Protective effect of Asparagus adscendens on 5-fluorouracil induced gastrointestinal lesions in Wistar rats

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Research Paper 05/05/2024
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Protective effect of Asparagus adscendens on 5-fluorouracil induced gastrointestinal lesions in Wistar rats

Diksha Khajuria, Nawab Nashiruddullah, Nrip Kishore Pankaj, Raja A.H Kuchay, Jafrin Ara Ahmed, Syedah Asma Andrabi, Dibyendu Chakraborty, A.A. Shah
Int. J. Biosci.24( 5), 117-125, May 2024.
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Abstract

The use of the anti-cancer drug 5-fluorouracil (5-FU) is known to induce intestinal mucositis in patients without known satisfactory preventive therapy. An ethanolic extract of Asparagus adscendens (A. a. EE) of was prepared with extractability percentage calculated as 27.2% (w/w) anda simple solution was made using CMC (carboxy methyl cellulose).Twenty-four five-week-old male Wistar rats were divided in four groups- Group-I acted as  control(receiving oral saline), Group-II receiving 5-FU, Group-III receiving 5-FU and Asparagus adscendens EE, and lastly Group-IV receiving Asparagus adscendens EE alone. Dosage of Asparagus adscendens EE (300mg/kg body weight) was prepared in three divided doses and administered by gavage to the rats. A single intraperitoneal dose of 5-FU (500 g/ml) was injected in the test groups II and III. A drastic and significant (p<0.01) fall in body weight between Group-II and III rats, together with severe diarrhoea score in these groups was noted. The histopathological scores derived from 11 devised parameters showed a severe and significant (p<0.01) affliction of the ileum as compared to the jejunum in Groups-II and III. With 5-FU administration, histopathological changes in the jejunum were associated with severe pathology, such as- villi shortening, disruption of tips, degenerate enterocytes, Goblet cell reduction, marked mucosal mononuclear cell infiltration, significant loss of crypts or their distortion/loss, congestion of blood vessels and submucosal oedema. Similar changes also appeared in the ileum, together with lacteal dilation and hyperplastic Peyer’s patches. In Group-III, enteric changes in the jejunum and ileum were indicative of mild enteritis, although far less in severity than observed in Group-II. In Group-IV changes were normal except for abundant Goblet cells, both in the jejunum and ileum. Overall Asparagus adscendens was found to significantly improve the detrimental effects induced by 5-FU.

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Ahmed SR, Rabbee MF, Roy A, Chowdhury R, Banik A, Kubra K, Hassan Chowdhury MM, Baek KH. 2021. Therapeutic promises of medicinal plants in Bangladesh and their bioactive compounds against ulcers and inflammatory diseases. Plants, 10(7), 1348.

Anilkumar TV, Sarraf CE, Hunt T, Alison MR. 1992. The nature of cytotoxic drug-induced cell death in murine intestinal crypts. British Journal Cancer, 65, 552–558.

Auniq RB, Chy MN, Adnan M, Chowdhury MR, Dutta T, Ibban SS, Jahan I, Tona MR, Shima, M, Sawon MI, Chakrabarty N. 2021. Evaluation of anxiolytic, sedative, and antioxidant activities of Vitexpeduncularis Wall. leaves and investigation of possible lead compounds through molecular docking study. Advances in Traditional Medicine 21, 507-518.

Bansode FW, Arya KR, Singh RK, Narender T. 2015. Dose-dependent effects of Asparagus adscendens root (AARR) extract on the anabolic, reproductive, and sexual behavioral activity in rats. Pharmaceutical Biology 53(2), 192-200.

Bhatnagar M, Sisodia SS. 2006. Antisecretory and antiulcer activity of Asparagus racemosus Willd. against indomethacin plus phyloric ligation-induced gastric ulcer in rats. Journal of Herbal Pharmacotherapy 6(1), 13–20.

Daniele B, Secondulfo M, De Vivo R, Pignata S, De Magistris L, Delrio O, Barletta E, Tambaro R, Carratu R. 2001. Effect of chemotherapy with 5-fluorouracil on intestinal permeability and absorption in patients with advanced colorectal cancer. Journal of Clinical Gastroenterology 32, 228–230.

Dixit PK, Mittal S. 2013. Comparative haematological study of ethanolic and hydroalcoholic extract of Asparagus racemosus roots by FCA induced arthritis in rats. World Journal of Pharmaceutical Research 2(3), 693-698.

Gou H, Gu LY, Shang BZ, Xiong Y, Wang C. 2016. Protective effect of Bu-Zhong-Yi-Qi decoction, the water extract of Chinese traditional herbal medicine, on 5-fluorouracil-induced intestinal mucositis in mice. Human and Experimental Toxicology 35(12), 1243-1251.

Howarth GS, Francis GL, Cool JC, Xu X, Byard RW, Read LC. 1996. Milk growth factors enriched from cheese whey ameliorate intestinal damage by methotrexate when administered orally to rats. Journal of Nutrition 126, 2519-2530.

Kato S, Hayashi S, Kitahara Y, Nagasawa K, Aono H, Shibata J, Utsumi D, Amagase K, Kadowaki M. 2015. Saireito (TJ-114), a Japanese traditional herbal medicine, reduces 5-fluorouracil-induced intestinal mucositis in mice by inhibiting cytokine-mediated apoptosis in intestinal crypt cells. PLoS One 10(1), e0116213.

Khan KM, Nahar L, Mannan A, Arfan M, Khan GA, Al-Groshi A, Evans A, Dempster NM, Ismail FM, Sarker SD. 2017. Liquid chromatography mass spectrometry analysis and cytotoxicity of Asparagus adscendens roots against human cancer cell lines. Pharmacognosy Magazine, 13(4), S890.

Kumar P, Rai S, Verma SK, Prakash PS, Chitara D. 2022. Classification, Mode of Action and Uses of Various Immunomodulators. In: Kesharwani, R.K., Keservani, R.K., Sharma, A.K. (eds) Immunomodulators and Human Health. Springer, Singapore p 3-38.

Logan R, Stringer A, Bowen J, Gibson R, Sonis S, Keefe D. 2009. Is the pathobiology of chemotherapy-induced alimentary tract mucositis influenced by the type of mucotoxic drug administered? Cancer Chemotherapy and Pharmacology 63, 239–251.

Longley B, Harkin DP, Johnston PG. 2003. 5-fluorouracil: mechanisms of action and clinical strategies. Nature Reviews Cancer 3, 330–338.

Mangal A, Panda D, Sharma MC. 2006. Peptic ulcer healing properties of Shatavari (Asparagus racemosus Wild.). Indian Journal of Traditional Knowledge 5(2), 227-228.

Mishra JN, Verma NV. 2017. Asparagus racemosus: chemical constituents and pharmacological activities- a review. European Journal of Biomedical and Pharmaceutical Sciences, 4(6), 207-213.

Palanisamy N, Manian S. 2012. Protective effects of Asparagus racemosus on oxidative damage in isoniazid-induced hepatotoxic rats: an in vivo study. Toxicology and Industrial Health 28(3), 238–244.

Pritchard DM, Potten CS, Hickman JA. 1998. The relationships between p53-dependent apoptosis, inhibition of proliferation, and 5-fluorouracil-induced histopathology in murine intestinal epithelia. Cancer Research 58, 5453–5465.

Sairam K, Priyambada S, Aryya NC, Goel RK. 2003. Gastroduodenal ulcer protective activity of Asparagus racemosus: an experimental, biochemical and histological study. Journal of  Ethnopharmacology 86(1), 1–10.

Saran PL, Singh S, Solanki V, Choudhary R, Manivel P. 2021. Evaluation of Asparagus adscendens accessions for root yield and shatavarin IV content in India.

Saxena VK, Chourasia S. 2001. A new isoflavone from the roots of Asparagus racemosus, Fitoterapia, 72(3), 307–309.

Sharma S, Chand R, Sati OP. 1982. Steroidal Sapogenins of Asparagus adscendens. Phytochemistry 21(8), 2075-2078.

Singh KP, Singh RH. 1986. Clinical trial on Shatavari (Asparagus racemosus Willd) on duodenal ulcer disease. Journal of Research in Ayurveda and Siddha 7, 91–100.

Singh M, Shrivastava D, Kale RK. 2011. Chemomodulatory potential of Asparagus adscendens against murine skin and forestomach papillomagenesis. European Journal of Cancer Prevention 20, 240–247.

Soares PMG, Mota JMSC, Souza EP, Justino PFC, Franco AX, Cunha FQ, Ribeiro RA, Souza MHLP. 2013. Inflammatory intestinal damage induced by 5-fluorouracil requires IL-4. Cytokine, 61(1), 46-49.

Sonis ST. 1993. Complications of cancer and their treatment: oral complications. In: Holland, J.F., Frei, E., Bast, R.C., Kufe, D.W., Morton, D.L., Weichselbaum, R.R. (eds). Cancer Medicine (3rd edition). London: Lea and Febiger. 2381–2388 p.

Sonis ST. 2004. The pathobiology of mucositis. Nature Reviews Cancer 4(4), 277–284.

Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, HauerJensen M, Bekele BN, Raber-Durlacher J, Rubenstein EB. 2004. Perspectives on cancer therapy–induced mucosal injury. Cancer 100(S9), 1995–2025.

Vanhoecke B, Bateman E, Mayo B, Vanlancker E, Stringer A, Thorpe D, Keefe D. 2015. Dark Agouti rat model of chemotherapy-induced mucositis: establishment and current state of the art. Experimental Biology and Medicine 240(6), 725-741.

Yasuda M, Kato S, Yamanaka N, Iimori M, Matsumoto K, Utsumi D, Kitahara Y, Amagase K, Horie S, Takeuchi K. 2013. 5-HT3 receptor antagonists ameliorate 5-fluorouracil-induced intestinal mucositis by suppression of apoptosis in murine intestinal crypt cells. British Journal of Pharmacology 168(6), 1388-140.