A mucoadhesive nanolipo gel containing Aegle marmelos gum to enhance transdermal effectiveness of linezolid for vaginal infection: In vitro evaluation, in vitro-ex vivo correlation, pharmacokinetic studies.

Effective treatment of vaginal infections with conventional antibiotics often faces challenges like unavoidable dose-related side effects with increased risk of bacterial resistance. The study aims to deliver linezolid through natural gum based mucoadhesive nano lipogel to improve therapeutic effectiveness against vaginal infections. The linezolid loaded nanoliposomes (LNLs) were developed by thin film hydration method and were characterized by FTIR, DSC, XRD, FESEM, particle size analysis, zeta potential, drug loading capacity, in vitro release study etc. Selected LNLs was loaded into suitable gel formulation containing Aegle marmelos gum (as the mucoadhesive agent) and evaluated for in vitro, in vivo potentiality. FTIR/DSC test confirmed absence of any major interaction between selected drug and excipients. XRD showed amorphization of the drug encapsulated in NLs. FESEM studies showed spherical LNLs having smooth surface. LNLs had nanosize (51.03 nm), negative surface charge (-25.7 mV), satisfied drug loading capacity (11.5 ± 0.7 %) with sustained drug release. The experimental LNLs loaded lipogel showed desired physico-chemical properties viz. viscosity (37000 cps), spreadability (6.5 gm.cmsec-1), mucoadhesion (21.9 gf) and 61.04 % release of drug across rabbit vaginal mucosal membrane. The nanolipo gel exhibited improved antimicrobial activity against E. coli and C. albicans with respect to the pure linezolid. A good correlation was observed in between in vitro drug release and ex vivo permeation. Improved pharmacokinetic parameters like AUC, AUMC, MRT, Vd was observed for experimental nanolipo gel Vs. marketed formulation. The experimental nanolipo gel could be explored further for futuristic clinical application.

Green Synthesis of Copper Oxide Nanoparticles from the Leaves of Aegle marmelos and Their Antimicrobial Activity and Photocatalytic Activities.

The leaves of the Aegle marmelos plant were used for the green synthesis of copper oxide nanoparticles and further characterized by different techniques, including (Ultra Violet-Visible) UV-Vis, Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), Transmission electron microscopy (TEM) and X-ray diffraction (XRD). The UV-Vis showed a peak at 330 nm, which may be due to the Surface Plasmon Resonance phenomenon. XRD analysis showed the crystalline nature of copper oxide nanoparticles (CuO NPs). In contrast, SEM showed that nanoparticles were not aggregated or clumped, EDX showed the presence of elemental copper., and further, the TEM analysis revealed the average particle size of copper oxide nanoparticles to be 32 nm. The Minimum Inhibitory Concentration (MIC) for Escherichia coli (E. coli) and Staphylococcusaureus (S. aureus) was found to be 400 µg/mL, whereas for Candida albicans (C. albicans) and Candida dubliniensis (C. dubliniensis) it was 800 µg/mL. The zone of inhibition in the well diffusion assay showed the antimicrobial activity of copper oxide nanoparticles, and it also showed that as the concentration of copper oxide nanoparticles increased, the zone of inhibition also increased. Further, the electron microscopic view of the interaction between copper oxide nanoparticles and C. albicans cells showed that CuO NPs were internalized and attached to the cell membrane, which caused changes in the cellular structure and caused deformities which eventually led to cell death. The prepared CuO NPs showed significant photocatalytic degradation of organic dyes in the presence of sunlight.

Bael (Aegle marmelos L. Correa) fruit extracts encapsulated alginate nanoparticles as a potential dietary supplement with improved bioactivities.

Nanoencapsulated bael fruit (Aegle marmelos L. Correa (Family: Rutaceae)) extracts reveal novel prospects in the development of dietary supplements with improved biological activities in the field of the food industry. The main objectives of this study were to prepare and characterize aqueous, ethanol, 50% ethanol, and 50% acetone extracts of bael fruit encapsulated alginate nanoparticles and investigate the effect of encapsulation on in vitro release of polyphenols, antidiabetic, antioxidant, and anti-inflammatory activities, and their stability. Bael fruit extracts encapsulated alginate nanoparticles were prepared using the ionic gelation method. Characterization, in vitro release profiles of polyphenols, determination of antidiabetic, anti-inflammatory, antioxidant activity, and accelerated stability were conducted. The results of the characterization confirmed the successful encapsulation of extracts of bael fruit in the alginate matrix. The aqueous extract of bael fruit encapsulated alginate nanoparticles exhibited a more controlled slow-release profile, accounting for 21.82% ± 1.17% and 48.14% ± 0.52% of polyphenols at solutions of pH 1.2 and pH 6.8, respectively. In general, the results of the bioactivity assessment suggested that nanoencapsulation could facilitate the enhancement of its antidiabetic, antioxidant, and anti-inflammatory properties. The results of thermogravimetric analysis and thin layer chromatography fingerprint showed the stability of aqueous bael fruit extract encapsulated alginate nanoparticles at 27 and 4°C over a month. In summary, the results of this study revealed the potency of nanoencapsulated aqueous extract of bael fruit to develop a dietary supplement with improved antidiabetic, antioxidant, and anti-inflammatory activities. PRACTICAL APPLICATION: The encapsulation of bael fruit extracts into a nanocarrier enhances bioactivities and promotes the controlled release of bioactive compounds. This could be useful in the future food industry, based on scientifically proven data, and inspire the market by means of the development of dietary supplements. Overall, the results would facilitate the formulation of novel commercially elegant nanoencapsulated dietary supplements with improved potential to manage a healthy life.

Proposal of a novel subspecies: Alicyclobacillus hesperidum subspecies aegles.

Alicyclobacillus sp. DSM 11985T was isolated from geothermal soil but had not yet been classified at the species level. The strain produced guaiacol, which is of interest from the viewpoint of food spoilage in the food industry. 16S rRNA gene sequence analysis revealed that strain DSM 11985T was closely related (99.6 % similarity) to Alicyclobacillus hesperidum DSM 12489T. However, strains of A. hesperidum did not produce guaiacol; therefore, we performed the taxonomic characterization of strain DSM 11985T. The results showed that strain DSM 11985T and strains of A. hesperidum showed different phenotypic characteristics in biochemical/physiological tests including guaiacol production. Average nucleotide identity values between strain DSM 11985T and strain DSM 12489T were 95.4-95.9 %, and the in silico DNA-DNA hybridization value using the Genome-to-Genome Distance Calculator between strains DSM 11985T and DSM 12489T was 65.5 %. These values showed that strain DSM 11985T was genetically closely related but separated from strains of A. heparidum. From the above results, a novel subspecies of A. hesperidum, named Alicyclobacillus hesperidum subsp. aegles subsp. nov. is proposed. The type strain is DSM 11985T (=FR-12T=NBRC 113041T).

Green synthesis-assisted copper nanoparticles using Aegle marmelos leaves extract: physical, optical, and antimicrobial properties.

In the present report, Aegle marmelos leaf powder was used to synthesize copper nanoparticles (CuNPs) using a simple and cost-effective method. A. marmelos leaves have various medicinal uses including for the treatment of diarrhoea, constipation, diabetes, cholera, skin diseases, earache, blood purification, heart problems, and so on. The plant biomolecules induce the reduction of Cu2+ ions to CuNPs and also act as a capping and stabilizing agent. The formation of CuNPs was confirmed using photoluminescence (PL) excitation and emission spectra on a Shimadzu RF-5301 PC spectrofluorophotometer and the absorbance spectra of a UV-visible spectrophotometer at different stages during the synthesis process. In addition, other properties of synthesized CuNPs were also investigated using X-ray diffraction, Fourier transform infrared spectroscopy, and transmission electron microscopy techniques. The average size of the synthesized CuNPs was in the range 20-40 nm. Furthermore, the synthesized NPs were also considered for an antimicrobial study against Gram-positive Staphylococcus aureus and Proteus, and Gram-negative Escherichia coli and Salmonella spp. using the agar well diffusion method. The zone of inhibition against the Gram-positive bacteria was greater than the zone of inhibition against the Gram-negative bacteria. These investigation results suggest that synthesized NPs are promising nanomaterials for use as antimicrobial agents.

Process optimization for spray dried Aegle marmelos fruit nanomucilage: Characterization, functional properties, and in vitro antibiofilm activity against food pathogenic microorganisms.

Recently, mucilage extraction from plant sources has been remarkably explored due to its potential applications. Several underutilized fruits such as Aegle marmelos are the potential source of mucilage that can be utilized for agri-food-pharma applications. Therefore, in this study, we explored vital functional and antimicrobial properties of Aegle marmelos nanomucilage. Spray drying conditions such as inlet temperature, feed flow, and atomization speed were optimized to assess the influence on yield and moisture content using response surface methodology. In addition, during the optimized spray drying conditions, the maximum mucilage yield was 16.23 % (w/w). The particle size (178.4 ± 5.06 nm) at the nanoscale, polydispersity index (0.432), and zeta potential (-16.4 ± 1.14 mV) confirmed the stability of the nanomucilage. Moreover, the spray-dried nanomucilage powder exhibited high thermal stability (55.70 J) and excellent industrially important techno-functional properties with water-holding capacity (8.01 ± 0.04 g/g), oil-holding capacity (3.43 ± 0.7 g/g), emulsifying capacity (91.50 ± 0.78 %), emulsifying stability (92.65 ± 0.46 %), solubility (89.36 ± 1.69 %), and foaming capacity (16.13 ± 0.41 %). Moreover, the powder showed strong antibiofilm activity against food-pathogenic bacteria, including Escherichia coli (73.52 ± 1.14 %) and Staphylococcus aureus (79.57 ± 1.23 %), with minimum inhibitory concentrations of 3.125 mg/mL and 1.562 mg/mL respectively. Overall, based on the above findings the spray-dried powder of Aegle marmelos fruit nanomucilage could be utilized as a potential functional ingredient in various food products formulations.

In Vitro Dengue Virus Inhibition by Aqueous Extracts of Aegle marmelos, Munronia pinnata and Psidium guajava.

Dengue is an arboviral (insect-transmitted) infection of global concern. Currently, there are still no specific dengue antiviral agents to treat the disease. Plant extracts have been used in traditional medicine for treating various viral infections - thus, in the present study, aqueous extracts of dried flowers of Aegle marmelos (AM), whole plant of Munronia pinnata (MP) and leaves of Psidium guajava (PG) were investigated for their potential capacity to inhibit dengue virus infection of Vero cells. The maximum non-toxic dose (MNTD) and the 50% cytotoxic concentration (CC50) were determined by using the MTT assay. A plaque reduction antiviral assay was carried out with dengue virus types 1 (DV1), 2 (DV2), 3 (DV3) and 4 (DV4), in order to calculate the half-maximum inhibitory concentration (IC50). AM extract inhibited all four virus serotypes tested; MP extract inhibited DV1, DV2 and DV4, but not DV3; PG extract inhibited DV1, DV2 and DV4, but not DV3. Thus, the results suggest that AM is a promising candidate for the pan-serotype inhibition of dengue viral activity.

Aegle marmelos (L.) Correa: An Underutilized Fruit with High Nutraceutical Values: A Review.

Aegle marmelos (L.) Correa (Bael) fruit, a member of the Rutaceae family, is a major cultivated fruit plant in tropical and subtropical regions in countries of southeast Asia. Bael fruit has been a major topic for studies in recent years mainly due to its high nutritional (carbohydrates, proteins, minerals, and vitamins) value and presence of various phytochemicals, which attributed to its high medicinal value. These phytochemicals include various compounds, e.g., alkaloids, flavonoids, and phenolic acids (protocatechuic acid, gallic, and ellagic acid). The fruit extract of bael has been also an important study area for its pharmacological activities, including antidiarrheal, antioxidant, antidiabetic, hepatoprotective, radioprotective, anticancer, antiulcer properties. The current review mainly highlighted the nutritional and pharmacological activities of bael fruit. The nutritional profile and phytochemical profile were discussed in the review, along with their concentration in the fruit. Moreover, the experiments carried out in vivo and in vitro of bael fruit extracts with respect to their pharmacological activities were also discussed in the article. The recent literature based on nutritional and pharmacological values of bael fruit showed its high potential as a food and pharmaceutical product. Despite having high nutritional and pharmacological value, research related to molecular mechanisms of bael fruit is still limited, and clinical trials are needed to ensure its safety as a product in the food and pharma industries.

Anti-inflammatory effects of Pikad Tri-phol-sa-mut-than remedy, consisting of dried fruits of Aegle marmelos (L.) Corrêa, Coriandrum sativum L., and Morinda citrifolia L.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation has been known to possess some essential roles in many diseases, especially those with chronic or severe conditions. Pikad Tri-phol-sa-mut-than, a Thai traditional herbal remedy, has long been used to treat gastrointestinal sicknesses, fever, and severe illness caused by the deformities of Tridosha. In particular, this recipe has also been applied for inflammation-related conditions including gout and rheumatoid arthritis. The Pikad Tri-phol-sa-mut-than recipe consists of dried fruits of three herbs including Aegle marmelos (L.) Corrêa, Morinda citrifolia L., and Coriandrum sativum L. Each of these plant components of Pikad Tri-phol-sa-mut-than exhibited anti-inflammatory activities. However, anti-inflammatory effect of Pikad Tri-phol-sa-mut-than remedy has not been reported. AIM OF THE STUDY: The objective of this study was to elucidate the anti-inflammatory activities of Pikad Tri-phol-sa-mut-than extract (TS) against acute and chronic inflammation in rats. MATERIALS AND METHODS: To study the effects of TS on acute inflammation, ethyl phenylpropiolate (EPP)-induced ear edema, carrageenan- and arachidonic acid (AA)-induced hind paw edema models were carried out. In addition, cotton pellet-induced granuloma formation was performed to specify the inhibitory effects of TS on chronic inflammation. RESULTS: The topical application of TS significantly inhibited EPP-induced ear edema in rats. In the carrageenan- and AA-induced paw edema models, the oral administration of TS significantly reduced paw volumes, compared to those of the control groups. In addition, the 7-day oral treatment of TS demonstrated a significant suppressive effect on cotton pellet-induced granuloma formation. CONCLUSIONS: The current study revealed that TS possesses anti-inflammatory activities against acute and chronic inflammation. Our studies support the use of TS in traditional medicine, and the development of TS as a novel natural product for treating diseases associated with inflammation.

Bimetallic p-ZnO/n-CuO nanocomposite synthesized using Aegle marmelos leaf extract exhibits excellent visible-light-driven photocatalytic removal of 4-nitroaniline and methyl orange.

In the current study, the photocatalytic activity of bimetallic ZnO-CuO hetero-nanocomposite was evaluated and compared with the monometallic ZnO and CuO nanoparticles using 4-nitroaniline (4-NA) and methyl orange (MO). Bimetallic ZnO-CuO hetero-nanocomposite, ZnO, and CuO nanostructure were synthesized utilizing leaf extract of Aegle marmelos and characterized by transmission electron microscopy, X-ray diffraction, and XPS. Benefiting from the p-n heterostructures formation, bimetallic ZnO-CuO hetero-nanocomposite exhibits an excellent photocatalytic activity against 4-NA as well as MO compared to pure ZnO and CuO. In particular, bimetallic ZnO-CuO hetero-nanocomposite expressed the highest photocatalytic activity by reducing 90% of 4-NA in 20 min and by degrading 96% of MO in 10 min, whereas 65% reduction of 4-NA in 30 min and 93% degradation of MO in 45 min was exhibited by CuO and 48% reduction of 4-NA in 30 min and 98% degradation of MO in 50 min was exhibited by ZnO. Moreover, bimetallic ZnO-CuO hetero-nanocomposite maintains excellent photocatalytic activity even after five cycles indicating its stability as photocatalyst and reusability. Based on the experimental findings, bimetallic ZnO-CuO hetero-nanocomposite could be used as a photocatalyst for wastewater treatment with excellent regeneration efficiency.

Herbal root extracts in Ben-Cha-Moon-Yai remedy attenuated pain-like behaviors and inflammation through the opioid and prostaglandin systems.

ETHNOPHARMACOLOGICAL RELEVANCE: Ben-Cha-Moon-Yai (BMY) remedy used in Thai traditional medicine as an anti-inflammatory, analgesic, and antipyretic agent compromises five herbal root extracts of equal weights: Aegle marmelos (L.) Corrêa (AM), Oroxylum indicum (L.) Kurz (OI), Dimocarpus longan Lour. (DL), Dolichandrone serrulata (Wall. ex DC.) Seem. (DS), and Walsura trichostemon Miq. (WT). AIM OF THE STUDY: To assess the anti-nociceptive and anti-inflammatory effects of the root extracts of all five species of BMY in experimental animal (mouse) models to ensure the rational use of herbal products in Thai traditional medicine. MATERIALS AND METHODS: Root extracts prepared by ethanol and water extraction were used for the biological assays in animal models at five dose levels: 25, 50,100,200 & 400 mg/kg. The anti-nociceptive activity was evaluated based on hot-plate latency, duration of paw licking induced by formalin, and abdominal writhing induced by acetic acid. Carrageenan- and prostaglandin-induced paw oedema models were used to determine the anti-inflammatory activity. RESULTS: The oral administration of AM, DS and WT root extracts displayed significant analgesic effects in the hot-plate test, both phases (early and late) of formalin test and acetic-acid induced writhing test at different dose levels. OI and DL only produced significant analgesia in the late phase of the formalin test and writhing test. The pretreatment of animals with the non-selective opioid receptor antagonist naloxone, reverse AM, DS and WT induced-antinociceptive activity. In both carrageenan and prostaglandin-induced paw oedema tests, all five herbal plant root extracts significantly reduced paw oedema at 3 h or more at different dose levels. Rotarod test results showed no effects of five herbal plant root extracts on the balance and the motor coordination at the highest dose level evaluated (400 mg/kg). CONCLUSION: The root extracts of AM, DS, and WT possess both central and peripheral anti-nociceptive properties, while OI and DL possess only peripheral analgesic properties. All five root extracts own anti-inflammatory properties, which might be due to their activity on the prostaglandin system. Altogether these findings ensure the rational use of BMY remedy in Thai traditional medicine.

Performance enhancing, immunomodulatory, anti-hyperlipidaemic, and antimicrobial properties of bael (Aegle marmelos) leaf powder in broiler chicken.

This study investigated the effects of bael leaf powder (BLP) on growth performance, immunity, serum biochemistry, and caecal microbiology of broiler chickens. Following completely randomised design, a total of 288-day-old CARIBRO-Vishal broiler chickens were randomly divided into six treatment groups consisting of experimental diets formulated as follows - T1 (basal diet), T2 (basal diet + 250 mg bacitracin methylene disalicylate-BMD/kg diet), T3 (basal diet + 5 g BLP/kg diet) T4 (basal diet + 10 g BLP/kg diet), T5 (basal diet + 15 g BLP/kg diet), and T6 (basal diet + 20 g BLP/kg diet). Proximate analysis of green bael leaves revealed 65.6% moisture and on dry matter basis, BLP contained 14.31% protein, 1.89% fat, 16.30% crude fibre, 4.25% calcium, and 2.08% phosphorous. This study revealed no adverse effects of BLP supplementation on growth performance and carcass characteristics of broiler chicken. The BLP supplementation at 20 g/kg diet resulted in higher relative weights of bursa and thymus with better cell mediated (higher foot web index) and humoral immune (higher antibody titre against sheep RBCs) responses in broiler chicken. Lower abdominal fat deposition was observed in broiler chicken fed 20 g BLP/kg diet. Significantly lower serum uric acid, creatinine, AST, and ALT were observed in BLP supplemented chicken which indicates nephro-protective and hepato-protective functions of BLP. Serum cholesterol, triglycerides, and tissue cholesterol content of broiler chicken decreased progressively with increasing dietary BLP levels. The supplementation of 20 g BLP/kg diet resulted in lower E. coli and Coliform counts, whereas, increasing trend was observed in Lactobacillus count in caecum of broiler chicken. In conclusion, the BLP supplementation at 20 g/kg diet exerted immunomodulatory, anti-hyperlipidaemic, and antibacterial effects in broiler chicken without any adverse effects on the growth performance.

Dry ripe fruit of Aegle marmelos as anti-ulcer agent against ethanol induced gastric mucosal injury.

Aegle marmelos is cost-effective valuable South Asian tree. The folklore data reported its wide range pharmacological effects. In spite of vast reported work on various parts, the dry ripe fruit extract has not yet been studied for gastric ulcers. Present study is planned to investigate its potential protective effects against ethanol-induced gastric injury in rats. In current study the gastro protective effect of ethanolic crude extract of A. marmelos dried ripe fruit at 200, 400 and 800mg/kg body weight were studied in albino rats. Ranitidine used as standard drug (50mg/kg body weight). Absolute ethanol increase the degree of ulceration (UI) in rats while a significant improvement in the level of inhibition against ulceration was observed in test and standard groups as compare to control. Pre-fed test drug exhibited a significant reduction in the sore area (UI), accelerate % age protection and increased of gastric content in dose dependence manner. Test drug at 800mg/kg dose showed marked deduction in mean UI 3.0, significant increase in protection 83% with pH 7.3 (p<0.01). Standard drug exhibited 3.25 UI, 81% protection with pH 7.1. In conclusion, it was found that dry ripe fruit of A. marmelos possesses a significant anti-ulcer effect in rats.

Antidepressive-Like Effect of Aegle marmelos Leaf Extract in Chronic Unpredictable Mild Stress-Induced Depression-Like Behaviour in Rats.

Background: Depression is a psychiatric disorder leading to anhedonia and lack of interest and motivation. Depressive symptoms are triggered by stressful life events, and patients with major depression are at significantly increased risk of attempting suicide. The crucial concern in depression treatment with antidepressant medications is that few weeks are required to show the therapeutic effect along with moderate side effects. The use of herbal medications is a new strategy for the treatment of depression which is often based on medicinal plants.Aegle marmelos (L.) Corr. (family: Rutaceae) is reported to have several actions on the central nervous system producing beneficial effects in anxiety, Alzheimer's disease, Parkinson's disease, epilepsy, and convulsion. Thus, the current investigation designed to assess the antidepressant activity of the standardized hydroethanolic extract of Aegle marmelos (EAM) leaves in male rats exposed to the chronic unpredictable mild stress (CUMS) paradigm. Methods: Rats were divided in 5 groups. The control group was not subjected to experimental CUMS paradigm, while 4 other groups were subjected to CUMS paradigm to induce depression-like behaviour from day 1 to day 28. Following the CUMS paradigm, 4 groups were divided as CUMS disease control, CUMS+EAM (150 mg/kg, p.o.), CUMS+EAM (300 mg/kg, p.o.), and CUMS+imipramine (15 mg/kg, p.o.), and treatment was given for seven consecutive days to the respective groups (day 29 to day 35). Behavioural parameters such as open field test, forced swim test, sucrose feeding test, and tail suspension test on day 1, day 28, and day 35 were measured, and biochemical parameters such as plasma corticosterone level, serotonergic system (5-HT, 5-HIAA, and 5-HT/5-HIAA), mitochondrial function, and proinflammatory mediators (TNF-α, IL-1ß, and IL-6) were estimated in hippocampus (HIP) and prefrontal cortex (PFC) regions of the brain on day 35, after the behavioural observations. On the other hand, phytochemical profile of Aegle marmelos was done. Results: On day 35, EAM (300 mg/kg) significantly reduced the immobility time during the tail suspension test from 208.66 ± 4.72 s to 108.83 ± 4.81 s and forced swim test from 200.16 ± 4.12 s to 148.5 ± 4.58 s. It also enhanced the behavioural parameters in the open field test such as ambulation from 26.5 ± 2.14 to 56.5 ± 1.80, rearing from 8.33 ± 0.71 to 19 ± 0.57, time spent in centre from 9.16 ± 0.9 to 17.16 ± 0.79 s, total distance travelled from 2.36 ± 0.12 to 4.68 ± 0.10 m, and anhedonia in the sucrose feeding test from 109.33 ± 1.08 to 135.83 ± 3.91 mL. The stimulation of the HPA axis resulting elevated corticosterone level caused by CUMS was reduced by EAM (300 mg/kg) from 80.12 ± 2.020 to 48.25 ± 2.407 µg/dL. Furthermore, EAM (300 mg/kg) increase CUMS-induced changes in serotonin (5-HT) level in HIP and PFC from 3.132 ± 0.09586 to 4.518 ± 0.1812 and 4.308 ± 0.1593 to 5.262 ± 0.1014 ng/mg protein, respectively. EAM (300 mg/kg) significantly attenuated the CUMS-induced changes in proinflammatory cytokine production and mitochondrial function in HIP and PFC. One group used to determine the acute toxicity as per OECD-23 standard protocol which resulted that 300 mg/kg EAM has no significant acute toxicity. Total phenolic content and total flavonoid content of standardized hydroalcoholic extract of AM was found 95.024 ± 2.431 and 36.820 ± 3.41, respectively, and additional identification tests showed the presence of alkaloids, tannins, saponins, cardiac glycosides, flavonoids, and terpenoids. Conclusion: On the basis of findings, EAM can be inferred as a potential antidepressant-like effect of this plan in preclinical research.

Impacts of Aegle marmelos fruit extract as a medicinal herb on growth performance, antioxidant and immune responses, digestive enzymes, and disease resistance against Streptococcus agalactiae in Nile tilapia (Oreochromis niloticus).

An experiment was conducted to investigate the effects of Aegle marmelos fruit (AMF) extract on the growth performance, biochemical parameters, immune response, antioxidative capacity, and digestive enzyme activity of Nile tilapia (Oreochromis niloticus). Fish were fed a diet supplemented with AMF at concentrations of 0 (AMF0; control), 5 (AMF5), 10 (AMF10), 15 (AMF15), or 20 (AMF20) g/kg for 8 weeks. The results show that the final body weight, weight gain, specific growth rate, average daily gain, and feed conversion ratio were significantly higher in fish fed AMF15 and AMF20 compared to those fed the control diet (P < 0.05). Moreover, significant increases in antioxidant enzyme activities and non-specific immune responses were observed in groups fed AMF15 and AMF20. Interestingly, the level of cholesterol decreased with increasing AMF concentrations in the diet. As dietary AMF levels increased, digestive enzyme activities significantly improved. After the feeding trial, fish were injected intraperitoneally with Streptococcus agalactiae, and the 14-day cumulative mortality was calculated. A high survival rate after challenge with S. agalactiae was observed in all groups that received AMF-supplemented feed. Therefore, the present study suggests that supplementing the diet of Nile tilapia with AMF at a concentration of 20 g/kg could encourage their growth, improve their immunity and antioxidant status, and provide strong protection against S. agalactiae.

Thermo-chemical potential of solid waste seed biomass obtained from plant Phoenix dactylifera and Aegle marmelos L. Fruit core cell.

The present study explores thermo-chemical potential of two biomasses namely; Phoenix dactylifera seed (PDS) and Aegle marmelos L core (AMP). These biomasses contain high amount of cellulose and exhibit heating value of 3-18 MJ/kg. The thermal kinetic of both the biomasses have been extensively studied using thermogravimetric analysis (TGA) at four different heating rates 5, 10, 15, and 20 °C/min. Kinetic analysis was carried out using three model-free techniques including Flynn-Wall-Ozawa (FWO), Kissinger-Akahira-Sunose (KAS) and Starink. The average activation energy has been found to be 173.75, 172.94 and 170.71 kJ/mol, for PDS whereas 170.26, 167.24 and 164.80 kJ/mol, for AMP analyzed through KAS, FWO and Starink methods, respectively. Further, among all these models, the Starink model exhibits better result for the biofuels potential point of view.

Inhibition of multiple SARS-CoV-2 proteins by an antiviral biomolecule, seselin from Aegle marmelos deciphered using molecular docking analysis.

Our earlier experimental and computational report produced evidence on the antiviral nature of the compound seselin purified from the leaf extracts of Aegle marmelos against Bombyx mori Nuclear Polyhedrosis Virus (BmNPV). In the pandemic situation of COVID-19 caused by the SARS-COV-2 virus, an in silico effort to evaluate the potentiality of the seselin was made to test its efficacy against multiple targets of SARS-COV-2 such as spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease. The ligand seselin showed the best interaction with receptors, spike protein S2, COVID-19 main protease and free enzyme of the SARS-CoV-2 (2019-nCoV) main protease with a binding energy of -6.3 kcal/mol, -6.9 kcal/mol and -6.7 kcal/mol, respectively. Docking analysis with three different receptors identified that all the computationally predicted lowest energy complexes were stabilized by intermolecular hydrogen bonds and stacking interactions. The amino acid residues involved in interactions were ASP1184, GLU1182, ARG1185 and SER943 for spike protein, SER1003, ALA958 and THR961 for COVID-19 main protease, and for SARS-CoV-2 (2019-nCoV) main protease, it was THR111, GLN110 and THR292. The MD simulation and MM/PBSA analysis showed that the compound seselin could effectively bind with the target receptors. The outcome of pharmacokinetic analysis suggested that the compound had favourable drugability properties. The results suggested that the seselin had inhibitory potential over multiple SARS-COV-2 targets and hold a high potential to work effectively as a novel drug for COVID-19 if evaluated in experimental setups in the foreseeable future. Communicated by Ramaswamy H. Sarma.

Analysis of polyphenols in Aegle marmelos leaf and ameliorative efficacy against diabetic mice through restoration of antioxidant and anti-inflammatory status.

The biomedical survey reports edible plant Aegle marmelos has been utilized for centuries by tribal communities in India as a dietary supplement for the management of diabetes. Herein, we have investigated cytotoxicity, cytoprotective and antidiabetic activity of characterized alkaloid-free hydroalcoholic extract of A. marmelos (AFEAM; 200 and 400 mg/kg). Identification of polyphenols and quantification of major compounds were done using UPLC-MS and HPTLC, respectively. AFEAM showed good cytocompatibility and cytoprotective potential against oxidative stress induced by hyperglycemia in HepG2 cells. The AFEAM intake had significantly ameliorated the serum blood glucose level, state of dyslipidemia, level of pro-inflammatory markers (tumor necrosis factor-α, interleukin-6, and interleukin-1ß), and antioxidant (superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde) status in diabetic mice. Histological examination of the treated groups showed amelioration of damaged pancreas, liver, and kidney tissues. Conclusively, AFEAM intake might be promising dietary supplements for prediabetics as well as an adjuvant to modern treatment in diabetics. PRACTICAL APPLICATIONS: Different reports have been published on Aegle marmelos but as per our understanding till date, no study has been reported on the amelioration of diabetes due to alkaloid free hydroalcoholic extract of A. marmelos /polyphenolic content in the animal model. The result of this study indicated that A. marmelos supplementation effectively ameliorates diabetes through the restoration of antioxidant and anti-inflammatory status. This study has collated sufficient scientific evidence for the dietary application of A. marmelos in society especially for prediabetics, however, it can also be used as an adjuvant to modern treatments in diabetics.

Evaluation of the Antidepressant-like Effect of Total Sterols Fraction and Stigmasterol Isolated from Leaves of Aegle marmelos and Possible Mechanism( s) of Action Involved.

BACKGROUND: Aegle marmelos Corr. (Rutaceae) commonly known as 'Indian Bael' has been used as a brain tonic traditionally. However, despite this traditional use, not enough scientific report is present that can confirm the use of this plant in neurological disorders. Thus, the total sterols fraction and stigmasterol from the leaves of Aegle marmelos were investigated for antidepressant-like effect along with their possible mechanism(s) of action by primarily performing acute toxicity study of total sterols. METHODS: An acute toxicological study was carried out at a single oral dose of 2000 mg/kg. Sign of toxicity was observed by estimating biochemical and performing histopathological analysis. For the antidepressant-like effect, different doses of total sterols (50-200 mg/kg, p.o. for seven days) and stigmasterol (5- 20 mg/kg, i.p. acute) were administered in mice using TST and FST models. To evaluate the mechanism of action, mice were pretreated with GABA, 5-HT, DA, adrenergic antagonists, and glutamate agonists. Furthermore, a neurochemical study was performed following TST and molecular docking study was also performed to determine the binding affinity of stigmasterol. RESULTS: Total sterols fraction presents no sign of toxicity up to the oral dose of 2000 mg/kg. Oral treatment of total sterols and acute intraperitoneal treatment of stigmasterol (except 5 mg/kg) reduced the immobility time significantly. Pretreatment with pCPA (5-HT synthesis inhibitor) and NMDA (an agonist of the glutamate site) effectively reversed the immobility time of total sterols and stigmasterol (except pCPA) in TST. However, bicuculline (competitive GABA antagonist), haloperidol (D2 dopaminergic antagonist) and prazosin (α1 adrenergic antagonist) could not reverse the immobility time. Meanwhile, total sterols also effectively altered the hippocampus 5-HT and Glu levels. Also, the result of the molecular docking study depicted that stigmasterol has an affinity to the NMDA receptor. CONCLUSIONS: The present study suggests that the total sterols fraction did not produce any acute toxicity in rats. Also, we reported that total sterols, stigmasterol and sub-effective stigmasterol coadministration with fluoxetine significantly reduced the time of immobility in TST and FST confirmed the antidepressant-like effect of total sterols fraction and stigmasterol. Moreover, further findings suggest that the antidepressant-like effect of total sterols might be mediated by the serotonergic and glutamatergic systems. Whereas only the glutamatergic system was involved in the antidepressant activity of stigmasterol.

Larvicidal and repellent activity of N-methyl-1-adamantylamine and oleic acid a major derivative of bael tree ethanol leaf extracts against dengue mosquito vector and their biosafety on natural predator.

Aegle marmelos (L.) Correa belongs to the family Rutaceae is generally known as "bael fruit tree" occuring across the south Asian countries. The current investigation screened the main derivatives from crude ethanolic extracts of the Bael tree leaf and evaluated activity effects on the larvae and adults of Aedes aegypti (L.) Dengue vector mosquito and a non-target aquatic predator. The GC-MS results showed that the peak area was found to be profound in N-methyl-1-adamantaneacetamide (N-M 1a) followed by oleic acid (OA) with 63.08 and 11.43% respectively. The larvicidal activity against the fourth instar larvae and the crude Ex-Am showed prominent mortality rate (93.60%) at the maximum dosage of 100 ppm. The mortality rate of N-M 1a and OA was occurred at 10 ppm (97.73%) and 12 ppm (95.4%). The repellent activity was found to be prominent at crude Ex-Am (50 ppm) as compared to the pure compounds (N-m 1a and OA) with maximum protection time up to 210 min. The non-target screening of Ex-Am, N-M 1a, and OA on mosquito predator Tx. splendens showed that they are scarcely toxic even at the maximum dosage of 1000 ppm (34.13%), 100 ppm (27.3%), and 120 ppm (31.3%) respectively. Thus, the present investigation clearly proved that the crude Ex-Am and their major derivatives Nm 1-a and OA showed their acute larval toxicity as well as potential mosquito repellent against the dengue mosquito and eco-safety against the mosquito predator.