Toxicological evaluations of betulinic acid and ursolic acid; common constituents of Houttuynia cordata used as an anthelmintic by the Naga tribes in North-east India

Arun Kumar Yadav,Amar Deep Soren,Vijaya Mishra

doi:10.1186/s43094-020-00173-4

Abstract

BackgroundBetulinic acid (BA) and ursolic acid (UA) are two major phytoconstituents of Houttuynia cordata Thunb., (Saururaceae) which is used as an anthelmintic in the traditional medicine system of the Nagas in Nagaland, India. This study evaluates their toxic potentials using rodent models (Swiss albino mice and Wistar rats) according to the OECD (Organization for Economic Cooperation and Development) guidelines. Acute and 28-day sub-acute oral toxicity studies were conducted, and evaluations were made based on biochemical, hematological, and histopathological observations.ResultsAcute oral toxicity study revealed the oral LD50 of both the test compounds to be > 2000 mg/kg in mice. Sub-acute administration of BA at 10 mg/kg body weight (b.w.) revealed a significant increase in serum glutamic oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), urea concentrations and eosinophil and lymphocyte counts in rats. Animals administered with 10 mg/kg b.w. UA revealed elevated neutrophil count, SGOT, ALP, and urea concentrations, whereas white blood cells (WBC), lymphocyte, and platelet counts were found to be low. Histopathological examinations of body organs revealed alterations in the architecture of the liver, kidney, and spleen tissues. Notably, all these alterations were recoverable as evident in the satellite group, indicating a recovering pattern from the toxic effects caused by the oral administration of these phytocompounds.ConclusionAlthough UA and BA possess several therapeutic properties, their long-term usage can cause mild toxicity in their users. This study also paves way for evaluating the optimum effective and safe dose of these phytocompounds.

Highlights

Betulinic acid (BA) and ursolic acid (UA) are two major phytoconstituents of Houttuynia cordata Thunb., (Saururaceae) which is used as an anthelmintic in the traditional medicine system of the Nagas in Nagaland, India
Sub-acute toxicity study Effect on body weights Oral administration of BA (Table 1) and UA (Table 2) did not reveal any significant changes in body weights of animals from both the sexes in all the groups; no mortality was observed during the study
Effects on biochemical parameters The sub-acute oral administration of BA revealed a dose-dependent increase in serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) in animals of both the sexes, and the highest treated dose (10 mg/kg) showed an elevation in urea levels (Table 5)

Summary

Introduction

Betulinic acid (BA) and ursolic acid (UA) are two major phytoconstituents of Houttuynia cordata Thunb., (Saururaceae) which is used as an anthelmintic in the traditional medicine system of the Nagas in Nagaland, India This study evaluates their toxic potentials using rodent models (Swiss albino mice and Wistar rats) according to the OECD (Organization for Economic Cooperation and Development) guidelines. Unregulated consumption of the medicinal plants or their compounds has been an essential part of various studies that reveal the effects, doses, and toxicity exhibiting mild to lethal effects [7]. Several compounds such as capsaicin, cycasin, genistein, and ptaquiloside used as food/ supplements have been found to be carcinogenic [8]. Several compounds possessing anthelmintic efficacy such as doramectin, eprinomectin, and selamectin have been tested for their potential toxic effects [12]

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