Acute and Sub-chronic Toxicity Evaluation on Stomach and Liver of Balinese Azadirachta Indica (Neem) Ethanolic Extracts: as a Basis for Covid-19 and Other Diseases Herbal Treatment Ni Luh Kadek Alit Arsani(a*), I Gede Surya Dinata (b), I Wayan Mudianta (c)
a) Biomedical Department, Faculty of Medicine, Universitas Pendidikan Ganesha, Jl. Udayana No. 11, Buleleng, Bali, 81116, Indonesia.
b) Surgery Department, Faculty of Medicine, Universitas Pendidikan Ganesha, Jl. Udayana No. 11, Buleleng, Bali, 81116, Indonesia.
c) Department of Chemistry,F aculty of Mathematics and Sciences, Universitas Pendidikan Ganesha, Jl. Udayana No. 11, Buleleng, Bali, 81116, Indonesia.
Abstract
COVID-19 pandemic forced drug and vaccine research to improvise. Low resources country may be benefited from local herbal therapies mostly through gastrointestinal (GI) route. Neem had been massively investigated for its potential to complement modern medicine in treating various diseases. Different geography of neem tree origin could influence the bioactive constituent of it. Therefore, evaluation on bioactive substance and toxicity on GI system is critical. So far, there were few studies on toxicity of neem ethanolic extract on stomach and liver. This study aimed to evaluate the safety profile and active chemical content of Neem leaves ethanolic extract from Bali origin. Acute and sub chronic oral toxicities conducted in accordance with the guidelines of Indonesian food and drug agency (BPOM RI). Ethanolic extract from neem leaves was made for toxicity study and liquid chromatography. An LC-MS/MS analysis of the crude extract of neem leaves revealed the presence of nimbolide. After oral administration of ethanolic extract of neem leaves in different doses, toxicities and mortality was not observed. The LD50 of ethanolic extract of neem leaves was considered above 5000mg/kgbw. In sub chronic exposure of the neem extract, study found no clinical sign of toxicity. Ethanol extract of neem leaves caused elevation of AST and ALT compared to normal control in dose above 50mg/kgbw and may also cause gastric mucosal erosion in dose above 2000mg/kgbw. The major constituent of ethanolic extract of neem leaves is nimbolide and is relatively safe if given orally
