Therapeutic potential of Leea asiatica: Chemical isolation and validation of ethnomedicinal claims through in vitro and in silico assessment of antioxidant and anti-inflammatory properties
Khem Raj Joshi,
Hari Prasad Devkota,
Khalid Awadh Al-Mutairi,
Koji Sugimura,
Shoji Yahara,
Ravindra Khadka,
Shankar Thapa,
Mohammad Ujair Shekh,
Sandesh Poudel,
Takashi Watanabe
Affiliations
Khem Raj Joshi
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan; School of Health and Allied Sciences, Faculty of Health Sciences, Pokhara University, Pokhara, 33700, Nepal; Corresponding author. School of Health and Allied Sciences, Faculty of Health Sciences, Pokhara University, Pokhara, 33700, Nepal.
Hari Prasad Devkota
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan
Khalid Awadh Al-Mutairi
University of Tabuk, Department of Biology, Faculty of Science, Tabuk, P.O. Box 741, Tabuk, 741, Saudi Arabia
Koji Sugimura
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan; Corresponding author.
Shoji Yahara
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan
Ravindra Khadka
School of Health and Allied Sciences, Faculty of Health Sciences, Pokhara University, Pokhara, 33700, Nepal
Shankar Thapa
Department of Pharmacy, Madan Bhandari Academy of Health Sciences, Hetauda, Nepal
Mohammad Ujair Shekh
School of Health and Allied Sciences, Faculty of Health Sciences, Pokhara University, Pokhara, 33700, Nepal
Sandesh Poudel
School of Health and Allied Sciences, Faculty of Health Sciences, Pokhara University, Pokhara, 33700, Nepal
Takashi Watanabe
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan
Leea asiatica (L.) Ridsdale has been used by different ethnic communities to manage diseased conditions that can be traced to oxidative stress and cellular inflammations but scientific evidences to support the claim are scanty. The objective of this study was to isolate and identify the antioxidants present in the aerial parts of Leea asiatica, perform their molecular docking against proteins to inspect whether the traditional uses of the plant can be validated by an in-silico approach. Quercetin (1), gallic acid (2), kaempferol (3), methyl gallate (4), myricetin 3-O-α-L-rhamnopyranoside (5), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) were isolated from the 70 % methanolic extract of the aerial parts. Compounds 2, 4, 6, and 7 are reported for the first time from Leea asiatica. Quercetin (1), gallic acid (2), (−)-epicatechin-3-O-gallate (6) and (−)-epigallocatechin-3-O-gallate (7) showed potent antioxidant activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. Molecular docking with NADPH oxidase and TNF-α revealed that epicatechin-3-O-gallate, epigallocatechin-3-O-gallate and quercetin bound with the least binding energy amongst the isolated compounds as well as standard (Trolox and Prednisolone). By molecular dynamics analysis, epicatechin-3-O-gallate maintained stable conformation with NADPH oxidase and TNF-α and was found to possess good ADMET profile thereby validating the ethnic use of the plant as a medicine in the management of inflammatory conditions by an in vitro and in silico approach.
