Protective effect of a hydromethanolic extract from Fraxinus excelsior L. bark against a rat model of aluminum chloride-induced Alzheimer's disease: Relevance to its anti-inflammatory and antioxidant effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Fraxinus excelsior L. (FE), commonly known as the ash, belongs to the Oleaceae family and has shown several pharmacological and biological properties, such as antioxidant, immunomodulatory, neuroprotective, and anti-inflammatory effects. It has also attracted the most attention toward neuroinflammation. Moreover, FE bark and leaves have been used to treat neurological disorders, aging, neuropathic pain, urinary complaints, and articular pain in traditional and ethnomedicine. Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder resulting from the involvement of amyloid-beta, metal-induced oxidative stress, and neuroinflammation. AIM OF THE STUDY: The objective of the current study was to assess the neuroprotective effects of hydromethanolic extract from FE bark in an AlCl3-induced rat model of AD. MATERIALS AND METHODS: The maceration process was utilized to prepare the hydromethanolic extract of FE bark, and characterized by LC-MS/MS. To assess the anti-AD effects of the FE extract, rats were categorized into five different groups, AlCl3; normal control; FE-treated groups at 50, 100, and 200 mg/kg. Passive avoidance learning test, Y-maze, open field, and elevated plus maze behavioral tests were evaluated on days 7 and 14 to analyze the cognitive impairments. Zymography analysis, biochemical tests, and histopathological changes were also followed in different groups. RESULTS: LC-MS/MS analysis indicated the presence of coumarins, including isofraxidin7-O-diglucoside in the methanolic extract of FE as a new isofraxidin derivative in this genus. FE significantly improved memory and cognitive function, maintained weight, prevented neuronal damages, and preserved the hippocampus's histological features, as demonstrated by behavioral tests and histopathological analysis. FE increased anti-inflammatory MMP-2 activity, whereas it decreased that of inflammatory MMP-9. Moreover, FE increased plasma antioxidant capacity by enhancing CAT and GSH while decreasing nitrite levels in the serum of treated groups. In comparison between the treated groups, the rats that received high doses of the FE extract (200 mg/kg) showed the highest therapeutic effect. CONCLUSION: FE rich in coumarins could be an effective anti-AD adjunct agent, passing through antioxidant and anti-inflammatory pathways. These results encourage further studies for the development of this extract as a promising agent in preventing, managing, or treating AD and related diseases.

Neuroprotective effects of a combination of Boswellia papyrifera and Syzygium aromaticum on AlCl3 induced Alzheimer's disease in male albino rat.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by hippocampal, and cortical neuron deterioration, oxidative stress, and severe cognitive dysfunction. Aluminum is a neurotoxin inducer for cognitive impairments associated with AD. The treatment approaches for AD are unsatisfactory. Boswellia papyrifera and Syzygium aromaticum are known for their pharmacological assets, including antioxidant activity. Therefore, the current study explored the possible mitigating effects of a combination of Boswellia papyrifera and Syzygium aromaticum against aluminum chloride (AlCl3) induced AD. The AD model was established using AlCl3 (100 mg/kg), and the rats were orally administrated with Boswellia papyrifera or Syzygium aromaticum or a combination of them daily for 8 weeks. The Y-maze test was used to test cognition in the rats, while acetylcholinesterase (AChE) and oxidative stress markers were estimated in homogenates of the cerebral cortex and hippocampus. Also, the histopathological examination of the cortex and hippocampus were investigated. The results revealed that administration of either B. papyrifera or S. aromaticum extracts significantly improved the cognitive functions of AD rats, enhanced AChE levels, increased oxidative enzymes levels, including SOD and GSH, and reduced MDA levels in homogenates of the cerebral cortex and hippocampus and confirmed by improvement in histological examination. However, using a combination therapy gave better results compared to a single treatment. In conclusion, the present study provided primary evidence for using a combination of B. papyrifera and S. aromaticum to treat cognitive dysfunction associated with AlCl3 Induced AD by improving the AChE levels and modulating oxidative stress in the brain.

A comparative evaluation of aluminum chloride hexahydrate gel iontophoresis versus tap water iontophoresis in people with primary palmar hyperhidrosis: A randomised clinical trial.

Background Primary palmar hyperhidrosis causes a lot of problems for patients and negatively affects their quality of life. Currently, iontophoresis with tap water and aluminum chloride hexahydrate is used for primary palmar hyperhidrosis. Yet, little evidence exists about iontophoresis with aluminum chloride hexahydrate in the form of gel. This study investigated the effect of aluminum chloride hexahydrate gel iontophoresis compared to tap water iontophoresis on primary palmar hyperhidrosis. Methods In this randomised controlled trial study, 32 patients with primary palmar hyperhidrosis were divided randomly into two groups (n = 16). Participants received 7 sessions of iontophoresis with aluminum chloride hexahydrate gel or tap water every other day on the dominant hand. The sweating rate was measured by gravimetry and iodine-starch tests before and after the last treatment session. Results Following the iontophoresis, the rate of sweating in both hands in the two groups was significantly reduced (P < 0.001). However, the sweating rate in the treated hand and the non-treated hand showed no significant difference. There was no significant difference observed in sweating rate reduction between both groups over time, but the larger effect size values observed in the aluminum chloride hexahydrate gel iontophoresis group may suggest the superiority of this gel over tap water in reducing the rate of sweating. Limitations Further investigations with longer follow-up are needed to confirm the hypothesis regarding the effectiveness of aluminum chloride hexahydrate gel iontophoresis over other types of iontophoresis. In addition, contraindications of iontophoresis such as pregnancy, pacemakers, and epilepsy should be considered. Conclusion The present study provides preliminary evidence suggesting that aluminum chloride hexahydrate gel iontophoresis is an effective alternative treatment to decrease sweating rate in extended areas with fewer side effects in patients with primary palmar hyperhidrosis.

Neuroprotective efficacy of the bacterial metabolite, prodigiosin, against aluminium chloride-induced neurochemical alternations associated with Alzheimer's disease murine model: Involvement of Nrf2/HO-1/NF-κB signaling.

Prodigiosin (PDG) is a bacterial metabolite with numerous biological and pharmaceutical properties. Exposure to aluminium is considered a root etiological factor in the pathological progress of Alzheimer's disease (AD). Here, in this investigation, we explored the neuroprotective potential of PDG against aluminium chloride (AlCl3 )-mediated AD-like neurological alterations in rats. For this purpose, rats were gavaged either AlCl3 (100 mg/kg), PDG (300 mg/kg), or both for 42 days. As a result of the analyzes performed on the hippocampal tissue, it was observed that AlCl3 induced biochemical, molecular, and histopathological changes like those related to AD. PDG pre-treatment significantly decreased acetylcholinesterase activity and restored the levels of brain-derived neurotrophic factor, monoamines (dopamine, norepinephrine, and serotonin), and transmembrane protein (Na+ /K+ -ATPase). Furthermore, PDG boosted the hippocampal antioxidant capacity, as shown by the increased superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione contents. These findings were accompanied by decreases in malondialdehyde and nitric oxide levels. The antioxidant effect may promote the upregulation of the expression of antioxidant genes (Nrf2 and HO-1). Moreover, PDG exerted notable anti-inflammatory effects via the lessening of interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, nuclear factor kappa B, and decreases in the gene expression of inducible nitric oxide synthase. In addition, noteworthy decreases in pro-apoptotic (Bax and caspase-3) levels and increases in anti-apoptotic (Bcl-2) biomarkers suggested an anti-apoptotic effect of PDG. In support, the hippocampal histological examination validated the aforementioned changes. To summarize, the promising neuromodulatory, antioxidative, anti-inflammatory, and anti-apoptotic activities of PDG establish it as a potent therapeutic option for AD.

Pharmacological evaluation of bromelain in mouse model of Alzheimer's disease.

The current study elucidates pharmacological evaluation of bromelain as a bioactive compound obtain from pineapple stem belongs to family Bromeliaceae in AlCl3 and D - galactose induced mice. In mice, co-administration of AlCl3 at dose 5 mg/kg b.w., via the oral route, and D - galactose at dose 60 mg/kg b.w., via intraperitoneal route for 90 days resulted in cognitive impairment, spatial learning, and memory deficits, as well as neurotoxicity. However, 30 consecutive days, treatments via an intraperitoneal route with bromelain low dose (Brm L) at dose 10 mg/kg b.w., bromelain high dose (Brm H) at dose 20 mg/kg b.w., donepezil (Dnpz) at dose 2 mg/kg b.w., and Brm L + Dnpz at doses 10, 2 mg/kg b.w. were considerably reversed the effect of AlCl3 and D - galactose induced AD mice. Consequences of behavioral parameters (Morris water maze, elevated plus maze and locomotor), biochemical estimation (MDA, GSH, SOD, CAT, Nitrite and AChE), and ELISA tests (mouse BACE, Aß1 - 42, TNF-α, IL-6, and BDNF) confirmed significant (p < 0.05) neuroprotective effect of treatments in AlCl3 and D - galactose induced mice. Additionally, hematoxylin and eosin staining of the cerebral cortex and the hippocampus exposed eosinophilic lesions and hyperchromatic nuclei in AD mice, but these neurodegenerative effects were eliminated by Brm L, Brm H, Dnpz, and Brm L + Dnpz treatments. Thus, bromelain alone and in combination with donepezil prevent AlCl3 and D - galactose induced spatial learning and memory deficits, as well as cognitive impairment, by increasing cholinergic activity and synaptic plasticity, as well as reducing oxidative damage, neuroinflammation, Aß 1-42 aggregations, and histopathological damage, according to our findings. The present study consequences indicate that bromelain alone and in combination with donepezil appears to have neuroprotective properties. Henceforward, this may be a promising treatment option for Alzheimer's disease.

Potential neuroprotective activity of Mentha longifolia L. in aluminum chloride-induced rat model of Alzheimer's disease.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder manifested by cognitive deterioration where the available treatments failed to delay its progression. The objective of this study was to investigate the neuroprotective activity in an aluminum chloride (AlCl3 )-induced AD in vivo model and phytochemical profile of the traditional Egyptian herb Mentha longifolia (Ml). Male albino rats were injected with Ml fractions and essential oil for 15 days followed by AlCl3 for 30 days. Oxidative stress and neuroinflammatory markers were measured namely: malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NO), and nuclear factor-κB (NF-κB). Furthermore, cholinesterase activity was tested and analysis of brain neurotransmitters using HPLC was performed. Results showed that methylene chloride and ethyl acetate fractions were able to reverse the AlCl3 mediated MDA increase, GSH decrease and exhibited anticholinesterase activity. EaFr reversed the increased levels of NF-κB and NO. Ml fractions and oil counteracted the AlCl3 effect on brain neurotransmitters. Forty metabolites were tentatively characterized in the bioactive fractions using UPLC-PDA-ESI-MS. 5,6,4'-trihydroxy-3',7,8-trimethoxy flavone was isolated from Ml as a first report, in addition to 5,6-dihydroxy-3',4',7,8-tetramethoxy flavone and rosmarinic acid. These findings suggest that Ml is a promising nutraceutical and source of lead compounds halting AD progression. PRACTICAL APPLICATIONS: The results presented in this paper unravels the neuroprotective effect of Mentha longifolia fractions and oil by acting as anti-inflammatory, antioxidant agents, and regulating the levels of neurotransmitters. This provides basic knowledge for the development of Ml as a source of lead compounds and a promising food supplement protective against Alzheimer's disease.

Hemostatic agents in endodontic surgery of maxillary molars: A randomized controlled pilot study of polytetrafluoroethylene (PTFE) strips as an adjunct to epinephrine impregnated gauze versus aluminum chloride

BACKGROUND: Hemostasis is of critical importance in endodontic surgery. Studies on bleeding control in maxillary molars are scarce. The present study compares the efficacy of two hemostatic techniques in controlling bleeding in endodontic surgery. MATERIAL AND METHODS: A randomized two-arm pilot study involving 30 patients with peri-radicular lesions in maxillary molars (first and second molars) was carried out including the following hemostatic agents: polytetrafluoroethylene (PTFE) strips as an adjunct to epinephrine impregnated gauze (test group; n = 15) and aluminum chloride (Expasyl(TM)) (control; n = 15). Bleeding control was independently assessed by the surgeon and by two blinded observers before and after application of the hemostatic agent, and was classified as either adequate (complete bleeding control) or inadequate (incomplete bleeding control). RESULTS: Bleeding control was similar in both groups. Simple binary logistic regression analysis failed to identify variables affecting bleeding control. Only the height of the keratinized mucosal band (≥ 2 mm) suggested a decreased risk of inadequate bleeding control of up to 89% (OR = 0.11; p = 0.06). CONCLUSIONS: No difference in the efficacy of bleeding control was observed between PTFE strips as an adjunct to epinephrine impregnated gauze and aluminum chloride in maxillary molars

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Apoptotic Inducement of Neuronal Cells by Aluminium Chloride and the Neuroprotective Effect of Eugenol in Wistar Rats.

Aluminium is known to accelerate oxidative stress, amyloid beta (Aß) deposition, and plaque formation in the brain of rats. Objective. The present study is aimed at studying the neuroprotective effects of eugenol following aluminium-induced neurotoxicity on caspase-3, apoptotic proteins (Bcl-2 and Bax), and oxidative stress markers in Wistar rats such as superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), and assay oxidative stress to mitochondrial DNA (mtDNA) by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG). Materials and methods. Twenty (20) adult Wistar rats were randomly divided into four (4) groups with five animals in each group. Route of administration was oral throughout the duration of this study and this study lasted for 21 days. Rats were sacrificed 24 hours after administration of the last dose (i.e., day 22) with 0.8 mg/kg ketamine as an anaesthetic agent. Results. Exposure to AlCl3 resulted in a significant (p < 0.01) elevation in the levels of nitric oxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), enhanced the activity of caspase-3, increased the level of proapoptotic protein Bax and reduced the levels of antiapoptotic protein Bcl-2, and significantly (p < 0.01) reduced the levels of SOD and GPx. However, treatment with eugenol resulted in a significant reduction (p < 0.01) in the levels of nitric oxide (NO) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, inhibited the activity of caspase-3, increased levels of Bcl-2 and significantly (p < 0.05) reduced levels of Bax protein, respectively, and also significantly (p < 0.05) increased the levels of SOD and GPx. Our results would hereby suggest that eugenol would provide a therapeutic value against aluminium-induced oxidative stress as related to antioxidant and antiapoptotic activities.

Hemostatic Agents in Endodontic Surgery: A Randomized Controlled Pilot Study of Polytetrafluoroethylene Strips as an Adjunct to Epinephrine Impregnated Gauze Versus Aluminum Chloride.

INTRODUCTION: Bleeding control is an important aspect in endodontic surgery. Two hemostatic techniques were compared with regard to their efficacy to bleeding control in endodontic surgery. METHODS: A randomized, 2-arm, parallel pilot study involving 30 patients with periradicular lesions was performed including the following hemostatic agents: polytetrafluoroethylene strips as an adjunct to epinephrine-impregnated gauze (test group, n = 15) and aluminum chloride (control, n = 15). Bleeding control was independently assessed by the surgeon and 2 blinded observers before and after application of the hemostatic agent. Bleeding control was classified either as adequate (complete bleeding control) or inadequate (incomplete bleeding control). RESULTS: Hemostasis in both groups proved similar. Simple binary logistic regression analysis failed to identify variables affecting bleeding control. Only the height of the keratinized mucosa band (≥2 mm) suggested a risk reduction for an inadequate bleeding control up to 79% (odds ratio = 0.21, P > .05). CONCLUSIONS: No differences in the efficacy of bleeding control were observed between polytetrafluoroethylene strips as an adjunct to epinephrine-impregnated gauze and aluminum chloride.

The Treatment of Primary Focal Hyperhidrosis

Primary focal hyperhidrosis is a relatively common disease that has a significant impact on afflicted patient's quality of life. The pathogenesis of the disease is thought to stem from increased cholinergic activity on eccrine sweat glands. Topical aluminum chloride based antiperspirants are good first-line agents for all affected body sites. Anticholinergic agents are emerging as effective topical alternatives. Iontophoresis passes an electrical current through the skin and is an excellent treatment option for palmoplantar disease. Botulinum toxin type A injections remain a mainstay second-line treatment. Local procedural advances including microwave thermolysis, laser therapy and focused ultrasound are emerging as safe and effective alternatives for refractory disease. Oral anticholinergics are generally well tolerated and can also be used for intractable disease. Last-line interventions include local surgical options and sympathectomy, though some patients may prefer permanent treatment. Further investigation of novel treatments as well as ways to optimize existing therapeutic options are needed.

Influence of Hemostatic Agents in the Prognosis of Periapical Surgery: A Randomized Study of Epinephrine versus Aluminum Chloride.

INTRODUCTION: Several variables have been associated with a better prognosis of periapical surgery. The aim of this study was to evaluate the influence of 2 hemostatic agents on the prognosis of periapical surgery at 12 months. METHODS: A prospective study was designed with 2 randomized parallel groups established depending on the hemostatic agent used: epinephrine or aluminum chloride. The analysis of the hemorrhage control was recorded as 0 (no hemorrhage control), 1 (slight but apparent intermittent bleeding persisted after application of the material), or 2 (complete hemorrhage control). At 12 months, periapical lesion healing was determined clinically and radiologically as success, improvement, or failure. RESULTS: Ninety-five patients (67 women and 28 men) with periapical lesions involving a single tooth were enrolled in this study; in 45 teeth, epinephrine was used and in 50 teeth aluminum chloride. In the epinephrine group, 28 teeth were classified as successes, 10 as improvements, and 7 as failures. In the aluminum chloride group, 34 teeth were classified as successes, 11 as improvements, and 5 as failures. No statistically significant difference was found. CONCLUSIONS: The present study found no association between the use of epinephrine or aluminum chloride as hemostatic agents on the prognosis of periapical surgery. The efficacy of hemostatic agents at the time of surgery showed no relationship with the healing outcome.