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.

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.

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.

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.

Therapeutic effect of Aegle marmelos fruit extract against DMBA induced breast cancer in rats.

Breast cancer is among most common form of cancer worldwide. It is also the major cause of death in female cancer patient around the world. Despite various therapeutic measures, it remains associated with high mortality rate. Aegle marmelos (L.) Correa has been extensively used in Indian medicine system Ayurveda, due to its various medicinal properties. However, there are very limited reports regarding its anticancer activity. Thus, the present research work has been aimed to study the anticancer activity of Aegle marmelos fruit extract on 7,12-dimethylbenz(a)anthracene (DMBA) induced breast cancer in rats. Female Charles Foster rats, 55-60 days old weighing around (150 ± 10 g) were used for the study and were induced DMBA (20 mg/mL dissolved in Olive oil) orally. After the development of breast tumors (about 0.5 cm), the rats were treated with Aegle marmelos ethanolic fruit pulp extract (200 mg/kg b.w./day) orally for 5 weeks and then volume of tumor was measured. Aegle marmelos treatment showed significantly reduced mammary tumor volume (P < 0.05), along with significant reduction (P < 0.0001) in the different serum biomarkers such as TNF-α level, serum malondialdehyde (MDA) level and glucose levels. Significant (P < 0.0001) improvement in both, the kidney and liver serum biomarker parameters were also observed after the treatment with Aegle marmelos ethanolic fruit pulp extract. From the entire study, taking everything into account it can be interpreted that Aegle marmelos ethanolic fruit pulp extract possesses anti-proliferative activity by suppressing the progression of breast tumors in rat model. The plant extract also possesses hepato-renal protective effect. Hence, it can be targeted as novel and safe anti-cancer drug against breast cancer.

Chemistry and Antioxidant Potential of Phytoconstituents from Aegle Marmelos Fruit-Shell.

BACKGROUND: Oxidative stress is among the main causes of metabolic disorders. Hence, there is a need to discover potent antioxidants for therapeutic applications. OBJECTIVE: The objective of this study has been to investigate the phytoconstituents of the methanolic extract of the hard shell of Aegle marmelos fruit and their antioxidant potential. METHODS: Methanolic extract was fractionated using different solvents by liquid-liquid extraction. Characterization of the phytoconstituents was done by using phytochemical tests and GC-MS analysis. The free radical scavenging activity, total reducing power, lipid peroxidation inhibition and cell protection assays against oxidative stress were performed with methanolic extract and its fractions. RESULTS: Therapeutically significant class of compounds, for example, polyphenols, glycosides and sterols were revealed in the hard-shell extract. Differential separation of compounds was achieved by liquid-liquid extraction using different solvents. Six compounds: 4-Hydroxybenzeneacetic acid; 5-Oxo-pyrrolidine-2-carboxylic acid methyl ester; 1-[3-Methyl-3-Butenyl] Pyrrolidine; Trans-sinapyl alcohol; 5-[Hydroxymethyl]-2-furaldehyde and 2,4- Dihydroxy-2,5-dimethyl-3[2H]-furan-3-one, identified in the fruit-shell extract, are being reported for the first time from this plant. Strong antioxidant potential of the extract was evident from efficient scavenging of free radicals. The extract also conferred protection to yeast cells against oxidative damage. CONCLUSION: Results showed that the hard shell of the Aegle marmelos fruit was a potent source for antioxidant compounds, which can be developed for therapeutic applications in the control and management of metabolic diseases.

A review of the pharmacological and therapeutic effects of auraptene.

There is a growing awareness in herbal medications as they are usually safe and devoid of significant adverse effects. Auraptene is a natural bioactive monoterpene coumarin ether and is consumed all over the world. There is growing evidence of the therapeutic benefits of auraptene. Auraptene, also known as auraptene and 7-geranyloxycoumarin, is a bioactive monoterpene coumarin from Rutaceae family, which is isolated from Citrus aurantium (Seville orange) and Aegle marmelos (bael fruit). Auraptene is a highly pleiotropic molecule, which can modulate intracellular signaling pathways that control inflammation, cell growth, and apoptosis. It has a potential therapeutic role in the prevention and treatment of various diseases due to its anti-inflammatory and antioxidant activities as well as its excellent safety profile. In the present article, various pharmacological and therapeutic effects of auraptene were reviewed. Different online databases using keywords such as auraptene, therapeutic effects and pharmacological effects were searched until the end of September 2018, for this purpose. Auraptene has been suggested to be effective in the treatment of a broad range of disorders including inflammatory disorders, dysentery, wounds, scars, keloids, and pain. In addition, different studies have demonstrated that auraptene possesses numerous pharmacological properties including anti-inflammatory, anti-oxidative, anti-diabetic, anti-hypertensive and anti-cancer as well as neuroprotective effects. The present review provides a detailed survey of scientific researches regarding pharmacological properties and therapeutic effects of auraptene.

Osteogenic stimulatory effect of heraclenin purified from bael in mouse mesenchymal stem cells in vitro.

Osteoporosis is a major health concern occurring to the aging adult population across the globe. Currently, there is an increasing demand for treatment of osteoporosis with plant-based medicines. In the present study, we report that heraclenin was extracted and purified from unripe fruit portion of Bael (Aegle marmelos Corr.) using silica gel column chromatography. The identification and characterization of heraclenin were carried out by UV-Vis, HPLC, LC-MS, NMR, FT-IR, and XRD analyses. The standardized purification method recorded a yield efficiency of 42% heraclenin microcrystals with 99% purity from bael fruit. SEM image revealed the shape of the purified compound to be an orthorhombic-sphenoid prism. Cytotoxicity studies indicated that heraclenin-treatment did not alter cell viability in mouse mesenchymal stem cells (mMSCs, C3H10T1/2). The mRNA expression of Runx2, a bone transcription factor was found to be stimulated by heraclenin in these cells. At the cellular level, heraclenin-treatment enhanced osteoblast differentiation and mineralization in mMSCs. Thus, these results suggested that heraclenin purified from bael fruit has an osteogenic effect, indicating its potential towards bone regeneration.

Sesquiterpene rich essential oil from Nepalese Bael tree (Aegle marmelos (L.) Correa) as potential antiproliferative agent.

Aegle marmelos (L.) Corr. (Rutaceae), also known as Bael tree, is an herbal traditional remedy in the South East Asia. In the present work, the leaf essential oil distilled from a population collected in Nepal was analyzed for the chemical composition by GC-MS showing different phytochemical constituents compared with literature data. The obtained oil was rich in sesquiterpenes, mainly ß-Caryophyllene (26%), whereas monoterpenes, known in literature as the major components, were present in little amounts. Due to richness in sesquiterpenes which are promising as anticancer drugs, the oil was tested against several human tumor cell lines namely pancreatic (PSN-1), colon (LoVo), lung (H157) and ovarian (2008) cells showing IC50 of 5.6 µg/mL, 6.5 µg/mL, 6.7 µg/mL and 2.3 µg/mL, respectively. In vivo distribution of oil was studied with a dose of 41.5 mg/kg in mice allowing the quantification of ß-Caryophyllene, α-Humulene, γ-Muurulene and ar-Curcumene at 30 and 60 min after oral administration. Sesquiterpene were found in higer amount in, liver, kidney and heart whereas lung and blood contained lower levels. The tissue distribution study demonstrated that active sesquiterpenoids of the oil can efficiently reach different organs.

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).

Experimental assessment and multi-response optimization of diesel engine performance and emission characteristics fuelled with Aegle marmelos seed cake pyrolysis oil-diesel blends using Grey relational analysis coupled principal component analysis.

This research focuses on the detailed experimental assessment of compression ignition (CI) engine behavior fuelled with Aegle marmelos (AM) seed cake pyrolysis oil blends. The study on effects of engine performance and emission a characteristic was designed using L25 orthogonal array (OA). These multi-objectives were normalized through gray relational analysis (GRA). Likewise, the principal component analysis (PCA) was performed to assess the weighting values respective to every performance and emission characteristics. The variability induced by using the input process parameters was allocated using analysis of variance (ANOVA). Hence, GRA-coupled PCA were employed to determine the optimal combination of CI engine control factors. The greater combination of engine characteristics levels were selected with F5 and W5. The higher brake thermal efficiency (BTE) have been obtained for F20 fuel as 22.01% at peak engine load, which is 11.43% for diesel. At peak load condition, F20 fuel emits 14.99% lower HC and 18.52% lower CO as compared to diesel fuel. The improved engine performance and emission characters can be attained by setting the optimal engine parameter combination as F20 blend at full engine load condition. The validation experiments show an improved average engine performance of 67.36% and average lower emission of 64.99% with the composite desirability of 0.8458.

Characterization of pyrolysis bio-oil derived from intermediate pyrolysis of Aegle marmelos de-oiled cake: study on performance and emission characteristics of C.I. engine fueled with Aegle marmelos pyrolysis oil-blends.

The present research focuses on the analyzing the characteristics of bio-oil derived from intermediate pyrolysis of Aegle marmelos (AM) seed cake and its suitability for C.I. engine adaptation. Owing to the high volatile matter content of 73.69%, Aegle marmelos biomass was selected as the feedstock for this research. The intermediate pyrolysis was carried out at 600 °C in a 2-kg fixed bed type pyrolysis reactor at a heating rate of 10 °C/min and the obtained bio-oil was characterized by different analytical methods. As per American Society for Testing and Materials (ASTM) standards, physicochemical properties of the bio-oil were tested and it was observed that bio-oil is a highly viscous fluid with low calorific value. Analysis of bio-oil through FT-IR and GC-MS examination confirmed the presence of phenol, esters, alkyl, and oxygenated compounds. The performance and emission testing of direct injection diesel engine were conducted with various bio-oil blends and the results were compared with baseline diesel fuel. The experimental results showed that the addition of bio-oil decreased BTE (%) while increasing the BSEC (MJ/kW-h). At the same time, increasing the bio-oil ratio with diesel decreases dangerous emissions such as carbon monoxide and oxides of nitrogen emissions in the engine exhaust. According to engine test result, it was suggested that up to 20% of AM bio-oil (F20) can be employed as engine fuel for better engine operating characteristics.

Molecular and Metabolic Markers of Fructose Induced Hepatic Insulin Resistance in Developing and Adult Rats are Distinct and Aegle marmelos is an Effective Modulator.

The time course of pathogenesis of fructose mediated hepatic insulin resistance (HepIR) is not well-delineated and we chronicle it here from post-weaning to adulthood stages. Weaned rats were provided for either 4 or 8 weeks, i.e., upto adolescence or adulthood, chow + drinking water, chow + fructose, 15% or chow + fructose, 15% + hydroalcoholic extract of leaves of Aegle marmelos (AM-HM, 500 mg/kg/d, po) and assessed for feed intake, fructose intake, body weight, fasting blood sugar, oral glucose tolerance test, HOMA-IR, insulin tolerance test and lipid profile. Activities of enzymes (glucose-6-phosphatase, hexokinase, phosphofructokinase, aldehyde dehydrogenase), hormones (leptin, ghrelin, insulin), insulin signaling molecules (Akt-PI3k, AMPK, JNK) hallmarks of inflammation (TNF-α), angiogenesis (VEGF), hypoxia (HIF-1), lipogenesis (mTOR) and regulatory nuclear transcription factors of de novo lipogenesis and hepatic insulin resistance gene (SREBP-1, FoxO1) that together govern the hepatic fructose metabolism, were also studied. The effect of fructose-rich environment on metabolic milieu of hepatocytes was confirmed using (human hepatocellular carcinoma) HepG2 cells. Using in vitro model, fructose uptake and glucose output from isolated murine hepatocytes were measured to establish the HepIR under fructose environment and delineate the effect of AM-HM. The leaves from the plant Aegle marmelos (L) Correa were extracted, fractionated and validated for rutin content using LC-MS/MS. The rutin content of extract was quantified and correlated with oral pharmacokinetic parameters in rat. The outcomes of the study suggest that the molecular and metabolic markers of fructose induced HepIR in developing and adult rats are distinct. Further, AM-HM exerts a multi-pronged attack by raising insulin secretion, augmenting insulin action, improving downstream signaling of insulin, reducing overall requirement of insulin and modulating hepatic expression of glucose transporter (Glut2). The butanol fraction of AM-HM holds promise for future development.

Antioxidant and anti-inflammatory properties of marmelosin from Bael (Aegle marmelos L.); Inhibition of TNF-α mediated inflammatory/tumor markers.

Oxidative stress and inflammation are important critical factors that are implicated in almost all life style disorders such as diabetes, cardiovascular disease, ulcer and cancer. Current study aimed at isolation and characterization of a furanocoumarin from Bael (Aegle marmelos L.) fruit that can modulate both oxidative stress and inflammation effectively. Ethyl acetate extract of Bael fruit (EAFB) was subjected to HPLC for identification, purified and characterized using FTIR, NMR and ESI-MS analysis. Predominant peak of EAFB at RT 12.54 min on HPLC was identified as marmelosin with molecular weight of m/z ∼ 271.2. Marmelosin was evaluated for antioxidant, antiproliferative, apoptotic, cancer (Tyrosinase & Galectin-3) and immunomodulatory (NO, TNF-α) potentials employing standard assay systems. Marmelosin possessed potent antioxidant activity with IC50 of ∼ 15.4 ±â€¯0.32 µM as opposed to standard - gallic acid (IC50 1.1 ±â€¯0.08 µM), antiproliferative activity with IC50 of ∼ 6.24 ±â€¯0.16 µM as opposed to deferoxamine (∼10.8 ±â€¯0.28 µM) and protected cells against cellular/DNA damage. Anti-inflammatory property was evident with significant reduction in the release of NO (∼3.9 fold) and TNF-α (∼3.4 fold), a pro-inflammatory cytokine, in addition to the inhibition of NFκB (∼2.7 fold), a transcription factor in Raw 264.7 cells. Marked down regulation of galectin-3 (∼5.5 folds) and tyrosinase (∼11.1 folds) by gene expression analysis substantiated by tyrosinase inhibition (IC50 - 20.3 ±â€¯1.26 µM Vs. Kojic acid - IC50 - 24.1 ±â€¯1.41 µM) and molecular docking studies strengthened the cancer modulatory property of marmelosin. In addition, marmelosin induced apoptotic bodies, chromatin condensation and nulcear blebbing in Raw 264.7 cells commending the apoptotic effect of marmelosin. Marmelosin thus displayed potential multi-potent antioxidant, anti-inflammatory and anticancer properties via TNF-α mediated Akt signaling pathway.

Phytochemical profile and pharmacological activity of Aegle marmelos Linn.

Aegle marmelos Linn. (Rutaceae), commonly known as "bael" in Nepal and India, is a valuable medicinal plant and is considered sacred by the Hindus. It is used to cure several diseases in the Indian traditional medicine system of Ayurveda and has had similar uses among many ethnic communities residing in Indian subcontinent for over 5000 years. Its leaves, bark, stem, fruits and seeds have been used for various medicinal purposes. Bael fruits are especially effective in the treatment of chronic diarrhea, dysentery and peptic ulcers, while they are also useful as a laxative and cure for respiratory infections. Scientific studies have validated many of the ethnomedicinal uses of A. marmelos, which include antibacterial, antiviral, antidiarrheal, gastroprotective, anti-ulcerative colitis, hepatoprotective, antidiabetic, cardioprotective and radioprotective effects. Recently, this plant has also received attention as an anticancer agent for the treatment of various types of cancers. Thus, this review focuses on scientific evidence verifying the important pharmacological activity such as antioxidant, antidiabetic, antimicrobial, hepatoprotective, cardioprotective and anticancer activity of A. marmelos.

Poly herbal formulation with anti-elastase and anti-oxidant properties for skin anti-aging.

BACKGROUND: Skin forms an important part of human innate immune system. Wrinkles, thinning and roughening of skin are some of the symptoms that affect the skin as it ages. Reactive oxygen species induced oxidative stress plays a major role in skin aging by modulating the elastase enzyme level in the skin. Extrinsic factors that affect skin aging such as UV radiation can also cause malignant melanoma. Here we selected four medicinal plant materials, namely, leaves of Nyctanthes arbor-tristis, unripe and ripe Aegle marmelos fruit pulp and the terminal meristem of Musa paradisiaca flower and investigated their anti-aging properties and cytotoxicity in vitro individually as well as in a poly herbal formulation containing the four plant extracts in different ratios. METHODS: The phytochemical contents of the plant extracts were investigated for radical scavenging activity and total reducing power. Based upon its anti-oxidant properties, a poly herbal formulation containing leaves of Nyctanthes arbor-tristis, unripe and ripe fruit pulp of Aegle marmelos, and the terminal meristem of Musa paradisiaca flower in the ratio 6:2:1:1 (Poly Herbal Formulation 1) and 1:1:1:1 (Poly Herbal Formulation 2), respectively were formulated. RESULT: It has been observed that the Poly Herbal Formulation 1 was more potent than Poly Herbal Formulation 2 due to better anti-oxidant and anti-elastase activities in NIH3T3 fibroblast cells. In addition Poly Herbal formulation 1 also had better anti-cancer activity in human malignant melanoma cells. CONCLUSION: Based on these results these beneficial plant extracts were identified for its potential application as an anti-aging agent in skin creams as well as an anti-proliferation compound against cancer cells.

Aegle marmelos differentially affects hepatic markers of glycolysis, insulin signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose versus glucose-rich environment.

Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated. Human hepatocellular carcinoma cells (HepG2) were grown under standard conditions in either-DMEM without glucose (NC), DMEM with high glucose 25 mM (Glu), DMEM-glucose+0.55 mM fructose (FC1), DMEM-glucose+1 mM fructose (FC2) or DMEM-glucose+1 mM fructose+0.1 µM insulin (FC3). The cells were treated with either AM, rutin, quercetin, metformin or pioglitazone and assessed for levels of hexokinase, phosphofructokinase (PFK), aldehyde dehydrogenase, phosphatidylinositol kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3), mitochondrial target of rapamycin (mTOR), hypoxia-induced factor (HIF-1α), vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF-α). Summarily, when results from fructose- and glucose-rich environment were compared, then (1) IR was more pronounced in former; (2) AM performed better in former; (3) metformin and pioglitazone were equivocal in either; (4) rutin and quercetin showed deviant effects from AM; and lastly (5) effects of rutin were closer to AM than quercetin. We hypothesize that AM ameliorates fructose-induced IR through a mechanism which is distinct from standard drugs and not shared by individual phytoconstituents in toto.

Anti-hyperglycemic activity of Aegle marmelos (L.) corr. is partly mediated by increased insulin secretion, α-amylase inhibition, and retardation of glucose absorption.

BACKGROUND: Aegle marmelos (commonly known as Bael, golden apple) was formerly described to have anti-hyperglycemic activity. The present study aimed to explore the possible effects, in depth, of A. marmelos extracts on carbohydrate absorption, glucose utilization, and α-amylase inhibition and insulin content in pancreases of type 2 diabetic rats. METHODS: This research begins with fasting blood glucose and oral glucose tolerance test (OGTT) to evaluate the primary anti-hyperglycemic effect in chemically induced type 2 diabetic rats. Furthermore, the plasma insulin concentration and serum glucose level were studied, which include measuring the sucrose content in six different segments of the gastrointestinal (GI) tract of the rats following oral sucrose feeding. An in situ, perfused, intestinal model in rats and glucose-fiber binding assay were conducted to find the effects of A. marmelos extracts on glucose absorption. Extract effects on carbohydrate breakdown, intestinal disaccharidase enzyme activity, and α-amylase inhibition were assessed. Effect on GI motility was evaluated using BaSO4 milk traverse test. RESULTS: Treatment of extracts suppressed blood glucose elevation after oral sucrose (2.5 g/kg) administration and significantly (p<0.05) improved oral glucose tolerance in type 2 diabetic rats. Aegle marmelos extracts showed remarkable (p<0.05) changes in plasma insulin secretion at 30 min and 60 min, respectively. A noticeable reduction in glucose absorption was observed in the in situ perfused rat intestinal model at two different doses (250 and 500 mg/kg). The extract was also found to inhibit the action of both α-amylase and intestinal disaccharidase enzyme, and this study was affirmed again by the sucrose malabsorption test, where sucrose digestion was inhibited throughout the length of the GI tract. During this chronic study, body mass of rats became normal and their polydipsic and polyphagic conditions were ameliorated also. CONCLUSIONS: The findings demonstrate that anti-hyperglycemic activity of A. marmelos is mediated by the inhibition of carbohydrate digestion and absorption, and improvement of insulin action to uptake glucose in peripheral tissue. Additional study is required to correlate A. marmelos extracts' specific mechanism of glucose-fiber binding capacity and glucose transporters.

Aggravation of cyclophosphamide-induced reproductive toxicity in mice by aqueous extract of Aegle marmelos (L. )

ABSTRACT Aegle marmelos (L.) (Rutaceae) commonly known as bael is an important medicinal fruit tree. The present study focused on the effects of aqueous extract of Aegle marmelos (AEAM) on the testis and sperm characteristics induced by cyclophosphamide (CPA) in mice. Thirty six adult Parke's strain mice were divided into six groups: group I given only distilled water (control); group II administered with AEAM alone once in a week for five weeks; group III administered with CPA (200 mg/kg b.w., intraperitoneally) once in a week for five weeks and group IV-VI CPA along with AEAM (400, 500 and 600 mg/kg b.w., orally). CPA was found to reduce gonadosomatic index (GSI), sperm counts, motility, viability, antioxidant activities and induced histopathological changes of testis. In the group administered AEAM with CPA an exacerbation of sperm count, motility and viability of the cauda epididymis, GSI, antioxidant activities and architecture of testis was observed. The results suggest that the administration of AEAM may aggravate CPA-induced reproductive toxicity. It may be helpful in preparation of natural male contraceptives.