Effects In Rat Model Research Articles

Aqueous extract of Terminalia arjuna bark attenuates blood brain barrier disruption in rat model of transient focal cerebral ischemia

BackgroundTerminalia arjuna (TA) is a widely used medicinal plant in Indian traditional medicinal system. In the Ayurvedic system of medicine it is used as a cardiotonic and also well documented in experimental studies for its efficacy in various cardiac ailments. Few recent studies have reported its neuroprotective effects in rat model of cerebral ischemia. However, the effect of TA on cerebral ischemia induced Blood brain barrier (BBB) damage is still unclear. PurposeThe present study is aimed to evaluate the ameliorative effect of aqueous extract of Terminalia arjuna (aeTA) against transient focal cerebral ischemia induced BBB damage. Study designAdult male Sprague-dawley rats (270–300g) were randomly divided into three groups: Sham, Lesion (Middle cerebral artery occlusion for 2 hours) and aeTA pre-treatment at a dose of 500 mg /kg body weight/day orally for 15 days prior to MCAo. Materials and MethodsAfter 24 h of ischemic-reperfusion injury, the rats were assessed for behavioral deficits by Modified neurological severity scoring (mNSS), infarct measurement by Triphenyl tetrazolium chloride (TTC) staining, BBB integrity by Evans blue (EB) staining, protein and mRNA expressions of TJ proteins (Claudin5 & Occludin), MMPs (MMP2 & MMP9) and TIMPs (TIMP1 & TIMP2) through western blot analysis and real time PCR. ResultsThe pre-treatment with aeTA for 15 days exhibited significant improvement in neurological outcome and reduced infarct volume compared with the MCAo rats. The aeTA treatment also reduced the BBB damage which was confirmed through decreased EB extravasations, significant reduction in protein levels of MMPs (MMP2 &MMP9) and maintaining the protein levels of tight junction proteins. We also found that aeTA treatment downregulated the mRNA levels of MMPs and upregulated mRNA expression levels of TIMPs and tight junction proteins (Claudin5 & Occludin). ConclusionThese results demonstrate the neuroprotective property of aeTA treatment by reducing the MMPs mediated BBB damage after focal cerebral ischemia.

VEGF165 gene-modified human umbilical cord blood mesenchymal stem cells protect against acute liver failure in rats.

Human umbilical cord blood mesenchymal stem cells (HUCB-MSCs) can exert a protective effect in rat models of acute liver failure (ALF). Vascular endothelial growth factor 165 (VEGF165 ) is the predominant VEGF isoform and possesses a strong pro-angiogenic function. In the present study, HUCB-MSC served as the gene delivery vehicle for the VEGF165 gene, and we explored the therapeutic effects of this system on ALF. HUCB-MSCs were infected with an adenovirus expressing green fluorescent protein (GFP)-VEFG fusion protein (Ad-VEGF165 ) to overexpress VEGF165 or an adenovirus expressing GFP (Ad-GFP) as control. The control and modified HUCB-MSCs were then transplanted into ALF model rats. Liver function and liver pathological changes were assessed by biochemical tests and liver histology. Immunohistochemistry was carried out to determine the expression of, CD34, Ki67 and VEGF. VEGF165 overexpression enhanced the multipotency of HUCB-MSCs and promoted the homing and colonization of HUCB-MSC in the liver tissues of ALF rats. Furthermore, although HUCB-MSC transplantation ameliorated liver damage and promoted liver regeneration to some extent in ALF rats, Ad-VEGF165 -HUCB-MSC transplantation showed stronger therapeutic effects on ALF. In summary, transplantation of VEGF165 -modified HUCB-MSCs exert stronger therapeutic effects on ALF than HUCB-MSCs. The present study provides a novel therapeutic approach for ALF.

Combination effect of laser diode for photodynamic therapy with doxycycline on a wistar rat model of periodontitis

BackgroundPeriodontitis is a chronic inflammatory disease characterized by progressive damage on the structure of tooth-supporting tissues. The aim of the study is determining the combination photodynamic effect of diode laser 405 nm treatments and the administration of doxycycline 0.1% within 1, 3, 5, and 7 days on a Wistar rat model of periodontitis.MethodsSamples were induced with Porphyromonas gingivalis ATCC33277 to allow periodontitis development and were treated with combination of doxycycline and laser diode, then statistical analysis was carried out (One-Way ANOVA test and the post-hoc Duncan test; Kruskal–Wallis test and Mann–Whitney follow-up test for non-parametric data). Samples were divided into five groups, laser exposure used was 405-nm diode laser with energy density of 8 J/cm2. The expression level of histomorphometric was calculated by measuring the number of macrophages, lymphocytes, fibroblasts and the distance between the CEJ-AV.ResultsThe results showed that the combination treatment of doxycycline and laser exposure yielded immunomodulatory effects. The expression level of fibroblast and the distance between CEJ-AV bone showed that the combination of doxycycline and laser therapy exerted healing effect in rat models of periodontitis on day 5 and 7.ConclusionThe combination of doxycycline 0.1% and diode laser therapy provides a healing effect in rats models of periodontitis.

Triterpenoid saponins from Ilex cornuta protect H9c2 cardiomyocytes against H2O2-induced apoptosis by modulating Ezh2 phosphorylation

Ethnopharmacological relevanceIlex cornuta Lindl. et Paxt. (Aquifoliaceae family) belongs to the Ilex genus. The leaves of this plant are used for the popular herbal tea “Ku-Ding-Cha” in China due to their health benefits for sore throat, obesity and hypertension. Our previous studies have shown that the extract of Ilex cornuta root exerts cardioprotective effects in rat models of myocardial ischaemic injury, and several new kinds of triterpenoid saponins from Ilex cornuta (TSIC) have protective effects against hydrogen peroxide (H2O2)-induced cardiomyocyte injury. Aim of the studyThe aim of this study was to clarify the underlying mechanisms by which TSIC protect against H2O2-induced cardiomyocyte injury. Materials and methodsAn H2O2-treated H9c2 cardiomyocyte line was used as an in vitro model of oxidation-damaged cardiomyocytes to evaluate the effects of TSIC. Apoptosis was detected with CCK-8 and annexin V assays and via analysis of the levels of apoptosis-associated proteins or genes. The underlying mechanisms related to Akt signalling, Ezh2 expression and activity, and ROS were clarified by Western blotting, quantitative PCR, flow cytometry and rescue experiments. ResultsTSIC protected H9c2 cells from H2O2-induced apoptosis. This effect of TSIC was attributable to inhibition of Ezh2 activity, as exhibited by attenuation of H2O2-induced Akt signalling-dependent phosphorylation of Ezh2 at serine 21 (pEzh2S21) upon TSIC pretreatment. In addition, feedback pathway between Akt-dependent Ezh2 phosphorylation and ROS was involved in TSIC-mediated protection of H9c2 cells from apoptosis. ConclusionsOur findings indicate a pivotal role of the pEzh2S21 network in TSIC-mediated protection against cardiomyocyte apoptosis, potentially providing evidence of the mechanism of TSIC in the treatment and prevention of cardiovascular diseases.

Preventing oxaliplatin-induced neuropathic pain: Using berberine to inhibit the activation of NF-κB and release of pro-inflammatory cytokines in dorsal root ganglions in rats.

Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a serious, undesirable effect of cancer treatment which is particularly difficult to prevent. Berberine and its derivatives have been reported to display robust antioxidant and analgesic effects in rat models of diabetic neuropathic pain and peripheral nerve injury. However, the analgesic role of berberine on oxaliplatin-induced CIPNP remains unknown. The present study aimed to explore the analgesic effect of berberine on CIPNP. Sprague Dawley rats were used to create the CIPNP animal model by oxaliplatin administration. Behavioral tests were performed by von Frey test, acetone drop test, hot plate test, and motor coordination. The protein expression levels of NF-κB p65 and phosphorylated p65 in dorsal root ganglions (DGRs) were detected by western blot analysis. Finally, TNF-α and IL-6 levels in DRGs were measured using specific ELISA kits. The results from the behavioral analysis demonstrated that a single injection of berberine ameliorated the mechanical and cold allodynia and thermal hyperalgesia in the model rats in a dose-dependent manner. Cumulative administration of berberine prevented the mechanical and cold allodynia and thermal hyperalgesia in the development of CIPNP induced by oxaliplatin. This prophylactic effect of berberine was associated with reduced phosphorylation of p65 and with decreased levels of pro-inflammatory cytokines IL-6 and TNF-α. The present study indicated that berberine may have a role in preventing the development of CIPNP and may serve as a therapeutic compound for the treatment of CIPNP.

Red Propolis and Its Dyslipidemic Regulator Formononetin: Evaluation of Antioxidant Activity and Gastroprotective Effects in Rat Model of Gastric Ulcer.

Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50–500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.

Pyrazolo[4,3-c]pyridine-4-one (PP-4-one) Exhibits Anti-Epileptogenic Effect in Rat Model of Traumatic Epilepsy by Mammalian Target of Rapamycin (mTOR) Signaling Pathway Downregulation

BackgroundPost-traumatic epilepsy (PTE) is a common type of acquired epilepsies secondary to traumatic brain injury (TBI), accounting for approximately 10–25% of patients. The present study evaluated activity of PP-4-one against mTOR signaling activation in a rat model of FeCl2-induced post-traumatic epilepsy.Material/MethodsEpilepsy in rats was induced by injecting 10 μl FeCl2 (concentration 100 mM) at a uniform rate of 1 μl/minute. The iNOS expression was detected using a Leica microscope connected to a digital camera system. Reverse transcription polymerase chain reaction (RT-PCR) was used for determination of NR1 mRNA expression.ResultsThe post-traumatic epilepsy induced neuronal degeneration in the hippocampus and frontal cortex of the rats. Treatment with PP-4-one prevented neuronal degeneration in the hippocampus and frontal cortex in rats with post-traumatic epilepsy. The data revealed markedly higher levels of p-mTOR and p-P70S6K in rat hippocampal tissues after induction of traumatic epilepsy. Treatment of post-traumatic epilepsy rats with PP-4-one significantly suppressed p-mTOR and p-P70S6K expression, and PP-4-one treatment reduced epileptic brain injury in the rats with post-traumatic epilepsy.ConclusionsPP-4-one exhibits an anti-epileptogenic effect in the rat model of PTE by inhibiting behavioral seizures through suppression of iNOS and astrocytic proliferation. Moreover, PP-4-one treatment suppressed NR1 expression and targeted the mTOR pathway in PTE-induced rats. Thus, PP-4-one shows promise as a novel and effective therapeutic agent for treatment of epilepsy induced by PTE.

N-3 PUFA Have Antidepressant-like Effects Via Improvement of the HPA-Axis and Neurotransmission in Rats Exposed to Combined Stress.

Early life and adulthood stress increase vulnerability for mental illness, and eventually trigger depression. N-3 polyunsaturated fatty acids (PUFA) have antidepressant effects, but their effect on rats exposed to combined stress has been not investigated. This study aimed to investigate whether n-3 PUFA supplementation had antidepressant-like effects in rat models of depression induced by a combination of chronic mild stress (CMS) and maternal separation (MS) through the modulation of the hypothalamic-pituitary-adrenal (HPA) axis and neurotransmission. Rats were fed the n-3 PUFA diet during the pre-weaning or post-weaning period or for lifetime, and allocated to different groups based on the type of induced stress: non-stress (NS), CMS + MS, or CMS alone. N-3 PUFA improved the depressive behaviors of the CMS alone and CMS + MS groups and modulated the HPA-axis by reducing the circulating adrenocorticotropic hormone, corticosterone, and corticotropin-releasing factor expression, and increasing glucocorticoid receptor expression. N-3 PUFA also modulated brain phospholipid fatty acid concentration, thus reducing inflammatory cytokines; improved the serotonergic pathway, thus increasing the expression of the brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), serotonin-1A receptor, and serum levels of serotonin; but did not affect glutamatergic neurotransmission. Furthermore, n-3 PUFA decreased the hippocampal expression of microRNA-218 and -132, increased that of microRNA-155, and its lifetime supplementation was more beneficial than pre- or post-weaning supplementation. This study suggests that n-3 PUFA has an antidepressant effect in rats exposed to combined stress, through the improvement of the HPA-axis abnormalities, the BDNF-serotonergic pathway, and the modulation of microRNAs.

Galantamine in rheumatoid arthritis: A cross talk of parasympathetic and sympathetic system regulates synovium-derived microRNAs and related pathogenic pathways

The acetylcholinesterase inhibitor, galantamine, has shown therapeutic effect in rat model of rheumatoid arthritis. Hence, the current study aims at determining the mode of action of galantamine by examining different synovium-derived microRNAs (miRs) and their related pathogenic pathways. The study also focuses on how parasympathetic and sympathetic pathways in the synovial tissue could affect the mode of action and anti-arthritic effect of galantamine.Chemical sympathectomy was initiated in 12 adjuvant arthritic rats by exposure to 6-hydroxydopamine (6-OHDA; 2 × 50 mg/kg) on day 9 after adjuvant injection and again (2 × 100 mg/kg) one week later. Six rats were treated with galantamine (2.5 mg/kg/day) to explore the influence of sympathetic impairment on galantamine effect. Another twelve additional adjuvant arthritic rats were exposed to the selective α7 nicotinic acetylcholine receptor blocker methylcaconitine citrate (MLA; 5.6 mg/kg/day), 15 min before galantamine treatment. As control, six adjuvant arthritic rats were treated with galantamine alone. Treatment proceeded for 5 days, from day 14 till day 18 post-adjuvant injection. Different miRs and their related pathogenic pathways were examined. Tyrosine hydroxylase (TH) expression was also measured in joint tissue. Galantamine affected the expression of the different miRs and their related parameters. Both, 6-OHDA and MLA, interrupted the anti-inflammatory/anti-arthritic effect of galantamine to different extent. Additionally, TH expression in the synovium was affected by galantamine, suggesting a novel pathogenic target in the treatment of rheumatoid arthritis.

ASP8477, a fatty acid amide hydrolase inhibitor, exerts analgesic effects in rat models of neuropathic and dysfunctional pain

Exogenous cannabinoid receptor agonists are clinically effective for treating chronic pain but frequently cause side effects in the central nervous system. Fatty acid amide hydrolase (FAAH) is a primary catabolic enzyme for anandamide, an endogenous cannabinoid agonist. 3-Pyridyl 4-(phenylcarbamoyl)piperidine-1-carboxylate (ASP8477) is a potent and selective FAAH inhibitor that is orally active and able to increase the brain anandamide level and is effective in rat models of neuropathic and osteoarthritis pain without causing motor coordination deficits. In the present study, we examined the pharmacokinetics and pharmacodynamics, analgesic spectrum in pain models, and the anti-nociceptive mechanism of ASP8477. Single and four-week repeated oral administration of ASP8477 ameliorated mechanical allodynia in spinal nerve ligation rats with similar improvement rates. Further, single oral administration of ASP8477 improved thermal hyperalgesia and cold allodynia in chronic constriction nerve injury rats. ASP8477 also restored muscle pressure thresholds in reserpine-induced myalgia rats. This analgesic effect of ASP8477 persisted for at least 4 h, consistent with the inhibitory effect observed in an ex vivo study using rat brain as well as the increasing effect on oleoylethanolamide and palmitoylethanolamide levels but not the ASP8477 concentration in rat brain. ASP8477 also improved α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, N-methyl-D-aspartic acid (NMDA)-, prostaglandin E2-, prostaglandin F2α-, and bicuculline-induced allodynia in mice, showing broader analgesic spectra than existing drugs. In contrast, however, ASP8477 did not affect acute pain. These results indicate that the FAAH inhibitor ASP8477 exerts analgesic effects on neuropathic and dysfunctional pain, and its pharmacological properties are suitable for use in treating chronic pain.

MEMANTINE IS ASSOCIATED WITH DECREASED HOSPITAL ADMISSIONS FOR HEART FAILURE EXACERBATION, BUT NOT ARRHYTHMIA: A SINGLE-CENTER STUDY

N-methyl-d-aspartate receptor (NMDAR) modulation recently has been shown to have striking cardiac effects in rat models of heart failure (HF). NMDAR blockade reduced arrhythmias and decreased cardiac remodeling. Memantine, an NMDAR antagonist, is a commonly used dementia drug. We sought to determine

Current Status and Prospects in the Treatment of Erectile Dysfunction by Adipose-Derived Stem Cells in the Diabetic Animal Model.

Erectile dysfunction (ED) is defined as the persistent inability to achieve and maintain an erection status sufficient to permit satisfactory sexual performance. Current evidence suggests that diabetes mellitus erectile dysfunction (DMED) is one of the leading causes of ED which remains a difficult condition to manage because of its complicated pathophysiological mechanisms. Recently, stem cell therapies have been added to the therapeutic treatment options for ED. Stem cells derived from adipose tissue are now considered an alternative approach to DMED with preliminary studies demonstrating their capability of promoting endothelial cell, smooth muscle cell, and cavernous nerve regeneration. We will review the epidemiology and pathophysiology of ED, rat models, and adipose-derived stem cell (ASC) therapy and its effects. The relevant literature and contemporary data, using keywords "adipose-derived stem cells and diabetes erectile dysfunction," were reviewed. The main outcome measure was the evidence supporting the association between ASCs, diabetes ED, and rat model. ASCs can restore erectile function of DMED rats by promoting vascularization and neuralization of corpus cavernosum. They can also inhibit fibrosis and inflammation and protect smooth muscle cells. ASCs have achieved satisfactory therapeutic effects in rat models of ED, but effectiveness and safety of their application in clinical research remain to be determined. Yan H, Ding Y, Lu M. Current Status and Prospects in the Treatment of Erectile Dysfunction by Adipose-Derived Stem Cells in the Diabetic Animal Model. Sex Med Rev 2020;8:486-491.

Doxazosin down-regulates sodium-glucose cotransporter-2 and exerts a renoprotective effect in rat models of acute renal injury.

Sodium-glucose cotransporter-2 (SGLT2) is known to be involved in the progression of acute renal injury (ARI) and is regulated by different mediators in the kidneys including extracellular signal-regulated kinase (ERK), hypoxia-inducible factor 1 alpha (HIF1α) and prostaglandin E2 (PGE2). In the present study, we investigated the possible protective effect of doxazosin on renal ischaemia/reperfusion (IR) and glycerol-induced ARI by determining its effect on SGLT2 via modifying ERK-HIF1α pathway and/or PGE2. Rats were divided into control, sham or IR where the rats received the vehicle, doxazosin (8mg/kg) or the SGLT2 inhibitor, dapagliflozin (10mg/kg) for 3days followed by 45minutes bilateral renal ischaemia then 24hours reperfusion. Another group of rats received the vehicle, doxazosin or dapagliflozin for three days followed by injection of 50% glycerol (8mL/kg, IM) or saline. Kidney function tests, systolic blood pressure (SBP), oxidative stress markers (malondialdehyde [MDA] and NADPH oxidase), nitric oxide (NO), inducible nitric oxide synthase(iNOS), HIF1α, ERK phosphorylation and PGE2 levels were determined. Additionally, renal sections were used for immunological expression of SGLT2. ARI rats showed significantly increased SBP; worsened kidney function tests; increased oxidative stress, iNOS, NO, HIF1α levels; and decreased PGE2 and ERK phosphorylation along with up-regulated SGLT2. Doxazosin treatment protected against the kidney damage and attenuated the associated biochemical changes. Doxazosin has a direct renoprotective effect possibly by down-regulating SGLT2.

P.616 Propolis prevents vascular endothelial dysfunction by antiinflammatory effect in rat model of chronic unpredictable mild stress-induced depression

P.616 Propolis prevents vascular endothelial dysfunction by antiinflammatory effect in rat model of chronic unpredictable mild stress-induced depression

Analgesic Effect of Dizocine Combined with Ropivacaine on Recurrent Neuropathic Pain in Peripheral Nerve Compression Rats

To explore the analgesic effect of dizocine combined with ropivacaine on recurrent neuropathic pain in rat model of peripheral nerve compression. Rats were randomly divided into 5 groups: sham control group (S), peripheral nerve compression model group (M), dizocine group (D), ropivacaine group (R), and combined drug group (DR). Rat peripheral nerve compression model was constructed to observe the symptoms of the rats before and after surgery. Mechanical withdrawal threshold was measured on the 21st day after surgery. The electrophysiological changes of rat peripheral nerve were measured by biopotential recording system, including proximal latency, distal latency, and compound muscle action potential. The incubation period and nerve conduction velocity were further obtained. Histological changes were observed by HE staining and toluidine blue staining. Axon number and myelin damage grade were performed, and the ultrastructure was observed by transmission electron microscopy (TEM). The mechanical withdrawal threshold, nerve conduction velocity, and compound muscle action potential were effectively increased in combination group. However, the proximal latency, distal latency, and incubation period were significantly reduced. Furthermore, dizocine combined with ropivacaine can effectively reduce the degree of myelination. TEM shown that the DR group had the best therapeutic effect, and the histological appearance of the cross section was quite similar to that of the S group. Dizocine combined with ropivacaine has a significant analgesic effect in rat model of peripheral nerve compression.

Research and development of κ opioid receptor agonists and δ opioid receptor agonists.

Delta opioid delta receptor (DOP) agonists were expected to be analgesics and many researchers tried to develop the SNC80 derivatives. However, the derivatives were dropped at the stage of early clinical trials because of undesirable side effects and weak analgesia. On the other hand, DOP agonists have been proposed as attractive candidates for the novel psychotropic drugs. We recently succeeded in synthesizing a novel selective DOP agonist KNT-127. KNT-127 produced neither catalepsy nor convulsive effects. We have demonstrated that KNT-127 has potent anxiolytic-like effect in rat models of innate anxiety. This anxiolytic-like effect was independent from known adverse effect of benzodiazepine, such as memory impairment, motor coordination deficits, and ethanol interactions. We have also demonstrated that KNT-127 showed potent and rapid antidepressant-like effects in rat models of depression. This antidepressant-like effect was independent from known adverse effect of selective serotonin reuptake inhibitor (SSRI), such as digestive symptoms. Therefore, we propose that DOP should be considered as an attractive target for the development of novel psychotropic drugs, without producing the adverse effects associated with benzodiazepine anxiolytics and SSRI antidepressants. Very recently, we developed another delta agonist NC-2800 with a different structure. NC-2800 is now in the preclinical stage using the CiCLE fund supported by AMED (Japanese Agency for Medical Research and Development).

Neurological recovery and antioxidant effects of resveratrol in rats with spinal cord injury: a meta-analysis

Objective:To critically assess the neurological recovery and antioxidant effects of resveratrol in rat models of spinal cord injury.Data sources:Using “spinal cord injury”, “resveratrol” and “animal experiment” as the main search terms, all studies on the treatment of spinal cord injury in rats by resveratrol were searched for in PubMed, EMBASE, MEDLINE, Web of Science, Science Direct, China National Knowledge Infrastructure, Wanfang, VIP, and SinoMed databases by computer. The search was conducted from their inception date to April 2017. No language restriction was used in the literature search.Data selection:The methodological quality of each study was assessed by the initial Stroke Therapy Academic Industry Roundtable recommendations. Two reviewers independently selected studies according to the title, abstract and full text. The risk of bias in the included studies was also evaluated. Meta-analyses were performed with Review Manager 5.3 software.Outcome measures:Neurological function was assessed by the Basso, Beattie, and Bresnahan scale score, inclined plane score and Gale’s motor function score. Molecular-biological analysis of antioxidative effects was conducted to determine superoxide dismutase levels, malondialdehyde levels, nitric oxide synthase activity, nitric oxide levels, xanthine oxidase and glutathione levels in spinal cord tissues.Results:The methodological quality of the 12 included studies was poor. The results of meta-analysis showed that compared with the control group, resveratrol significantly increased the Basso, Beattie, and Bresnahan scale scores after spinal cord injury (n = 300, mean difference (MD) = 3.85, 95% confidence interval (CI) [2.10, 5.59], P < 0.0001). Compared with the control group, superoxide dismutase levels were significantly elevated (n = 138, standardized mean difference (SMD) = 5.22, 95% CI [2.98, 7.45], P < 0.00001), but malondialdehyde levels were significantly diminished (n = 84, SMD = –3.64, 95% CI [–5.84, –1.43], P = 0.001) in the spinal cord of the resveratrol treatment group.Conclusions:Resveratrol promoted neurological recovery and exerted antioxidative effects in rat models of spinal cord injury. The limited quality of the included studies reduces the application of this meta-analysis. Therefore, more high-quality studies are needed to provide more rigorous and objective evidence for the pre-clinical treatment of spinal cord injury.

PEGylated Lipova E120 liposomes loaded with celecoxib: in-vitro characterization and enhanced in-vivo anti-inflammatory effects in rat models

The goal of the current investigation was to prepare PEGylated Lipova E120 liposomes loaded with celecoxib for the effective treatment of rheumatoid arthritis (RA). PEGylated liposomes were prepared and were characterized using techniques such as particle size distribution, polydispersity index (PDI), zeta potential, encapsulation efficiency and in-vitro release, in-vivo and stability studies. The morphological study was characterized by scanning electron microscopy and transmission electron microscopy. To determine the interaction between drug and polymer Fourier transform infrared, Raman, thermogravimetric analysis and differential scanning calorimetry studies were performed. Results show that formulation F6 was optimized with a particle size of 92.12 +/- 1.7 nm, a PDI of 0.278 +/- 0.22, a zeta potential of - 40.8 +/- 1.7 mV with a maximum encapsulation of 96.6 +/- 0.05% of drug in the PEGylated liposomes. The optimized formulation shows a maximum release of drug i.e. 94.45 +/- 1.13% in 72 h. Tail immersion assay shows that the optimized formulation F6 significantly increases the reaction time and carrageenan-induced assay shows that the optimized formulation inhibits the increase in paw edema thus providing a pain relief treatment in RA. These results suggest that the PEGylated liposomes provide a sustained release of celecoxib and helps in effective treatment of RA.

Flurbiprofen loaded ethosomes - transdermal delivery of anti-inflammatory effect in rat model

BackgroundEthosomes have been widely used in Transdermal Drug Delivery System (TDDS) as they increase the permeation of drug across the skin.MethodsFlurbiprofen loaded vesicular ethosomes were formulated, optimized and characterized for particle size, entrapment efficiency, poly dispersive index (PDI), microscopy using Atomic force microscopy (AFM), Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) and Interaction of drug and excipients were studied using Fourier transform infra-red (FTIR) spectroscopy, Differential scanning colorimetry (DSC), Thermo gravimetric analysis (TGA). Further, ethosomal formulations of flurbiprofen were evaluated for stability study of three months and in vitro drug permeation study was carried out using albino rat skin. In addition, skin irritation test was evaluated by Draize test and in vivo study of prepared formulation was examined through paw edema assay by inducing carrageenan and cold plate method.ResultsAmongst all formulations, EF5 formulation exhibited ideal surface morphology, with maximum entrapment efficiency (95%) with optimal excipient concentration i.e. 200 mg phospholipid and 35% ethanol. The ideal vesicle size was achieved as 162.2 ± 2 nm, with zeta potential − 48.14 ± 1.4 mV with the PDI of 0.341. In-vitro permeation study shows a release of 82.56 ± 2.11 g/cm2 in 24 h and transdermal flux was found as 226.1 μg/cm2/h. Cold plate test indicates that the formulation EF5 showed a marked analgesic activity and Carrageenan induced paw edema test indicates that the formulation EF5 inhibits the increase in paw edema. Ethosomal suspension at 4 °C showed maximum stability.ConclusionsThe overall study concluded that this ethosomal approach offers a new delivery system for sustained and targeted delivery for flurbiprofen.

Exosomes Derived from TIMP2-Modified Human Umbilical Cord Mesenchymal Stem Cells Enhance the Repair Effect in Rat Model with Myocardial Infarction Possibly by the Akt/Sfrp2 Pathway.

Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSCs) are a promising new therapeutic option for myocardial infarction (MI). The tissue matrix metalloproteinase inhibitor 2, also known as TIMP2, is a member of the tissue inhibitor family of metalloproteinases. Since TIMP2-mediated inhibition of matrix metalloproteinases (MMPs) is a key determinant of post-MI remodeling, we analyzed the therapeutic effects of exosomes derived from TIMP2-overexpressing hucMSCs (huc-exoTIMP2) on the MI rat model. The huc-exoTIMP2 significantly improved in vivo cardiac function as measured by echocardiography and promoted angiogenesis in MI injury. It also restricted extracellular matrix (ECM) remodeling, as indicated by the reduced collagen deposition. In addition, huc-exoTIMP2 administration increased the in situ expression of the antiapoptotic Bcl-2 and decreased that of the proapoptotic Bax and pro-caspase-9 in the infracted myocardium. Meanwhile, huc-exoTIMP2 upregulated superoxide dismutase (SOD) as well as glutathione (GSH) and decreased the malondialdehyde (MDA) level in MI models. In vitro huc-exoTIMP2 pretreatment could inhibit H2O2-mediated H9C2-cardiomyocyte apoptosis and promote human umbilical vein endothelial cell (HUVEC) proliferation, migration, and tube formation, as well as decrease TGFβ-induced MMP2, MMP9, and α-SMA secretion by cardiac fibroblasts (CFs). Besides that, huc-exoTIMP2 pretreatment also increased the expression of Akt phosphorylation in the infarcted myocardium, which may relate to a high level of secreted frizzled-related protein 2 (Sfrp2) in huc-exoTIMP2, indicating a mechanistic basis of its action. Importantly, Sfrp2 knockdown in huc-exoTIMP2 abrogated the protective effects. Taken together, huc-exoTIMP2 improved cardiac function by alleviating MI-induced oxidative stress and ECM remodeling, partly via the Akt/Sfrp2 pathway.