Neurological recovery and neurogenesis by curcumin sustained-release system cross-linked with an acellular spinal cord scaffold in rat spinal cord injury: Targeting NLRP3 inflammasome pathway.

In the context of treating spinal cord injury (SCI), the modulation of inflammatory responses, and the creation of a suitable region for tissue regeneration may present a promising approach. This study aimed to evaluate the effects of curcumin (Cur)-loaded bovine serum albumin nanoparticles (Cur-BSA NPs) cross-linked with an acellular spinal cord scaffold (ASCS) on the functional recovery in a rat model of SCI. We developed an ASCS using chemical and physical methods. Cur-BSA, and blank (B-BSA) NPs were fabricated and cross-linked with ASCS via EDC-NHS, resulting in the production of Cur-ASCS and B-ASCS. We assessed the properties of scaffolds and NPs as well as their cross-links. Finally, using a male rat hemisection model of SCI, we investigated the consequences of the resulting scaffolds. The inflammatory markers, neuroregeneration, and functional recovery were evaluated. Our results showed that Cur was efficiently entrapped at the rate of 42% ± 1.3 in the NPs. Compared to B-ASCS, Cur-ASCS showed greater effectiveness in the promotion of motor recovery. The implantation of both scaffolds could increase the migration of neural stem cells (Nestin- and GFAP-positive cells) following SCI with the superiority of Cur-ASCS. Cur-ASCS was successful to regulate the gene expression and protein levels of NLRP3, ASC, and Casp1in the spinal cord lesion. Our results indicate that using ASCS can lead to the entrance of cells into the scaffold and promote neurogenesis. However, Cur-ASCS had greater effects in terms of inflammation relief and enhanced neurogenesis.

The Radioprotective Effect of Combination of Melatonin and Metformin on Rat Duodenum Damage Induced by Ionizing Radiation: A Histological Study.

BACKGROUND: Radiation toxicity is one of the major concerns for patients with gastrointestinal cancers that undergo radiotherapy. Duodenum is one of the most radiosensitive parts of gastrointestinal system that may be exposed to a high dose of radiation during radiotherapy for some cancers. The development or identification of appropriate radioprotectors with less toxicity is an interesting aim in radiobiology for clinical radiotherapy applications. In the present study, we aimed to evaluate the radioprotective effect of melatonin and metformin combination in rat's duodenum. In addition, we compared our results with the radioprotective effect of melatonin, when administered alone. MATERIALS AND METHODS: Thirty male rats were divided into six groups: control, melatonin treatment, melatonin plus metformin treatment, whole-body irradiation, irradiation with melatonin treatment, and irradiation with melatonin plus metformin treatment. Irradiation was performed with 10 Gy cobalt-60 gamma rays, while 100 mg/kg of melatonin and metformin were administered 24 h before to 72 h after irradiation. After 3.5 days, their duodenum tissues were removed for histopathological evaluation. RESULTS: Irradiation of rats led to mild-to-moderate mucositis signs, infiltration of inflammatory cells, necrosis, and damage to Brunner's glands and reduction of goblet cells. Melatonin was able to alleviate these damages, while melatonin plus metformin could reduce some radiation toxicity signs. CONCLUSION: Administration of melatonin plus metformin could reduce mucositis in duodenum. However, the administration of melatonin is more effective for mitigation of duodenal injury compared with melatonin plus metformin.

Trachyspermum ammi (L.) Sprague, superb essential oil and its major components on peptic ulcers: in vivo combined in silico studies.

BACKGROUND: Trachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on. OBJECTIVES: The present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats. METHODS: Primarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase. RESULTS: Analysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase. CONCLUSIONS: The findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent. Graphical abstract.

Efficacy of topical application of standardized extract of Tragopogon graminifolius in the healing process of experimental burn wounds.

Tragopogon graminifolius DC. is a perennial plant from the family Asteraceae which grows in West parts of Iran. Several biological activities like antimicrobial, antioxidant and anti-inflammatory effects are reported for the plant. The aim of this study was to assess the wound healing activity of standardized extract from T. graminifolius (TG) aerial parts. Topical standardized TG extract with 5% and 10% concentrations in eucerine base was assessed for its healing properties on second degree burn in rats during a 14-day period. Biomarkers of oxidative damage including total antioxidant power, lipid peroxidation and total thiol molecules of the skin tissue samples were also evaluated. Results showed that 10%TG had the best efficacy with 80 ±â€¯3% wound closure and tissue repair in comparison to negative control (p < 0.05). Significant reduction of tissue oxidative stress biomarkers was also observed. Histological analyses confirmed wound healing activity of TG extract, as well. Considering the antioxidative stress and anti-inflammatory activities of TG, explained by the high content of phenolic compounds of the plant, standardized TG extract could be considered as a natural remedy for the treatment of burn wounds. Further clinical studies are suggested to confirm the effectiveness of TG as a wound healing agent.

Evaluation of phytochemicals, antioxidant and burn wound healing activities of Cucurbita moschata Duchesne fruit peel.

OBJECTIVES: Cucurbita moschata Duchesne (pumpkin) is a well-known plant with several pharmacological effects. The aim of the present study was to assess burn wound healing activity of C. moschata peel extract (CE). Also, standardized CE was assessed for antioxidant activity and antibacterial effects against major pathogens of burns. MATERIALS AND METHODS: Healing properties of topical preparation of 10% and 20% concentrations of CE were assessed on second degree burn in rats during a 14-day period as well as histological studies, total antioxidant power, lipid peroxidation and total thiol content of skin tissue samples. RESULTS: Radical scavenging IC50 and ferric-reducing antioxidant power value were 4.015±0.20 mg/ml and 142.63±2.65 mmol Fe2+/g, respectively. Total mucilage content was 13.8%. The optimal results were obtained by 20% CE that showed 90.80±5.86 % wound closure and tissue repair as well as significant reduction of tissue oxidative stress biomarkers. Histological analyses confirmed wound healing activity of pumpkin peel extract. CONCLUSION: Considering the high mucilage content of the plant, providing a moist environment for wound, C. moschata peel extract could be a natural remedy for treatment of burns. Further clinical studies are suggested to confirm C. moschata peel extract as a wound healing agent.

Evaluation of the Wound Healing Activity of a Traditional Compound Herbal Product Using Rat Excision Wound Model.

Iranian Traditional Medicine (ITM) manuscripts contain prescriptions that have long been used for healing of wounds. The present study evaluates the healing effect of a poly herbal paste (PHP), retrieved from ITM sources, containing Aloe vera, Commiphora myrrha and Boswellia carteri using rat excision wound model. Excision wounds were induced in six groups consisting of six rats each. Group 1 received no treatment, while groups 2 and 6 received tetracycline ointment, Alpha ointment, PHP 40%, PHP 10% and paste base every day, respectively. The percentage of wound contraction on days 2, 7, 14 and 21 and histopathology parameters of healed wounds on 14th and 21st days were evaluated. Moreover, antioxidant activity of PHP was evaluated using DPPH method. There was a significant improvement in wound healing in PHP 10% group on the 7th day of the treatment (p<0.05). Moreover, the healing effect of PHP 10% was significantly greater than the control, tetracycline and paste base groups on the 2nd, 14th and 21st days (p<0.05). On day 14, PHP 40% showed significant healing effect compared to the control, tetracycline and paste base groups (p<0.05). Fewer inflammatory cells were observed in PHP 10%-treated animals and this group demonstrated better re-epithelialization with remarkable neovascularization. Besides, the PHP 10% formulation exhibited antioxidant activity. In vivo and histopathologic examinations showed considerable wound healing in PHP 10% group. This finding could probably be due to the antioxidant, anti-inflammatory and antimicrobial activities of phytoconstituents of A. vera, B. carteri and C. myrrha.

The Neuroprotective Effects of Flaxseed Oil Supplementation on Functional Motor Recovery in a Model of Ischemic Brain Stroke: Upregulation of BDNF and GDNF.

Cerebral ischemic stroke is a common leading cause of disability. Flaxseed is a richest plant-based source of antioxidants. In this study, the effects of flaxseed oil (FSO) pretreatment on functional motor recovery and gene expression and protein content of neurotrophic factors in motor cortex area in rat model of brain ischemia/reperfusion (I/R) were assessed. Transient middle cerebral artery occlusion (tMCAo) in rats was used as model brain I/R. Rats (6 in each group) were randomly divided into four groups of Control (Co+normal saline [NS]), Sham (Sh+NS), tMCAo+NS and tMCAo+FSO. After three weeks of pretreatment with vehicle or FSO (0.2 ml~800 mg/kg body weight), the rats were operated in sham and ischemic groups. Ischemia was induced for 1 h and then reperfused. After 24 h of reperfusion, neurological examination was performed, and animals were sacrificed, and their brains were used for molecular and histopathological studies. FSO significantly improved the functional motor recovery compared with tMCAo+NS group (P<0.05). A significant reduction in brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) mRNAs and protein levels were observed in the tMCAo+NS group compared with Co+NS and Sh+NS group (P<0.05). A significant increase of BDNF and GDNF mRNAs and proteins was recorded in the tMCAo+FSO group compared with Co+NS, Sh+NS and tMCAO+NS groups (P<0.05). The results of the current study demonstrated that pretreatment with FSO had neuroprotective effects on motor cortex area following cerebral ischemic stroke by increasing the neurotrophic factors (BDNF, GDNF).

Transforming growth factor-ß (TGF-ß) activation in cutaneous wounds after topical application of aloe vera gel.

Aloe vera is a medicinal plant used to treat various skin diseases. The effects of using aloe vera gel on the healing process were investigated by microscopic methods, cell counting, and TGF-ß gene expression in the wound bed. Sixty Wistar rats weighing 200-250 g were placed under anesthesia in sterile conditions. A square 1.5 cm × 1.5 cm wound was made on the back of the neck. The rats were divided into control and 2 experimental groups. Additionally, the control and experimental groups were separated into 3 subgroups corresponding to 4, 7, and 14 days of study. In the first experimental group, aloe vera was used twice on the wound. The second experimental group received aloe vera overtreatment once on the wound. The positive control group received daily application of 1% phenytoein cream following surgical wound creation. The control group did not receive any treatment. This tissue was examined using histological staining (H&E) and Masson's Trichrome. Wound surface and wound healing were evaluated separately. TGF-ß gene expression was analyzed by RT-PCR. Results showed that fibroblasts in both experimental groups were significantly increased, thereby acceleration wound healing. Application of aloe vera gel will increase TGF-ß gene expression, ultimately accelerating the wound healing process.

A Wound Healing Formulation Based on Iranian Traditional Medicine and Its HPTLC Fingerprint.

Herbal therapy was the common treatment prescribed by Iranian physicians for wound healing. "Zemad" was the most ancient pharmaceutical dosage form used in Iranian Traditional Medicine (ITM) for skin diseases. In the present research, formulation of a traditionally used Poly Herbal Paste (PHP) for wound healing was performed. Moreover, the fingerprint of the product was prepared by HPTLC method for identification and quality assessment of the formulation. 3.33 % of each plant materials containing Aloe vera, Boswellia carteri and Commiphora myrrha were used in a hydrophilic base. The physical stability and rheological behavior of the formulation was evaluated. Moreover, microbiological tests was performed. Methanol fraction of A. vera, C. myrrha and B. carterri were used as standard materials in HPTLC method. Stability and rheological behavior evaluations as well as microbiological tests showed that the prepared formulation was stable towards physical changes with no growth of pathogenic microorganisms and suitable for topical application. HPTLC fingerprinting of PHP confirmed the presence of compounds corresponding to the plants used in the formula. Regarding to the antioxidant, anti-inflammatory and antimicrobial effects of the constituents of PHP, the product could be an appropriate candidate for wound healing with respect to its traditional use in ITM. In addition, HPTLC fingerprinting could be used as an applicable method for quality control assessment of the prepared formulation.

BDNF modifies hippocampal KCC2 and NKCC1 expression in a temporal lobe epilepsy model.

Excitatory GABA actions, induced by altered expression of chloride transporters (KCC2/NKCC1), can contribute to seizure generation in temporal lobe epilepsy. In the present study, we evaluated whether BDNF administration can affect KCC2/NKCC1 expression, ictogenesis and behavioral alterations in this paradigm. Status epilepticus was induced in male rats with pilocarpine, followed by a treatment of either a single high dose or multiple injections of BDNF during the latent phase of temporal lobe epilepsy. Chloride transporters expression, spontaneous recurrent seizures, and hyperexcitability post-seizural behaviors were evaluated after treatment. NKCC1 protein expression was markedly upregulated, whereas that of KCC2 was significantly downregulated in epileptic hippocampi compared to intact controls. Application of BDNF (both single high dose and multiple injections) increased KCC2 expression in epileptic hippocampi, while NKCC1 expression was downregulated exclusively by the single high dose injection of BDNF. Development of spontaneous recurrent seizures was delayed but not prevented by the treatment, and hyperexcitability behaviors were ameliorated for a short period of time. To prevent GABA-A mediated depolarization and design appropriate treatment strategies for temporal lobe epilepsy, chloride transporters can be considered as a target. Future studies are warranted to investigate any possible therapeutic effects of BDNF via altering chloride transporters expression.

Amelioration by chicory seed extract of diabetes- and oleic acid-induced non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) via modulation of PPARα and SREBP-1.

We evaluated the effect of chicory (Cichorium intybus L.) seed extract (CI) on hepatic steatosis caused by early and late stage diabetes in rats (in vivo), and induced in HepG2 cells (in vitro) by BSA-oleic acid complex (OA). Different dosages of CI (1.25, 2.5 and 5 mg/ml) were applied along with OA (1 mM) to HepG2 cells, simultaneously and non-simultaneously; and without OA to ordinary non-steatotic cells. Cellular lipid accumulation and glycerol release, and hepatic triglyceride (TG) content were measured. The expression levels of sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptor alpha (PPARα) were determined. Liver samples were stained with hematoxylin and eosin (H&E). Significant histological damage (steatosis-inflammation-fibrosis) to the cells and tissues and down-regulation of SREBP-1c and PPARα genes that followed steatosis induction were prevented by CI in simultaneous treatment. In non-simultaneous treatment, CI up-regulated the expression of both genes and restored the normal levels of the corresponding proteins; with a greater stimulating effect on PPARα, CI acted as a PPARα agonist. CI released glycerol from HepG2 cells, and targeted the first and the second hit phases of hepatic steatosis. A preliminary attempt to characterize CI showed caffeic acid, chlorogenic acid, and chicoric acid, among the constituents.

Pharmacological and histological effects of Centaurea bruguierana ssp. belangerana on indomethacin-induced peptic ulcer in rats.

The species Centaurea bruguierana (DC.) Hand.-Mazz. ssp. belangerana (DC.) Bornm. (CBB) (Asteraceae), known as "Baad-Avard" in Borazjan, Bushehr Province, southern Iran, is used in folk medicine as a hypoglycemic herb in diabetes and as a remedy for peptic ulcer disorders. Total 80% EtOH extract and petroleum ether, CHCl(3), EtOAc, n-BuOH, and remaining fractions obtained by solvent-solvent fractionation of dried aerial flowering parts of the plant were investigated for anti-ulcer activity against indomethacin-induced ulcerogenesis in rats. Anti-ulcer activity was evaluated by measuring the ulcer index (UI) and ulcer inhibition. The UI was significantly reduced in all treated animals. A dramatic decrease in the UI was observed following the administration of total extract (100 mg/kg, p < 0.001) and CHCl(3) fraction (42 mg/kg, ***p < 0.001) in comparison with the control group. The percentage ulcer inhibition with total extract at a dose of 100 mg/kg (97.66%) and CHCl(3) fraction at a dose of 42 mg/kg (96.96%) was found to be higher (p < 0.001) than the reference group (cimetidine 100 mg/kg) (87.08%). The pharmacological and histological results of the present study proved that the aerial flowering parts of CBB possess preventive activity against peptic ulcer, supporting the traditional assertion in southern Iranian folk medicine.