Anti-Acanthamoeba synergistic effect of chlorhexidine and Garcinia mangostana extract or \u03b1-mangostin against Acanthamoeba triangularis trophozoite and cyst forms

Suthinee Sangkanu,Polrat Wilairatana,Polydor Ngoy Mutombo,Mohammed Rahmatullah,Veeranoot Nissapatorn,Maria De Lourdes Pereira,Ajoy K Verma,Ana Paula Girol,Abolghasem Siyadatpanah,Tajudeen O Jimoh,Roghayeh Norouzi,Christophe Wiart,Watcharapong Mitsuwan,Wilawan Mahabusarakam

doi:10.1038/s41598-021-87381-x

Abstract

Acanthamoeba spp. can cause amoebic keratitis (AK). Chlorhexidine is effective for AK treatment as monotherapy, but with a relative failure on drug bioavailability in the deep corneal stroma. The combination of chlorhexidine and propamidine isethionate is recommended in the current AK treatment. However, the effectiveness of treatment depends on the parasite and virulence strains. This study aims to determine the potential of Garcinia mangostana pericarp extract and α-mangostin against Acanthamoeba triangularis, as well as the combination with chlorhexidine in the treatment of Acanthamoeba infection. The minimal inhibitory concentrations (MICs) of the extract and α-mangostin were assessed in trophozoites with 0.25 and 0.5 mg/mL, for cysts with 4 and 1 mg/mL, respectively. The MIC of the extract and α-mangostin inhibited the growth of A. triangularis trophozoites and cysts for up to 72 h. The extract and α-mangostin combined with chlorhexidine demonstrated good synergism, resulting in a reduction of 1/4–1/16 of the MIC. The SEM results showed that Acanthamoeba cells treated with a single drug and its combination caused damage to the cell membrane and irregular cell shapes. A good combination displayed by the extract or α-mangostin and chlorhexidine, described for the first time. Therefore, this approach is promising as an alternative method for the management of Acanthamoeba infection in the future.

Highlights

Acanthamoeba spp. can cause amoebic keratitis (AK)
The rate of infectious keratitis is becoming alarming in recent times, a problem that may be related to a sudden increase in the population of contact lens w earers[2] Acanthamoeba encysts penetrated deeply into the corneal s troma[8] as such, the cyst wall becomes impervious to existing drugs, and this becomes a drawback for further studies in the areas of drug formulations and designed for this organism
We present in this study an effective treatment for A. triangularis infection with herb-drug based combination strategy

Summary

Introduction

Acanthamoeba spp. can cause amoebic keratitis (AK). Chlorhexidine is effective for AK treatment as monotherapy, but with a relative failure on drug bioavailability in the deep corneal stroma. This study aims to determine the potential of Garcinia mangostana pericarp extract and α-mangostin against Acanthamoeba triangularis, as well as the combination with chlorhexidine in the treatment of Acanthamoeba infection. The extract and α-mangostin combined with chlorhexidine demonstrated good synergism, resulting in a reduction of 1/4–1/16 of the MIC. A good combination displayed by the extract or α-mangostin and chlorhexidine, described for the first time. This approach is promising as an alternative method for the management of Acanthamoeba infection in the future. Major compound in the mangosteen pericarps is xanthone group, α-mangostin, which exhibited antibacterial a ctivity[12], antifungal activity[13], antioxidant a ctivity[14] anti-cancer a ctivity[15,16,17], anti-inflammatory a ctivity[18,19], antiparasitic activity[20,21,22]

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