of ceramide (69%) and, to a lesser extent, hexosylceramide (18%) and phosphatidylethanolamine (7%) of the total amount. Additionally, there was a statistically significant difference between the percentage of wound contraction in the CG-treated and control groups in both Staphylococcus aureus-infected and non-infected wounds (p < 0.01). The colonization of the infected wounds was lower in the group treated with CG than in the control group (p < 0.01). In both non-infected and infected wounds, the CG-treated group showed significant statistical differences in inflammatory cell infiltration, collagen fibres, re-epithelization and granulation tissue formation compared with the control group (p < 0.01). The CG extract possesses antibacterial and anti-inflammatory properties that induce wound healing.     

Pongamia pinnata seed extract‐mediated green synthesis of silver nanoparticles: Preparation,formulation and evaluation of bactericidal and wound healing potential

Pongamia pinnata – a plant used since olden times in Ayurvedic treatment – is reported to have diverse functions including antibacterial, antidiabetic, antineurodegenerative, antiepileptic, antiulcer, etc. In this study, our objective was to prepare silver nanoparticles (AgNPs) by green synthesis mediated by methanolic seed extract of P. pinnata and to determine their antimicrobial and antioxidant potential and wound healing activity. AgNPs were characterized for particle size and shape and for antioxidant potential. Further, the AgNPs were incorporated in a gel. The wound healing activity was investigated using an excision wound healing model in Wistar rats. The AgNP‐loaded gel was applied topically to the wounded rats daily for 30 days. The wound contraction was calculated and histopathological studies of the healed tissues were conducted. Karanjin content of the extract was found to be 349 ± 2.16 mg g^?1. Formation of AgNPs was confirmed using transmission and scanning electron microscopies and X‐ray diffraction. AgNPs showed good antioxidant potential and were active against Staphylococcus aureus, Escherichia coli, Bacillus subtilis and Pseudomonas aeruginosa. Significant wound healing activity (p < 0.05) was shown by the AgNP gel as compared to 5% Betadine ointment. Thus, the prepared AgNPs have antimicrobial and wound healing effects that may be useful in treatment of topical infections especially in wounds.     

The Wound-Healing Effect of Mango Peel Extract on Incision Wounds in a Murine Model

Mangifera indica can generate up to 60% of polluting by-products, including peels. However, it has been shown that flavonoids and mangiferin are mainly responsible for the antioxidant, anti-inflammatory, and antibacterial activities closely related to the wound-healing process. The chemical composition of MEMI (methanolic extract of M. indica) was analyzed by HPLC-DAD, as well as concentrations of total phenol (TPC) and flavonoids (TFC) and antioxidant activity (SA₅₀). Wound-healing efficacy was determined by measurements of wound contraction, histological analysis, and tensiometric method; moreover, anti-inflammatory, antibacterial, and acute dermal toxicity (OECD 402) were also evaluated. Phenol, resorcinol, conjugated resorcinol, and mangiferin were detected. TPC, TFC, and SA₅₀ were 136 mg GAE/g, 101.66 mg QE/g, and 36.33 µg/mL, respectively. Tensile strength and wound contraction closure did not show significant differences between MEMI and dexpanthenol groups. Histological analysis (after 14 days) shows a similar architecture between MEMI treatment and normal skin. MEMI exhibits a reduction in edema. Staphylococcus epidermidis had an MIC of 2 mg/mL, while Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli reached 4 mg/mL. The MEMI showed no signs of toxicity. Therefore, this study demonstrates multiple targets that flavonoids and mangiferin of MEMI may present during the healing process.     

Effect of Holoptelea integrifolia (Roxb.) Planch. n-Hexane Extract and Its Bioactive Compounds on Wound Healing and Anti-Inflammatory Activity

The stem bark of Holoptelea integrifolia (Roxb.) Planch. has been applied for the treatment of human cutaneous diseases as well as canine demodicosis in several countries. However, no detailed mechanistic studies have been reported to support their use. In this study, thin-layer chromatography and gas chromatography were used to screen phytochemicals from the fresh stem bark extract of H. integrifolia. We found the two major bioactive compounds, friedelin and lupeol, and their activity on wound healing was further investigated in keratinocytes. Both bioactive compounds significantly reduced wound area and increased keratinocyte migration by increasing matrix metalloproteinases-9 production. Subsequently, we found that the mRNA gene expressions of cadherin 1 and desmoglobin 1 significantly decreased, whereas the gene expression involved in keratinocyte proliferation and homeostasis (keratin-17) increased in compound-treated human immortalized keratinocytes cells. The expression of inflammatory genes (cyclooxygenase-2 and inducible nitric oxide synthase) and pro-inflammatory cytokine genes (tumor necrosis factor-alpha and interleukin-6) was reduced by treatment with n-hexane extract of H. integrifolia and its bioactive compounds. Our results revealed that H. integrifolia extract and its bioactive compounds, friedelin and lupeol, exhibit wound-healing activity with anti-inflammatory properties, mediated by regulating the gene expression involved in skin re-epithelialization.     

The Effect of Rainbow Trout (Oncorhynchus mykiss) Collagen Incorporated with Exo-Polysaccharides Derived from Rhodotorula mucilaginosa sp. on Burn Healing

Burn is one of the physically debilitating injuries that can be potentially fatal; therefore, providing appropriate coverage in order to reduce possible mortality risk and accelerate wound healing is mandatory. In this study, collagen/exo-polysaccharide (Col/EPS 1–3%) scaffolds are synthesized from rainbow trout (Oncorhynchus mykiss) skins incorporated with Rhodotorula mucilaginosa sp. GUMS16, respectively, for promoting Grade 3 burn wound healing. Physicochemical characterizations and, consequently, biological properties of the Col/EPS scaffolds are tested. The results show that the presence of EPS does not affect the minimum porosity dimensions, while raising the EPS amount significantly reduces the maximum porosity dimensions. Thermogravimetric analysis (TGA), FTIR, and tensile property results confirm the successful incorporation of the EPS into Col scaffolds. Furthermore,the biological results show that the increasing EPS does not affect Col biodegradability and cell viability, and the use of Col/EPS 1% on rat models displays a faster healing rate. Finally, histopathological examination reveals that the Col/EPS 1% treatment accelerates wound healing, through greater re-epithelialization and dermal remodeling, more abundant fibroblast cells and Col accumulation. These findings suggest that Col/EPS 1% promotes dermal wound healing via antioxidant and anti-inflammatory activities, which can be a potential medical process in the treatment of burn wounds.     

Anti-Inflammatory and Wound Healing Properties of Leaf and Rhizome Extracts from the Medicinal Plant Peucedanum ostruthium (L.) W. D. J. Koch

Peucedanum ostruthium (L.) W. D. J. Koch (Apiaceae) is a worldwide perennial herb native to the mountains of central Southern Europe. The rhizome has a long tradition in popular medicine, while ethnobotanical surveys have revealed local uses of leaves for superficial injuries. To experimentally validate these uses, plant material was collected in the Gran Paradiso National Park, Aosta Valley, Italy, and the rhizome and leaves were micromorphologically and phytochemically characterized. Polyphenol-enriched hydroalcoholic rhizome and leaf extracts, used in cell-free assays, showed strong and concentration-dependent antioxidant and anti-inflammatory activities. In vitro tests revealed cyclooxygenase and lipoxygenase inhibition by the leaf extract, while the rhizome extract induced only lipoxygenase inhibition. MTT assays on HaCaT keratinocytes and L929 fibroblasts showed low cytotoxicity of extracts. In vitro scratch wound test on HaCaT resulted in a strong induction of wound closure with the leaf extract, while the effect of the rhizome extract was lower. The same test on L929 cells showed similar wound closure induction with both extracts. The results confirmed the traditional medicinal uses of the rhizome as an anti-inflammatory and wound healing remedy for superficial injuries but also highlighted that the leaves can be exploited for these purposes with equal or superior effectiveness.     

Collagen Peptides Derived from Sipunculus nudus Accelerate Wound Healing

Marine collagen peptides have high potential in promoting skin wound healing. This study aimed to investigate wound healing activity of collagen peptides derived from Sipunculus nudus (SNCP). The effects of SNCP on promoting healing were studied through a whole cortex wound model in mice. Results showed that SNCP consisted of peptides with a molecular weight less than 5 kDa accounted for 81.95%, rich in Gly and Arg. SNCP possessed outstanding capacity to induce human umbilical vein endothelial cells (HUVEC), human immortalized keratinocytes (HaCaT) and human skin fibroblasts (HSF) cells proliferation and migration in vitro. In vivo, SNCP could markedly improve the healing rate and shorten the scab removal time, possessing a scar-free healing effect. Compared with the negative control group, the expression level of tumor necrosis factor-α, interleukin-1β and transforming growth factor-β1 (TGF-β1) in the SNCP group was significantly down-regulated at 7 days post-wounding (p < 0.01). Moreover, the mRNA level of mothers against decapentaplegic homolog 7 (Smad7) in SNCP group was up-regulated (p < 0.01); in contrast, type II TGF-β receptors, collagen I and α-smooth muscle actin were significantly down-regulated at 28 days (p < 0.01). These results indicate that SNCP possessed excellent activity of accelerating wound healing and inhibiting scar formation, and its mechanism was closely related to reducing inflammation, improving collagen deposition and recombination and blockade of the TGF-β/Smads signal pathway. Therefore, SNCP may have promising clinical applications in skin wound repair and scar inhibition.     

Preparation,characterization, and evaluation of cytotoxicity,antioxidant, cutaneous wound healing,antibacterial, and antifungal effects of gold nanoparticles using the aqueous extract of Falcaria vulgaris leaves

The new age drugs are nanoparticles of metals, which can combat conditions like wounds and fight human pathogens like bacteria. The aim of the experiment was preparation, characterization, and assessment of cytotoxicity, antioxidant, cutaneous wound healing, antibacterial, and antifungal potentials of gold nanoparticles using the aqueous extract of Falcaria vulgaris leaves (AuNPs@F. vulgaris) under in vitro and in vivo condition. These nanoparticles were characterized by FT‐IR, UV, XRD, FE‐SEM, TEM, and AFM. The synthesized AuNPs@F. vulgaris had great cell viability dose‐dependently (Investigating the effect of the nanoparticles on HUVEC cell line) and indicated these nanoparticles were nontoxic. DPPH free radical scavenging test was done to evaluate the antioxidant potentials, which showed similar antioxidant potentials for AuNPs@F. vulgaris and butylated hydroxytoluene. In part of cutaneous wound healing effect of F. vulgaris, after creating the cutaneous wound, the rats were randomly divided into six groups: untreated control, treatment with Eucerin basal ointment, treatment with 3% tetracycline ointment, treatment with 0.2% HAuCl₄ × H₂O ointment, treatment with 0.2% F. vulgaris ointment, and treatment with 0.2% AuNPs@F. vulgaris ointment. These groups were treated for 10 days. Use of AuNPs@F. vulgaris ointment in the treatment groups substantially decreased (p ≤ 0.01) the wound area, total cells, neutrophil, and lymphocyte and remarkably raised (p ≤ 0.01) the wound contracture, hydroxyl proline, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate compared to other groups. In antimicrobial part, MIC, MBC, and MFC were specified by macro‐broth dilution assay. AuNPs@F. vulgaris revealed higher antibacterial and antifungal properties than many standard antibiotics (p ≤ 0.01). Also, AuNPs@F. vulgaris prevented the growth of all bacteria at 2‐8 mg/ml concentrations and removed them at 2‐16 mg/ml concentrations (p ≤ 0.01). In case of antifungal potentials of AuNPs@F. vulgaris, they inhibited the growth of all fungi at 2‐4 mg/ml concentrations and destroyed them at 2‐8 mg/ml concentrations (p ≤ 0.01). In conclusion, synthesized AuNPs@F. vulgaris revealed non‐cytotoxicity, antioxidant, cutaneous wound healing, antibacterial, and antifungal activities.