|
 |
| RESEARCH ARTICLE |
|
|
|
| Year : 2012 | Volume
: 44
| Issue : 5 | Page : 614-618 |
| |
Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease
Jayanti P Behera1, Bisweswar Mohanty2, Y Roja Ramani1, Bandana Rath1, Supriya Pradhan1
1 Department of Pharmacology, MKCG Medical College, Berhampur, Odisha, India
2 Department of Pharmacology, Officer Grade II, Sun Pharma, Sikkim, India
| Date of Submission | 30-Nov-2011 |
| Date of Decision | 12-Jun-2012 |
| Date of Acceptance | 01-Jul-2012 |
| Date of Web Publication | 31-Aug-2012 |
Correspondence Address:
Jayanti P Behera
Department of Pharmacology, MKCG Medical College, Berhampur, Odisha
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0253-7613.100389
Objective: The present study was designed to evaluate the effect of Aegle marmelos unripe fruit extract (AMFE) on inflammatory bowel disease (IBD) in Wistar albino rats.
Materials and Methods: Effect of AMFE was studied on acetic acid induced ulcerative colitis (1 ml of 4% acetic acid solution, transrectal) and indomethacin-induced enterocolitis (10 mg/kg, single dose, p.o) in Wistar albino rats. The extract was administered orally at different dose of 150, 200 and 250 mg/kg body weight. Disease pathogenesis was assessed by measuring disease activity index (DAI), macroscopic score, microscopic score, mesenteric mast cell protection, superoxide dismutase (SOD), and malonaldehyde (MDA) levels in the above two models.
Results: The results showed a dose dependent decrease in intestinal inflammation following treatment with AMFE. Significant protection in mast cell degranulation was observed in acetic acid and indomethacin-induced IBD models. Treatment with AMFE significantly decreased the MDA levels and increased SOD activity.
Conclusion: In our study, AMFE produced anti-inflammatory, antioxidant, and mast cell stabilizing effects demonstrating protective effect in inflammatory bowel disease.
Keywords: Aegle marmelos (bael), aqueous extract, inflammatory bowel disease
How to cite this article:
Behera JP, Mohanty B, Ramani Y R, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol 2012;44:614-8 |
How to cite this URL:
Behera JP, Mohanty B, Ramani Y R, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol [serial online] 2012 [cited 2023 Sep 25];44:614-8. Available from: https://www.ijp-online.com/text.asp?2012/44/5/614/100389 |
| » Introduction | |  |
Inflammatory bowel disease (IBD), a spectrum of chronic idiopathic inflammatory intestinal conditions, [1] is the second most common chronic inflammatory disease [2],[3] after rheumatoid arthritis. It causes significant morbidity in the population of European origin with two major forms like Crohn's disease (CD) and ulcerative colitis (UC) having a combined prevalence of 150-250/100,000 population. [4],[5] The prevalence of hospitalization is estimated to be 50.1 and 50.6 per 100,000 population for CD and UC, respectively. [6] IBD is a multi-factorial inflammatory disease of the intestine having immunological, genetic, and environmental origin. [6] Mediators like TNF-α, IL-6, and LB 4 play an important role in the inflammation of the intestinal mucosa in animal models of IBD. [7] Other findings with IBD are abnormal histopathological features and increased intestinal permeability. [8] Oxidative stress also plays an important role in the pathophysiology of IBD. [9],[11]
Herbal remedies are increasingly being used for the treatment of IBD. Aegle marmelos (Bael), one of the oldest and most popular species in the world belonging to the family Rutaceae, is found abundantly throughout India. Its fruits are useful in gastrointestinal (GI) disorders like diarrhea, dysentery, and constipation. It is also used as a medicine for its antiinflammatory, immunomodulatory, antibacterial, and antioxidant properties. [10] Hence, the present study was undertaken to evaluate the effect of Aegle marmelos unripe fruit extract (AMFE) on IBD in Wistar albino rats.
| » Materials and Methods | | |
Fresh powder form of A. marmelos pulp extract (unripe fruit) was collected from the Indian Herbs Research and Supply Co. Ltd. Sharda Nagar, Saharanpur, Uttar Pradesh [Ref. No. R &D/2008-09/5456]. Adult albino Wistar rats of either gender (200-250 g) were housed under standard condition of temperature (22°C ± 2°C), relative humidity of 55 ± 5% and 12 h light/dark cycles. The animals were given standard pellet diet and water ad libitum. The study protocol was approved by Institutional Animal Ethics Committee according to the CPCSEA guidelines [472/CPCSEA]. The aqueous extract of unripe fruit of A. marmelos was studied for their phytoconstituents using different phytochemical tests as mentioned in [Table 1]. | Table 1: Qualitative phytochemical screening of aqueous extract of Aegle marmelos unripe fruit
Click here to view |
An acute oral toxicity study was performed as per OECD-423 guidelines. Adult albino Wistar rats were administered 5, 50, 300, and 2000 mg/kg b.w. of aqueous extract of unripe fruit of A. marmelos orally. The control group received distilled water. The animals were observed for 14 days. There was no mortality or behavioral changes observed during the study period.
Induction of UC [12]
An 8Fr (2.7 mm) soft pediatric catheter was advanced 6 cm from the anus under low dose ether anesthesia and 1 ml of 4% acetic acid solution (pH 2.4) was slowly administered transrectally. The rat was maintained in head down position for 30 s to prevent leakage. The rest of the solution was aspirated out after which 2 ml of phosphate buffer solution with pH7 was administered transrectally.
Induction of Enterocolitis [13]
Around 10 mg/kg indomethacin was administered orally as a single dose. Enterocolitis developed after 24 h.
The study comprised of 12 groups of 6 animals each as follows:
Group 1: Normal control (no disease)
Group 2: UC control (treated with normal saline)
Group 3 to 5: A. marmelos (AMFE) 150, 200, and 250 mg/ kg dose was administered orally for 10 days, respectively. UC was induced on the 10 th day.
Group 6: Prednisolone (1 mg/kg) was administered orally for 3 days. On the 3 rd day, UC was induced.
Group 7: Normal control (no disease)
Group 8: Enterocolitis control (treated with normal saline)
Group 9 to 11: A. marmelos (AMFE) 150, 200, and 250 mg/ kg dose was administered orally for 10 days. Enterocolitis was induced on the 10 th day.
Group 12: Prednisolone (1 mg/kg) was administered orally daily for 3 days. On the 3 rd day enterocolitis was induced.
In all groups, animals were observed for decrease in body weight, stool consistency, and rectal bleeding for 48 h after inducing IBD and disease activity index [14] was scored. After 48 h, the rats in all the groups were sacrificed by cervical dislocation. A 10 cm length of colonic segment (UC groups) and ileum segment (enterocolitis groups) were resected out along with mesenteric attachments. The mesentries were preserved separately in Ringer Locke solution to study mast cell degranulation. The contents of the intestinal segments were cleaned gently with normal saline by hand and then dried. The distal 5 cm of the segments were scored macroscopically and preserved with 4% formalin for microscopic evaluation. The remaining 5 cm was used for biochemical analysis (malonaldehyde [MDA] and superoxide dismutase [SOD] levels).
Parameters Evaluated
Disease activity index (DAI)
The DAI during the study period (48 h) was scored as follows : 0-no weight loss, normal stool consistency, and no rectal bleeding; 1-weight loss (1-5%), normal stool consistency with no rectal bleeding; 2-weight loss (5-10% ), loose stool with no rectal bleeding; 3-weight loss (10-20%), normal stool consistency with no rectal bleeding; and 4-weight loss (>20% ), diarrhea with gross rectal bleeding.
Macroscopic score [15]
After resection of the portion of intestine (colon/jejunum), the mucosal surface is fixed over a wax tray and graded with the help of a magnifying lens as follows: Grade 0-Normal mucosal pattern, Grade 1-Scattered erosions, Grade 2-Linear ulcerations, Grade 3-Diffuse inflammatory tissue featuring small lesions of less than 5 mm, and Grade 4-Diffuse ulceration with wide lesions.
Microscopic score [16]
A piece of colon/ileum was fixed in phosphate-buffered formaldehyde, embedded in paraffin, sectioned (4 μm thick), and stained with hematoxylin and eosin. Each sample was observed and evaluated under light microscopy by two independent observers. The histopathological score was assessed as follows: 0-no lymphoid hyperplasia, neutrophil infiltration, crypt damage, or submucosal inflammation, 1-mild lymphoid hyperplasia, neutrophil infiltration, crypt damage with no submucosal inflammation, 2-moderate lymphoid hyperplasia, neutrophil infiltration, crypt damage with or without submucosal inflammation, and 3-severe lymphoid hyperplasia, neutrophil infiltration, crypt damage, and submucosal inflammation.
Biochemical estimations
Tissues (colon/ileum) were thoroughly washed and homogenized in 2 ml of normal saline using a glass-teflon homogenizer for 5 min at 5000 rpm. Both MDA (nmol/mg of protein) and SOD levels were measured in the homogenate as described in literature. [17],[18] The protein concentration of the homogenate was determined according to Lowry's method.
Percent of mesenteric mast cell protection
The percent mast cell protection is suggested by the degree of its degranulation. Mesenteric pieces were placed in Ringer Locke solution (NaCl 0.9%, KCl 0.042%, CaCl 2 0.024%, NaHCO 3 0.015%, and dextrose 0.1%) and then stained and fixed with 4% formaldehyde containing 0.1% toluidine blue. The percentage of mast cell protection was evaluated under light microscope at 40× magnification. [19]
Statistical Analysis
The data were analyzed by one way ANOVA followed by Tukey's multiple comparison test for MDA level and SOD activity and Kruskal-Wallis test followed by Dunn's multiple comparison test for disease activity index score, macroscopic and microscopic score using Graph Pad Prism software (version 5.0).
| » Results | | |
Preliminary phytochemical screening of aqueous extract of unripe fruit of A. marmelos revealed the presence of alkaloids, carbohydrates, glycosides, tannins, phenolics, gums, mucilage, saponins, flavins, flavinoids, steroids, sterols, and terpinoids [Table 1].
Disease activity index was assessed by changes in body weight, stool consistency, and rectal bleeding during the 48 h period following colitis induction. The groups treated with AMFE in all the doses produced significant improvement in the disease activity index in comparison to disease control in both the models. There was no significant difference between the three doses of AMFE in both the models [Table 2] and [Table 3]. The parameters used for evaluating the degree of inflammation in both the models were changed in mucosal pattern and the severity of lesions. The groups treated with AMFE at all the doses produced significant improvement in macroscopic score in comparison to disease control, which is comparable to that of normal control group in both the IBD models. There was no significant difference between the three doses of AMFE [Table 2] and [Table 3]. | Table 2: Effect of aqueous extract of Aegle marmelos unripe fruit on acetic acid induced ulcerative colitis
Click here to view |
 | Table 3: Effect of aqueous extract of Aegle marmelos unripe fruit on indomethacin induced enterocolitis
Click here to view |
Histopathological analysis of the colon/ileum in acetic acid induced UC as well as in indomethacin induced enterocolitis clearly showed that there was a significant degree of lymphoid hyperplasia, neutrophillic infiltration, crypt damage, and sub mucosal inflammation compared with normal control. In the groups treated with AMFE, the progression of IBD was less prominent characterized by significant dose dependent decrease in lymphoid hyperplasia, neutrophillic infiltration, and crypt damage and sub mucosal inflammation [Figure 1] and [Figure 2]. | Figure 1: Histological changes seen with aqueous extract of Aegle marmelos unripe fruit on acetic acid induced ulcerative colitis (a) normal control (b) disease control (c) prednisolone (1 mg/kg) (d) AMFE (250
mg/kg)
Click here to view |
 | Figure 2: Histological changes seen with aqueous extract of Aegle marmelos unripe fruit on indomethacin induced enterocolitis (a) normal control (b) disease control (c) prednisolone (1 mg/kg) (d) AMFE (250 mg/kg)
Click here to view |
Transrectal administration of acetic acid and high oral dose of indomethacin used in the disease models produced significant oxidative stress as evident by significant increase in the MDA levels and decrease in SOD activity. AMFE at all the doses produced significant antioxidant effect [Table 2] and [Table 3]. The animals treated with acetic acid and indomethacin showed 9.44% and 8.94% protection of mast cell degranulation, respectively, whereas a protection of 80% was observed in normal control. AMFE (150, 200, and 250 mg/kg) produced dose dependent decrease in the mast cell degranulation [Table 2] and [Table 3]. The percentage protection offered by AMFE 250 mg/ kg was comparable to the protection given by the standard, prednisolone (1 mg/kg) in both the models of IBD.
| » Discussion | | |
UC and CD are the common IBDs seen in day to day clinical practice. Acetic acid induced UC is an easily inducible model which produces mucosal injury similar to UC due to inflammation and generation of reactive oxygen species. Indomethacin induced enterocolitis is the standard procedure for induction of CD. In the present study, the effect of AMFE was observed on the above experimental animal models of IBD, in albino rats. The pathogenesis of the disease was assessed by evaluating the different parameters like disease activity index, macroscopic score, microscopic score, mesenteric mast cell degranulation, and oxidative stress markers like MDA level and SOD activity. Prednisolone was used as the standard drug which produced no significant difference in the above parameters in comparison to AMFE at all doses.
The results showed a decrease in severity of intestinal inflammation following treatment with AMFE. This effect may be due to inhibition of inflammatory mediators like IL 1 , IL 6 , IL 8 , and TNF-α. [20] The phytochemical constituents of AMFE like flavinoids, phenolic compounds, and steroids [21] may be responsible for this antiinflammatory effect. AMFE showed increase in SOD activity and decrease in MDA levels in the tissue homogenate. This effect may be due to presence of antioxidants like carotene, thiamine, riboflavin, niacin, and vitamin C in the A. marmelos fruit. [10] Many studies report that antioxidants show beneficial effect in experimental colitis. [22],[23] Mast cell degranulation causes mucosal edema, mucus secretion, increased gut permeability, and release of inflammatory mediators, which contribute to the clinical signs and symptoms of IBD. [24],[25] A marked increase in mast cell degranulation was observed in acetic acid and indomethacin induced IBD models which were attenuated by AMFE (250 mg/kg) similar to the standard drug prednisolone. This finding is suggestive of the mast cell stabilization activity of AMFE.
It is evident from this study that AMFE produces anti-inflammatory, antioxidant, and mast cell stabilizing effects. A. marmelos contains a number of polar and nonpolar phytoconstituents, which are the key factors in the medicinal value of this plant. Therefore it can be concluded that aqueous extract of unripe fruit of A. marmelos has protective effect against IBD.
| » References | | |
| 1. | Sellin JH, Pasricha PJ. Pharmacotherapy of inflammatory bowel disease. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 11 th ed. McGraw-Hill Publications,NewYork; 2006. p. 1009. 
|
| 2. | Bickson SJ. Treatment of chronic disease at the turn of the century. N Engl J Med 1998;339:401-2.
|
| 3. | Hana Strul MD, Nadir Arber MD. Inflammatory bowel disease, ulcerative colitis, Crohn's disease, pathophysiology, new therapies. IMAJ 2000;2:607-9.
|
| 4. | Parkes M, Jewell D. Ulcerative Colitis and Crohn's disease: Molecular genetics and clinical implications. Expert Rev Mol Med 2001;2001:1-1800391-Xa.pdf
|
| 5. | Calkins BM, Mendeloff AI. The epidemiology of idiopathic inflammatory bowel disease. In: Kirsner JB, Shorter RG, editors Inflammatory Bowel Disease. 4 th ed. 1995; p. 31-68.,Williams and wilkins, Baltimore.
|
| 6. | Button LA, Roberts SE, Goldacre MJ, Akbari A, Rodgers SE, Williams JG. Hospitalized prevalence and 5-year mortality for IBD: Record linkage study World. J Gastroenterol 2010;16:431-8.
|
| 7. | Giriþ M, Depboylu B, Doðru-Abbasoðlu S, Erbil Y, Olgaç V, Aliþ H, et al. Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzene sulphonic acid-induced colitis. Clin Exp Immunol 2008;152:102-10.
|
| 8. | Razavi A, Khodadadi A, Eslami MB Eshraghi S. Therapeutic effect of sodium alginate in experimental chronic ulcerative colitis. Iran J Allergy Asthma Immunol 2008;7:13-8.
|
| 9. | Patel MA, Patel PK, Patel MB. Effect of ethanol extract of Ficus begalensis on inflammatory bowel disease. Indian J Pharmacol 2010;42:214-8.
|
| 10. | Dhankhar S, Ruhil M, Balhar M. Aegle marmelos (Linn.) Correa: A potential source of Phytomedicine. J Med Plants Res 2011;5:1497-507.
|
| 11. | Narushima S, Spitz DR. Evidence for oxidative stress in NSAID- induced colitis in IL-10 mice. Free Radic Biol Med 2003;34:1153-66.
|
| 12. | Jagtap AG, Shirke SS, Phadke AS. Effect of polyherbal formulation on experimental model of IBD. J Ethnopharmacol 2004;90:195-204.
|
| 13. | Fedorak RN, Empey LR, MacArthur C, Jewell LD. Misoprostal provides a colonic mucosal protective effect during Acetic acid induced colitis in rats. Gastroenterology 1990;98:615-25.
|
| 14. | Kakimoto K, Takai S, Murano M, Ishida K, Yoda Y, Inoue T, et al. Significance of Chymase-Dependent Matrix Metalloproteinase-9 Activation on Indomethacin-Induced Small Intestinal Damages in Rats. J Pharmacol Exp Ther 2010;332:684-9.
|
| 15. | Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulphate sodium experimental murine colitis. Lab invest 1993;69:238-49.
|
| 16. | Zeytunlu M, Korkut M, Akgün E, Firat O, Aynaci M, Içöz G, et al. The comparative effects of calcium channel blockers in an experimental colitis model in rats. Turk J Gastroenterol 2004;15:243-9.
|
| 17. | Ayan f, Aydin S, Uzun H. Effects of clinoptilolite (Froximun Cama) on Trinitrobenzene sulfonic acid (TNBS)-induced colitis colitis model in the study as a new agent for Prevention and Treatment. Available from: http://www.froximun.at/pdfs/13.pdf. [24.02.2012]
|
| 18. | Dahel LK, Hill EG, Holman RT. The thiobarbituric acid reaction and autooxidation of polyunsaturated fatty acid methyl esters. Arch Biochem Biophys 1962;98:253-61.
|
| 19. | Kakkar P, Das B, Viswanathan PN. Mechanisms of Gastric Mucosal Hemorrhagic Ulceration in Salmonella typhimurium-infected Rats: Protection by Several Drugs. Indian J BiochemBiophys 1984;21:130-2.
|
| 20. | Norton S. Quantitative determination of mast cell fragmentation by compound 48/80. Br J Pharmacol Chemother 1954;9:494-7.
|
| 21. | Rajan S, Gokila M, Jency P, Brindha P, Sujatha RK. Antioxidant and phytochemical properties of Aegle marmelos fruit pulp. Int J Curr Pharm Res 2011;3:65-70.
|
| 22. | Harputluoglu MM, Demirel U, Yücel N, Karadað N, Temel I, Firat S. The effects of Gingko biloba extract on acetic acid induced colitis in rats. Turk J Gastroenterol 2006;17:177-82.
|
| 23. | Kurutas EB, Cetinkaya A, Bulbuloglu E, Kantarceken B. Effects of Antioxidant Therapy on Leukocyte Myeloperoxidase and Cu/Zn-Superoxide Dismutase and Plasma Malondialdehyde Levels in Experimental Colitis. Mediators Inflamm 2005;2005:390-4.
|
| 24. | MacDonald TT, Muresh SH. Aetiology and pathogenesis of chronic inflammatory bowel disease. Baillieres Clin Gastroenterol 1994;8:1-34.
|
| 25. | Goldsmith P, McGarity B, Walls AF, Church MK, Millward-Sadler GH, Robertson DA. Corticosteroid treatment reduces mast cell numbers in inflammatory bowel disease. Dig Dis Sci 1990;35:1409-13.
|
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]
| This article has been cited by | | 1 |
Phytochemical and biological review of Aegle marmelos Linn |
|
| S Monika, M Thirumal, PR Kumar | | Future Science OA. 2023; 9(3) | | [Pubmed] | [DOI] | | | 2 |
Optimization and Validation of Polyherbal Formulation by Applying Boxbehnken
Design for the Treatment of Inflammatory Bowel Disease in Experimental
Animals |
|
| Tejal Gandhi, Bhagyabhumi Patel, Divya Patel, Saloni Dalwadi, Vaishali Thakkar | | Current Drug Therapy. 2022; 17(1): 17 | | [Pubmed] | [DOI] | | | 3 |
Indian Indigenous Fruits as Radioprotective Agents: Past, Present and Future |
|
| Avinash Kundadka Kudva, Shamprasad Varija Raghu, Suresh Rao, Ponemone Venkatesh, Sanath Kumar Hegde, Rhea Katherine D’souza, Manjeshwar Poonam Baliga-Rao, Paul Simon, Manjeshwar Shrinath Baliga | | Anti-Cancer Agents in Medicinal Chemistry. 2022; 22(1): 53 | | [Pubmed] | [DOI] | | | 4 |
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. |
|
| Bing Tan, Natthakarn Chiranthanut, Sunee Chansakaow, Seewaboon Sireeratawong, Parirat Khonsung, Wutigri Nimlamool, Mingkwan Na Takuathung, Nirush Lertprasertsuke | | Journal of Ethnopharmacology. 2022; : 115639 | | [Pubmed] | [DOI] | | | 5 |
Enteric-Coated Cologrit Tablet Exhibit Robust Anti-Inflammatory Response in Ulcerative Colitis-like In-Vitro Models by Attuning NF?B-Centric Signaling Axis |
|
| Acharya Balkrishna, Rani Singh, Vivek Gohel, Sagar Arora, Rishabh Dev, Kunal Bhattacharya, Anurag Varshney | | Pharmaceuticals. 2022; 16(1): 63 | | [Pubmed] | [DOI] | | | 6 |
GB1a Ameliorates Ulcerative Colitis via Regulation of the NF-?B and Nrf2 Signaling Pathways in an Experimental Model |
|
| Yuanyuan Yu, Congmin Zheng, Xu Lu, Changsheng Deng, Qin Xu, Wenfeng Guo, Qingye Wu, Qi Wang, Changhui Liu, Xinan Huang, Jianping Song | | Frontiers in Medicine. 2021; 8 | | [Pubmed] | [DOI] | | | 7 |
l-Glutamine and Physical Exercise Prevent Intestinal Inflammation and Oxidative Stress Without Improving Gastric Dysmotility in Rats with Ulcerative Colitis |
|
| Raisa de Oliveira Santos, Geovane da Silva Cardoso, Lara da Costa Lima, Mickael Laudrup de Sousa Cavalcante, Mariana Sousa Silva, Ana Karolina Martins Cavalcante, Juliana Soares Severo, Francisca Beatriz de Melo Sousa, Gabriella Pacheco, Even Herlany Pereira Alves, Lívia Maria Soares Nobre, Jand Venes Rolim Medeiros, Roberto Cesar Lima-Junior, Armênio Aguiar dos Santos, Moisés Tolentino | | Inflammation. 2021; 44(2): 617 | | [Pubmed] | [DOI] | | | 8 |
Design, synthesis and molecular modeling studies of novel mesalamine linked coumarin for treatment of inflammatory bowel disease |
|
| Biswabhusan Rath, Faizan Abul Qais, Randeep Patro, Sujata Mohapatra, Tripti Sharma | | Bioorganic & Medicinal Chemistry Letters. 2021; 41: 128029 | | [Pubmed] | [DOI] | | | 9 |
Characterization of phytochemicals, minerals and in vitro medicinal activities of bael (Aegle marmelos L.) pulp and differently dried edible leathers |
|
| Sudipta Kumar Hazra, Tanmay Sarkar, Molla Salauddin, Hassan I. Sheikh, Siddhartha Pati, Runu Chakraborty | | Heliyon. 2020; 6(10): e05382 | | [Pubmed] | [DOI] | | | 10 |
In-depth pharmacological and nutritional properties of bael (Aegle marmelos): A critical review |
|
| Tanmay Sarkar, Molla Salauddin, Runu Chakraborty | | Journal of Agriculture and Food Research. 2020; 2: 100081 | | [Pubmed] | [DOI] | | | 11 |
Bioactive Compounds and Distinctive Pharmacological Activity Guided Review of Aegle marmelos: A Miraculous Plant of Indigenous Medicine System |
|
| Sourav Ghosh, Arvind Kumar, Neetu Sachan, Phool Chandra | | Current Bioactive Compounds. 2020; 16(7): 965 | | [Pubmed] | [DOI] | | | 12 |
Animal models of inflammatory bowel disease: a review |
|
| Nidhi Goyal,Ajay Rana,Abhilasha Ahlawat,Krishna Reddy V. Bijjem,Puneet Kumar | | Inflammopharmacology. 2014; | | [Pubmed] | [DOI] | |
|
|
|
|
|
|
|
|
