Wound Healing In Diabetes Mellitus Research Articles

The effect of 5% Curcuma xanthorrhiza extract gel on diabetic rat socket: A fibroblast analysis

Background: Predominant advanced glycation end products (AGEs) in diabetes mellitus (DM) patients lead to increased reactive oxygen species, causing oxidative stress and cell apoptosis, which hinders wound healing. Curcuma xanthorrhiza contains active compounds such as curcumin, flavonoids, and saponins, which can increase fibroblast cell production, the primary indicator of wound healing, and serve as AGE inhibitors. Purpose: This study aimed to determine the effect of 5% C. xanthorrhiza extract gel on the number of fibroblasts in diabetic Wistar rats during the healing of tooth extraction over a specific duration. Methods: The left mandibular incisor was extracted after using alloxan to induce diabetes in the rats. The socket was then treated with different compounds, including 5% C. xanthorrhiza extract gel, placebo CMC-Na, or Gengigel. A histopathological examination of the socket was conducted to assess the presence of fibroblasts on days one, three, and five after treatment. Results: The number of fibroblasts in the sockets treated with 5% C. xanthorrhiza extract gel was lower than in the Gengigel group but higher than in the placebo group (p < 0.05). Conclusion: 5% C. xanthorrhiza extract gel can increase the number of fibroblasts, thereby potentially accelerating wound healing in DM.

Genome-wide screening of m6A profiling of cutaneous wound healing in diabetic mice.

Impaired wound healing in diabetes mellitus (DM) is a major health burden on patients, their families, and society. The present study aimed to systematically profile the m6A modification landscape in cutaneous wounds in a diabetic mouse model. Diabetes was induced in mice through a single intraperitoneal injection of streptozotocin (STZ); a single intraperitoneal injection of PBS was made in control mice for comparisons. Both groups then received an 8-mm diameter, full-thickness dorsal body wound with a biopsy punch. Five days after wound surgery, western blot analysis of harvested wound tissues from both groups was used to assess the expression of m6A-related enzymes. Genome-wide profiling of m6A-tagged transcripts was performed through MeRIP-seq and RNA-seq. ALKBH5, an m6A eraser, was significantly upregulated, while METTL3, METTL14, and WTAP, m6A writers, were markedly downregulated in the diabetic wounds. Additionally, a total of 1335 m6A peaks were differentially expressed in MeRIP-seq and RNA-seq analyses, with 558 upregulated and 777 downregulated peaks. Finally, there was hypomethylated and hypermethylated differentiation at the gene and transcript levels. The present study was the first to reveal the m6A landscape in diabetic wounds in an animal model. This study, by deeply analyzing the role of m6A modifications in diabetic wound healing, provides new insights and understanding into the molecular mechanisms of diabetic wound healing. Future research could further explore how m6A modifications regulate the wound healing process, thereby offering new potential targets for the treatment of diabetic wounds.

Effect and mechanism of microRNAs on various diabetic wound local cells.

The difficulty of wound healing in diabetes mellitus has long been regarded as a thorny problem in the medical field. One of the important reasons is the abnormal function of wound-related cells. A large number of recent studies have shown that microRNA (miR), a noncoding RNA that exists in eukaryotic cells, is closely linked to the functions of various cells in diabetic wound, and ultimately affects the healing of wound. This paper establishes for the first time the connection between miR and wound healing from the cellular perspective and summarizes the effects of various miRs on one or more kinds of wound cells, including their targets and related mechanisms. The abnormal expression of miRs in the wound has certain value for the early diagnosis of diabetic wounds. Moreover, it seems that correcting miRs that are abnormal expressed in the wound or artificially adding miRs that can promote wound healing has an essential therapeutic value.

Double-network hydrogel enhanced by SS31-loaded mesoporous polydopamine nanoparticles: Symphonic collaboration of near-infrared photothermal antibacterial effect and mitochondrial maintenance for full-thickness wound healing in diabetes mellitus.

Diabetic wound healing has become a serious healthcare challenge. The high-glucose environment leads to persistent bacterial infection and mitochondrial dysfunction, resulting in chronic inflammation, abnormal vascular function, and tissue necrosis. To solve these issues, we developed a double-network hydrogel, constructed with pluronic F127 diacrylate (F127DA) and hyaluronic acid methacrylate (HAMA), and enhanced by SS31-loaded mesoporous polydopamine nanoparticles (MPDA NPs). As components, SS31, a mitochondria-targeted peptide, maintains mitochondrial function, reduces mitochondrial reactive oxygen species (ROS) and thus regulates macrophage polarization, as well as promoting cell proliferation and migration, while MPDA NPs not only scavenge ROS and exert an anti-bacterial effect by photothermal treatment under near-infrared light irradiation, but also control release of SS31 in response to ROS. This F127DA/HAMA-MPDA@SS31 (FH-M@S) hydrogel has characteristics of adhesion, superior biocompatibility and mechanical properties which can adapt to irregular wounds at different body sites and provide sustained release of MPDA@SS31 (M@S) NPs. In addition, in a diabetic rat full thickness skin defect model, the FH-M@S hydrogel promoted macrophage M2 polarization, collagen deposition, neovascularization and wound healing. Therefore, the FH-M@S hydrogel exhibits promising therapeutic potential for skin regeneration.

Is in-Shoe Microclimate a Neglected Contributor in the Pathway to Diabetic Foot Ulceration?

The identification of the key contributing factors which predispose the foot to ulceration, increasing the risk of recurrence and slow wound healing in diabetes mellitus (DM), has led to some significant research studies over the last 30 years, providing valuable insight into the mechanism leading to diabetic foot ulceration (DFU). Although, these contributory factors are similar to those identified in pressure ulceration occurring in other parts of the body (such as "bed pressure sores') where magnitude and/or duration of mechanical stress in the presence of sensory deficits are key causal factors, research investigating pressure ulceration has also included measurement of temperature and relative humidity at the interface between the skin and supporting surface. The possible influence of these parameters (in-shoe temperature and humidity) does not appear frequently in diabetic foot ulceration research. Referred to as "microclimate", this has an important role in the pathway to tissue breakdown evidenced in pressure ulcer research and may be particularly relevant in countries with warm and humid climates. As the microclimate is influential in the ulceration pathway for other body sites, its role in the DFU causal pathway justifies further investigation.

Huangbai liniment and berberine promoted wound healing in high-fat diet/Streptozotocin-induced diabetic rats.

Diabetic ulcer is a challenging complication of diabetes mellitus but current treatments cannot achieve satisfactory results. In this study, the effect of Huangbai liniment (HB) and berberine on the wound healing in high fat diet/streptozotocin injection induced diabetic rats was investigated by RNA-seq technology. HB topical treatment promoted wound healing in the diabetic patients and diabetic rats, and it affected multiple processes, of which IL-17 signalling pathway was of importance. Inhibiting IL-17a by its inhibitor or antibody remarkably facilitated wound healing and HB significantly repressed the high IL-17 expression and its downstream targets, including Cxcl1, Ccl2, Mmp3, Mmp9, G-CSF, IL1B and IL6, in diabetic wounds, promoted T-AOC, SOD activity and GSH levels; decreased the levels of nitrotyrosine and 8-OHdG; enhanced angiogenesis-related CD31, PDGF-BB and ANG1 expression; inhibited cleaved caspase-3 levels and promoted TIMP1 and TGFB1. Moreover, berberine (a major component in HB) repressed the IL-17 signalling pathway, and promoted wound healing in diabetes mellitus. This study highlights the strategy of targeting IL-17a in diabetic wounds, deepens the understanding of wound healing in diabetes mellitus in a dynamic way and reveals the characteristics of HB and berberine in promoting wound healing of type 2 diabetes mellitus.

Evaluation of the Effects of Topical Application of Chlorhexidine, Ozone, and Metronidazole on Palatal Wound Healing: A Histopathological Study.

This study aimed to evaluate the effects of chlorhexidine, metronidazole, and ozone application on the healing of palatal wounds in diabetic rats. A defect in the form of a 4 mm-diameter wound was created on the palatal mucosa of 84 adult female Wistar albino rats, which were randomly divided into 4 groups: control, chlorhexidine, metronidazole, and ozone groups. The animals were euthanized after 3, 6, and 10 days, and wound closure was histologically assessed. On day 3, polymorphonuclear leukocytes were significantly higher in the control group than in the chlorhexidine and ozone groups ( P < 0.05). Fibrosis was higher in the ozone group than in the control and chlorhexidine groups ( P < 0.05). Vascular endothelial growth factor was higher in the metronidazole and ozone groups than in the control group ( P < 0.05). On day 6, the quantity of polymorphonuclear leukocytes was higher in the control, metronidazole, and chlorhexidine groups than in the ozone group ( P < 0.05). Vascular endothelial growth factor was higher in the ozone group than in the control, chlorhexidine, and metronidazole groups ( P < 0.05). On day 10, Vascular endothelial growth factor was higher in the control, chlorhexidine, and metronidazole groups than in the ozone group ( P < 0.05). The authors concluded that the use of chlorhexidine, ozone, and metronidazole pastes resulted in enhanced wound healing, as determined histologically.The authors suggest that ozone supplementation can be an alternative therapy to chlorhexidine in impaired wound healing in diabetes mellitus.

Nicotinamide Riboside Enhances Endothelial Precursor Cell Function to Promote Refractory Wound Healing Through Mediating the Sirt1/AMPK Pathway.

Lack of vascularization is directly associated with refractory wound healing in diabetes mellitus (DM). Enrichment of endothelial precursor cells (EPCs) is a promising but challenging approach for the treatment of diabetic wounds. Herein, we investigate the action of nicotinamide riboside (NR) on EPC function for improved healing of diabetic wounds. Db/db mice that were treated with NR-supplemented food (400 mg/kg/d) for 12 weeks exhibited higher wound healing rates and angiogenesis than untreated db/db mice. In agreement with this phenotype, NR supplementation significantly increased the number of blood EPCs and bone marrow (BM)-derived EPCs of db/db mice, as well as the tube formation and adhesion functions of BM-EPCs. Furthermore, NR-supplemented BM-EPCs showed higher expression of sirtuin 1 (Sirt1), phosphorylated adenosine monophosphate–activated protein kinase (p-AMPK), and lower expression of acetylated peroxisome proliferator–activated receptor γ coactivator (PGC-1α) than BM-EPCs isolated from untreated db/db mice. Knockdown of Sirt1 in BM-EPCs significantly abolished the tube formation and adhesion function of NR as well as the expression of p-AMPK and deacetylated PGC-1a. Inhibition of AMPK abolished the NR-regulated EPC function but had no effect on Sirt1 expression, demonstrating that NR enhances EPC function through the Sirt1-AMPK pathway. Overall, this study demonstrates that the oral uptake of NR enhances the EPC function to promote diabetic wound healing, indicating that NR supplementation might be a promising strategy to prevent the progression of diabetic complications.

Bletilla striata Polysaccharide Promotes Diabetic Wound Healing Through Inhibition of the NLRP3 Inflammasome.

The aim of this study was to evaluate the therapeutic effects of Bletilla striata polysaccharide (BSP) on wound healing in diabetes mellitus (DM) and to explore the underlying mechanisms. DM mouse models were induced by high fat-diet feeding combined with low-dose streptozocin injection. To establish diabetic foot ulcer (DFU) models, DM mice were wounded on the dorsal surface. Subsequently, mice were treated with vehicle or BSP for 12 days and wound healing was monitored. The effects of BSP on the production of interleukin-1β (IL-1β), tumor necrosis factor-α, macrophages infiltration, angiogenesis, the activation of nucleotide-binding and oligomerization (NACHT) domain, leucine-rich repeat (LRR), and pyrin domain (PYD)-containing protein 3 (NLRP3) inflammasome, and insulin sensitivity in wound tissues were subsequently evaluated. Separated- and cultured- bone marrow-derived macrophages (BMDMs) and cardiac microvascular endothelial cells (CMECs) were isolated from mice and used to investigate the effects of BSP on cell viability, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation and insulin sensitivity in vitro following exposure to high glucose (HG). BSP administration accelerated diabetic wound healing, suppressed macrophage infiltration, promoted angiogenesis, suppressed NLRP3 inflammasome activation, decreased IL-1β secretion, and improved insulin sensitivity in wound tissues in DM mice. In vitro, co-treatment with BSP protected against HG-induced ROS generation, NLRP3 inflammasome activation, and IL-1β secretion in BMDMs, and improved cell viability and decreased ROS levels in CMECs. Moreover, in HG exposed BMDMs-CMECs cultures, BSP treatment suppressed NLRP3 inflammasome activation and IL-1β secretion in BMDMs, and improved cell viability and insulin sensitivity in CMECs. Furthermore, treatment with IL-1β almost completely suppressed the beneficial effects of BSP on the NLRP3 inflammasome, IL-1β secretion, and insulin sensitivity in HG-treated BMDMs-CMECs. BSP promotes DFU healing through inhibition of the HG-activated NLRP3 inflammasome.

WITHDRAWN: Endothelial progenitor cells deliver exogenous miR-126 via exosomes to accelerate wound healing in diabetes mellitus

This article has been withdrawn at the request of the author(s) and editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Involvement of miRNA203 in the proliferation of epidermal stem cells during the process of DM chronic wound healing through Wnt signal pathways

BackgroundThe biological role of miR-203 and the underlying mechanisms on the proliferation of epidermal stem cells (ESCs) have not yet been reported during the progression of chronic wound healing in diabetes mellitus. Our previous studies have observed that the expression of miR-203 showed a marked upregulation and ESC proliferation capacity was impaired in diabetes mellitus skin wounds in rats.MethodsWound models were established in normal rats and rats with type 2 diabetes. Expression level of miR-203 and the alteration of ESCs’ number and function were detected. ESCs were isolated from the back skin of fetal rats to assess the effects of glucose in vitro. An antagomir to miR-203 was used to assess its effect on ESCs. Using microarray analysis, we further identified potential target genes and signaling pathways of miR-203.ResultsWe found that high glucose significantly upregulated the expression of miR-203 and subsequently reduced the number of ESCs and impaired their proliferation capacity. Meanwhile, over-expression of miR-203 reduced the ESCs’ numbers and impaired the proliferation capacity via downregulation of the Notch and Wnt signaling pathways. Conversely, inhibition of miR-203 enhanced the proliferation capacity. Additionally, silencing miR-203 in skin of rats with type 2 diabetes accelerated wound healing and improved healing quality via the upregulation of the Notch and Wnt signaling pathways. Finally, over-expression of miR-203 downregulated genes ROCK2, MAPK8, MAPK9, and PRKCA.ConclusionOur findings demonstrated that induced expression of miR-203 by high glucose in type 2 diabetic rats decreased the number of ESCs and impaired ESC proliferation capacity via downregulating genes related to Notch and Wnt signaling pathways, resulting in a delayed wound healing.

Topical administration of mangiferin promotes healing of the wound of streptozotocin-nicotinamide-induced type-2 diabetic male rats

Purpose This study identifies the potential use of mangiferin gel to promote wound healing in diabetes mellitus (DM). Materials and methods Male rats were rendered diabetes mellitus via intraperitoneal injection of streptozotocin and nicotinamide. Following diabetes development, wound was created at the back of the neck. 1% and 2% mangiferin gel and 1% silver sulphurdiazine (SS) gel (positive control) were applied to the wound for twenty-one (21) days. Fasting blood glucose (FBG) levels were weekly monitored. At the end of the treatment, rats were sacrificed and wound was excised and subjected for histopathological and molecular biological analysis. Results No changes to serum FBG levels was noted throughout the period of mangiferin treatment. Albeit, a significant decrease in the size of the wound with increased in the skin thickness of surrounding the wound were observed. Increased expression and distribution of EGF, FGF, TGF-β, VEGF, PI3K, MMP and Nrf2 and decreased expression and distribution of TNFα and NF-κB p65 were observed in diabetic wound treated with topical mangiferin. Conclusions Mangiferin has potential to be used as an agent to promote wound healing in diabetic condition.

THE ROLE OF NITROGEN OXIDE AND NITROSATIVE STRESS IN BURN WOUND HEALING IN DIABETES MELLITUS

Relevance. The risk of developing of diabetic foot ulcers is 25% over the lifetime of patients with diabetes mellitus. Inhibition of wound healing is associated with impaired macrophage polarization, decreased bioavailability of growth factors, enhanced activation of matrix metalloproteinases, which in turn is probably associated with severity of not only oxidative stress, but also nitrosative one.&#x0D; Objective. To investigate the indices of nitrosative stress in connective tissue regeneration in the healing of burn wound in rats with simulated diabetes, compared with rats without diabetes.&#x0D; Materials and methods. Two groups of laboratory rats of the Wistar line were used: diabetes mellitus and thermal burns were simulated in the experimental group (n=24), and only burns were modelled in the control group (n=24). Diabetes mellitus was reproduced by administering of streptozotocin at a dose of 50 mg/kg to rats of the experimental group. Thermal burns with a total area of ​​18-20% of the body surface were reproduced by applying of copper plates heated in water to 100°C to the skin of rats. Animals were removed from the experiment by decapitation under thiopental anesthesia, 6 rats of each group at a time on 3, 7, 14 and 21 day of observation. Concentration of inducible NO-synthase (iNOS), 3-nitrotyrosine proteins and vascular endothelial growth factor (VEGF) were measured in tissue regenerate samples by Western-blot analysis. The content of malondialdehyde (MDA) was determined in the blood serum of rats by reaction with thiobarbituric acid and subsequent spectrophotometric analysis. The measured values ​​are expressed in arbitrary optical density units (arbitrary units, a.u.).&#x0D; Results. The expression of inducible NO-synthase (iNOS) was shown to be significantly decreased during burn wound healing in diabetes mellitus compared with controls at 7 and 14 day of burn wound healing. Thus, iNOS level was 1.24±0.05 a.u. in the control group and 0.72±0.03 a.u. in the experimental one at 7 day of observation; 0.93±0.08 a.u. and 0.32 ± 0.02 a.u., respectively, at 14 day.&#x0D; Statistically significant differences in the level of 3-nitrotyrosine compounds between the control and experimental groups were detected only at 3 day of observation: 1.0±0.05 and 0.69±0.04 a.u., respectively.&#x0D; The level of malondialdehyde (MDA) increased significantly in the experimental group from 3 to 14 day of observation, from 0.77±0.01 a.u. to 8.17±0.07 a.u., which indicates the severity of lipid peroxidation in diabetes. A statistically significant difference in MDA levels between the control and experimental groups was observed at all observation periods: from 4.13±0.09 and 0.77±0.01 a.u., respectively, at 3 day of observation to 4.18±0.09 and 3,46±0.25 a.u., respectively, at 21 day.&#x0D; A positive correlation between the level of malondialdehyde and 3-nitrotyrosine compounds (R=0.647; р&lt;0.05) in diabetes mellitus is described, while in the non-diabetic group, it was negative (R=-0.528, p&lt;0.05).&#x0D; A decrease in the level of VEGF in tissue regeneration samples in diabetes mellitus was found compared with the control group at 3, 7 and 21 days of observation, which correlated with impaired expression of iNOS (R=-0.703; p&lt;0.05) in diabetes mellitus. Thus, at 3 day of observation, VEGF level was 1.0±0.06 a.u. in the control group and 0.4±0.03 a.u. in the experimental group; on 7 day - 2.76±0.05 and 1.46±0.08 a.u., respectively; on 21day - 2.61±0.09 and 1.26±0.06 a.u., respectively.&#x0D; Conclusions. It is shown that in diabetes mellitus during healing of the burn wound, there is a local decrease in the level of iNOS expression, which leads to inhibition of NO formation and its physiological effects. Increased oxidative stress, while further reducing the bioavailability of NO through the formation of peroxynitrite. One of the important effects of NO during wound healing is the enhancement of VEGF formation. Shown reduction of NO (due to the reduced expression of iNOS) is correlated with the decrease of VEGF level in tissue regeneration in diabetes, which is one of the important factors of impaired wound healing.

Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats.

Wound healing in diabetes mellitus (DM) patients is one of the major health concerns globally. Intense pulsed light (IPL) has been widely used in cosmetic dermatology via mechanisms involving fibroblast stimulation, collagen synthesis, and dermal remodeling, which are events that also occur during the process of wound healing. This present study was aimed to evaluate the possible beneficial effect of IPL on the wound healing in diabetic rats. Diabetes was induced in Sprague-Dawley rats using streptozotocin. The rats were randomly divided into four groups: normal group, DM only group, DM rats with IPL treatment 2 weeks before wounding (DM + IPL-Pre group), and DM rats with concurrent IPL exposure and wounding (DM + IPL-Con group). The wounds were created on the dorsal skin of rats. Wound closure rate, collagen deposition, and angiogenesis were assessed. There were no significant differences in the wound closure rate and mean time to wound closure between IPL-treated diabetic rats and normal rats. By contrast, delayed wound closure and prolonged mean time to wound closure were both noticed in DM only group. Enhanced collagen deposition and angiogenesis were observed in IPL-Pre, but not IPL-Con diabetic rats, as compared with untreated DM rats. Results of this study may provide novel insight into future preventive strategies using IPL for the management of wounds in diabetic patients. Lasers Surg Med. © 2019 Wiley Periodicals, Inc.

The Effect of Topical Toman Fish (Channa micropeltes) Extract on Macrophages and Lymphocytes in Diabetes Mellitus Wound Healing

Oral administration of Toman fish extract is proven to accelerate wound healing in rat model of Diabetes Mellitus. Toman fish extract contains albumin which may elevate antioxidant level and reduce inflammation. These changes will later enhance cell proliferation and inflammatory cell activity in wound healing process. This study was aimed to determine the topical application effect of 20% toman fish extract on macrophages and lymphocytes in Diabetes Mellitus wound healing. It was an experimental research using post-test only with control group design. This study was performed on 36 diabetic male wistar rats which was comprised of negative control group without given any treatment, 20% Toman fish extract ointment group and 10% Haruan fish (Channa striata) extract ointment group. Rats were sacrificed on day 4, 8, and 14 to investigate wounded area with biopsy technique which later obtained histological preparation using Haematoxylin-Eosin staining. The preparation was then observed using microscope to count macrophages and lymphocytes number. One-Way ANOVA test demonstrated a significant difference in macrophage number on day 4 (p=0.002), day 8 (p=0.000), day 14 (p=0.000). The result of the test also indicated a significant difference in lymphocyte number on day 4 (p=0.001), day 8 (p=0.001), and day 14 (p=0.001). Furthermore, Post Hoc LSD test resulted in a significant difference (p<0.05) of macrophage and lymphocyte in day four, eight, and fourteen among all treatment groups. Toman fish extract ointment at 20% concentration for topical application may raise the number of macrophage and lymphocyte than those of negative control and 10% haruan fish extract ointment on day 4 and 8 with gradual decrease on day 14.

Prima Krim sebagai Solusi Penyembuh Luka pada Penderita Diabetes Meli

Number of patients with diabetes mellitus are very large, according to International Diabetes Federation (IDF) in 2013 reaches 382 billion people between the ages of 40-59 years. Diabetic has been characterized as a chronic wounds. The animal blood waste from a slaugther house is still untapped, containing PRP (Platelet Rich Plasma) that can accelerates heal of bone and soft tissue. PRP (Platelet Rich Plasma) was made from the cattle blood waste using centrifugation. The purpose of the study is to prove that the Prima cream can heal the wounds in diabetic patients. Animals used in this study is 20 Wistar rats. Induction of diabetes was using streptozootocin 65 mg/kg and nicotinamide 235 mg/kg. The animal were divided into 4 groups: non-diabetes given placebo (ND-), diabetes given placebo (DM-), diabetic rat given commercial drug were containing chloramphenicol base 20 mg + prednisolone 2.5 mg (DM+), and diabetes given cream PRP at 20% concentration (DM PRP). Parameters used to measure the rate of wound healing is wound size and histopathologic examination. The data were analyzed using Anova One Way at 95% significant rate. PRP DM group had a wound healing faster than ND- group, DM- and DM+. Based on histopathologic examination, such as epitelialization, basal membrane, fibroblasts, collagen tissue, and presence of inflammatory cells, the best curing reaction was showed in DM PRP. PRP 20% cream produces from cow blood waste can accelerate wound healing in diabetes mellitus.

THE EFFECT OF GIANT SNAKEHEAD(Channa micropeltes)EXTRACT ON THE NUMBER OF MACROPHAGE IN DIABETES MELITUS WOUND HEALING (Research report)

Background :Giant snakehead contains albumin and omega-6 fatty acids which play an important role in diabetes mellitus wound healing. Wounds in people with diabetes mellitus have low level of albumin, thus inhibiting the macrophage function. Objective : To prove the effect of giant snakehead extract of 16mL/Kg dose of rats’ weight toward the number of macrophage on wistar rats’ back wounds with diabetes mellitus in day 4 , 8 and 14. Method and Materials : This study applied pure experimental method with posttest-only control design. This study 36 wistar rats as sample which divided into 9 groups; group of giant snakehead extract with 16mL/Kg dose of rats’ weight, positive control group using haruan fish extract with 13.54mL/Kg dose of rats’ weight, and negative control group using BR2 feed. Result s : The test result of One-way ANOVAon day 4 (p=0.022), day 8 (p=0.251) and day 14 (0.028). The test result of Post-hoc LSD showedthat there wereno significant differences on day 4 and 14 (p>00.5) between the groups of the giant snakehead extract and haruan fish extract. There wassignificant difference (p<00.5) between groups of the giant snakehead extract and BR2 feed. Conclusion : It can be concluded that giant snakehead extract at 16 mL / kg dose administered orally may increase the number of macrophage in wistar rat (Rattusnovergicus) induced diabetes mellitus back woundon day 4 and decreased macrophage cell count onday 8 and day 14.

THE INFLUENCE OF TOMAN FISH (Channa micropeltes) EXTRACT ON THE NUMBER OF NEOVASCULAR IN DIABETES MELLITUS WOUND HEALING In Vivo Study on the Back of Male Wistar Rat (Rattus novergicus)

Background: Patients with diabetes mellitus (DM) have delayed wound healing. This happens because of the depletion of neovascular number. Neovascular plays an important role in wound healing by restoring blood flow to the wound area, so the new tissue gets enough oxygen and nutrition supply to proliferate. Toman fish (Channamicropeltes) contains albumin that can increase and decrease the number of neovascular, so it’s potentially become an alternative medicine to accelerates wound healing in DM. Purpose: The aim of this research to prove the effect of toman extract dose 16 ml/Kg BW rat orally on the number of neovascular in wound of diabetic wistar rats on the 4th,8th and 14th day. Materials and methods: This research used true experimental method with posttest only control group design. This research used 36 wistar rats which were then divided into 9 groups, toman fish extract dose 16 ml/Kg BW of rat group, haruan fish extract dose 13,54 ml/Kg BW of rat group and BR2 feed only group. Research result: The results of One Way-Anova and Post Hoc Least Significant Difference tests showed there was a significant difference between group of toman extract and group of feed only, while on group of toman extract and group of haruan extract showed there was no significant difference on 4th,8th and 14th day. The average value of toman extract-given group on 4th, 8thand 14th day were 14,75. 7,5 and 6,75 respectively. Conclusion: Toman extract has effects which are increasing the number of neovascular on 4th day and decreasing the number of neovascular on 8th and 14th day in wound healing with DM.

Herbs for Effective Treatment of Diabetes Mellitus Wounds: Medicinal Chemistry and Future Therapeutic Options.

The incidence of diabetes mellitus (DM) has increased globally. Various complications such as blindness, nephropathy leading to renal failure, neuropathy, foot ulceration, amputation, and disturbance in autonomic nervous system were reported. Although, allopathy treatment still remains the treatment of choice, there is a need to look at the easy availability, patient compliance and cheaper cost of the drugs used in day-day practice. In this regard, complementary and alternative medicine has a greater role to play. Numerous plant extracts were shown to exhibit antihyperglycemic properties. In the present review, we surfed published literature in Pubmed and google databases with regard to the herbs used for DM wound treatment. We also discuss the possible mechanism of wound healing in DM with regard to advanced glycation end products, inflammation, macrophages, non-leukocytic cells such as keratinocytes, fibroblasts and endothelial cells, matrix metalloproteinase and miRNA. The review opens the door for effective treatment of DM wounds with plant extracts and plan future treatment options.

Piper betel leaves induces wound healing activity via proliferation of fibroblasts and reducing 11β hydroxysteriod dehydrogenase-1 expression in diabetic rat

BackgroundIncreased oxidative stress and stress enzyme 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) served as the major contributing factors for delayed wound healing in diabetes mellitus (DM). Piper betel (PB) leaves are reported to possess anti-diabetic, anti-oxidant and anti-microbial properties. ObjectiveThe objective was to investigate the effectiveness of topical application of PB leaves extract on oxidative stress and 11β hydroxysteriod dehydrogenase-1 (11β HSD-1) expression in diabetic wounds. Materials and methodsA total 64 male Sprague-Dawley rats were randomly chosen. The experimental rats received a single intramuscular injection of streptozotocin (45 mg/kg). Four full thickness (6 mm) wounds were created on the dorsum of each rat. The animals were equally divided (n = 8) into four groups based on the days of treatment (i.e. days 3 and 7): Control (Ctrl), diabetic untreated (DM-Ctrl), diabetic treated with 1% silver nitrate cream (DM-SN) and diabetic treated with 50 mg/kg of P. betel leaves extract (DM-PB). The rats were sacrificed on day 3 and 7 of post wound creations. ResultsFollowing day 7 wound creation, topical application of PB extract showed significant increase in hydroxyproline content, superoxide dismutase (SOD) level and decreased malondialdehyde (MDA) level, 11β-HSD-1 enzyme expression in the diabetic wounds compared to untreated diabetic wounds. The results were supported by the observations based on histological and ultrastructural features of the wound tissue applied with PB extract. ConclusionPB leaves extract improved the delayed wound healing in diabetes mellitus by decreasing the oxidative stress markers and 11β HSD-1 expression.