A metabolomic approach to identify anti-hepatocarcinogenic compounds from plants used traditionally in the treatment of liver diseases

Fitoterapia. 2018 Feb 23. pii: S0367-326X(18)30119-9. doi: 10.1016/j.fitote.2018.02.021. [Epub ahead of print] Chassagne F1, Haddad M1, Amiel A1, Phakeovilay C2, Manithip C3, Bourdy G1, Deharo E2, Marti G4. Author information 1 PHARMADEV, Université de Toulouse, IRD, Toulouse, France. 2 PHARMADEV, Université de Toulouse, IRD, Toulouse, France; Faculty of Pharmacy, University of Health Sciences, Vientiane, Lao Democratic People's Republic. 3 Faculty of Pharmacy, University of Health Sciences, Vientiane, Lao Democratic People's Republic. 4 PHARMADEV, Université de Toulouse, IRD, Toulouse, France. Electronic address: guillaume.marti@univ-tlse3.fr. Abstract Liver cancer is a major health burden in Southeast Asia, and most patients turn towards the use of medicinal plants to alleviate their symptoms. The aim of this work was to apply to Southeast Asian plants traditionally used to treat liver disorders, a successive ranking strategy based on a comprehensive review of the literature and metabolomic data in order to relate ethnopharmacological relevance to chemical entities of interest. We analyzed 45 publications resulting in a list of 378 plant species, and our point system based on the frequency of citation in the literature allowed the selection of 10 top ranked species for further collection and extraction. Extracts of these plants were tested for their in vitro anti-proliferative activities on HepG2 cells. Ethanolic extracts of Andrographis paniculata, Oroxylum indicum, Orthosiphon aristatus and Willughbeia edulis showed the highest anti-proliferative effects (IC50 = 195.9, 64.1, 71.3 and 66.7 μg/ml, respectively). A metabolomic ranking model was performed to annotate compounds responsible for the anti-proliferative properties of A. paniculata (andrographolactone and dehydroandrographolide), O. indicum (baicalein, chrysin, oroxylin A and scutellarein), O. aristatus (5-desmethylsinensetin) and W. edulis (parabaroside C and procyanidin). Overall, our dereplicative approach combined with a bibliographic scoring system allowed us to rapidly decipher the molecular basis of traditionally used medicinal plants. KEYWORDS: Anti-proliferative effect; HepG2; Hepatocellular carcinoma; Medicinal plants; Metabolomics; Southeast Asia PMID: 29477305 DOI: 10.1016/j.fitote.2018.02.021