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Current Drug Therapy


ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Research Article

Optimization and Validation of Polyherbal Formulation by Applying Boxbehnken Design for the Treatment of Inflammatory Bowel Disease in Experimental Animals

Author(s): Tejal Gandhi*, Bhagyabhumi Patel, Divya Patel, Saloni Dalwadi and Vaishali Thakkar

Volume 17, Issue 1, 2022

Published on: 16 February, 2022

Page: [17 - 29] Pages: 13

DOI: 10.2174/1574885517666211220130024

Price: $65


Background: The use of herbal medicine in inflammatory bowel disease (IBD) has increased significantly. Allopathic treatment of IBD leads to several side effects; therefore, the use of the herbal formulation is promising. Aegle Marmelos, Bombax malabericum, and Hollarrhena antidysentrica plants have been used to treat IBD.

Objective: This study aimed to evaluate a designed polyherbal formulation in experimentally induced inflammatory bowel disease in rats and validate a mathematical model derived by Box-Behnken experimental design for optimized polyherbal formulation for the treatment of IBD in experimental rats by checkpoint analysis.

Methods: Three-level Box-Behnken design was selected to optimize the dose. Polyherbal formulation that consisted of plant extracts of Aegle Marmelos (X1), Bombax malabericum (X2), and Hollarrhena antidysentrica (X3) in different ratios was selected as an independent variable. Polynomial equations were established based on analysis of variance (ANOVA). To validate the chosen polynomial equation, checkpoint analyses were performed. The percentage of predictive error is presented.

Results: ANOVA reveals that X2 plant does not have any significant impact on the response surface. The checkpoint batch showed the experimental values of CMDI and Disease activity index (DAI) as 1.33 and 0.66, respectively. It is worthwhile to note that the observed values were quite close to the calculated values of CMDI. A little difference in the value of DAI may be attributed to the inherent variation observed in animal studies.

Conclusion: From this study, it was concluded that a dose of 100 mg/kg of Aegle marmelos, a dose of 300 mg/kg of Bombax malabericum, and a dose of 200 mg/kg of Holarrhena antidysentrica will be effective in IBD patients.

Keywords: Polyherbal formulation, inflammatory bowel disease, box-behnken design, Aegle marmelos, Bombax malabericum, Hollarrhena antidysentrica.

Graphical Abstract
Talley NJ, Abreu MT, Achkar JP, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol 2011; 106(Suppl. 1): S2-S25.
[] [PMID: 21472012]
Hendrickson BA, Gokhale R, Cho JH. Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev 2002; 15(1): 79-94.
[] [PMID: 11781268]
Nitta M, Hirata I, Toshina K, et al. Expression of the EP4 prostaglandin E2 receptor subtype with rat dextran sodium sulphate colitis: Colitis suppression by a selective agonist, ONO-AE1-329. Scand J Immunol 2002; 56(1): 66-75.
[] [PMID: 12100473]
Kamboj VP. Herbal medicine. Curr Sci 2000; 78(1): 35-9.
Gaur PK, Shanmugam SK. Box-Behnken design–directed optimization of wickerhamomyces anomalous–mediated biotransformation process to enhance the flavonoid profile of polyherbal extract. J Pharm Innov 2020.
Behera JP, Mohanty B, Ramani YR, Rath B, Pradhan S. Effect of aqueous extract of Aegle marmelos unripe fruit on inflammatory bowel disease. Indian J Pharmacol 2012; 44(5): 614-8.
[] [PMID: 23112424]
Anandarajagopal K, Sunilson J, Ajaykumar T. In-vitro Anti-inflammatory evaluation of Crude Bombax ceiba Extarct. Eur. J Med plants 2013; 3(1): 99-104.
Darji VC, Shrikalp D, Aditi B. Effects of methanolic extract of Holarrhena antidysenterica bark against experimentally induced inflammatory bowel disease in rats. Int J Pharm Res 2012; 3(9): 152-4.
Darji VC, Bariya AH, Deshpande SS. Natural agents for inflammatory bowel disease. Int J Res Ayurveda Pharm 2011; 2(1): 84-9.
Darji VC, Bariya AH, Deshpande SS. Comparision between the effect of Holarrhena antidysentrica bark against experimentally induced inflammatory bowel disease. Int Res J Pharm 2013; 4(1): 131-4.
Darji VC. M.pharm thesis, Effect of Punica granatum Linn and Aegle marmelos Correa ex Roxb in experimentally induced inflammatory bowel disease in rats. Sardar Patel University, July 2005.
Trivedi N. M.pharm thesis, To evaluate an anti-inflammatory activity of herbal (Bombax malabericum) drug A and (Asparagus racemosus) drug B in experimentally induced inflammatory bowel disease. Sardar Patel University, July 2008.
Darji VC, Bariya A, Deshpande S, Patel D. Effect of Punica granatum fruits in inflammatory bowel disease. J Pharm Res 2010; 3: 2850-2.
Vasina V, Broccoli M, Ursino MG, et al. Effects of the non-peptidyl low molecular weight radical scavenger IAC in DNBS-induced colitis in rats. Eur J Pharmacol 2009; 614(1-3): 137-45.
[] [PMID: 19383495]
Blandizzi C, Fornai M, Colucci R, et al. Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by alpha2-adrenoceptors in the presence of experimental colitis. Br J Pharmacol 2003; 139(2): 309-20.
[] [PMID: 12770936]
Dong WG, Liu SP, Yu BP, Wu DF, Luo HS, Yu JP. Ameliorative effects of sodium ferulate on experimental colitis and their mechanisms in rats. World J Gastroenterol 2003; 9(11): 2533-8.
[] [PMID: 14606091]
Uritski R, Barshack I, Bilkis I, Ghebremeskel K, Reifen R. Dietary iron affects inflammatory status in a rat model of colitis. J Nutr 2004; 134(9): 2251-5.
[] [PMID: 15333712]
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95(2): 351-8.
[] [PMID: 36810]
Joshi SV, Vyas BA, Shah PD, Shah DR, Shah SA, Gandhi TR. Protective effect of aqueous extract of Oroxylum indicum Linn. (root bark) against DNBS-induced colitis in rats. Indian J Pharmacol 2011; 43(6): 656-61.
[PMID: 22144769]
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 1972; 247(10): 3170-5.
[] [PMID: 4623845]
Harputluoglu MM, Demirel U, Yücel N, et al. The effects of Gingko biloba extract on acetic acid-induced colitis in rats. Turk J Gastroenterol 2006; 17(3): 177-82.
[PMID: 16941250]
Debnath T, Kim DH, Lim BO. Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease. Molecules 2013; 18(6): 7253-70.
[] [PMID: 23783459]
Gupta K, Karale S, Warad V. Antidiarrhoeal activity of a Polyherbal formulation in various animal models of diarrhoea. Int. Res J Pharm 2012; 3(8): 289-90.
Parronchi P, Romagnani P, Annunziato F, et al. Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn’s disease. Am J Pathol 1997; 150(3): 823-32.
[PMID: 9060820]
Salvatore C, Emanuela M, Rosanna P. Erythropoietin reduces the development of experimental, inflammatory bowel disease. J Pharmacol Exp Ther 2004; 10: 1124.
Stein J, Ries J, Barrett KE. Disruption of intestinal barrier function associated with experimental colitis: Possible role of mast cells. Am J Physiol 1998; 274(1): G203-9.
[PMID: 9458791]
Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J Pharmacol Exp Ther 2000; 294(3): 822-9.
[PMID: 10945829]
Soriano-Izquierdo A, Gironella M, Massaguer A, et al. Effect of cyclosporin A on cell adhesion molecules and leukocyte-endothelial cell interactions in experimental colitis. Inflamm Bowel Dis 2004; 10(6): 789-800.
[] [PMID: 15626898]
Tuin A, Poelstra K, de Jager-Krikken A, et al. Role of alkaline phosphatase in colitis in man and rats. Gut 2009; 58(3): 379-87.
[] [PMID: 18852260]
Wang QG, He LY, Chen YW, Hu SL. Enzymohistochemical study on burn effect on rat intestinal NOS. World J Gastroenterol 2000; 6(3): 421-3.
[] [PMID: 11819616]
Millar AD, Rampton DS, Chander CL, et al. Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 1996; 39(3): 407-15.
[] [PMID: 8949646]
Jackson L, Evers BM. Chronic inflammation and pathogenesis of GI and pancreatic cancersCancer Treat Res. 2006; 130: pp. 39-65.
[] [PMID: 16610702]
Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 1995; 41(12 Pt 2): 1819-28.
[] [PMID: 7497639]
Devasagayam TPA, Boloor KK, Ramasarma T. Methods for estimating lipid peroxidation: An analysis of merits and demerits. Indian J Biochem Biophys 2003; 40(5): 300-8.
[PMID: 22900323]
Niki E. Lipid peroxidation products as oxidative stress biomarkers. Biofactors 2008; 34(2): 171-80.
[] [PMID: 19706982]
Halliwell B. What nitrates tyrosine? Is nitrotyrosine specific as a biomarker of peroxynitrite formation in vivo? FEBS Lett 1997; 411(2-3): 157-60.
[] [PMID: 9271196]

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