Effects of Sambiloto (Andrographis paniculata) Extract and Spirulina (Spirulina platensis) Administration on Ki-67 Protein Expression in the Colon Epithelial Cells of Plasmodium berghei-infected Mice

Kusmardi Kusmardi, Bagas Ariffandi, Nadar Sukri Lubis, Tri Wahyuni Lestari, Putri Reno Intan, Alfred Pakpahan


BACKGROUND: Malaria remains a global health concern and an endemic disease in Indonesia. Sambiloto (Andrographis paniculata) and spirulina (Spirulina platensis) are two potential antimalarial agents which act as antioxidants and antiinflammatories that can suppress morbidities during chronic inflammation in malaria, such as proliferation in the colon. This study aims to investigate the effects of A. paniculata extract and S. platensis administration on Ki-67 expression in medial colon epithelial cells of Plasmodium berghei-infected mice measured by H-score.

METHODS: Thirty P. berghei-infected male Swiss-Webster mice were divided into five groups: negative controls (carboxymethyl cellulose/CMC); positive controls (dihydroartemisinin-piperaquine/DHP); A. paniculata extract alone (AP); A. paniculata extract in combination with S. platensis extract (AP+ES); and with S. platensis powder (AP+PS). All mice were infected with P. berghei on day 0. The treatment for each group were given 3 days before infection (D-3) until the day of infection (D0) for 28 days after infection. Colon tissues were processed with immunohistochemistry to detect Ki-67.

RESULTS: A difference in Ki-67 expression was observed among the groups (p<0.01). The mean H-score for the CMC control group is 135.503±6.723. The lowest level of Ki-67 expression was observed in the AP+PS group (H-score= 110.941±7.079). AP group did not show a significant difference from the CMC group (p=0.514) and neither did the AP+ES group (p=0.234).

CONCLUSION: In conclusion, administration of A. paniculata extract and S. platensis powder lowers Ki-67 expression in medial colon epithelial cells of P. berghei-infected mice.

KEYWORDS: malaria, spirulina, Ki-67, Andrographis paniculata, Spirulina platensis

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World Health Organization. World Malaria Report 2018. Geneva: World Health Organization; 2018, article.

Masrizal M, Putri T, Hasni I. Environmental and behavioral conditions that affect malaria events in padang city. J Berk Epidemiol. 2020; 8(2): 164–71, CrossRef.

Enns R, Bressler B. Dysplasia and colitis. Can J Gastroenterol J Can Gastroenterol. 2009; 23(5): 345–7, CrossRef.

Kusmardi K, Jabir R, Wisnubaroto R, Firzani D. The combination of Spirulina extract and Sambiloto effect histopathologically on medial colon from Plasmodium berghei Anka infected mice. Pharmacogn J. 2019; 11(3): 564–9, CrossRef.

World Health Organization. Guidelines for the Treatment of Malaria. 3rd ed. Geneva: World Health Organization; 2015, article.

Ouji M, Augereau JM, Paloque L, Benoit-Vical F. Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination. Parasite Paris Fr. 2018; 25: 24, CrossRef.

Woodrow CJ, White NJ. The clinical impact of artemisinin resistance in Southeast Asia and the potential for future spread. FEMS Microbiol Rev. 2017; 41(1): 34–48, CrossRef.

Nsanzabana C. Resistance to artemisinin combination therapies (ACTs): do not forget the partner drug!. Trop Med Infect Dis. 2019; 4(1): 26, CrossRef.

Deng R, Chow TJ. Hypolipidemic, antioxidant, and antiinflammatory activities of microalgae Spirulina. Cardiovasc Ther. 2010; 28(4): e33–45, CrossRef.

Ali EAI, Barakat BM, Hassan R. Antioxidant and angiostatic effect of Spirulina platensis suspension in complete Freund’s adjuvant-induced arthritis in rats. PloS One. 2015; 10(4): e0121523, CrossRef.

Okhuarobo A, Falodun JE, Erharuyi O, Imieje V, Falodun A, Langer P. Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology. Asian Pac J Trop Dis. 2014; 4(3): 213–22, CrossRef.

Dhiman A, Goyal J, Sharma K, Nanda A, Dhiman S. A review of medicinal prospectives of Andrographis Paniculata Nees. J Pharm Sci Innov. 2012; 1: 1–4, article.

Kusmardi K, Elya B, Wahyuni T, Paramita RI. Combination of sambiloto (Andrographis paniculata (Burm.F.) nees) extract and spirulina (Arthrospira platensis gomont) to prevent anemia in mice infected with Plasmodium berghei anka. Asian J Pharm Clin Res. 2017; 10: 269, CrossRef.

Li LT, Jiang G, Chen Q, Zheng JN. Ki67 is a promising molecular target in the diagnosis of cancer (review). Mol Med Rep. 2015; 11(3): 1566–72, CrossRef.

Zeng H, Umar S, Rust B, Lazarova D, Bordonaro M. Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation, and cancer. Int J Mol Sci. 2019; 20(5): 1214, CrossRef.

Huang BW, Pearman E, Kim CC. Mouse models of uncomplicated and fatal malaria. Bio-Protoc. 2015; 5(13): e1514, CrossRef.

Déchamps S, Maynadier M, Wein S, Gannoun-Zaki L, Maréchal E, Vial HJ. Rodent and nonrodent malaria parasites differ in their phospholipid metabolic pathways. J Lipid Res. 2010; 51(1): 81–96, CrossRef.

Mawson AR. The pathogenesis of malaria: a new perspective. Pathog Glob Health. 2013; 107(3): 122–9, CrossRef.

Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, et al. Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis. Sci Rep. 2015; 5(1): 15699, CrossRef.

Marwa KJ, Konje ET, Kapesa A, Kamugisha E, Mwita S, Swedberg G. Artemether-lumefantrine and dihydroartemisinin-piperaquine treatment outcomes among children infected with uncomplicated Plasmodium falciparum malaria in Mwanza, Tanzania. Trop Med Health. 2021; 49(1): 94, CrossRef.

Landén NX, Li D, Ståhle M. Transition from inflammation to proliferation: a critical step during wound healing. Cell Mol Life Sci CMLS. 2016; 73(20): 3861–85, CrossRef.

Cuylen-Haering S, Petrovic M, Hernandez-Armendariz A, Schneider MWG, Samwer M, Blaukopf C, et al. Chromosome clustering by Ki-67 excludes cytoplasm during nuclear assembly. Nature. 2020; 587(7833): 285–90, CrossRef.

Yang LL, Zhou QJ, Wang Y, Gao Y, Wang YQ. Comparison of the therapeutic effects of extracts from Spirulina platensis and amnion membrane on inflammation-associated corneal neovascularization. Int J Ophthalmol. 2012; 5(1): 32–7, CrossRef.

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, article.

Gaur P. Evaluation of safety aspects of Andrographis paniculata in Swiss-albino mice at sub acute level. IAMJ. 2014; 2(5): 681–6, article.

DOI: https://doi.org/10.18585/inabj.v14i1.1737

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