Phytochemical and Toxicological Evaluation of Croton Menyharthii From Tana River County, Kenya

Abstract

The use of plants for primary health care has increased tremendously over the last few decades especially in developing countries. However, the health benefits claims and safety profile of most plants is yet to be validated. Croton menyharthii is an indigenous plant in Kenya and has been used to treat reproductive health ailments and for fertility regulation in Tana River County. Despite its use, its toxicological and phytochemical profile is yet to be validated. The main objective of this study was to determine the phytochemical composition of Croton menyharthii root bark extracts and to evaluate its acute and sub-acute toxicity. Air dried root barks of the plant were obtained from Tana River County and were ground to powder. The powder was used to make aqueous and dichloromethane (DCM)/Methanolic extracts. Qualitative phytochemical analysis was done on both extracts. The acute oral toxicity study protocol was conducted according to the Organization for the Economic Co-operation and Development (OECD) test guideline 423 using twenty-four mature female wistar rats. The sub-acute oral toxicity protocol was carried out as per the OECD test guideline 407 using 40 mature female wistar rats. Three graded doses of 200, 400 and 800 mg/kg body weight of both aqueous and DCM/Methanolic extract of Croton menyharthii root bark were administered. Both aqueous and DCM/Methanolic extracts revealed presence of alkaloids, saponins, tannins, phenols and cardiac glycosides. The LD50 for both the aqueous and DCM/Methanolic extracts was found to be above 2000 mg/kg body weight. In both acute oral and sub-acute toxicity studies, there were no significant clinical symptoms observed apart from lethargy and sedation that resolved within four hours. Rats that received a single dose of 5000 mg/kg body weight C. menyharthii aqueous extract had a significant (P<0.013) low body weight gain compared to the control. There were however signs of irritation among the rats that received the DCM/Methanolic extract. All rats showed remarkable gross necropsy findings.

In the sub-acute toxicity study, there was a significant (P<0.016) increase in feed consumption among the rats that received 400 mg/kg body weight aqueous extract and 200 mg/kg body weight DCM/Methanolic extract (P<0.03) compared to their respective controls. There was also a significant (P<0.04, P<0.003) more water consumption in the rats that received 200 and 400 mg/kg body weight Croton menyharthii aqueous extract respectively compared to the control. Average water and food consumption reduced over time in rats that received the DCM/Methanolic extract. There was a non-significant increase in mean body weight of all treatment rats compared to their respective controls. Both extracts had a non-significant effect on haematological parameters. However, there was a significant (P<0.006, P<0.00, P<0.00) dose related decrease in serum protein levels in the treatment groups that received the C. menyharthii aqueous extract. There was a significant (P<0.045) lower relative-organ weight ratio of the liver from the rats that received 200 mg/kg body weight dose of the DCM/Methanolic extract. For both extracts, histopathology of all treatment groups revealed diffuse portal blood vessel congestion in the liver and parenchymal blood vessel congestion in the kidneys. In addition, treatment groups that received DCM/Methanolic extract revealed dose related lymphocytic infiltration and multifocal hemorrhage of renal parenchyma indicating renal tubular injury. In conclusion, C. menyharthii root bark extracts are of pharmaceutical importance since they contain useful phytochemicals that can be explored for drug discovery. They can be deemed safe when used as single doses of < 2000 mg/kg body weight. However, on long term use, they can be nephrotoxic. Quantitative phytochemical analysis of Croton menyharthii needs to be done. Kidney function needs to be monitored in long term use due to the possibility of nephrotoxicity. A detailed study needs to be done to reveal the effects of the extract on body weight gain, food and water consumption.