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.

Identification of a New Compound (4-Fluoro-2-Trifluoromethyl Imidazole) Extracted from a New Halophilic Bacillus aquimaris Strain Persiangulf TA2 Isolated from the Northern Persian Gulf with Broad-Spectrum Antimicrobial Effect.

Background: The unique ecosystem of the Persian Gulf has made it a rich source of natural antimicrobial compounds produced by various microorganisms, especially bacteria, which can be used in the treatment of infectious diseases, especially those of drug-resistant microbes. Objectives: This study aimed to identify antimicrobial compounds in the bacteria isolated from the northern region of the Persian Gulf in Abadan (Chavibdeh port), Iran, for the first time. Materials and Methods: Sampling was performed in the fall on November 15, 2019, from 10 different stations (water and sediment samples). The secondary metabolites of all isolates were extracted, and their antimicrobial effects were investigated. 16S ribosomal ribonucleic acid sequencing was used for the identification of the strains that showed the best inhibition against selected pathogens, and growth conditions were optimized for them. A fermentation medium in a volume of 5000 mL was prepared to produce the antimicrobial compound by the superior strain. The extracted antimicrobial compounds were identified using the gas chromatography-mass spectrometry technique. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for the superior strain. The effects of salinity, pH, and temperature on the production of antimicrobial compounds were determined by measuring the inhibitory region (mm) of methicillin-resistant Staphylococcus aureus (MRSA). Results: Four new strains with antimicrobial properties (i.e., Halomonas sp. strain Persiangulf TA1, Bacillus aquimaris strain Persiangulf TA2, Salinicoccus roseus strain Persiangulf TA4, and Exiguobacterium profundum strain Persiangulf TA9) were identified. The optimum growth temperatures were determined at 37-30, 37, and 40 °C for TA1 and TA2, TA4, and TA9 strains, respectively. The optimum pH values for the four strains were 7, 6-7, 7.5, and 6.5-7.5, respectively. The optimal salt concentrations for the four strains were 15%, 2.5-5%, 7.5%, and 5%, respectively. The ethyl acetate extract of strain Persiangulf TA2 showed extensive antimicrobial activity against human pathogens (75%) and MRSA. The most abundant compound identified in TA2 extract was the new compound 4-fluoro-2-trifluoromethyl imidazole. The MBC and MIC for the ethyl acetate extract of strain TA2 were 20 and 5 mg. mL-1 (Staphylococcus aureus), 40 and 20 mg. mL-1 (MRSA, Escherichia coli, and Enterococcus faecalis), 40 and 10 mg. mL-1 Acinetobacter baumannii), and 80 and 40 mg. mL-1 (Staphylococcus epidermidis, Shigella sp., Bacillus cereus, and Klebsiella pneumoniae), respectively. The optimal conditions for antibiotic production by TA2 strain were 5% salt concentration, pH of 7, and temperature of 35 °C. Conclusion: Newly detected natural compounds in TA2 strain due to superior antimicrobial activity even against MRSA strain can be clinically valuable in pharmacy and treatment.