Carica papaya L. Leaf: A Systematic Scoping Review on Biological Safety and Herb-Drug Interactions.

X Y Lim,T Y C Tan,N Japri,J S W Chan,J C Lee,Hicham Harhar

doi:10.1155/2021/5511221

Abstract

Introduction The Carica papaya L. leaf is gaining interest as a potential therapeutic agent for alleviating dengue- and non-dengue-associated thrombocytopaenia. In that regard, safety considerations are as important as efficacy potential. The safety evaluation of botanical products for human use is complicated by variable formulations, complex phytochemical composition, and extrinsic toxicants. This review aimed to systematically collate related safety clinical and preclinical data, as well as reports on herb-drug interactions of C. papaya leaf consumption. Methods A systematic search using predetermined keywords on electronic databases (MEDLINE, Cochrane Library Central, LILACS, and Web of Science) and grey literature was conducted. Relevant clinical and preclinical studies were identified, screened, and analysed to present an overall safety profile of C. papaya leaf consumption. Results A total of 41 articles were included (23 clinical, 5 ongoing trials, and 13 preclinical) for descriptive analysis on study characteristics, adverse reactions, toxicity findings, and herb-drug interactions, from which 13 randomised controlled and quasiexperimental trials were further assessed for risk of bias and reporting quality. Overall, C. papaya leaf consumption (in the form of juice and standardised aqueous extract) was well tolerated by adult humans for short durations (<five days) while one randomised controlled trial reported safe consumption of C. papaya leaf standardised aqueous extract in children (aged 1–12 years). Minor gastrointestinal side effects were most commonly reported. There are concerns about hepatotoxicity and reproductive toxicity in long-term use, supported by animal studies. Unfavourable herb-drug interactions with metformin, glimepiride, digoxin, ciprofloxacin, and artemisinin were accounted. Conclusion C. papaya leaf consumption in adults is generally safe for short-term use though cautioned in pregnancy and people with liver impairment. It has potential herb-drug interactions with oral hypoglycaemic agents, p-glycoprotein substrates, and antibiotics with cation chelating properties.

Highlights

Carica papaya L. is a common medicinal plant used in folk medicine [1]
C. papaya leaf consumption in adults is generally safe for short-term use though cautioned in pregnancy and people with liver impairment
The leaves of C. papaya, in decoction or infusion form, are consumed orally to reduce blood pressure and sugar levels. e juice of C. papaya leaf is used for irregular menstruation while infusion of young leaf is used for fever [2, 3]. ere is long standing interest in the use of C. papaya leaf as an adjunctive treatment to the standard care for improving platelet counts, especially in cases of dengue fever [4], or more recently, in cancer treatments [5]

Summary

Introduction

Carica papaya L. is a common medicinal plant used in folk medicine [1]. Traditionally, the leaves of C. papaya, in decoction or infusion form, are consumed orally to reduce blood pressure and sugar levels. e juice of C. papaya leaf is used for irregular menstruation while infusion of young leaf is used for fever [2, 3]. ere is long standing interest in the use of C. papaya leaf as an adjunctive treatment to the standard care for improving platelet counts, especially in cases of dengue fever [4], or more recently, in cancer treatments [5]. Among the most important clinical findings on the efficacy of C. papaya leaf is its use in thrombocytopaenia management during dengue infection [6], a common and potentially life-threatening complication during the course of infection [7]. Such clinical benefits and potential mechanisms of action have been investigated and backed by preclinical data [8,9,10]. C. papaya leaf has been reported to contain several important phytochemical compounds including flavonoids, alkaloids, tannins, quinones, and steroids which may collectively contribute towards its biological activities [17, 18]. In addition to the abundance of phenolic compounds with antioxidant properties identified in a methanol extract of C. papaya leaf [19], the alkaloid carpaine was reported to be a major contributor towards the leaf’s antithrombocytopaenic properties [20]

Objectives

Methods

Results

Conclusion