Intrasite Gel Research Articles

A bitter flavonoid gum from Dorema aucheri accelerate wound healing in rats: Involvement of Bax/HSP 70 and hydroxyprolin mechanisms.

Dorema aucherigum (DAG) is a bitter flavonoid gum widely used for numerous medicinal purposes including wound recovery. The present work investigates the acute toxicity and wound-healing effects of DAG in excisional skin injury in rats. Sprague Dawley rats (24) were clustered into four groups, each rat had a full-thickness excisional dorsal neck injury (2.00cm) and addressed with 0.2mL of the following treatments for 15 days: Group A (vehicle), rats addressed with normal saline; Group B, rats received intrasite gel; C and D, rats addressed with 250 and 500mg/kg of DAG, respectively. The results revealed the absence of any toxic signs in rats who received oral dosages of 2 and 5g/kg of DAG. Wound healing was significantly accelerated following DAG treatments indicated by smaller open areas and higher wound contraction percentages compared to vehicle rats. Histological evaluation revealed higher fibroblast formation, collagen deposition, and noticeably lower inflammatory cell infiltration in granulated skin tissues of DAG-addressed rats compared to vehicle rats. DAG treatment caused significant modulation of immunohistochemical proteins (decreased Bax and increased HSP 70) and inflammatory mediators (reduced TNF-α, IL-6, and magnified IL-10), which were significantly varied compared to vehicle rats. Moreover, topical DAG treatment led to significant upregulation of the hydroxyproline (HDX) (collagen) and antioxidant content. At the same time, decreased the lipid peroxidation (MDA) levels in healed tissues obtained from DAG-treated rats. The present wound contraction by DAG might be linked with the modulatory effect of its phytochemicals (polysaccharides, flavonoids, and phenolic) on the cellular mechanisms, which justify their folkloric use and provokes further investigation as therapeutic drug additives for wound contraction.

A hydrogel based on Bletilla striata polysaccharide and hyaluronic acid topically administers tetramethylpyrazine for diabetic wound therapy

The delayed and incomplete wound healing often gives rise to the disability and mortality of diabetic patients. Conventional regimens are frequently inefficient to achieve diabetic wound recovery, and innovative alternatives are therefore needed to provide therapeutic benefits. Over the past decades, the advances in phytomedicines have revolutionized the field of wound healing and tissue regeneration. In the present study, tetramethylpyrazine (TMP), an alkaloid isolated from Ligusticum chuanxiong Hort, was applied for diabetic wound treatment. A hydrogel was developed using two biopolymers namely Bletilla striata polysaccharide (BSP) and hyaluronic acid (HA) for facilitating in situ administration of TMP on full-thickness wound in mice with streptozocin-induced diabetes. The resulting hydrogel formulation (termed TMP-BSP-HA) fulfilled inflammation attenuation, blood vessel growth, and collagen deposition. Consequently, TMP-BSP-HA significantly expedited diabetic wound healing relative to a TMP-loaded hydrogel formulation prepared by INTRASITE Gel (a commercial carboxymethylcellulose-based wound dressing). The present study demonstrates the pro-healing efficacy of TMP-BSP-HA, and provides a promising approach for diabetic wound therapy.

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2mL of 250 and 500mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-β1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

Effectiveness of stingless bee (Kelulut) honey versus conventional gel dressing in diabetic wound bed preparation: A randomized controlled trial

PurposeKelulut honey contains trehalulose and has high antioxidant content, such as phenolic and flavonoid substances, which can promote wound healing. This study evaluated the effectiveness of Kelulut honey in diabetic wound healing compared to a commercially available conventional gel dressing (Intrasite gel). MethodsA prospective, randomized, single-blinded control trial was performed on eligible diabetic patients with full-thickness cavity wounds. Patients’ demographics, size and site of wounds, and baseline routine blood investigations were recorded. The wounds were dressed every other day with Kelulut honey for the intervention group or gel for the control group. The wound size reduction and granulation tissue formation percentage were calculated every 6 days for 1 month. ResultsSeventy-one patients were randomized. After 30 days of follow-up, 62 participants were available for analysis: 30 from the control group and 32 from the treatment group. The control group had increased granulation tissue at baseline and more wounds on the lower limb and posterior trunk. Both groups showed an increasing mean and median percentage of wound epithelialization and granulation tissue over time, with significantly higher values at every timepoint in the honey group (p < 0.05). However, repeated measures analysis of variance and analysis of covariance revealed no significant interaction effect between the different treatments and time, with F (2.02, 121.28) = 0.88, p = 0.417 and F (1.60, 93.95) = 0.79, p = 0.431, respectively. ConclusionThis study revealed that Kelulut honey was comparable to and as effective as the conventional gel in treating diabetic wounds in terms of promoting epithelialization and granulation tissue formation.

A tetramethylpyrazine-loaded hyaluronic acid-based hydrogel modulates macrophage polarization for promoting wound recovery in diabetic mice

The failure of wound healing often causes lower limb disability and amputation of diabetic patients. Current strategies for diabetic wound management often fail to achieve the expected outcomes, and emerging alternatives are urgently needed. Recent advances in the identification of active compounds from traditional herbal medicines provide promising therapeutics for tissue repair and regeneration. In this study, the pro-healing effects of tetramethylpyrazine (TMP, a natural alkaloid found in Ligusticum chuanxiong Hort) for diabetic wounds were for the first time demonstrated. The cutaneous healing was mainly achieved by TMP-mediated macrophage polarization from pro-inflammatory to pro-healing phenotype. In addition, the topical administration of TMP was facilitated by the hyaluronic acid (HA) hydrogel for promoting the full-thickness wounds in the experimental diabetic mice. Consequently, TMP-loaded HA hydrogel (TMP-HA) profoundly accelerated the wound closure in comparison with TMP-loaded INTRASITE Gel (it is a commercial hydrogel), which was evident with the inflammation mitigation, the angiogenesis enhancement, and the collagen deposition. Our work reveals the macrophage-modulatory function of TMP for diabetic wound healing and demonstrates great potential of TMP-HA for clinical application.

Green Synthesis of Silver Nanoparticles from Aqueous Extract of Tinospora crispa Stems Accelerate Wound Healing in Rats.

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Application of Topical Autologous Platelet-Rich Plasma for Treatment of Pemphigus Foliaceus Wounds: A Case Report

Background: Pemphigus foliaceus (PF) includes lesions on the skin, generally without involving the mucosa. Wounds in PF arise on the outer layer of the superficial skin, but if left untreated, the wound will not heal and will multiply. Platelet-rich plasma (PRP) containing a variety of different growth factors can be used in wound care. This study was at a time to describe autologous PRP therapy in the treatment of excoriated erosional wounds in patients with pemphigus foliaceus.&#x0D; Case presentation: A woman, 35 years old, married, a housewife living in suburban, comes to the emergency department with complaints of blisters accompanied by pain in the face, body, and back which has been increasing since 1 month ago. Examination of the skin showed palpebral blisters on the eyelids of the left and right eyes. In the anterior and posterior trunk regions, proximal 1/3rd and suprapubic extremities, there are hyperpigmented erythematous macules, multiple, nummular-plaque, discrete, partially confluent, with white to brownish scales, single layer and exfoliative. In the posterior trunk region, Nikolsky's sign was positive. Laboratory evaluation showed an increase in leukocytes and neutrophils. ANA examination showed negative results and anti-ds-DNA 54.91. Management of pemphigus in the form of topical and systemic treatment. Topical management in the form of an open compress with 0.9% NaCl solution, Intrasite gel®, and closed Cutimed sorbact® for erosion and excoriation. Topical PRP was administered on the 7th day of treatment. On the 14th day after treatment with topical PRP, the patient is allowed to go home with the repair of lesions throughout the region.&#x0D; Conclusion: PRP therapy in cases of pemphigus foliaceus is very useful in improving the clinical condition of the patient.

Local Administration of Ginkgolide B Using a Hyaluronan-Based Hydrogel Improves Wound Healing in Diabetic Mice.

The delayed and incomplete healing of diabetic wounds remains a major concern of global healthcare. The complex biological processes within the diabetic wound, such as chronic inflammation, impaired blood vessel growth and immature collagen remodeling, dramatically cause the failure of current treatments. Thus, emerging therapeutic strategies are highly desirable. Ginkgolide B (GB, a natural product extracted from the leaves of Ginkgo biloba L.) has been applied in the treatment of cerebrovascular and cardiovascular disorders, which is mainly due to the anti-oxidative, anti-inflammatory and proliferative effects. In this study, the role of GB in facilitating the anti-inflammatory and pro-healing effects on diabetic wounds was for the first time confirmed using in vitro, ex vivo and in vivo experimental methods. As a consequence, GB was able to significantly achieve the activities of anti-inflammation, re-epithelialization, and pro-angiogenesis. Previously, a hydrogel has been developed using the high molecular weight hyaluronan (hyaluronic acid, HA) in our laboratory. In this study, this hydrogel was utilized in vivo for local administration of GB to the full-thickness wounds of diabetic mice. The resultant hydrogel formulation (HA-GB) resulted in the reduction of inflammation, the enhancement of re-epithelialization and angiogenesis, and the modulation of collagens from type III to type I, significantly promoting the healing outcome as compared with a commercially available wound dressing product (INTRASITE Gel). This study confirms a great therapeutic promise of HA-GB for the chronic wounds of diabetic patients.

A chlorogenic acid-loaded hyaluronic acid-based hydrogel facilitates anti-inflammatory and pro-healing effects for diabetic wounds

The impaired wound healing of diabetic patients is a major healthcare issue worldwide. Current therapeutic strategies usually fail due to the complex biological processes within diabetic wounds such as chronic inflammation, damaged blood vasculature, and immature collagen remodeling. Therefore, emerging treatments are urgently required. Chlorogenic acid (CGA, a phenolic compound found in human dietary products) has demonstrated a number of health-improving properties, including anti-oxidant, anti-inflammatory, anti-microbial, anti-diabetic, and lipid-lowing functions. In this study, the capacity of CGA for promoting diabetic wound healing was assessed using in vitro and ex vivo experimental approaches. Consequently, CGA significantly achieved the anti-inflammatory activity, re-epithelializing effect, and pro-angiogenic function. A hyaluronic acid-based hydrogel (HA, it has been previously developed in our laboratories) was subsequently used in vivo for local administration of CGA to the full-thickness wounds of diabetic mice. The resulting formulation (CGA-HA) significantly improved the healing effects relative to a commercial wound dressing (INTRASITE Gel), which was accompanied with the reduction of inflammation, enhancement of re-epithelialization and angiogenesis, and maturation of collagen remodeling. Our study confirms the potential of CGA-HA in the clinical application for diabetic wound healing.

Topical opioid use in dermatologic disease: A systematic review.

Topical opioid formulations offer a potential solution to manage pain and decrease the use of systemic opioids. Synthesis of use and efficacy of topical opioids in dermatological conditions has not been well characterized. We conducted a systematic search of the PubMed, Embase, and Cochrane databases from 1980 to February 2021. This study analyzed data from 14 articles and 263 patients on the use of topical opioids for pain related to chronic ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts. Topical opioids included in this review were topical morphine and diamorphine. Common formulations consisted of 0.2-10mg of opioid compounded with hydrogel or IntraSite gel. Topical opioids were variably effective in the use for pain control related to chronic ulcers and other dermatologic conditions. For example, the use of topical opioids appears to be effective in the reduction of pain related to pressure ulcers. Topical opioids were generally well tolerated. Insufficient data exist to adequately evaluate the efficacy and safety of topical opioid use in the context of nonpressure ulcers, burns, oral lichen planus, photodynamic therapy, and split-thickness skin grafts.

Modulation of macrophages by a paeoniflorin-loaded hyaluronic acid-based hydrogel promotes diabetic wound healing.

The impaired wound healing in diabetes is a central concern of healthcare worldwide. However, current treatments often fail due to the complexity of diabetic wounds, and thus, emerging therapeutic approaches are needed. Macrophages, a prominent immune cell in the wound, play key roles in tissue repair and regeneration. Recent evidence has demonstrated that macrophages in diabetic wounds maintain a persistent proinflammatory phenotype that causes the failure of healing. Therefore, modulation of macrophages provides great promise for wound healing in diabetic patients. In this study, the potential of paeoniflorin (PF, a chemical compound derived from the herb Paeonia lactiflora) for the transition of macrophages from M1 (proinflammatory phenotype) to M2 (anti-inflammatory/prohealing phenotype) was confirmed using ex vivo and in vivo experimental approaches. A hydrogel based on high molecular weight hyaluronic acid (HA) was developed for local administration of PF in experimental diabetic mice with a full-thickness wound. The resultant formulation (HA-PF) was able to significantly promote cutaneous healing as compared to INTRASITE Gel (a commercial hydrogel wound dressing). This outcome was accompanied by the amelioration of inflammation, the improvement of angiogenesis, and re-epithelialization, and the deposition of collagen. Our study indicates the significant potential of HA-PF for clinical translation in diabetic wound healing.

The Evaluation of 3-(2-Hydroxyphenyl)-1-Phenyl–Propenone as a Targeted Drug for Wound Healingin Sprague dawleyRats

This study designed to evaluate the effects of 3-(2-Hydroxyphenyl)-1-phenyl–propenone (HPPP) as atargeted drug on enhancement the process of wound healing in Sprague dawley (SD) rats. A skin excisionwound was dissected from posterior neck area of each rat. Group 1 received no treatment, while group2 received Intrasite gel treatment. Wounds of groups 3 and 4 were dressed with HPPP 25 and 50 mg/kg, respectively. After 10 days, histological evaluation, immunohistochemistry and biochemical analysiswere investigated.Catalase (CAT), superoxide dismutase (SOD)enzymes and malondialdehyde (MDA)levels were determined in wound homogenates.Groups 3 and 4 showed remarkably a higher rate of woundhealing process when compared with the others. The microscopic results indicated increases in fibroblasts,collagen fibers and angiogenesis. Moreover, chalcone groups showed respectively an increase and reductionin antioxidant activity, and lipid peroxidation level. There were no signs of toxicity or mortality in the acutetoxicity experiment up to 1000 mg/kg.Our data provided an evidence for the first time that HPPP couldhasten significantly the wound healing process in rats.

Morphine Versus Loperamide with Intrasite Gel in the Treatment of Painful Dermal Ulcers: A Randomized, Crossover Study

BACKGROUND: Topical morphine along with intrasite gel has been proven to be a simple and effective method to relieve pain. However, morphine is still not freely available in developing countries due to drug restrictions and stringent laws governing it. Loperamide has been reported to relieve pain caused by stomatitis effectively when given topically. Loperamide, being an mu receptor agonist with no systemic absorption, can serve a dual purpose here. Also loperamide being freely available as an over-the-counter drug can be a surrogate drug for topical application. OBJECTIVES: The primary aim was to compare the efficacy of loperamide and morphine in treating pain when applied topically along with intrasite gel. STUDY DESIGN: Adult patients with healthy wounds with pain on Numeric Rating Scale (NRS-11) greater than 5 with no systemic comorbid illness were divided randomly into 2 groups – group morphine or group loperamide – for 24 hours followed by a 1-day washout and crossover in the other group for 24 hours. Pain was assessed once every day. SETTING: Medical college and hospital. METHODS: The parameters assessed included: (1) characteristics of the ulcer; (2) pain was assessed by NRS-11 at 12-hour intervals for a period of 72 hours; and (3) patient satisfaction. Statistical analysis used repeated measures analysis of variance to measure change in mean NRS-11 within each group. Analysis of covariance was used to compare the mean change in NRS-11 in the 2 groups. RESULTS: Morphine and loperamide were equivocal in pain relief after 12 and 24 hours (P = 0.400 and P = 0.753); however, the patient satisfaction scores were better in the morphine group. LIMITATIONS: The earlier studies performed used injectable forms of morphine, for the sake of comparison, we used powdered morphine and powdered Loperamide diluted with saline. Confounding variables include ulcer size and aetiology, which can be a source of bias. The ulcer size was not standardized due to the paucity of sample to study. Equianalgesic doses of loperamide and morphine could not be found even after an extensive literature search. The loperamide dose used in our case was equal to the dose used orally since the same dose appears effective across a range of oral opioid analgesics. The morphine dose was standardized as 10 mg based on a mixture previously used to treat pain due to epidermolysis bullosa. CONCLUSIONS: Topical loperamide can be an efficacious and novel intervention to treat painful ulcers while avoiding systemic effects. KEY WORDS: Loperamide, morphine, painful ulcer

A retrospective analysis of Drawtex hydroconductive dressing compared with standard silver sulphadiazine mixed with a hydrogel, in an adult provincial tertiary burn centre in the Western Cape Province, South Africa

Background . The standard of care for slough and exudative burn wounds in our unit is a combination of Intrasite gel and Flamazine. Objective. To analyse our standard of care method in comparison with Drawtex hydroconductive dressings. Methods. A retrospective record review was done of a 3-month period in 2016 during which we had a large amount of the hydroconductive dressing available. The inclusion criteria were the use of Drawtex on the wounds of patients who were not operated on within 48 hours of dressing application, where there was another wound of the same depth on an opposite limb, on which a control dressing was used. The exclusion criteria were skin-grafted areas and patients who had had operations within 48 hours. Results . There were 100 patients with acute burn wounds admitted in the period from February to April 2016. A limited quantity of Drawtex had been donated. The total number of patients with complete clinical documentation available was 39. Of these, 36 met the inclusion criteria, with 48 wounds treated. Eleven patients had wounds that could be assessed with controls, but only 8 had adequate follow-up data for study. Of the eligible 36 patients, 28 were treated with Drawtex without the use of control areas. Eight patients were found who had good control areas for comparison. Drawtex was clearly better than control areas by such a large margin that during the application period in 2016, the control treatment areas were abandoned for Drawtex, hence the low number of controls. Drawtex was also found to be less expensive when a cost comparison was done. Conclusion. The study found that Drawtex delivered better results than the control method, and was more cost-effective than our standard operating procedure. Therefore, we recommend Drawtex for burns with moderate to highly exuding wounds with slough.

In vivo evaluation of wound healing improvement of a new Schiff base derived bromine compound (CNBP) in rats

BackgroundThe effect of delivered bromine vapor and also bromine substitutions are shown to play an important role in anti-inflammatory activity. The present study encompasses a broad in vivo study to size up healing activity of a novel dibromide substituted Schiff based compound against cutaneous wound model in Sprague Dawley (SD) rats. Methodology/principal findings2, 2′-[1, 2-Cyclohexanediylbis(nitriloethylidyne)] bis[4-bromophenol], CNBP, is synthesized through a Schiff base reaction applying the related ketone and diamine as the initiators. Four groups of six in each male SD rats are divided as negative group which are treated with gum acacia, positive control animals which are treated with topical dosage of Intrasite gel, and testing groups treated with low (10 mg/kg) and high (20 mg/kg) doses of CNBP. The excisional wounds are created on the posterior neck area of each group and the wound closure percentage was measured in the two separated days of the experiment. Moreover, the histopathological evaluation and determination of activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), and malondialdehyde (MDA) of the skin sections are performed. Furthermore, the immunohistochemistry consists of the evaluation of Hsp70 and BAX proteins. Conclusions/significanceThe wound closure percentage showed a significant increase in high dose CNBP-treated group compared to the negative control. Histopathological evaluation of the skin sections showed that granulation tissue contained more proliferating fibroblast, collagen deposition, angiogenesis, and also less inflammatory cells in the high dose CNBP-treated group compared to the normal rats. In the treated groups with CNBP, SOD, CAT, and GPx activities were found significantly higher, however, the MDA level was shown to be lower (*P < 0.05; **P < 0.01; ***P < 0.001) than the negative control. At the molecular level, CNBP (20 mg/ml, HD) improved wound-healing process via down and up regulation of Bax and Hsp70 protein, respectively at the wound site.

Effect of Rhus coriaria extract on wound healing potential in Sprague Dawley rats

Background and objective: Rhus coriaria, a well-known spice grown in the Kurdistan region of Iraq, commonly known in the Middle East Region by (Sumac), is reported to enclose many medical benefits. This study assessed the effects of topical application of Rhus coriaria extract on the rate of wound closure, the Hydroxyproline (HXP) and Nitric Oxide (NO) levels were measured using the healed skin tissue homogenate the elemental composition of the plant was screened. Methods: Adult male Sprague Dawley rats were topically treated with 0.2 mL of the vehicle (gum accacia), Intrasite gel (positive control), 100 and 200 mg/kg of Rhus coriaria extract. Results: Wounds dressed with the extract and Intrasite gel healed significantly earlier than those with the vehicle. The high content of HXP and NO proves that the effect of Rhus coriaria extract on an excision wound model was significantly higher than that of the vehicle itself. The highest mineral contents were in Potassium, Calcium, Phosphorus, Magnesium and the extract was rich in energy content. Conclusion: The current study concluded that Rhus coriaria showed high potential in wound healing activity.

In vivo Assessment of Antioxidant and Wound Healing Improvement of a New Schiff Base Derived Co (II) Complex in Rats.

Co (II) complex (CMLA) was investigated to evaluate the rate of wound healing in rats. Animals were placed into four groups: gum acacia, Intrasite gel, 10 and 20 mg/ml of CMLA. Wounds were made on the dorsal neck area, then treated with Intrasite gel or CMLA; both of these treatments led to faster healing than with gum acacia. Histology of the wounds dressed with CMLA or Intrasite gel displayed a smaller scar width, required less time to heal and showed more collagen staining and fewer inflammatory cells in comparison to wounds dressed with the vehicle. Immunohistochemistry for Hsp70 and TGF-β showed greater staining intensity in the treated groups compared to the vehicle group. Bax staining was less intense in treated groups compared to the vehicle group, suggesting that CMLA and Intrasite gel provoked apoptosis, responsible for the development of granulation tissue into a scar. CD31 protein analysis showed that the treated groups enhanced angiogenesis and increased vascularization compared to the control group. Furthermore, a significant increase in the levels of GPx and SOD and a decrease in MDA were also observed in the treated groups. This results suggest that CMLA is a potentially promising agent for the wounds treatment.

Curcuma purpurascens BI. rhizome accelerates rat excisional wound healing: involvement of Hsp70/Bax proteins, antioxidant defense, and angiogenesis activity.

PurposeCurcuma purpurascens BI. is a member of Zingiberaceae family. The purpose of this study is to investigate the wound healing properties of hexane extract of C. purpurascens rhizome (HECP) against excisional wound healing in rats.Materials and methodsTwenty four rats were randomly divided into 4 groups: A) negative control (blank placebo, acacia gum), B) low dose of HECP, C) high dose of HECP, and D) positive control, with 6 rats in each group. Full-thickness incisions (approximately 2.00 cm) were made on the neck area of each rat. Groups 1–4 were treated two-times a day for 20 days with blank placebo, HECP (100 mg/kg), HECP (200 mg/kg), and intrasite gel as a positive control, respectively. After 20 days, hematoxylin and eosin and Masson’s trichrome stainings were employed to investigate the histopathological alterations. Protein expressions of Bax and Hsp70 were examined in the wound tissues using immunohistochemistry analysis. In addition, levels of enzymatic antioxidants and malondialdehyde representing lipid peroxidation were measured in wound tissue homogenates.ResultsMacroscopic evaluation of wounds showed conspicuous elevation in wound contraction after topical administration of HECP at both doses. Moreover, histopathological analysis revealed noteworthy reduction in the scar width correlated with the enhanced collagen content and fibroblast cells, accompanied by a reduction of inflammatory cells in the granulation tissues. At the molecular level, HECP facilitates wound-healing process by downregulating Bax and upregulating Hsp70 protein at the wound site. The formation of new blood vessel was observed in Masson’s trichrome staining of wounds treated with HECP (100 and 200 mg/kg). In addition, HECP administration caused a significant surge in enzymatic antioxidant activities and a decline in lipid peroxidation.ConclusionThese findings suggested that HECP accelerated wound-healing process in rats via antioxidant activity, angiogenesis effect and anti-inflammatory responses involving Hsp70/Bax.

Effect of Clausena excavata Burm. f. (Rutaceae) leaf extract on wound healing and antioxidant activity in rats.

Clausena excavata is a well-known plant used in folkloric medicine for the treatment of different ailments. This study aimed to determine the in vitro cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT (keratocyte) and Vero cell lines were used for evaluation of the in vitro cytotoxic effects, while the in vivo wound healing and antioxidant activities were determined in skin wounds inflicted on rats. Twenty adult male Sprague-Dawley rats were divided into five groups of four animals each. Approximately 3.14 cm2 excisional wound was inflicted on the nape of each rat following anesthesia. The treatment groups received topical application of MECE at 50 mg/mL (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD [high dose]), while the negative control group was treated with gum acacia in normal saline and the positive control group with intrasite gel. Wound contraction was evaluated on days 5, 10, and 15 after wound infliction, and tissue from wound area was collected at day 15 post-wound infliction for antioxidant enzyme evaluation and histopathological analyses. Generally, Vero cells were more resistant to the cytotoxic effects of the solvent extracts as compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C. excavata were toxic to HaCaT cells at 200 and 400 µg/mL, but the same concentrations showed higher (P<0.05) viability in Vero cells. There was significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound infliction in all the treatment groups than in the control groups. Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05) lesser inflammatory cell proliferation, degeneration, and distribution of granulation tissue than other groups. Similarly, the degree of collagen maturation, angiogenesis, and collagen distribution were significantly (P<0.05) lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite treatment groups showed a significantly (P<0.05) higher number of VEGF-positive and TGF-β1-positive cells in the skin wound than the control groups. The activities of superoxide dismutase and catalase were significantly (P<0.01) higher in the MECE-HD and intrasite treatment groups than in the other groups. Lipid peroxidase activity of the treated groups was significantly (P<0.01) lower than that in the control group. The study showed that MECE is a potent wound healing agent through anti-inflammatory and antioxidant effects that enhanced the rate of wound contraction, re-epithelialization, and collagen deposition. The effect of MECE is suggested to be due to its high polyphenolic compound content.