Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Croton Oil-induced Hemorrhoidal Rats: Evaluation of Anti-inflammatory Mediated Anti-hemorrhoidal Activity of Tridax procumbens Whole Plant

Author(s): Sai Krishna Nallajerla* and Suhasin Ganta

Volume 19, Issue 7, 2023

Published on: 15 March, 2023

Article ID: e070223213490 Pages: 12

DOI: 10.2174/1573407219666230207105946

Price: $65

Abstract

Background: Hemorrhoids are anorectal disorders characterized by dilation of rectal blood vessels, inflammation, and prolapse of the anal tissue. The disease affects both men and women equally. In consequence, the increasing prevalence of the disease needs potential agents with efficiency and low cost to support the treatment.

Objective: The treatment of hemorrhoids in modern medicine is still found to be in its infancy, as there is no precise treatment for the specific disease. Tridax procumbens Linn (T. procumbens) belongs to the family Asteraceae. From the literature, the plant was found to have a traditional use for the treatment of hemorrhoids. Hence, the present research was focused on evaluating the antiinflammatory mediated anti-hemorrhoidal potential of ethanolic whole plant extract of T. procumbens (EWETP) in croton oil-induced hemorrhoidal rats.

Methods: An in vitro study was conducted to evaluate the percentage inhibition of protein (egg albumin) denaturation by Tridax procumbens. This study determined the initial protective role of plant extracts against inflammatory proteins. An in vivo, anti-inflammatory-mediated anti-hemorrhoidal study was carried out on T. procumbens in various groups of croton oil-induced hemorrhoidal rats. Wistar albino rats were selected for the present research, and hemorrhoids were induced in experimental animals using a croton oil preparation containing 6% croton oil, deionised water, pyridine, and diethyl ether. Pilex ointment was taken as a reference drug in this study. Inflammation seems to be a major pathway for the progression of hemorrhoids. Hence, in the present research, Evans blue (EB) extravasation technique was applied to quantify inflammatory proteins. On the last day of the study, blood samples were drawn from experimental animals to analyse serum and blood for TNF- α, IL-6, and the percentage of neutrophils count. Recto anal coefficient was calculated to measure croton oil-induced rectal inflammation in animals. Histopathological studies were carried out separately on a second set of animals to identify the protective role of T.procumbens on rectal tissue cell histology. Molecular docking studies were carried out to rule out the possible interaction of plant phytoconstituents with the COX-2 enzyme.

Results: Results showed that intra rectal application of croton oil preparation in albino rats developed hemorrhoids by elevating serum TNF-α and IL-6 in positive control group animals compared to normal group rats. Treatment of albino rats with T. procumbens at doses of 200 mg/kg and 400 mg/kg in groups IV and V has shown a significant reduction in serum TNF-α and IL-6. Furthermore, in the study, T. procumbens exhibited a significant dose-dependent reduction of EB dye extravasation in study animals. The study observations also revealed the inhibitory effect of plant extract on the blood percentage of neutrophils count and recto anal coefficient compared to the positive control group rats. Histopathological studies conducted on rectoanal tissues showed the presence of minimal rectal tissue changes in plant extract-treated group animals compared to positive control group rats. Molecular docking studies explored the possible interaction of phenolic compounds of plant extract with the COX enzyme.

Conclusion: It was concluded that Tridax procumbens had a protective role against inflammatory mediators in hemorrhoids. In hemorrhoidal rats, ethanolic leaf extract was found to reduce the plasma percentage of neutrophils and other inflammatory cytokines, TNF-α, and IL-6. It could be used as a therapeutic anti-inflammatory mediated anti-hemorrhoidal agent.

Keywords: Tridax procumbens, cytokines, croton oil, hemorrhoids, TNF α, IL-6.

Graphical Abstract

[1]
Gardner, I.; Siddharthan, R.V.; Tsikitis, V.L. Benign anorectal disease: Hemorrhoids, fissures, and fistulas. Ann. Gastroenterol., 2019, 33(1), 9-18.
[http://dx.doi.org/10.20524/aog.2019.0438] [PMID: 31892792]
[2]
Gami, B. Hemorrhoids - a common ailment among adults, causes & treatment: A review. Int. J. Pharm. Pharm. Sci., 2011, 3(Suppl. 5), 5-12.
[3]
Sheikh, P.; Régnier, C.; Goron, F.; Salmat, G. The prevalence, characteristics and treatment of hemorrhoidal disease: Results of an international web-based survey. J. Comp. Eff. Res., 2020, 9(17), 1219-1232.
[http://dx.doi.org/10.2217/cer-2020-0159] [PMID: 33079605]
[4]
Salgueiro, P.; Caetano, A.C.; Oliveira, A.M.; Rosa, B.; Mascarenhas-Saraiva, M.; Ministro, P.; Amaro, P.; Godinho, R.; Coelho, R.; Gaio, R.; Fernandes, S.; Fernandes, V.; Castro-Poças, F. Portuguese society of gastroenterology consensus on the diagnosis and management of hemorrhoidal disease. GE Port. J. Gastroenterol., 2020, 27(2), 90-102.
[http://dx.doi.org/10.1159/000502260] [PMID: 32266306]
[5]
Johanson, J.F.; Sonnenberg, A. The prevalence of hemorrhoids and chronic constipation. Gastroenterology, 1990, 98(2), 380-386.
[http://dx.doi.org/10.1016/0016-5085(90)90828-O] [PMID: 2295392]
[6]
Najar, F.A.; Faisal, M. Prevalence of hemorrhoid among the patients visiting surgery OPD at NIUM hospital of biomedical and pharmaceutical sciences. Eur. J. Biomed. Pharm. Sci., 2018, 5(1), 435-437.
[7]
Mullaicharam, A.R.; Uma, M.R.; Geetha, K. Hemorrhoids: A review. Res. J. Pharm. and Tech., 2010, 3(2), 296-299.
[8]
Kaidar-Person, O.; Person, B.; Wexner, S.D. Hemorrhoidal disease: A comprehensive review. J. Am. Coll. Surg., 2007, 204(1), 102-117.
[http://dx.doi.org/10.1016/j.jamcollsurg.2006.08.022] [PMID: 17189119]
[9]
Thomson, H. The anal cushions-A fresh concept in diagnosis. Postgrad. Med. J., 1979, 55, 403-405.
[10]
Lohsiriwat, V. Hemorrhoids: From basic pathophysiology to clinical management. World J. Gastroenterol., 2012, 18(17), 2009-2017.
[http://dx.doi.org/10.3748/wjg.v18.i17.2009] [PMID: 22563187]
[11]
Lalisang, T.J.M. Hemorrhoid: Pathophysiology and surgical management literature review. New Ropanasuri J. Surg., 2016, 1(1), 31-36.
[http://dx.doi.org/10.7454/nrjs.v1i1.9]
[12]
Bhagat, V.C.; Kondawar, M.S. A comprehensive review on phytochemistry and pharmacological use of Tridax procumbens Linn. ~ 1 ~. J. Pharmacogn. Phytochem., 2019, 8(4), 1-10.
[13]
Anugrahwati, M.; Purwaningsih, T. Rustina; Manggalarini, J.A.; Alnavis, N.B.; Wulandari, D.N.; Pranowo, H.D. Extraction of ethanolic extract of red betel leaves and its cytotoxicity test on hela cells. Procedia Eng., 2016, 148, 1402-1407.
[http://dx.doi.org/10.1016/j.proeng.2016.06.569]
[14]
Shaikh, J.R.; Patil, M.K. Qualitative tests for preliminary phytochemical screening: An overview. Int. J. Chem. Stud., 2020, 8(2), 603-608.
[http://dx.doi.org/10.22271/chemi.2020.v8.i2i.8834]
[15]
Kumarasinghe, N.; Dharmadeva, S.; Galgamuwa, L.S.; Prasadinie, C. In vitro anti-inflammatory activity of Ficus racemosa L. bark using albumin denaturation method. Ayu, 2018, 39(4), 239-242.
[http://dx.doi.org/10.4103/ayu.AYU_27_18] [PMID: 31367147]
[16]
Azeemuddin, M.; Viswanatha, G.L.; Rafiq, M.; Thippeswamy, A.H.; Baig, M.R.; Kavya, K.J.; Patki, P.S.; Shyam, R. An improved experimental model of hemorrhoids in rats: Evaluation of antihemorrhoidal activity of an herbal formulation. ISRN Pharmacol., 2014, 2014, 1-7.
[http://dx.doi.org/10.1155/2014/530931] [PMID: 25006493]
[17]
Faujdar, S.; Sati, B.; Sharma, S.; Pathak, A.K.; Paliwal, S.K. Phytochemical evaluation and anti-hemorrhoidal activity of bark of Acacia ferruginea DC. J. Tradit. Complement. Med., 2019, 9(2), 85-89.
[http://dx.doi.org/10.1016/j.jtcme.2018.02.003] [PMID: 30963042]
[18]
Dwivedi, V.K.; Tiwari, A.K.; Pandey, A.; Singh, V.; Nayak, A. Therapeutic effect of pilescure in experimental model of hemorrhoids rats. J. Drug Des. Discov. Res., 2019, 1(1), 12-20.
[http://dx.doi.org/10.1254/fpj.92.215]
[19]
Dhaswadikar, S.R.; Parmar, K.M.; Kamble, S.K.; Kathuria, I.; Dhobi, M.; Birajdar, A.; Prasad, S.K.; Itankar, P.R. Anti-hemorrhoidal potential of standardized leaf extract of Dolichandrone falcata. Phytomedicine Plus, 2022, 2(1), 100172.
[http://dx.doi.org/10.1016/j.phyplu.2021.100172]
[20]
Shin, S.; Joo, S.S.; Park, D.; Jeon, J.H.; Kim, T.K.; Kim, J.S.; Park, S.K.; Hwang, B.Y.; Kim, Y.B. Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway. J. Vet. Sci., 2010, 11(1), 43-50.
[http://dx.doi.org/10.4142/jvs.2010.11.1.43] [PMID: 20195064]
[21]
Krzyzanowska, A.; Martin, Y.; Avendaño, C.; Piedras, M.J.; Piedras, M.J. Evaluation of evans blue extravasation as a measure of peripheral inflammation. Protocol Exchange, 2010.
[22]
Wang, J.L.; Limburg, D.; Graneto, M.J.; Springer, J.; Hamper, J.R.B.; Liao, S.; Pawlitz, J.L.; Kurumbail, R.G.; Maziasz, T.; Talley, J.J.; Kiefer, J.R.; Carter, J. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg. Med. Chem. Lett., 2010, 20(23), 7159-7163.
[http://dx.doi.org/10.1016/j.bmcl.2010.07.054] [PMID: 20709553]
[23]
Dallakyan, S.; Olson, A.J. Small-molecule library screening by docking with PyRx. Methods Mol. Biol., 2015, 1263, 243-250.
[http://dx.doi.org/10.1007/978-1-4939-2269-7_19] [PMID: 25618350]
[24]
Bartels, D.A.; Johnson, R.; Bayor, M.T.; Ainooson, G.K.; Ossei, P.P.S.; Etuaful, R.K.; Buamah, R. Formulation of suppositories of alum produced from bauxite waste in Ghana for the treatment of hemorrhoid. ScientificWorldJournal, 2021, 2021, 1-13.
[http://dx.doi.org/10.1155/2021/6667562] [PMID: 34093089]
[25]
Sun, Z.; Migaly, J. Review of hemorrhoid disease: Presentation and management. Clin. Colon Rectal Surg., 2016, 29(01), 022-029.
[http://dx.doi.org/10.1055/s-0035-1568144]
[26]
Nallajerla, S.; Ganta, S. A comprehensive review on hemorrhoids a recto anal disorder. Pharmacologyonline, 2021, 1, 270-282.
[27]
Kibret, A. A.; Oumer, M.; Moges, A. M. Prevalence and associated factors of hemorrhoids among adult patients visiting the surgical outpatient department in the university of gondar comprehensive specialized hospital, Northwest Ethiopia. PloS One, 2021, 16(4 April), 1-11.
[http://dx.doi.org/10.1371/journal.pone.0249736]
[28]
Singh, K. Surgery for hemorrhoids: A review. Indian J. Colo-Rectal Surg., 2018, 1(1), 14.
[http://dx.doi.org/10.4103/IJCS.IJCS_4_18]
[29]
Petrovska, B. Historical review of medicinal plants′ usage. Pharmacogn. Rev., 2012, 6(11), 1-5.
[http://dx.doi.org/10.4103/0973-7847.95849] [PMID: 22654398]
[30]
Ingole, V.V.; Mhaske, P.C.; Katade, S.R. Phytochemistry and pharmacological aspects of Tridax procumbens (L.): A systematic and comprehensive review. Phytomedicine Plus, 2022, 2(1), 100199.
[http://dx.doi.org/10.1016/j.phyplu.2021.100199]
[31]
Porwal, A.; Kundu, G.; Bhagwat, G.; Butti, R. Herbal medicine AnoSpray suppresses proinflammatory cytokines COX 2 and RANTES in the management of hemorrhoids, acute anal fissures and perineal wounds. Exp. Ther. Med., 2021, 23(1), 86.
[http://dx.doi.org/10.3892/etm.2021.11009] [PMID: 34938368]
[32]
Otuki, M.F.; Cabrini, D.A.; Moresco, H.H.; Imazu, P.; Silva, C.D. Da; Pietrovski, E. F.; Mendes, D. A. G. B.; Prudente, A. D. S.; Pizzolatti, M. G.; Brighente, I. M. C. Analysis of the potential topical anti-inflammatory activity of Averrhoa carambola L. in mice. Evid. -based Compl. Alter. Med., 2011, 2011, 1-7.
[http://dx.doi.org/10.1093/ecam/neq026]
[33]
Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 2018, 9(6), 7204-7218.
[http://dx.doi.org/10.18632/oncotarget.23208] [PMID: 29467962]
[34]
Hamer, P.W.; McGeachie, J.M.; Davies, M.J.; Grounds, M.D. Evans Blue Dye as an in vivo marker of myofibre damage: Optimising parameters for detecting initial myofibre membrane permeability. J. Anat., 2002, 200(1), 69-79.
[http://dx.doi.org/10.1046/j.0021-8782.2001.00008.x] [PMID: 11837252]
[35]
Mott, T.; Latimer, K.; Edwards, C. Hemorrhoids: Diagnosis and treatment options. Am. Fam. Physician, 2018, 97(3), 172-179.
[PMID: 29431977]
[36]
Nijveldt, R.J.; van Nood, E.; van Hoorn, D.E.C.; Boelens, P.G.; van Norren, K.; van Leeuwen, P.A.M. Flavonoids: A review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr., 2001, 74(4), 418-425.
[http://dx.doi.org/10.1093/ajcn/74.4.418] [PMID: 11566638]
[37]
Naegelen, I.; Beaume, N.; Plançon, S.; Schenten, V.; Tschirhart, E.J.; Bréchard, S. Regulation of neutrophil degranulation and cytokine secretion: A novel model approach based on linear fitting. J. Immunol. Res., 2015, 2015, 1-15.
[http://dx.doi.org/10.1155/2015/817038] [PMID: 26579547]
[38]
Jn, B.; Dhumal, K.T. Evaluation of anti-angiogenic properties of Tridax procumbens leaves extract, using shell less chick embryo culture. Int. J. Bioassays, 2014, 3(2), 1765-1767.
[39]
Hardy, A.; Cohen, C.R.G. The acute management of haemorrhoids. Ann. R. Coll. Surg. Engl., 2014, 96(7), 508-511.
[http://dx.doi.org/10.1308/003588414X13946184900967] [PMID: 25245728]
[40]
López-Posadas, R.; Ballester, I.; Mascaraque, C.; Suárez, M.D.; Zarzuelo, A.; Martínez-Augustin, O.; Sánchez de Medina, F. Flavonoids exert distinct modulatory actions on cyclooxygenase 2 and NF‐κB in an intestinal epithelial cell line (IEC18). Br. J. Pharmacol., 2010, 160(7), 1714-1726.
[http://dx.doi.org/10.1111/j.1476-5381.2010.00827.x] [PMID: 20649574]
[41]
Gryglewski, R.J. Korbut, R.; Robak, J.; Świȩs, J. On the mechanism of antithrombotic action of flavonoids. Biochem. Pharmacol., 1987, 36(3), 317-322.
[http://dx.doi.org/10.1016/0006-2952(87)90288-7] [PMID: 3101704]

Rights & Permissions Print Cite
Article Metrics
28
2
© 2024 Bentham Science Publishers | Privacy Policy