Effects of Plantago lanceolata L. extract on full-thickness excisional wound healing in a mouse model

Wound healing requires cells that increase both collagen production as a result of inflammatory events and regeneration of epithelial tissue. The Plantago species of herbs have been used in traditional treatment of skin disorders and infectious diseases, and digestive, respiratory, reproductive and circulatory conditions. We investigated the efficacy of different concentrations of Plantago lanceolata L. extract (PLE) for wound healing owing to its anti-inflammatory, anti-bacterial, anti-fungal, anti-oxidant, anti-ulcerative, analgesic and immunomodulatory properties. We used 72 mice in four groups of 18. An excisional 1 cm wound was created in the skin on the back of the mice in all groups. An ointment containing 10% PLE was applied to the wound in group 1, an ointment containing 20% PLE was applied in group 2 and vaseline was applied in group 3. In group 4, no treatment was applied to the wound. On days 7, 14, and 21 of the experiment, six animals in each group were sacrificed after the wounds were photographed and specimens from the wound sites were examined. On day 14, epithelialization was more prominent in group 2, while vascularization and collagen deposition was more advanced in groups 1 and 2 compared to the other groups. Immunohistochemical examination revealed that TGF-β1 expression was elevated on day 14 in all groups; however, this elevation was more limited in groups 1 and 2 than in groups 3 and 4. Although ANGPT-2 expression increased in groups 1 and 4 on day 14, it decreased significantly in groups 2 and 3. We found that different concentrations of PLE exhibited positive effects on wound healing. Application of 10% PLE ointment may be a useful strategy for wound healing.     

Wound healing in the trematode Schistosoma

The ability of adult Schistosoma mansoni to effect wound healing over an exposed surface has been demonstrated. In transected worm segments a new external plasma membrane formed over the exposed tegumental cytoplasm. An elevated leading edge of tegument developed around the margin of the wound; the surface of this region was highly convoluted and there was a proliferation of membranous bodies within its cytoplasm. Inward migration of the leading edge over the exposed internal tissues took place. The resulting new tegument lacked spines and sensory endings. There was no regeneration of basal lamina or tegumentary cytons. In vitro maintenance of worm segments for 3 weeks did not give rise to any major ultrastructural changes in the tissues away from the wound.     

Wound healing in development

Wound healing is the inherent ability of an organism to protect itself against injuries. Cumulative evidence indicates that the healing process patterns in part embryonic morphogenesis and may result in either organ regeneration or scarring, phenomena that are developmental stage‐ or age‐dependent. Skin is the largest organ. Its morphogenesis and repair mechanisms have been studied extensively due not only to its anatomical location, which allows easy access and observation, but also to its captivating structure and vital function. Thus, this review will focus on using skin as a model organ to illustrate new insights into the mechanisms of wound healing that are developmentally regulated in mammals, with special emphasis on the role of the Wnt signaling pathway and its crosstalk with TGF‐β signaling. Relevant information from studies of other organs is discussed where it applies, and the clinical impact from such knowledge and emerging concepts on regenerative medicine are discussed in perspective. Birth Defects Research (Part C) 96:213–222, 2012. © 2012 Wiley Periodicals, Inc.     

Wound healing activity of the human antimicrobial peptide LL37

Antimicrobial peptides (AMPs) are part of the innate immune system and are generally defined as cationic, amphipathic peptides, with less than 50 amino acids, including multiple arginine and lysine residues. The human cathelicidin antimicrobial peptide LL37 can be found at different concentrations in many different cells, tissues and body fluids and has a broad spectrum of antimicrobial and immunomodulatory activities. The healing of wound is a complex process that involves different steps: hemostasis, inflammation, remodeling/granulation tissue formation and re-epithelialization. Inflammation and angiogenesis are two fundamental physiological conditions implicated in this process. We have recently developed a new method for the expression and purification of recombinant LL37. In this work, we show that the recombinant peptide P-LL37 with a N-terminus proline preserves its immunophysiological properties in vitro and in vivo. P-LL37 neutralized the activation of macrophages by lipopolysaccharide (LPS). Besides, the peptide induced proliferation, migration and tubule-like structures formation by endothelial cells. Wound healing experiments were performed in dexamethasone-treated mice to study the effect of LL37 on angiogenesis and wound regeneration. The topical application of synthetic and recombinant LL37 increased vascularization and re-epithelialization. Taken together, these results clearly demonstrate that LL37 may have a key role in wound regeneration through vascularization.     

Wound healing ability of Xenopus laevis embryos. I. Rapid wound closure achieved by bisectional half embryos

We examined wound closure in 'half embryos' produced by the transverse bisection of Xenopus laevis embryos at the primary eye vesicle stage. Both the anterior- and posterior-half embryos survived for more than 6 days, and grew into 'half tadpoles'. Histology and videomicroscopy revealed that the open wound in the half embryo was rapidly closed by an epithelial sheet movement in the wound marginal zone. The time-course of wound closure showed a downward convex curve: the wound area decreased to one-fifth of the original area within 30 min, and the wound continued to contract slowly thereafter. The rapidity of closure of the epidermis as well as the absence of inflammatory cells are typical features of an embryonic type of wound healing. There was a dorso-ventral polarity in the motility of the epidermis: the wound was predominantly closed by the ventral and lateral epidermis. The change in the contour of the wound edge with time suggested a complex mechanism involved in the wound closure that could not be explained only by the purse-string theory. The present experimental system would be a unique and useful model for analyses of cellular movements in the embryonic epithelia.     

创伤渗出液对创伤成纤维细胞增殖的影响

创伤后不同时期渗出液(wound fluid,WF)的质和量的变化,在很大程度上反映伤口组织的愈合进程.研究伤口不同天数的WF对小鼠伤口组织的成纤维细胞(mouse wound fibrolast,mWFb)体外增殖能力的影响,探讨伤口微环境WF在调控mWFb的增殖规律.用两种培养基进行检测：1640培养基-10% FCS(fetal calf serum 胎牛血清)-10% WF或1640-1% FCS-10% WF.发现第1、3、7天的WF能刺激mWFb增殖.在高浓度(10%)FCS条件下,9、11、15天WF对mWFb生长产生抑制作用.而同一WF在低浓度(1%)FCS时导致mWFb死亡.结果提示,在损伤后一周期间伤口微环境能刺激mWFb增殖,但伤后更长时间的WF使细胞生长受阻止.在创伤愈合晚期的微环境中可能存在一些生长抑制因子.     

脱落酸对锁阳茎切口愈合及抗氧化酶活性的影响

为了探讨脱落酸（ABA）对锁阳茎切口愈合及抗氧化酶活性的影响,测定了锁阳茎3个部位（上部、中部和下部）内源ABA含量和切口愈合能力（抗失水力）以及苯丙氨酸解氨酶（PAL）、过氧化物酶（SOD）、过氧化氢酶（CAT）及抗坏血酸过氧化物酶（APX）活性随切口愈合时间的变化。结果表明,内源ABA含量随切口愈合天数的增加整体呈上升趋势。外源ABA处理明显增强了锁阳茎3个部位的PAL活性及抗氧化酶活性,加速了锁阳茎切口愈合,减少失水也提高了其抗氧化能力。比较3个部位,各指标均呈现出上部高于中部,中部高于下部的趋势。     

Influence of sea buckthorn (Hippophae rhamnoides L.) flavone on dermal wound healing in rats

The present investigation was undertaken to determine the efficacy of topical administration of flavone of sea buckthorn (Hippophae rhamnoides L.) on cutaneous wound healing in rats. Four full-thickness excision wounds were created on the back of rat and 1.0% w/v flavone prepared in propylene glycol was applied topically. Control animals received the vehicle alone in an identical manner. The healing of the wound was assessed by the rate of wound contraction, period of epithelialization, hydroxyproline, hexosamine, antioxidants estimation and histopathology of the granulation tissue. The sea buckthorn flavone promoted the wound healing activity as indicated by improved rate of wound contraction, decreased time taken for epithelialization (16.3 days versus 24.8 days in controls) and significant increase in hydroxyproline (26.0%) and hexosamine (30.0%) content. These findings were also confirmed by histopathological examinations. In addition, it was observed that sea buckthorn flavone possesses potent antioxidant properties as evidenced by significant increase in reduced glutathione (55.0%), vitamin C (70.0%) and catalase (20.0%) activities in wound granulation tissue. The flavone treatment also resulted in significant decrease in lipid peroxide levels (39.0%). The results suggest that the sea buckthorn flavone promotes wound healing activity.     

Antioxidant activity of free radical reactions inhibitors, applied to the dressing material for wound healing

Antioxidant activity (AA) of inhibitors of free radical reactions (FRR) (dieton, mexidol, trypsin), applied to the dressing material for wound healing was studied using a model system containing suspension of laminated liposomes, formed from the fraction of total chicken yolk phospholipids. Lipid peroxidation (LPO) of liposome membranes was initiated by addition of Fe²⁺ ions. The kinetics of FRR was monitored by coumarin enhanced chemiluminescence (CL). AA of the inhibitors was determined by their ability to intercept aqueous and hydrophobic free radicals and chelate Fe²⁺ ions. Their ability to intercept radicals reduced in the following order: dieton > trypsin > mexidol. We have also found previously unknown ability of mexidol to interact with Fe²⁺ and to eliminate the FRR catalyst. Studying AA of the FRR inhibitors in the two-components mixture, containing dieton and mexidol, we have observed the multifunctional effect: dieton increased the duration of latent period of CL by intersepting lipid peroxyl radicals, while mexidol, decreased this parameter by interacting with Fe²⁺, i.e. mexidol masked the action of dieton. Study of AA of two-components mixture, containing mexidol and trypsin has demonstrated the same multifunctional effect. In the two-component mixture, containing trypsin and dieton, the inhibitors exhibit synergistic action. All the antioxidant properties of these FRR inhibitors were also preserved in the three component mixture. Thus, the mixture dieton, mexidol and trypsin, possesses high AA, that validates their use in the dressing materials employed for wound healing.     

Rosmarinus officinalis L. essential oils from Spain: composition,antioxidant capacity,lipoxygenase and acetylcholinesterase inhibitory capacities,and antimicrobial activities

Abstract

Six Rosmarinus officinalis L. essential oils (RoEOs) from Murcia (Spain) were studied using gas chromatography. Analysis of their relative and absolute composition showed 1,8-cineole, camphor, α-pinene and camphene to be the main compounds. Moreover, enantioselective gas chromatographies showed different enantiomeric ratios of camphor, limonene and borneol. The antioxidant and chelating capacities of RoEOs and their individual components were measured in an attempt to ascertain the cause of RoEO activity as a whole. All the essential oils were able to inhibit lipoxygenase activity due to bornyl acetate, camphor, terpinen-4-ol and 1,8-cineole and acetylcholinesterase activity due to 3-carene and 1,8-cineole, mainly. When the antimicrobial activities were tested against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Candida albicans, the least sensitive microorganism was P. aeruginosa and the most sensitive C. albicans. This study furthers our knowledge of six RoEOs from two chemotypes, all of which show potential for industrial applications.     

A hot‐water extract of Sanguisorba officinalis ameliorates endotoxin‐induced septic shock by inhibiting inflammasome activation

The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL‐1β secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation‐related diseases. In this study, it was found that a hot‐water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5′‐triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow‐derived macrophages. HSO was found to significantly suppress IL‐1β production in a dose‐dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO‐treated cells. The anti‐inflammatory activity of HSO was further confirmed in a mouse model of endotoxin‐induced septic shock. Oral administration of HSO reduced IL‐1β titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide‐binding domain and leucine‐rich repeat pyrin domain 3, nucleotide‐binding domain and leucine‐rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome‐mediated diseases.     

药用拟层孔菌石油醚提取物的GC-MS分析及各相提取物生物活性

通过形态学和分子生物学分析,实验菌株为药用拟层孔菌。采用不同有机溶剂提取药用拟层孔菌子实体,分别获得石油醚、氯仿、乙酸乙酯和甲醇提取物。采用GC-MS方法,分析药用拟层孔菌石油醚提取物中的化学成分,同时对不同有机溶剂提取物的生物活性进行检测。结果表明:药用拟层孔菌石油醚提取物中共鉴定出46个化合物。体外抑制肿瘤细胞活性实验表明,在100μg/m L时,不同有机溶剂提取物都表现出抑制肿瘤细胞活性。其中,石油醚提取物在50μg/m L时,其对NCI-H460和SGC-7901肿瘤细胞的抑制率分别为99.03%和82.57%。甲醇提取物在8mg/m L时,DPPH自由基清除率达93.35%。     

MicroRNA 在皮肤创伤愈合中的作用

皮肤创伤愈合过程是一个复杂而连续的过程,这一过程需要多种细胞、多种因子的参与,涉及细胞增殖、细胞分化、细胞运动、细胞黏附等多个细胞生物学过程。 MicroRNA（ miRNA）是一类高度保守的非编码RNA,它通过靶向结合信使RNA（ mRNA）并使其降解或抑制其翻译,实现转录后基因表达调控。 miRNA作为基因表达的重要调控分子,几乎参与了机体所有的生理和病理过程。除了在皮肤发育中发挥重要的作用,还参与多种皮肤病、皮肤癌和皮肤创伤愈合过程的调节。主要总结了miRNA调控皮肤创伤愈合的研究进展。     

Antimicrobial and wound healing activities of certain Sudanese medicinal plants

The emergence of drug-resistant organisms have been increasing globally; therefore, it is a burning need to find an alternative drug to get rid of the diseases caused by resistant strains. This study aims to evaluate the antimicrobial and wound healing activities of Loranthus acacia, Cassia obtusifolia and Cymbopogon proximus plants. All the plants were collected and extracted — by maceration method. Antimicrobial activities determined using standard ATCC strain for Gram-positive bacteria (Bacillus subtilis, Bacillus crew, Methicillin-resistant Staphylococcus aureus, Staphylococcus aureus) and Gram-negative bacteria (Shigella sonnnei, Salmonella Typhimurium, Salmonella typhi, Klebsiella pnuemoniae, Escherichia coli and Pseudomonas aeruginosa) following agar well diffusion method. Plants extracts were prepared as gel and investigated for in vivo wound healing activities in rats. Histological studies were performed on animals’ skin. The results showed that all tested plants have various antimicrobial and wound healing activities. Out of these plants, L. acacia exhibited the best result; it revealed a significant result for antimicrobial activities counter to all Gram-positive, Gram-negative bacteria and wound healing activities in comparing with the reference drug. Thus, it is essential to consider L. acacia as a prospective source in progress in the synthesis of a new antimicrobial drug for the treatment of infectious diseases.     

Curcumin improves wound healing by modulating collagen and decreasing reactive oxygen species

Wound healing consists of an orderly progression of events that re-establish the integrity of the damaged tissue. Several natural products have been shown to accelerate the healing process. The present investigation was undertaken to determine the role of curcumin on changes in collagen characteristics and antioxidant property during cutaneous wound healing in rats. Full-thickness excision wounds were made on the back of rat and curcumin was administered topically. The wound tissues removed on 4th, 8th and 12th day (post-wound) were used to analyse biochemical and pathological changes. Curcumin increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and type III collagen content of wound tissues. Curcumin treated wounds were found to heal much faster as indicated by improved rates of epithelialisation, wound contraction and increased tensile strength which were also confirmed by histopathological examinations. Curcumin treatment was shown to decrease the levels of lipid peroxides (LPs), while the levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), activities were significantly increased exhibiting the antioxidant properties of curcumin in accelerating wound healing. Better maturation and cross linking of collagen were observed in the curcumin treated rats, by increased stability of acid-soluble collagen, aldehyde content, shrinkage temperature and tensile strength. The results clearly substantiate the beneficial effects of the topical application of curcumin in the acceleration of wound healing and its antioxidant effect. Both the authors have contributed equally towards this paper.     

Effect of heparin on wound healing

Heparin with its ability to dissolve the fibrin clot exerts its major effect in the early stages of wound healing by depriving the fibroblasts of their scaffold. Heparin inhibits cross linking of collagen and accelerates its degradation. There is faulty orientation of the collagen fibrils in the heparinized wound. It may be concluded that heparin interferes with wound healing.     

Non-adenine based purines accelerate wound healing

Wound healing is a complex sequence of cellular and molecular processes that involves multiple cell types and biochemical mediators. Several growth factors have been identified that regulate tissue repair, including the neurotrophin nerve growth factor (NGF). As non-adenine based purines (NABPs) are known to promote cell proliferation and the release of growth factors, we investigated whether NABPs had an effect on wound healing. Full-thickness, excisional wound healing in healthy BALB/c mice was significantly accelerated by daily topical application of NABPs such as guanosine (50% closure by days 2.5–2.8). Co-treatment of wounds with guanosine plus anti-NGF reversed the guanosine-promoted acceleration of wound healing, indicating that this effect of guanosine is mediated, at least in part, by NGF. Selective inhibitors of the NGF-inducible serine/threonine protein kinase (protein kinase N), such as 6-methylmercaptopurine riboside abolished the acceleration of wound healing caused by guanosine, confirming that activation of this enzyme is required for this effect of guanosine. Treatment of genetically diabetic BKS.Cg-m+/+lepr db mice, which display impaired wound healing, with guanosine led to accelerated healing of skin wounds (25% closure by days 2.8–3.0). These results provide further confirmation that the NABP-mediated acceleration of cutaneous wound healing is mediated via an NGF-dependent mechanism. Thus, NABPs may offer an alternative and viable approach for the treatment of wounds in a clinical setting.     

In vitro anti-inflammatory and wound healing properties of Andrographis echioides and Andrographis paniculata

Andrographis echioides (L.) is an annual herbaceous plant in the family Acanthaceae. Anti-inflammatory is the property of a substance or treatment that reduces inflammation or swelling. Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. They are sometimes called "free-radical scavengers. Therefore, it is of interest to analyse the anti-inflammatory and antioxidant properties of Andrographis echioides and Andrographis paniculata. Protease inhibitor activity was done by bovine serum albumin was added to 100µl of plant sample with increase in concentrations (100-500µg/ml). Invitro antioxidant activity was done by DPPH free radical scavenging assay. 200 µL of 0.1 mM DPPH prepared in methanol was added to 100 µL of the plant extract with increase in concentration. Based on the results from the present study, it can be concluded that A.echioides is found to be a good natural antioxidant source and A. paniculata is found to be a good anti-inflammatory source. However, both the plant A.echioides and A.paniculata have these properties. Data shows that both A.echioides and A. paniculata have potential anti-inflammatory and antioxidant activity which could be due to the presence of bioactive compounds present in the plant extracts.