Topical administration of Juglans regia L. leaf extract accelerates diabetic wound healing.

BACKGROUND: Diabetic wounds are one of the most important issues in diabetic patients. It seems that Juglans regia L. leaf with antioxidant and anti-inflammatory potentials can be profitable for healing of diabetic wounds. The aim of present study was to investigate the topical administration of Juglans regia L. leaf extract in diabetic wound healing. METHODS: Seventy-five diabetic male rats were randomly divided into 5 groups (n = 15), including: untreated (Control) group, Eucerin group, 2% Juglans regia L. ointment (JRL 2%) group, 5% Juglans regia L. ointment (JRL 5%) group, and Phenytoin group as a reference drug. Sampling was performed at days 7, 14, and 21 after surgery. Evaluation tests included stereology, immunohistochemistry, molecular, and biomechanical. RESULTS: Our results showed that the wound closure rate, volumes of newly formed of epidermis and dermis, density of fibroblasts and blood vessels, collagen deposition, density of proliferation cells, expression levels of TGF-ß and VEGF genes, and biomechanical characteristics were significantly higher in extract groups compared to control and eucerin groups, however, these changes were considerable in the JRL 5% group (P < 0.05). This is while that the density of neutrophils and expression levels of TNF-α and IL-1ß genes in the extract groups, especially in the JRL 5% group, were significantly reduced compared to control and eucerin groups (P < 0.05). CONCLUSION: Topical administration of Juglans regia L. leaf extract, especially in 5% concentration, considerably accelerates diabetic wound healing.

The effects of Feijoa sellowiana fruit extract on wound healing in rats: a stereological and molecular study.

OBJECTIVE: The aim of this study was to evaluate the anti-inflammatory and wound-healing potential of Feijoa sellowiana fruit extract using stereological and molecular methods in experimental rat models. MATERIALS: Male Wistar rats were divided into four equal groups: non-treated, vehicle, Feijoa sellowiana fruit extract ointment (5% weight/weight) and the reference drug (madecassol). All animals were treated topically once per day. At the end of the study, wound samples were harvested for histological, stereological, immunohistochemical and molecular assessments to determine the in vivo healing potential and anti-inflammatory activity. A high-performance liquid chromatography (HPLC) analysis was performed for the characterisation of the phenolic acids in the extract. RESULTS: The study included 64 rats in total. Our results showed that the wound closure, volume of new epidermis and dermis, density of fibroblasts and blood vessels, and the deposition of collagen were significantly higher in both extract and madecassol groups compared to the non-treated and vehicle groups, with superior healing in the extract group. The transcript for the transforming growth factor (TGF)-ß gene was significantly upregulated in both extract and madecassol groups compared to non-treated and vehicle groups and was highest for the extract group. The density of inflammatory cells and expression levels of the cyclooxygenase (COX)-2 protein and tumour necrosis factor (TNF)-α gene in the extract and madecassol groups, especially in the extract group, were significantly reduced compared to non-treated and vehicle groups. CONCLUSION: Our results confirm that the Feijoa sellowiana fruit extract is a valuable source of antioxidant and anti-inflammatory activities and can allow for damaged tissue in wounds to recover markedly.

SDF-1α loaded bioengineered human amniotic membrane-derived scaffold transplantation in combination with hyperbaric oxygen improved diabetic wound healing.

Based on its multifactorial nature, successful treatment of diabetic wounds requires combinatorial approach. In this regard, we hypothesized that engraftment of a bioengineered micro-porous three-dimensional human amniotic membrane-scaffold (HAMS) loaded by SDF-1α (SHAMS) in combination with hyperbaric oxygen (HBO), throughout mobilization and recruitment of endothelial progenitor cells (EPCs), could accelerate wound healing in rats with type 1 diabetes mellitus. To test this hypothesis, 30 days after inducting diabetes, an ischemic wound was created in rat skin and treatments were performed for 21 days. In addition to wounded non-diabetic (ND) group, diabetic animals were randomly divided into non-treated (NT-D), HBO-treated (HBO-D), HBO-treated plus HAMS transplantation (HBO+HAMS-D) or HBO-treated in combination with SHAMS transplantation (HBO+SHAMS-D) groups. Our results on post-wounding days 7, 14 and 21 showed that the wound closure, volume of new dermis and epidermis, numerical density of basal cells of epidermis, fibroblasts and blood vessels, number of proliferating cells, deposition of collagen and biomechanical properties of healed wound were considerably higher in both HBO+HAMS-D and HBO+SHAMS-D groups in comparison to those of the NT-D and HBO-D groups, and were the highest in HBO+SHAMS-D ones. The transcripts for Vegf, bFgf, and Tgf-ß genes were significantly upregulated in all treatment regimens compared to NT-D group and were the highest for HBO+SHAMS-D group. This is while expression of Tnf-α and Il-1ß as well as cell density of neutrophil and macrophage decreased more significantly in HBO+SHAMS-D group as compared with NT-D or HBO-D groups. Overall, it was found that using both HAMS transplantation and HBO treatment has more impact on diabetic wound healing. Moreover, SDF-1α loading on HAMS could transiently improve the wound healing process, as compared with the HBO+HAMS-D group on day 7 only.

Synergistic neuroprotective effects of hyperbaric oxygen and methylprednisolone following contusive spinal cord injury in rat.

OBJECTIVE: Recent studies revealed the neuroprotective effects of hyperbaric oxygen (HBO) on spinal cord injury (SCI). Meanwhile, the use of methylprednisolone (MP) is one of the current protocols with limited effects in SCI patients. Accordingly, the aim of the present study was to investigate the effect of combined HBO and MP treatment on SCI. DESIGN: The present study was conducted on five groups of rats each as follows: Sham group (underwent laminectomy alone at T9 level vertebra); SCI group (underwent moderate contusive SCI); MP group (underwent SCI and received MP); HBO group (underwent SCI and received HBO); HBO + MP group (underwent SCI and simultaneously received MP and HBO). Blood serum and Spinal cord tissue samples were taken 48 h after SCI for analysis of serum ferric reducing antioxidant power (FRAP) and tissue malodialdehyde (MDA) levels as well as immunohistochemistry of caspase-3 and tumor necrosis factor-alpha (TNF-α). Neurological function was evaluated by the Basso-Beattie-Bresnehan (BBB) locomotion scores until the end of experiments. Additionally, histopathology was assessed at the end of the study. SETTING: Mazandaran University of Medical Sciences, Sari, Iran. RESULTS: Combination therapy with HBO and MP in the HBO + MP group significantly decreased MDA as well as increased FRAP levels compared to other treatment groups. Meanwhile, attenuated TNF-α and Caspase-3 expression could be significantly detected in the HBO + MP group. At the end of treatment, the neurological outcome was significantly improved and the extent of injured spinal tissue was also significantly reduced in the HBO + MP compared to other treatment groups. CONCLUSION: The results suggest that combined therapy with MP and HBO has synergistic effects on SCI treatment.

A review on the neuroprotective effects of hyperbaric oxygen therapy.

Hyperbaric oxygen therapy, intermittent breathing of 100% oxygen at a pressure upper than sea level, has been shown to be some of the neuroprotective effects and used therapeutically in a wide range of neurological disorders. This review summarizes current knowledge about the neuroprotective effects of hyperbaric oxygen therapy with their molecular mechanisms in different models of neurological disorders.

Effects of Juglans regia L. leaf extract supplementation on testicular functions in diabetic rats.

Testicular dysfunction is a complication of diabetes mellitus (DM). Juglans regia L. (JRL) leaf extract is a source of phenolic compounds that exhibits hypoglycemic and antioxidative properties. We investigated whether JRL leaf extract could inhibit the adverse effects of DM on oxidative stress, testis histology and testosterone hormone production. We used four groups of male rats: control group (non-diabetic) given saline, diabetic group, diabetic + JRL group that received JRL leaf extract, and JRL group (nondiabetic) that received JRL leaf extract only. To evaluate the effects of JRL leaf extract on testicular functions in diabetic animals, we evaluated histopathological and histomorphometric changes; serum testosterone; and malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. Decreased of MDA along with improved antioxidant status in the testis of diabetic rats; these abnormalities were attenuated by JRL leaf extract. We detected significantly decreased antioxidant biomarkers (GSH, SOD, CAT) and testosterone levels in the diabetic rats; these levels were normalized after JRL leaf extract administration. The MDA level and improved antioxidant status in the testis of diabetic rats was detected after JRL leaf extract administration. Our findings suggest that JRL leaf extract exerts preventive effects against diabetic dysfunction in the testis, which might be due to its antioxidant, anti-inflammatory and anti-apoptotic properties.

The green tea polyphenolic catechin epigallocatechin gallate and neuroprotection.

Epigallocatechin gallate is the most abundant composition of the tea catechins and is thought to be responsible for the majority of biological activity of green tea extracts such as antioxidant, anti-inflammatory, and antiapoptotic effects. Meanwhile, EGCG has been shown to be some of the neuroprotective effects against neural injuries and neurodegenerative diseases. This paper summarizes current knowledge on neuroprotective effects of EGCG and their molecular mechanisms responsible for the neuroprotection in various models of neurodegenerative and neural injury.

Zatariamultiflora ameliorates cisplatin-induced testicular damage via suppression of oxidative stress and apoptosis in a mice model.

OBJECTIVES: Cisplatin (CP), as an anti-neoplastic drug, causes testicular damage. Zataria multiflora Boiss (ZM), a medicinal plant, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of ZM against CP-induced testicular toxicity. MATERIALS AND METHODS: In this experimental study, thirty-two adult male mice were randomly divided into four groups. The control group received normal saline with oral gavage during 7 days; ZM group received ZM (200 mg/kg) during 7 days by gavage; CP group received CP (10 mg/kg) intraperitoneally (IP) in the 5th day of study; ZM + CP group received ZM during 7 days and CP was injected in 5th day. Sperm parameters, biochemical (MDA, GSH, and PC) levels, serum testosterone levels, and histopathological and immunohistochemical assays of testis were examined one day after the last drug treatment. RESULTS: CP treatment caused significant damage via changed sperm parameters (sperm motility, count, viability rate, and abnormalities), increased oxidative stress (increased MDA and PC levels, and decreased GSH level), histological changes (degeneration, necrosis, arrest of spermatogenesis, congestion, and decrease in thickness of the germinal epithelium, diameter of seminiferous tubules, and Johnsen's Score), decreased serum testosterone level, and increased caspase-3 immunoreactivity. ZM preserved spermatogenesis and mitigated the toxic effects of CP on the testis tissue. In addition, treatment with ZM significantly reduced caspase-3 immunoreactivity. CONCLUSION: The findings of this study suggest that ZM as a potential antioxidant compound and due to free radicals scavenging activities has a protective effect against CP-induced testicular toxicity.

Neuroprotective effects of hyperbaric oxygen (HBO) therapy on neuronal death induced by sciatic nerve transection in rat.

BACKGROUND: Recent studies shows that hyperbaric oxygen (HBO) therapy exerts some protective effects against neural injuries. The purpose of this study was to determine the neuroprotective effects of HBO following sciatic nerve transection (SNT). METHODS: Rats were randomly divided into five groups (n = 14 per group): Sham-operated (SH) group, SH + HBO group, SNT group, and SNT + pre- and SNT + post-HBO groups (100% oxygen at 2.0 atm absolute, 60 min/day for five consecutive days beginning on 1 day before and immediately after nerve transaction, respectively). Spinal cord segments of the sciatic nerve and related dorsal root ganglions (DRGs) were removed 4 weeks after nerve transection for biochemical assessment of malodialdehyde (MDA) levels in spinal cord, biochemical assessment of superoxide dismutase (SOD) and catalse (CAT) activities in spinal cord, immunohistochemistry of caspase-3, cyclooxigenase-2 (COX-2), S100beta (S100ß), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in spinal cord and DRG. RESULTS: The results revealed that MDA levels were significantly decreased in the SNT + pre-HBO group, while SOD and CAT activities were significantly increased in SNT + pre- and SNT + post-HBO treated rats. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the HBO-treated rats after nerve transection. Also, HBO significantly increased S100ß expression. CONCLUSIONS: Based on these results, we can conclude that pre- and post-HBO therapy had neuroprotective effects against sciatic nerve transection-induced degeneration.

Anti-Inflammatory and Wound-Healing Potential of Golden Chanterelle Mushroom, Cantharellus cibarius (Agaricomycetes).

The golden chanterelle mushroom, Cantharellus cibarius, is an edible mushroom with medicinal value. Given that this species has good radical scavenging activity and strong antioxidant potential and bactericidal effects, this study was designed to investigate the anti-inflammatory and wound-healing activity of C. cibarius extract in rats. For this experimental study, circular excision and linear incision wound models were used in 4 groups of male Wistar rats: nontreated, vehicle-treated, treated with C. cibarius extract ointment (2% w/w), and treated with the reference drug (Madecassol). All the animals were treated topically once a day. The circular and linear wounds were treated for 9 and 17 days, respectively. At the end of the study, samples from healing wounds were taken for histopathological assessment to determine the in vivo anti-inflammatory activity and investigate immunohistochemistry by cyclooxygenase-2 (COX-2). Significant wound-healing activity in each wound model was observed in the C. cibarius extract-treated and Madecassol-treated groups compared with the nontreated and vehicle-treated groups (P < 0.05). Histological assessment showed complete repair of the epidermal layer, increased collagen production, and a remarkable degree of neovascularization and epithelization in the extract group, which were significantly different from those in the other groups (P < 0.05). In addition, a significantly lower rate of COX-2 expression was detected in the extract group than in the nontreated and vehicle-treated groups (P < 0.0001). Therefore, the experimental data reveal that C. cibarius extract showed significant wound-healing and anti-inflammatory effects, which could be the scientific rationale for the medicinal use of the golden chanterelle mushroom in treating wounds.

Protective effects of methanolic extract of Juglans regia L. leaf on streptozotocin-induced diabetic peripheral neuropathy in rats.

BACKGROUND: Oxidative stress has a pivotal role in the pathogenesis and development of diabetic peripheral neuropathy (DPN), the most common and debilitating complications of diabetes mellitus. There is accumulating evidence that Juglans regia L. (GRL) leaf extract, a rich source of phenolic components, has hypoglycemic and antioxidative properties. This study aimed to determine the protective effects of Juglans regia L. leaf extract against streptozotocin-induced diabetic neuropathy in rat. METHODS: The DPN rat model was generated by intraperitoneal injection of a single 55 mg/kg dose of streptozotocin (STZ). A subset of the STZ-induced diabetic rats intragastically administered with GRL leaf extract (200 mg/kg/day) before or after the onset of neuropathy, whereas other diabetic rats received only isotonic saline as the same volume of GRL leaf extract. To evaluate the effects of GRL leaf extract on the diabetic neuropathy various parameters, including histopathology and immunohistochemistry of apoptotic and inflammatory factors were assessed along with nociceptive and biochemical assessments. RESULTS: Degeneration of the sciatic nerves which was detected in the STZ-diabetic rats attenuated after GRL leaf extract administration. Greater caspase-3, COX-2, and iNOS expression could be detected in the STZ-diabetic rats, which were significantly attenuated after GRL leaf extract administration. Also, attenuation of lipid peroxidation and nociceptive response along with improved antioxidant status in the sciatic nerve of diabetic rats were detected after GRL leaf extract administration. In other word, GRL leaf extract ameliorated the behavioral and structural indices of diabetic neuropathy even after the onset of neuropathy, in addition to blood sugar reduction. CONCLUSION: Our results suggest that GRL leaf extract exert preventive and curative effects against STZ-induced diabetic neuropathy in rats which might be due to its antioxidant, anti-inflammatory, and antiapoptotic properties. Protection against neuropathy.

Natural polyphenols and spinal cord injury.

Polyphenols have been shown to have some of the neuroprotective effects against neurodegenerative diseases. These effects are attributed to a variety of biological activities, including free radical scavenging/antioxidant and anti-inflammatory and anti-apoptotic activities. In this regard, many efforts have been made to study the effects of various well-known dietary polyphenols on spinal cord injury (SCI) and to explore the mechanisms behind the neuroprotective effects. The aim of this paper is to present the mechanisms of neuroprotection of natural polyphenols used in animal models of SCI.

The effect of aqueous cinnamon extract on the apoptotic process in acute myeloid leukemia HL-60 cells.

BACKGROUND: Acute promyelocytic leukemia (APL) is an acute leukemia diagnosed by translocation of chromosomes 15 and 17 [T (15,17)] and aggregation of neoplastic promyelocytes which are incapable of being converted into mature cells. Today, many tend to use medicinal herbs in studies and clinical applications for treatment of cancers. Cinnamon with scientific name "cinnamomumzelanicum" is a shrub of Laurales order, lauraceae family with cinnamomum genus. It is a medicinal shrub with anti-proliferation effect on tumor cells. This study was conducted to determine the effects of aqueous cinnamon extract on HL-60 cells as a model for APL. MATERIALS AND METHODS: In this in vitro experimental study, HL-60 cell line was cultured under the influence of cinnamon extract's concentrations of 0.01, 0.1, 1, and 2 mg/ml in with intervals of 24, 48, and 72 h. Growth inhibition and toxic effects of cinnamon extract were evaluated through tetrazolium salt reduction. The effect of this herb on the cell cycle was studied by flow cytometry. The Hoechst stain was used to detect apoptotic cell nuclei. RESULTS: Cinnamon extract inhibited the growth of HL-60 cells as correlated with concentration and time. After 72 h of treating HL-60 cells with 0.01 mg/l cinnamon extract, the growth of cells was inhibited by 90.1%. Cinnamon extract stopped the cell cycle in G1 phase and the Hoechst staining verified the apoptotic process in those cells. CONCLUSION: Considering the inhibitory property of cinnamon extract, we recommend it as a single drug or besides other medications for treating promyelocytic leukemia.

Olive oil phenols and neuroprotection.

Olive oil is a rich source of phenolic components which have a wide variety of beneficial health effects in vitro, in vivo, and clinically. The beneficial effects of olive oil phenols attributed to a variety of biological activities including free radical scavenging/antioxidant actions, anti-inflammatory effects, anti-carcinogenic properties, and anti-microbial activities. On the other hand, olive oil phenols have been shown to be some of neuroprotective effects against cerebral ischemia, spinal cord injury, Huntington's disease, Alzheimer's diseases, multiple sclerosis, Parkinson's disease, aging, and peripheral neuropathy. This paper summarizes current knowledge on the mechanisms of neuroprotective effects of olive oil phenols.