CELL BIOLOGY & DEVELOPMENT Volume 6, Number 1, June 2022 E-ISSN: 2580-4499 Pages: 13-19 DOI: 10.13057/cellbioldev/t060103 Effect of giving nanochitosan preparations ethanol extract of neem leaves (Azadirachta indica) against pancreatic histology of white rat male (Rattus norvegicus) Sprague Dawley SUCI HANDAYANI  , AGUNG JANIKA SITASIWI, SRI ISDADIYANTO, SITI MUFLICATUN MARDIATI Department of Biology, Faculty of Science and Mathematics, Universitas Diponegoro. Jl. Prof. H. Soedarto, Tembalang, Semarang 50275, Central Java, Indonesia. Tel.: +62-24-7474754,  email: suci5maret@gmail.com Manuscript received: 30 March 2022. Revision accepted: 2 June 2022. Abstract. Handayani S, Sitasiwi AJ, Isdadiyanto S, Mardiati SM. 2022. Effect of giving nanochitosan preparations ethanol extract of neem leaves (Azadirachta indica) against pancreatic histology of white rat male (Rattus norvegicus) Sprague Dawley. Cell Biol Dev 6: 13-19. The selection of herbal plants as a treatment in the community is considered safer, more practical, and cheaper than synthetic drugs. Neem (Azadirachta indica A.Juss.) is one of the herbal plants that have the potential as an antioxidant. However, the low bioavailability of drugs and the distribution of active compounds in herbal plants are constraints in administering drugs orally. The solution to overcome this problem is to prepare the test material in the form of nanochitosan. This study aimed to analyze the effect of nanochitosan ethanol extract of neem (A. indica) leaf extract on the pancreas histology of male Sprague Dawley rats. This study used a completely randomized design (CRD) with 32 rats aged 2 months divided into 4 treatments, and each treatment consisted of 6 replications. P0 (normal rat group treated with 2 mL distilled water, P1 (normal rats induced with Natrium tripolifosfat "NaTPP" and 2 mL chitosan), P2 (normal rat group induced by nanochitosan neem leaf ethanol extract 1:0.5), P3 (normal rat group induced nanochitosan ethanol extract of neem leaves 1:1). Data were analyzed by ANOVA test with a significance level of 5%. Data that were not normally distributed were tested by the Kruskal Wallis test and Duncan's test. The results showed that the administration of nanochitosan ethanol extract of neem leaves 1:0.5 and 1:1 had no significant effect on the diameter parameter of the islets of Langerhans (P≥0.05) but had a significant effect on the parameters of pancreatic weight and damage scoring of the islets of Langerhans (P≤0.05). The administration of nanochitosan preparations of ethanolic extract of neem leaves can deliver bioactive compounds neem to the pancreas and minimize damage to the cells that make up the islets of Langerhans due to toxic neem compounds. Keywords: Islet of Langerhans, nanoparticles, neem plant, pancreas INTRODUCTION The selection of herbal plants as a treatment in the community is considered safer, more practical, and cheaper than synthetic drugs, so they have become an alternative treatment for various diseases. The neem plant (Azadirachta indica A.Juss.) is one of the most studied herbal plants because of its properties that can treat various diseases (Pristiani and Astuti 2005; Fathoni et al. 2013). The benefits of the neem plant can be used as an antirheumatic, antioxidant, anti-inflammatory, immuno- potentiation, antifertility, antiviral, anticancer, and antipyretic (Ambarwati 2011). However, the side effects of neem are thought to cause kidney and pancreas damage. Wowiling's research (2013) stated that the advantages of neem include easy cultivation, its use as herbal medicine, relatively safe for humans, and the prevention of various diseases. However, the deficiency of the neem plant can cause liver and pancreas damage. That is presumably due to toxic compounds in neem and the low distribution of the active compound content of neem. Oral administration of drugs is the most widely used method of administering drugs to test animals because the process is easy, safe, inexpensive, and convenient. However, obstacles in oral administering the drug are the low bioavailability and the low distribution of neem compounds to the body. According to research by Ajazuddin and Saraf (2010), the solution to overcome the oral administration problem is to prepare drugs in the form of nanochitosan to facilitate the absorption and distribution of drugs into the body to increase the bioavailability of neem plants. Prasetiowati et al. (2018) stated that the excess use of nanochitosan in medicinal plant extracts can facilitate the absorption and distribution of drugs into the body and reduce the toxic effects of drugs. The polymer used to manufacture nanoparticles is chitosan with a soluble compound in sodium tripolyphosphate (NaTPP) (Kafshgari et al. 2011). Martien et al. (2012) stated that chitosan could reduce the toxic effects of neem exposure, so it is very efficient to be developed as the main ingredient for making nanoparticles. Therefore, nanoparticles can provide an effective solution to overcome the difficulty of drug delivery into the body, facilitate the distribution of bioactive compounds from neem plants into the pancreas, and reduce the toxic effects of neem plants. This study aimed to analyze the effect of neem leaf extracts chitosan nanoparticles on the histological structure of the pancreas of male Sprague Dawley rats.