Phyto-pharmacological Potential of Aegle marmelos (L.) for Neurological Disorders: Progress and Prospects.

BACKGROUND: Aegle marmelos, an Indian plant, has been extensively utilized by the people of the Indian subcontinent over about 5000 years. The leaves, bark, roots, and fruits, including seeds, are widely used to cure a variety of diseases in the Indian traditional system of medicine, Ayurveda, along with numerous folk medicines. By revealing the existence of significant bioactive chemicals, modern research has effectively substantiated the therapeutic effects of bael. OBJECTIVE: The objective of this study was to review the literature regarding A. marmelos geographical distribution, morphology, therapeutic benefits, and phytochemicals found in the bael leaves, fruits, and other parts of the plant that offer a wide range of pharmacological applications in neurological disorders. METHODOLOGY: A thorough literature search was conducted using five computerized databases, such as PubMed, Google Scholar, ScienceDirect, Elsevier, and Wiley Online Library (WOL), by using standard keywords "A. marmelos," "Geographical distribution," "Morphological description," "Ethnobotanical Uses," "Phytoconstituents" and "Neuroprotective activities" for review papers published between 1975 and 2023. A small number of earlier review articles focused on phyto-pharmacological potential of Aegle marmelos (L.) for neurological disorders. RESULTS: According to some research, Aegle marmelos extracts potentially have neuroprotective benefits. This is due to its capacity to alter cellular mechanisms that cause neuronal damage. CONCLUSION: Neurodegenerative illnesses usually induce permanent neuronal network loss overall the brain along with the spinal cord (CNS), resulting in chronic functional impairments. The review summarizes the multiple aspects and processes of A. marmelos extract and its components in several models of neurodegenerative diseases such as anxiety, epilepsy, depression, Parkinson's disease, Alzheimer's disease, and others. MDA, nitrite, TNF-, and IL-6 levels were dramatically elevated, whereas glutathione levels were significantly lowered in the hippocampus of STZ-treated rats. Furthermore, STZ-treated rats showed a substantial drop in catalase activity and an increase in AChE activity, indicating cholinergic hypofunction and neuronal injury. The neuroprotective ability of A. marmelos against STZ-induced oxidative stress and cognitive loss in rats suggests that it has therapeutic relevance in Alzheimer's disease (AD).

Characterization of Vancomycin Resistant Enterococci and Drug Ligand Interaction between vanA of E. faecalis with the Bio-Compounds from Aegles marmelos.

Objectives: Enterococcus faecalis is a gram positive diplococci, highly versatile and a normal commensal of the gut microbiome. Resistance to vancomycin is a serious issue in various health-care setting exhibited by vancomycin resistant Enterococci (VRE) due to the alteration in the peptidoglycan synthesis pathway. This study is thus aimed to detect the VRE from the patients with root caries from the clinical isolates of E. faecalis and to evaluate the in-silico interactions between vanA and the Aegles marmelos bio-compounds. Methods: E. faecalis was phenotypically characterized from 20 root caries samples and the frequency of vanA and vanB genes was detected by polymerase chain reaction (PCR). Further crude methanolic extracts from the dried leaves of A. marmelos was assessed for its antimicrobial activity. This is followed by the selection of five A. marmelos bio-compounds for the computational approach towards the drug ligand interactions. Results: 12 strains (60%) of E. faecalis was identified from the root caries samples and vanA was detected from two strains (16%). Both the stains showed the presence of vanA and none of the strains possessed vanB. Crude extract of A. marmelos showed promising antibacterial activity against the VRE strains. In-silico analysis of the A. marmelos bio-compounds revealed Imperatonin as the best compound with high docking energy (-8.11) and hydrogen bonds with < 140 TPSA (Topological polar surface area) and zero violations. Conclusion: The present study records the VRE strains among the root caries with imperatorin from A. marmelos as a promising drug candidate. However the study requires further experimentation and validation.

An eco-friendly saltless method of preservation of skins using A. marmelos extract.

In leather industries, raw hides/skins are always preserved before being processed into leather. Salting method of preservation is the general and age old popular practice of preservation used in these industries. The main drawbacks of this method are the generation of huge amounts of pollution load, in terms of total dissolved solids (TDS), total suspended salts (TSS), and chlorides; and ecological damage which occurs as a result of these waste effluents being discharged into the ground. Therefore, finding cheaper and eco-friendly methods of preservation has become a major necessity for these industries. In this manuscript, we have used ethanolic extract of Aegle marmelos for preservation which totally eliminates salt. The efficacy of this method was assessed by evaluating parameters such as microbial count, nitrogen content, and collagen content of the skin samples, and biological oxygen demand (BOD), chemical oxygen demand (COD), TDS, and TSS of the waste effluents collected during processing of leather. It was found that this method showed a remarkable reduction in pollution loads like BOD (46%), COD (3-fold), TDS (many folds), and increased values of collagen content. Thus, we could conclude that preservation using A. marmelos was found to be more effective and eco-friendly.

Aegle marmelos leaf extract ameliorates the cognitive impairment and oxidative stress induced by intracerebroventricular streptozotocin in male rats.

AIMS: Aegle marmelos (L.) Correa (A. marmelos) has been used in Ayurvedic medicine as a brain tonic however its neuroprotective effect against streptozotocin (STZ) induced cognitive impairment and oxidative stress has not been reported yet in vivo. Therefore, the present study was attempted to investigate the neuroprotective potential of ethanolic extract of A. marmelos leaves (AME) on STZ induced memory impairment in male rats. MAIN METHODS: Albino Wistar rats were pre-treated orally with AME at the doses 200 and 400 mg/kg for two weeks, followed by intracerebroventricular (i.c.v.) injection of STZ (3 mg/kg) on day 1 and 3. Two weeks after STZ administration, behavioural parameters were monitored using Morris water maze task. Biochemical and histopathological studies were carried out after three weeks of STZ administration. The levels of oxidative stress markers (malondialdehyde (MDA), glutathione, nitrite, catalase) neuroinflammatory mediators; tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and acetylcholinesterase (AChE) activity were estimated in hippocampus of rat brain. Donepezil (5 mg/kg) was taken as a standard drug. KEY FINDINGS: The levels of MDA, nitrite, TNF-α and IL-6 were significantly increased while glutathione levels were significantly decreased in hippocampus of STZ-treated rats. Further, a significant decrease in the activity of catalase and increase in AChE activity was observed indicating cholinergic hypofunction and neuronal damage in STZ-treated animals. All these alterations were significantly ameliorated by AME in a dose dependent manner. SIGNIFICANCE: The neuroprotective potential of A. marmelos against STZ induced oxidative stress and cognitive deficit in rats indicates its therapeutic value in Alzheimer's disease (AD).

Efficiency of the leaves and fruits of Aegle marmelos methanol extract (L.) Correa and their relative hepatotoxicity induced by CCL4 and identification of their active constituents by using LC/MS/MS.

The methanol extracts of both leaves and fruits (MEL & MEF) of A. marmelos (L.) Correa (family Rutaceae) were analyzed by using analytical method based on liquid chromatography-tandem mass spectrometry (LC/MS/MS). The objective of this study was to identify the active constituents of (MEL & MEF) of A. marmelos. Six, alkaloids namely aeglemarmelosine, marmesiline aegelinoside, shahidine, anhydromarmeline and N-2-methoxy-2-(4-methoxyphenyl) ethylcinnamide and two flavonoids, rutin and kaempferol-3-O-rutinoside in leaves were identified. Two alkaloids marmesiline and shahidine in the methanol extracts of fruits, also have been identified. Moreover, the efficiency of extracts was performed for measuring the reducing hepatotoxicity effect induced by carbon tetrachloride (CCl4) in mice. Accordingly, several biochemical parameters were performed such as lipid profile in serum, liver functions enzyme activities, glycolytic enzyme activities. In addition, LDH and SDH were investigated. The results obtained demonstrated, significant increase in lipid profile, liver function biomarkers in addition to glycolytic enzyme activities in CCl4-induced hepatotoxicity. Histopathological examination confirmed the biochemical results. Treatment of intoxicated mice with (MEL & MEF) of A. marmelos showed amelioration signs in biochemical findings as well as at cellular level. It could be concluded that both MEL & MEF can be used clinically for their potential effect as a hepatoprotective that normalized liver function biomarkers, hepatic architecture and restore physiologically status of the body against CCl4 intoxication.

Antibacterial activity of Aegle marmelos against leaf, bark and fruit extracts.

The antibacterial activity of the methanol, chloroform and aqueous extracts from the leaves, bark and fruit of A. marmelos was studied using disc diffusion method against Bacillus subtilis, Staphylococcus aureus (Gram Positive), Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli, Salmonella paratyphi A and Salmonella paratyphi B (Gram Negative). Results suggest that the methanolic extract has significant antibacterial activity against tested bacteria. The present study justifies the claimed uses of A. marmelos in the traditional system of medicine to treat various infectious diseases.