REVIEW Journey of Hydrocotyle sibthorpioides Lam.: From traditional utilization to modern therapeutics—A review Iswar Hazarika 1,2 | Geetha K. Mukundan 2 | P. Sivakami Sundari 3 | Damiki Laloo 4 1 Department of Pharmacology, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, India 2 Department of Pharmacology, College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, India 3 Department of Pharmacognosy, College of Pharmaceutical Sciences, Dayananda Sagar University, Bengaluru, India 4 Department of Pharmacognosy, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, India Correspondence Iswar Hazarika, Department of Pharmacology, Girijananda Chowdhury Institute of Pharmaceutical Sciences, Guwahati, Assam 781017, India. Email: iswarhazarika@gmail.com Geetha K. Mukunda, Department of Pharmacology, College of Pharmaceutical Sciences, Dayananda Sagar University, Shavige Malleshwara Hills, Kumaraswamy Layout, Bengaluru, Karnataka, 560078, India. Email: geetha-sps@dsu.edu.in Hydrocotyle sibthorpioides Lam. (Araliaceae) is a short and edible medicinal herb, which is used in the traditional system of medicines. The review aims to report the current information of H. sibthorpioides on the basis of its botanical and taxonomical description, traditional use, active phytoconstituents, pharmacological use and toxic- ity. The information on H. sibthorpioides with respect to its journey from traditional uses to scientific validation was gathered based on the online survey. The results from the review signify that the plant is used by the different tribes of the world for the treatment of patients suffering from fever, edema, dysentery, rheumatalgia, whooping cough, jaundice, throat pain, psoriasis, herpes zoster infection, hepatitis-B infection, soothing pain, dysmenorrhoea and carbunculosis. It is also used as a brain tonic, detoxifying agent and hepatoprotective agent. Scientific investigation reported that the plant has a significant pharmacological activity, viz. cognitive agent, anti- cancer, antiviral, antibacterial, anti-fungal and hepatoprotective. Moreover, based on the phytochemical aspects, a total of 50 phytoconstituents was identified and iso- lated from the plant. In conclusion, the outcome of this review will be useful for (a) developing a comprehensive plant profile; (b) assist investigators for exploring fur- ther research; and (c) to fulfil the gaps lacking in terms of clinical studies. KEYWORDS Apiaceae, Araliaceae, cognitive activity, Hydrocotyle sibthorpioides, traditional medicines 1 | INTRODUCTION Ever since time immemorial, plants have always been utilized as medi- cine and in the preparation of food in different cuisines. The demand for the use of medicinal plants is progressively rising throughout the world due to the growing recognition and applicability of natural products in the management of the disease (Ekor, 2014). Hydrocotyle sibthorpioides Lam., commonly known as “Lawn pennywort,” is a popu- lar plant growing throughout the Asian and African countries. It is widely used in the preparation of food in local cuisines and also as an important ingredient in the traditional system of medicines (Hazarika, Geetha, Sundari, & Madhu, 2019). The plant is commonly found in China and Taiwan provinces and has significant uses in folklore medi- cine, probably in the treatment of varying range of diseases, including throat pain, fever, edema, skin disease (psoriasis), herpes zoster, jaun- dice hepatitis-B, dysentery, rheumatalgia, liver diseases and also in improving immune functions (H. C. Huang, Liaw, et al., 2008; Yu, Yu, McGuire, Li, & Wang, 2007). In India, the plant is traditionally used to treat fever, edema and is also popularly used as a brain tonic, pain reliever and detoxification agent (Barukial & Sarmah, 2011). Based on the studies in the literature, many studies have aimed at validating Abbreviations: BHT, Butylated hydroxytoluene; cccDNA, Covalent closed circular DNA; CH 50 value, Haemolytic activity; DENV-2, Dengue virus type-2; DPPH, 2,2-diphenyl- 1-picrylhydrazyl; ED 50 , median effective dose; GSH, Glutathione; i.p, Intraperitoneal; IC 50 , 50% Maximal Inhibitory Concentration; kg, kilogram; MIC, Minimum Inhibitory Concentration; ml, millilitre; MLC, Minimum Lethal Concentration; MTT, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide; OECD, Organisation for Economic Co-operation and Development; p.o, Orally (from the Latin “per os”); pfu, Plaque- forming unit; μg, microgram; μL, microlitre. Received: 8 July 2020 Revised: 14 September 2020 Accepted: 6 October 2020 DOI: 10.1002/ptr.6924 Phytotherapy Research. 2020;1–25. wileyonlinelibrary.com/journal/ptr © 2020 John Wiley & Sons Ltd 1