Antimalarial and toxicological assessment of the tablet (AS201-01) ethyl acetate fraction of Andrographis paniculata Nees in animal models

Article published in J. Pharm. Pharmacogn. Res., vol. 11, no. 5, pp. 863-873, Sep-Oct 2023.

DOI: https://doi.org/10.56499/jppres23.1679_11.5.863

Original Article

Aty Widyawaruyanti^1,2*, Hilkatul Ilmi², Lidya Tumewu², Dwi Ayu Fitrianingtyas³, Yesinta Kurniawati³, Alfin Laila Najiha³, Hanifah Khairun Nisa², Che Puteh Osman^4,5, Nor Hadiani Ismail^4,5, Achmad Fuad Hafid^1,2

¹Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, Indonesia.

²Center for Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, Indonesia.

³Undergraduate Program of Faculty of Pharmacy, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia.

⁴Atta-ur-Rahman Institute for Natural Product Discovery, Universiti Teknologi MARA, Cawangan Selangor, Kampus Puncak Alam, 42300 Bandar Puncak Alam, Selangor Malaysia.

⁵Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia.

*E-mail: aty-w@ff.unair.ac.id

Abstract

Context: Andrographis paniculata has been used as a traditional medicine to treat malaria. The ethyl acetate fraction of A. paniculata containing diterpene lactone compounds was developed into a tablet dosage form, AS201-01.

Aims: To determine the antimalarial activity and toxicity of AS201-01 to guarantee its efficacy and safety.

Methods: Antimalarial assay in male Balb/c mice based on Peter’s four-day suppressive test at a dose of 6.25, 12.5, 25, and 50 mg/kg BW and 10 mg/kg BW of chloroquine as a positive control. In acute toxicity, AS201-01 was administered orally at a dose of 5, 50, 200, and 2,000 mg/kg BW in male rats (Wistar rats) and observed for 14 days to identify signs of toxicity and mortality. Meanwhile, AS201-01 was administered at 50, 327, and 1,000 mg/kg BW per day for 28 days in male and female rats to assess subchronic toxicity.

Results: AS201-01 has antimalarial activity and exhibited the highest suppressive effect at 50 mg/kg BW dose with inhibition of 73.48%. Meanwhile, chloroquine at 10 mg/kg BW has an inhibition of 97.94%. AS201-01 was highly active as an antimalarial with an ED₅₀ value of 5.95 mg/kg BW and increased survival time. Administration of AS201-01 is relatively safe in acute and subchronic toxicity studies. No clinical signs and mortality were observed in either study. The 50% lethal dose (LD₅₀) was above 2,000 mg/kg BW.

Conclusions: AS201-01 is effective as an antimalarial and non-toxic when administered orally at an equivalent therapeutic dose in an animal model.