Evaluating the Role of Biochanin A in Acetic acid-Induced Colitis in Rats: Involvement of Nitric Oxide Pathway

Document Type : Original paper


1 Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

2 Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

3 Persian Medicine Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.

4 Isfahan Cardiovascular Research Centre, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.


Background and objectives: Inflammatory bowel disease (IBD) refers to idiopathic chronic and inflammatory bowel disorders such as ulcerative colitis. Considering the lack of definitive treatment and the side effects of existing drugs, finding efficient compounds is needed. Biochanin A has attracted the attention of researchers due to its wide range of medicinal activities. Until now, no study was conducted to evaluate its effects on colitis. Therefore, the aim of this study was to determine the effect of biochanin A on the nitrogen pathway in rats with acetic acid-induced colitis. Methods: Male rats were divided into five groups: normal group, negative control group, positive control group, and groups receiving biochanin A (10 and 20 mg/kg). Colitis was induced with 4% acetic acid. Next, the samples were evaluated at different macroscopic and microscopic levels, and biochemical test of superoxide dismutase (SOD) and nitric oxide activity was investigated. Results: Macroscopic and microscopic investigations showed that treatment with biochanin A decreased mucosal damage in rats with acetic acid-induced colitis. Biochanin A reduced neutrophil infiltration in the intestinal tissue. It also led to the reduction in nitric oxide and enhancement of SOD in rats. The optimal dose of biochanin A was 20 mg/kg, which had the best effect on reducing inflammation and mucosal lesions in rats. Conclusion: Biochanin A, due to its anti-inflammatory effects by reducing nitric oxide and enhancement of SOD and reducing mucosal damage in rats with acetic acid-induced colitis, can be a useful alternative drug for the prevention or treatment of IBD patients.


Main Subjects

  • George Broughton I, Janis JE, Attinger CE. The basic science of wound healing. Plast Reconst Surg. 2006; 117(7S): 12–34.
  • Baumgart DC. The diagnosis and treatment of Crohn’s disease and ulcerative colitis. Int. 2009; 106(8): 123–133.
  • Sartor RB. Mechanisms of disease: pathogenesis of Crohn's disease and ulcerative colitis. Nat Rev Gastroenterol Hepatol. 2006; 3(7): 390–407.
  • Cioffi M, De Rosa A, Serao R, Picone I, Vietri MT. Laboratory markers in ulcerative colitis: current insights and future advances. World J Gastrointest Pathophysiol. 2015; 6(1): 13–22.
  • Farooq SM, Stillie R, Svensson M, Svanborg C, Strieter RM, Stadnyk AW. Therapeutic effect of blocking CXCR2 on neutrophil recruitment and dextran sodium sulfate-induced colitis. J Pharmacol Exp Ther. 2009; 329(1): 123–129.
  • Jameson JL. Harrison's principles of internal medicine. New York: McGraw-Hill,
  • Debnath T, Kim DH, Lim BO. Natural products as a source of anti-inflammatory agents associated with inflammatory bowel disease. Molecules. 2013; 18(6): 7253–7270.
  • Hajrezaie M, Salehen N, Karimian H, Zahedifard M, Shams K, Batran RA, Majid NA, Khalifa SA, Ali HM, El-Seedi H, Abdulla MA. Biochanin a gastroprotective effects in ethanol-induced gastric mucosal ulceration in rats. PLoS One. 2015; Article ID e0121529.
  • Gautam M, Goel S, Ghatule R, Singh A, Nath G, Goel R. Curative effect of Terminalia chebula extract on acetic acid-induced experimental colitis: role of antioxidants, free radicals and acute inflammatory marker. Inflammopharmacology. 2013; 21(1): 377–383.
  • Patel SS, Savjani JK. Systematic review of plant steroids as potential antiinflammatory agents: current status and future perspectives. J Phytopharm. 2015; 4(2): 121–125.
  • Nicolis E, Lampronti I, Dechecchi MC, Borgatti M, Tamanini A, Bezzerri V, Bianchi N, Mazzon M, Mancini I, Giri MG, Rizzotti P. Modulation of expression of IL-8 gene in bronchial epithelial cells by 5-methoxypsoralen. J Ethnopharmacol. 2009; 9(12): 1411–1422.
  • Darwish RS, Shawky E, Nassar KM, ElSayed RM, Hussein DE, Ghareeb DA, El Sohafy SM. Differential anti-inflammatory biomarkers of the desert truffles Terfezia claveryi and Tirmania nivea revealed via UPLC-QqQ-MS-based metabolomics combined to chemometrics. LWT. 2021; Article ID 111965.
  • Sarfraz A, Javeed M, Shah MA, Hussain G, Shafiq N, Sarfraz I, Riaz A, Sadiqa A, Zara R, Zafar S, Kanwal L. Biochanin A: a novel bioactive multifunctional compound from nature. Sci Total Environ. 2020; Article ID 137907.
  • Raheja S, Girdhar A, Lather V, Pandita D. Biochanin A: a phytoestrogen with therapeutic potential. Trends Food Sci Technol. 2018; 79(1): 55–66.
  • Wang L, Li L, Han Q, Wang X, Zhao D, Liu J. Identification and biological evaluation of natural product Biochanin A. Bioorg Chem. 2020; Article ID 103674.
  • Qiu L, Lin B, Lin Z, Lin Y, Lin M, Yang X. Biochanin A ameliorates the cytokine secretion profile of lipopolysaccharide-stimulated macrophages by a PPARγ-dependent pathway. Mol Med Rep. 2012; 5(1): 217–222.
  • Zhang Y, Chen WA. Biochanin A inhibits lipopolysaccharide-induced inflammatory cytokines and mediators production in BV2 microglia. Neurochem Res. 2015; 40(1): 165–171.
  • Liu X, Wang T, Liu X, Cai L, Qi J, Zhang P, Li Y. Biochanin A protects lipopolysaccharide/D-galactosamine-induced acute liver injury in mice by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Int Immunopharmacol. 2016; 38(1): 324–331.
  • Mahgoub AA. Thymoquinone protects against experimental colitis in rats. Toxicol Lett. 2003; 143(2): 133–143.
  • Bezerra GB, de Souza LD, Dos Santos AS, de Almeida GK, Souza MT, Santos SL, Camargo EA, dos Santos Lima B, de Souza Araújo AA, Cardoso JC, Gomes SV. Hydroalcoholic extract of Brazilian red propolis exerts protective effects on acetic acid-induced ulcerative colitis in a rodent model. Biomed Pharmacother. 2017; 85(1): 687–696.
  • Tahan G, Aytac E, Aytekin H, Gunduz F, Dogusoy G, Aydin S, Tahan V, Uzun H. Vitamin E has a dual effect of anti-inflammatory and antioxidant activities in acetic acid–induced ulcerative colitis in rats. Can J Surg. 2011; 54(5): 333–338.
  • El-Abhar HS, Hammad LN, Gawad HSA. Modulating effect of ginger extract on rats with ulcerative colitis. J Ethnopharmacol. 2008; 118(3): 367–372.
  • Deshmukh C, Veeresh B, Pawar A. Protective effect of Emblica officinalis fruit extract on acetic acid induced colitis in rats. J Herb Med Toxicol. 2010; 4(2): 83–87.
  • Morris G, Beck P, Herridge M, Depew W, Szewczuk M, Wallace J. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989; 96(2): 795–803.
  • Rashidian A, Rashki A, Abdollahi A, Haddadi NS, Chamanara M, Mumtaz F, Dehpour AR. Dapsone reduced acetic acid-induced inflammatory response in rat colon tissue through inhibition of NF-kB signaling pathway. Immunopharmacol Immunotoxicol. 2019; 41(6): 607–613.
  • Zhang C, Bruins ME, Yang ZQ, Liu ST, Rao PF. A new formula to calculate activity of superoxide dismutase in indirect assays. Anal Biochem. 2016; 503(1): 65–67.
  • El-Akabawy G, El-Sherif NM. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed Pharmacother. 2019; 111(1): 841–851.
  • Head KA, Jurenka JS. Colitis–pathophysiology U. Inflammatory bowel disease part I: ulcerative colitis–pathophysiology and conventional and alternative treatment options. Altern Med Rev. 2003; 8(3): 247–283.
  • Jun M, Hong J, Jeong WS, Ho CT. Suppression of arachidonic acid metabolism and nitric oxide formation by kudzu isoflavones in murine macrophages. Mol Nutr Food Res. 2005; 49(12): 1154–1159.
  • Fabia R, Willen R, Ar’Rajab A, Andersson R, Ahren B, Bengmark S. Acetic acid-induced colitis in the rat: a reproducible experimental model for acute ulcerative colitis. Eur Surg Res. 1992; 24(4): 211–225.
  • Rezayat SM, Dehpour AR, Motamed SM, Yazdanparast M, Chamanara M, Sahebgharani M, Rashidian A. Foeniculum vulgare essential oil ameliorates acetic acid-induced colitis in rats through the inhibition of NF-kB pathway. Inflammopharmacology. 2018; 26(1): 851–859.
  • Yamada T, Zimmerman BJ, Specian RD, Grisham MB. Role of neutrophils in acetic acid-induced colitis in rats. Inflammation. 1991; 15(5): 399–411.
  • DiCarlo AL, Bandremer AC, Hollingsworth BA, Kasim S, Laniyonu A, Todd NF, Wang SJ, Wertheimer ER, Rios CI. Cutaneous radiation injuries: models, assessment and treatments. Radiat Res. 2020; 194(3): 315–344.
  • Giri M, Divakar K, Goli D, Dighe S. Anti ulcer activity of leaves of Gmelina arborea plant in experimentally induced ulcer in Wistar rats. Pharmacologyonline. 2009; 1(1): 102–110.