A Novel Function for Kojic Acid, a Secondary Metabolite from Aspergillus Fungi, as Antileishmanial Agent

Abstract

Kojic acid (KA) is a fungal metabolite used as a topical treatment skin-whitening cosmetic agent for melasma in humans; however its potential as an anti-leishmanial agent is unknown. Chemotherapy is one of the most effective treatments for Leishmaniasis. However, the drugs available are expensive, invasive, require long-term treatment and have severe side effects. Thus, the development of new effective leishmanicidal agents is a necessity. In this study we investigated the anti-leishmanial effect of KA on L. amazonensis, following in vitro and in vivo infections. KA (50 μg/mL) was found to decrease the growth by 62% (IC50 34 μg/mL) and 79% (IC50 27.84 μg/mL) of promastigotes and amastigotes in vitro, respectively. Ultrastructural analysis of KA-treated amastigotes showed the presence of vesicles bodies into the flagellar pocket, and an intense intracellular vacuolization and swelling of the mitochondrion. During the in vitro interaction of parasites and the host cell, KA reverses the superoxide anions (O2 -) inhibitory mechanism promoted by parasite. In addition, 4 weeks after KA-topical formulation treatment of infected animals, a healing process was observed with a high production of collagen fibers and a decrease in parasite burden. Thus, these results demonstrated the great potential of KA as an anti-leishmanial compound.

Leishmanicidal Activity of (+)-Phyllanthidine and the Phytochemical Profile of Margaritaria nobilis (Phyllanthaceae)

“…Intracellular amastigotes are responsible for the clinical manifestations of leishmaniasis [37]. Considerable efforts have been done in searching for new substances that act on intracellular forms of Leishmania protozoa [38,39,40,41]. Alkaloids and derivatives have shown this effect, such as the diterpene alkaloid derivatives that exhibited antiproliferative action against amastigote forms of L. infantum without causing cytotoxic effects in host cells [42].…”

Antimicrobial activity of kojic acid from endophytic fungus Colletotrichum gloeosporioides isolated from Sonneratia apetala, a mangrove plant of the Sundarbans

“…Previous bioactivity studies on kojic acid (1) revealed its antioxidant [18], tyrosinase inhibitory [19], anti-pigmentation (skin whitening) [20,21], nematicidal [22], antifungal [23] and antileishmanial [24] properties. Kojic acid (1) is a chelation agent produced by several species of fungi, especially Aspergillus oryzae, which has the Japanese common name koji.…”

“…The approved and permitted maximum concentration of kojic acid (1) in cosmetic products, e.g., powders, serums, creams, cleansers, and soaps, is 1%. Some products, like soaps and cleansers, are meant to be washed off immediately, but others, like creams and serums, are formulated to be left on and absorbed into the skin [21][22][23][24]. Products containing kojic acid (1) are frequently used on the face and hands, but can be applied on all non-sensitive areas of the body.…”

“…antifungal properties and is incorporated to some antifungal products to enhance their efficacy. Moreover, kojic acid (1) could be useful in treating fungal infections of the skin including yeast infections, candidiasis and ringworm or athlete's foot [21][22][23][24]. Regular use of soap containing kojic acid (1) may help prevent both topical bacterial and fungal infections on the body.…”

Cytotoxic Screening and In Vitro Evaluation of Pentadecane AgainstLeishmania infantumPromastigotes and Amastigotes

“…These side effects and disadvantages demonstrate the necessity to identify new, effective, and safe compounds for the treatment of this disease (Croft et al, 2006b;Rodrigues et al, 2014). The domestic dog is the main reservoir for the transmission of the visceral form of leishmaniasis, thereby accounting for its widespread occurrence in the human population (Courtenay et al, 2002).…”