Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells

Sheri-Ann Tan; Luis Goya; Surash Ramanathan; Shaida Fariza Sulaiman; Maqsudul Alam; Visweswaran Navaratnam

doi:10.1016/j.foodres.2014.06.040

Chemopreventive effects of standardized papaya leaf fraction on oxidatively stressed human liver cells

Food Res Int. 2014 Oct:64:387-395. doi: 10.1016/j.foodres.2014.06.040. Epub 2014 Jul 4.

Authors

Sheri-Ann Tan¹, Luis Goya², Surash Ramanathan³, Shaida Fariza Sulaiman⁴, Maqsudul Alam⁵, Visweswaran Navaratnam⁶

Affiliations

¹ Centre for Chemical Biology (CCB), Universiti Sains Malaysia, 11800 Penang, Malaysia. Electronic address: sheriannccb@gmail.com.
² Consejo Superior de Investigaciones Científicas (CSIC), ICTAN, José Antonio Novais 10, 28040 Madrid, Spain.
³ Centre for Drug Research (CDR), Universiti Sains Malaysia, 11800 Penang, Malaysia.
⁴ School of Biological Sciences, Universiti Sains Malaysia, 11800 Penang, Malaysia.
⁵ Department of Microbiology, University of Hawaii, 96822 HI, USA.
⁶ Centre for Chemical Biology (CCB), Universiti Sains Malaysia, 11800 Penang, Malaysia.

PMID: 30011665
DOI: 10.1016/j.foodres.2014.06.040

Abstract

Extract from papaya leaves, a waste material from fruit farms in Malaysia was previously reported to possess remarkable antioxidative activities. In this study, papaya leaf extract was separated into fractions of different polarities [petroleum ether (PE), ethyl acetate (EA), n-butanol (NB) and water (W) fractions]. The aim of this research was to determine the most active fraction in terms of its chemopreventive effects towards oxidative stress and the chemical constituents involved. The cytoprotective nature of the papaya fractions was observed against t-BOOH-induced oxidative stress on HepG2 liver cell line. ROS assay indicated that only PE and EA effectively reduced the increment of radical due to the pro-oxidant, t-BOOH. Nevertheless, PE was a stronger ROS scavenger by demonstrating ROS reducing activity in a dose-dependent manner to the basal level. This fraction was also found to inhibit cell death caused by t-BOOH toxicity, attenuating lactate dehydrogenase enzyme leakage by more than 90% (p<0.05). In addition, gene expression of phase II antioxidant enzymes (hmox-1 and nqo-1) and their transcription factor (nrf-2) were shown to be upregulated upon PE treatment during a time-course study. A GC-MS fingerprint of the active fraction was subsequently obtained with standardization using the marker compound; α-tocopherol, a well known antioxidant. However, this pure compound was not as effective as its corresponding PE concentrations in ROS reduction. Hence, PE of papaya leaf extract was a strong antioxidant and cytoprotectant with tremendous potential to be harnessed into the next therapeutic remedy against oxidative stress of the liver.

Keywords: Antioxidant; Campesterol (PubChem CID: 173183); Carica papaya L; Hexadecanoic acid (PubChem CID: 985); Linoleic acid (PubChem CID: 5280450); Linolenic acid (PubChem CID: 5280934); Oxidative stress; Phytol (PubChem CID: 5280435); Stigmasterol (PubChem CID: 5280794); hmox-1; nqo-1; nrf-2; α-tocopherol (PubChem CID: 14985); γ-tocopherol (PubChem CID: 92729).