Pretreatment with aqueous Moringa oleifera Lam. leaf extract prevents cadmium-induced hepatotoxicity by improving cellular antioxidant machinery and reducing cadmium accumulation
Visarut Buranasudja,
Kittipong Sanookpan,
Sornkanok Vimolmangkang,
Asma Binalee,
Kamil Mika,
Sucheewin Krobthong,
Kittikhun Kerdsomboon,
Supeecha Kumkate,
Toemthip Poolpak,
Siraprapa Kidhakarn,
Kwang Mo Yang,
Tossapol Limcharoensuk,
Choowong Auesukaree
Affiliations
Visarut Buranasudja
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok, 10330, Thailand
Kittipong Sanookpan
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Nabsolute Co., Ltd., Bangkok, 10330, Thailand
Sornkanok Vimolmangkang
Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Center of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, 10330, Thailand
Asma Binalee
HPTLC Center, Chula PharTech Co., Ltd., Bangkok, 10330, Thailand
Kamil Mika
Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, Krakow, PL, 30-688, Poland
Sucheewin Krobthong
Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand
Kittikhun Kerdsomboon
Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, 12120, Thailand; Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Supeecha Kumkate
Department of Biology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Toemthip Poolpak
Department of Biology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), CHE, OPS, MHESI, Bangkok, 10400, Thailand
Siraprapa Kidhakarn
Department of Biology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Kwang Mo Yang
Department of Biology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Center of Excellence on Environmental Health and Toxicology (EHT), CHE, OPS, MHESI, Bangkok, 10400, Thailand
Tossapol Limcharoensuk
Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand
Choowong Auesukaree
Mahidol University-Osaka University Collaborative Research Center for Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Corresponding author. Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand.
Cadmium (Cd) is a highly harmful pollutant that poses a serious threat to human health. The liver is the primary organ for Cd accumulation, and Cd-induced hepatotoxicity has been shown to be strongly correlated with an oxidative imbalance in hepatocytes. Our previous studies in the eukaryotic model organism Saccharomyces cerevisiae revealed that not only co-treatment but also pretreatment with aqueous Moringa oleifera Lam. leaf extract (AMOLE) effectively mitigated Cd toxicity by reducing intracellular Cd accumulation and Cd-mediated oxidative stress. In this study, we therefore investigated the preventive effect of AMOLE against Cd toxicity in human HepG2 hepatocytes. The results showed that, similar to the case of the yeast model, pretreatment with AMOLE prior to Cd exposure also significantly inhibited Cd-induced oxidative stress in HepG2 cells. Untargeted LC-MS/MS-based metabolomic analysis of AMOLE revealed that its major phytochemical constituents were organic acids, particularly phenolic acids and carboxylic acids. Additionally, DPPH-HPTLC fingerprints suggested that quercetin and other flavonoids possibly contribute to the antioxidant activities of AMOLE. Based on our findings, it appears that pretreatment with AMOLE prevented Cd-induced hepatotoxicity via three possible mechanisms: i) direct elimination of free radicals by AMOLE antioxidant compounds; ii) upregulation of antioxidant defensive machinery (GPx1, and HO-1) via Nrf2 signaling cascade to improve cellular antioxidant capacity; and iii) reduction of intracellular Cd accumulation, probably by suppressing Cd uptake. These data strongly suggest the high potential of AMOLE for clinical utility in the prevention of Cd toxicity.