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Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats
Herbal Medicine Research Center, Institute for Medical Research, Jalan Pahang 50588, Kuala Lumpur, Malaysia
Infectious Disease Research Center, Institute for Medical Research, Jalan Pahang 50588, Kuala Lumpur, Malaysia
Faculty of Pharmacy, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz 50300, Kuala Lumpur, Malaysia
* Author to whom correspondence should be addressed.
Received: 22 February 2012; in revised form: 20 March 2012 / Accepted: 23 March 2012 / Published: 10 April 2012
Abstract: Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from ‘Sekaki’ C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.
Keywords: Carica papaya; papaya leaf; chemical fingerprinting; sub-acute toxicity study; 28-days repeated dose
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Afzan, A.; Abdullah, N.R.; Halim, S.Z.; Rashid, B.A.; Semail, R.H.R.; Abdullah, N.; Jantan, I.; Muhammad, H.; Ismail, Z. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats. Molecules 2012, 17, 4326-4342.
Afzan A, Abdullah NR, Halim SZ, Rashid BA, Semail RHR, Abdullah N, Jantan I, Muhammad H, Ismail Z. Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats. Molecules. 2012; 17(4):4326-4342.
Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah. 2012. "Repeated Dose 28-Days Oral Toxicity Study of Carica papaya L. Leaf Extract in Sprague Dawley Rats." Molecules 17, no. 4: 4326-4342.