Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats

Adlin Afzan, Noor Rain Abdullah, Siti Zaleha Halim, Badrul Amini Rashid, Raja Hazlini Raja Semail, Noordini Abdullah, Ibrahim Jantan, Hussin Muhammad, Zakiah Ismail

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)4326-4342
Number of pages17
JournalMolecules
Volume17
Issue number4
DOIs
Publication statusPublished - Apr 2012

Fingerprint

Carica
toxicity
leaves
rats
Sprague Dawley Rats
Toxicity
Rats
dosage
Biochemistry
Organic acids
Water levels
Glycosides
Alkaloids
Liver
HDL Cholesterol
Medicine
Traditional Medicine
food intake
fever
Derivatives

Keywords

  • 28-days repeated dose
  • Carica papaya
  • Chemical fingerprinting
  • Papaya leaf
  • Sub-acute toxicity study

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Afzan, A., Abdullah, N. R., Halim, S. Z., Rashid, B. A., Semail, R. H. R., Abdullah, N., ... Ismail, Z. (2012). Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats. Molecules, 17(4), 4326-4342. https://doi.org/10.3390/molecules17044326

Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats. / Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah.

In: Molecules, Vol. 17, No. 4, 04.2012, p. 4326-4342.

Research output: Contribution to journalArticle

Afzan, A, Abdullah, NR, Halim, SZ, Rashid, BA, Semail, RHR, Abdullah, N, Jantan, I, Muhammad, H & Ismail, Z 2012, 'Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats', Molecules, vol. 17, no. 4, pp. 4326-4342. https://doi.org/10.3390/molecules17044326
Afzan A, Abdullah NR, Halim SZ, Rashid BA, Semail RHR, Abdullah N et al. Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats. Molecules. 2012 Apr;17(4):4326-4342. https://doi.org/10.3390/molecules17044326
Afzan, Adlin ; Abdullah, Noor Rain ; Halim, Siti Zaleha ; Rashid, Badrul Amini ; Semail, Raja Hazlini Raja ; Abdullah, Noordini ; Jantan, Ibrahim ; Muhammad, Hussin ; Ismail, Zakiah. / Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats. In: Molecules. 2012 ; Vol. 17, No. 4. pp. 4326-4342.
@article{ece7c5a902724d08b48e2e738dbdaf78,
title = "Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats",
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 = "28-days repeated dose, Carica papaya, Chemical fingerprinting, Papaya leaf, Sub-acute toxicity study",
author = "Adlin Afzan and Abdullah, {Noor Rain} and Halim, {Siti Zaleha} and Rashid, {Badrul Amini} and Semail, {Raja Hazlini Raja} and Noordini Abdullah and Ibrahim Jantan and Hussin Muhammad and Zakiah Ismail",
year = "2012",
month = "4",
doi = "10.3390/molecules17044326",
language = "English",
volume = "17",
pages = "4326--4342",
journal = "Molecules",
issn = "1420-3049",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "4",

}

TY - JOUR

T1 - Repeated dose 28-days oral toxicity study of Carica papaya L. Leaf extract in Sprague Dawley rats

AU - Afzan, Adlin

AU - Abdullah, Noor Rain

AU - Halim, Siti Zaleha

AU - Rashid, Badrul Amini

AU - Semail, Raja Hazlini Raja

AU - Abdullah, Noordini

AU - Jantan, Ibrahim

AU - Muhammad, Hussin

AU - Ismail, Zakiah

PY - 2012/4

Y1 - 2012/4

N2 - 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.

AB - 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.

KW - 28-days repeated dose

KW - Carica papaya

KW - Chemical fingerprinting

KW - Papaya leaf

KW - Sub-acute toxicity study

UR - http://www.scopus.com/inward/record.url?scp=84860227337&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860227337&partnerID=8YFLogxK

U2 - 10.3390/molecules17044326

DO - 10.3390/molecules17044326

M3 - Article

VL - 17

SP - 4326

EP - 4342

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 4

ER -