The Effect of Artesunate and Brotowali (Tinospora Crispa) Combination on Histopathological, and Expression of Nuclear Factor Kappa B (NF-kβ) in Renal Tubules of Mice Infected With Plasmodium Berghei

Authors

  • Angela Merici Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Saiful Anwar Hospital, Malang
  • Loeki Enggar Fitri Parasitology Laboratory, Faculty of Medicine, Universitas Brawijaya, Malang
  • Niniek Budiarti Infectious and Tropical Diseases, Department of Internal Medicine, Faculty of Medicine, Universitas Brawijaya, Malang

DOI:

https://doi.org/10.21776/ub.crjim.2020.001.01.5

Keywords:

brotowali extract, Plasmodium berghei, renal tubule histopathology, NF-kB expression

Abstract

Brotowali (BR) extract (Tinospora crispa) can be used as an antimalarial. Aim: to determine the effect of BR extract in histopathological and expression of NFκB in mice tubules infected by Plasmodium berghei treated by artesunate (AR). Method: we used 42 C57BL / 6J strain mice as experimental animals, which were randomly divided into 7 groups : negative control (NC), positive control (PC), treatment group consist of AR 32 mg/kb (group 1); BR 70 mg/kg (group 2), combination of AR+BR 50 mg/kg (group 3), AR+BR 60 mg/kg (group 4), and AR+BR 70 mg/kg (group 5).  Histological examination (hematoxylin-eosin (HE) staining) and expression of NFKB (immunohistochemical staining) in the kidneys were performed on 7th and 14th. Result: compared to PC group, BR with doses of 70 mg until 14th day, improved the degree of tubular necrosis, interstitial fibrosis, tubular degeneration, and inflammatory cell infiltration (p <0.001) but did not reach NC group (p <0.05). The combination of AR+BR until the 14th  day with dose of 50, 60, 70 mg all of dose improves significantly in-term of degree of tubular cell necrosis and inflammatory cell infiltration. The degree of interstitial fibrosis on 14th day only improved in group 4 and 5 (p<0.001 and p=0.003). The level of NF-kB expression on day 7 and day 14 was reduced in group 2, group 4, and group 5 compared to PC group. There was positive correlation on 7th and 14th between NF-kβ expression and tubular degeneration, tubular cell necrosis, inflammatory cell infiltration, and interstitial fibrosis. Conclusion: the combination of AR+BR extract can improve histopathological features and reduce NF-kβ expression in mice tubules infected by Plasmodium berghei with an optimal dose was 60 mg/day for 7-14 days or 70 mg for 7 days.

References

Tabernero P, Fernández FM, Green M, Guerin PJ, Newton PN. Mind the Gaps - the Epidemiology of Poor-Quality Anti-Malarials in the Malarious World - analysis of the WorldWide Antimalarial Resistance Network database. Malaria Journal. [Research Article]. 2014;13(139). [https://doi.org/10.1186/1475-2875-13-139]

Chandy C, John, Peter JK. Malaria, Infectious Diseases. In: Kliegmen RM, Behrman R, Starton B, editors. Nelson Textbook of Pediatric. 19 ed. Philadelphia: WB Saunders. 2010. p. 1198-206.

Gowda DC. Pro-Inflammatory Responses and Cell Signalling during Malaria Infection: The Parasite Glycosylphosphatidylinositol Ligand. In: Denkers E, Gazzinelli R, editors. Protozoans in Macrophages. - ed. Hershey: Landes Bioscience. 2007. p. 84-98.

Punsawad SK, Y Maneerat, U Chaisri. Activation of Nuclear Factor Kappa β in Peripheral Blood Mononuclear Cells from Malaria Patients. Malaria Journal. 2012; 11:191. [https://doi.org/10.1186/1475-2875-11-191]

Billack B. Macrophage Activation: Roll of Toll-Like Receptor, Nitric Oxide, and Nuclear Factor kappa β. American Journal of Pharmaceutical Education. [102]. 2006; 70(5). [doi: 10.5688/aj7005102]

Punsaward C. Effect of Malaria Component on Blood Mononuclear Cells involved in Immune Response. Asian Pacific Journal Tropical Biomedicine. 2013; 28 sept 2013;3(9):351-756.

Das B. Renal Failure in Malaria. J Vector-Borne Diseases. 2008; 45:83-97.

Somsak V, Jaihan U. Protection of Renal function by Green Tea Extract during P.Berghei Infection. Elsevier Ireland. 2013. [https://doi.org/10.1016/j.parint.2013.08.004]

Patel JP, Gami B, and Patel K. Evaluation of In Vitro Schizonticidal Properties of Acetone Extract of Some Indian Medicinal Plants. Advanced in Biological Research. 2010; 4:253-258.

Muniz-Junqueira M and Tosta E. Immunomodulatory Therapy Associated to Anti-Parasite Drugs as a Way to Prevent Severe Forms of Malaria. Current Clin Pharmacology. 2007; 9:164-172.

Adnan AZ. Pemeriksaan dan Isolasi kandungan kimia tumbuhan brotowali. Padang: Pusat Penelitian Universitas Andalas. 1998.

Adnan A, Gusmali D, Mukhtar M. Aktivitas Antimalaria Senyawa Tinokrisposid secara In Vivo. Cermin Dunia Kedokteran. 2001; 131:27-31. [doi:https://doi.org/10.15294/biosaintifika.v9i1.5811]

Dweck AC and Cavin JP. A review of andawali (Tinospora crispa). Personal Care Magazine. 2006; 7:1-3. [https://doi.org/10.22159/ajpcr.2018.v11i4.23739 ]

Suryawati S, Suprapti H. Efek Anti Malaria Ekstrak Brotowali (Tinospora crispa) Pada Mencit yang di diinfeksi Plasmodium Berghei. Wijaya Kusuma. 2007;1(1):13-22.

Marthianti A. Pengaruh Pemberian Ekstrak Batang Tinospora crispa Dibandingkan Dengan Kloroquin Terhadap Jumlah Eritrosit Mencit Swiss Yang Dinfeksi Plasmodium berghei [Skripsi]. Semarang: Universitas Diponegoro; 2006.

Miranda AS, Brant F, Rocha NP, Cisalpino D, Rodrigues DH. Further Evidence for an Anti-Inflammatory Role of Artesunate in Experimental Cerebral Malaria. Malaria Journal. [Research Article]. 2013;12(388). [https://doi.org/10.1186/1475-2875-12-388]

Klopfleisch R. Multiparametric and Semiquantitative Scoring System for the Evaluation of Mouse Model Histopathology- Systemic Review. BMC Veterinary Research. 2013;9(123). [doi: 10.1186/1746-6148-9-123.]

Nowak M, Madej JA, Dziegiel P. Intensity of COX2 Expression in Cells of Soft Tissue Fibrosarcomas in Dogs as Related to Grade of Tumour Malignancy. Bull Vet Inst Pulawy. 2007; 17( 51):275-9.

Harijanto PN. Malaria dari Molekular ke Klinis. 2 ed. Jakarta: Penerbit Buku kedokteran EGC. 2009.

Harijanto PN. Malaria epidemiologi,Patogenesis,Manifestasi Klinis dan Penanganan. Jakarta: Penerbit Buku kedokteran EGC. 2000.

Idro R, Jenkins N, Newton N. Pathogenesis, Clinical Features, and neurological outcome of cerebral malaria. Lancet Neurology. 2005; 4:827-40.

White NJ and Bremen JG. Harrison's Principles of Internal Medicine, 17th ed. New York: McGraw-Hill, 2001; 1180-1189.

Eriksson EM, Sampaio NG, Schofield L. Toll-Like Receptors and Malaria-Sensing and Susceptibility. J Trop Dis. 2013; 20;2(1). [DOI: 10.4172/2329-891X.1000126]

Barsoum R. Malarial Acute Renal Failure. J Am Soc Nephrol. 2000; 11:2147- 54.

Saphiro T, Goldberg D. Chemotherapy of Protozoal Infections: Malaria: Goldman and Gilman's. The Pharmacological Basis of Therapeutics. 11 ed. USA: McGraw-Hill Inc,p; 2006.

Rathee P, Chaudhary H, Rathee S, Rathee a, Kumar V, Kohli K. Mechanism of Action of Flavonoids as Anti-inflammatory Agent. Inflammation & Allergy - Drug Targets. 2009; 8:229-35. [DOI: 10.2174/187152809788681029]

Sulaiman M, Zakaria Z, Lihan R. Antinociceptive and Anti-inflammatory Activities of Tinospora crispa in Various Animal Models. IntJTropics Sci. 2008;3(3):66-9.

Ibahim M, I'zzah WN, Narimah, Asyikin N, Nur S. Anti-Proliferative and Antioxidant Effect of Tinospora crispa (brotowali) Biomedical Research. 2011;22(1):57-62.

Lou J, Lucas R, Grau G. Pathogenesis of Cerebral Malaria: Recent Applications for Humans Experimental Data and Possible. Clin Microbiol Rev. 2001;14(4):810-20.

Basri. Formulasi Tablet Salut Ekstrak Etanolik Batang Brotowali (Tinospora Crispa) (L) Miers) dengan Bahan Penyalut Hidroksipropil Metilselulosa dan Polietilen Glikol 400. Surakarta: Universitas Muhammadiyah; 2009.

Koay YC, Amir F. A Review of the Secondary Metabolites and Biological Activities of Tinospora crispa (Menispermaceae). Review Article. [Review Article]. 2013; March 28;12(4):641-9. [https://doi.org/10.3389/fphar.2016.00059]

Roshental P. Review. Antimalarial Drug Discovery: Old and New Approaches. The Journal of Experimental Biology. 2003; 06:3735-44.

Boutlis C, Riley E, Anstey N. Glycosylphosphatidylinositols in Malaria Pathogenesis and Immunity: Potential for Therapeutic Inhibition and Vaccination. CTMI. 2005; 297:145-85.

Mishra SK, Das BS. Malaria and Acute Kidney Injury. Seminars in Nephrology. 2008; 28(4):395 - 408. [doi: 10.1016/j.semnephrol.2008.04.007.]

Birdsall TC, G.S.Kelly. Berberine: Therapeutic Potential of an Alkaloid Found in Several Medicinal Plants. Alternative Medicine Review. 1997;2(2):94-103.[https://doi.org/10.5402/2011/519371]

Niljan J, Jaihan U, Srichairatanakool S, Uthaipibull C, Somsak V. Antimalarial Activity of Stem Extract of Tinospora Crispa against Plasmodium Berghei Infection in Mice. J Health Res.2014;28(3):199-204.

Hipol R, Cariaga M, Hipol R. Anti-Inflammatory Activities of the Aqueous Extract of the Stem of Tinospora crispa. Journal of Nature Studies. 2012;11(1):88-95.

Liu CX, Yi XL, Si DY, Xiao XF, Li XHY-Z. Herb-drug Interactions Involving Drug Metabolizing Enzymes and Transporters Current drug Metabolism. 2011;12:835-49.

Wanwimolruk S, Prachayasittikul V. Cytochrome P450 Enzyme Mediated Herbal Drug Interactions. EXCLI Journal. 2014; 02 (13):347-91. [PMID: 26417310]

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Published

2020-05-18

How to Cite

Merici, A., Fitri, L. E., & Budiarti, N. (2020). The Effect of Artesunate and Brotowali (Tinospora Crispa) Combination on Histopathological, and Expression of Nuclear Factor Kappa B (NF-kβ) in Renal Tubules of Mice Infected With Plasmodium Berghei. Clinical and Research Journal in Internal Medicine, 1(1), crjim, 33–45. https://doi.org/10.21776/ub.crjim.2020.001.01.5