In this study, Berberine Antifungal activity, in vitro antidermatophytic activity against Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum cani, and Microsporum gypseum was studied by disk diffusion test and assessment of minimum inhibitory concentration (MIC) using CLSI broth macro dilution method (M38-A2). Moreover, antileishmanial and cytotoxicity activity of B. vulgaris and berberine against promastigotes of Leishmania major and Leishmania tropica were evaluated by colorimetric MTT assay.
Antifungal Activities of Various Extracts of Berberis vulgaris active compound Berberine
The findings indicated that the various extracts of B. vulgaris particularly berberine showed high potential antidermatophytic against pathogenic dermatophytes tested with MIC values varying from 0.125 to >4 mg/mL. The results revealed that B. vulgaris extracts as well as berberine were effective in inhibiting L. major and L. tropica promastigotes growth in a dose-dependent manner with IC50 (50% inhibitory concentration) values varying from 2.1 to 26.6 𝜇g/mL. Moreover, it could be observed that berberine as compared with B. vulgaris exhibited more cytotoxicity against murine macrophages with CC50 (cytotoxicity concentration for 50% of cells) values varying from 27.3 to 362.6 𝜇g/mL. Results of this investigation were the first step in the search for new antidermatophytic and antileishmanial drugs. However, further works are required to evaluate exact effect of these extracts in animal models as well as volunteer human subjects.
So far, in various investigations, antiparasitic effects of B.vulgaris and its bioactive compounds (particularly berberine) against some pathogenic parasite strains have been reported.
The study conducted by Kaneda et al. [16] showed that berberine significantly reduced growth of Entamoeba histolytica, Giardia lamblia, and Trichomonas vaginalis on an in vitro
model and caused morphological changes in their structure. Also, Sheng et al. [29] reported that, in chloroquine resistant malaria, the combination of berberine and pyrimethamine had a synergistic effect in the elimination of parasites and it was more effective than other drugs such as tetracycline or cotrimoxazole. In another survey, Vennerstrom et al.
[۱۷] demonstrated that berberine derivatives significantly suppressed the parasite load in liver or ulcer size in golden hamsters infected with Leishmania donovani and Leishmania braziliensis when compared with meglumine antimoniate. Fata et al. [15] also found that ethanolic extract of B. vulgaris significantly decreased ulcer size of cutaneous leishmaniasis of BALB/c mice after 2 weeks. Recently, Rouhani et al. [30] reported that aqueous extract of B. vulgaris fruits had an effective scolicidal activity at low concentration (4 mg/mL) and short exposure time (5 min). Thus, the present results were in agreement with those of previous studies in demonstrating antiparasitic activities of B. vulgaris and its bioactive
compound, berberine.
In this survey, it was indicated that various extracts of B. vulgaris had no significant cytotoxicity effect at low concentrations in peritoneal macrophage cells while berberine indicated moderate cytotoxicity effects on peritoneal macrophage cells. Similar to these findings, Peychev [31] revealed that oral administration of B. vulgaris was moderately toxic in mice (LD50 = 2.6 ± ۰٫۲۲ g/kg b.w). In contrast, Lin et al. [32] showed that berberine had strong inhibitory effect on proliferation of both hepatoma and leukemia cell lines on in vitro model. However, it has been proven that berberine is not considered toxic at the doses used in clinical situations nor has it been shown to be cytotoxic or mutagenic; however, some side-effects have been mentioned to result from high dosages [11]. In addition, SIs ≥ ۱۰ of extracts showed their safety to the macrophages and specificity to the parasite [23]. Thus, it could be proposed that B. vulgaris extracts were safe for mammalian cells considering that at high concentrations, they showed significant cytotoxicity in the host cells.
Conclusion
To conclude, findings of this study could provide the first step in the search for new antidermatophytic and antileishmanial drugs and aid the use of B. vulgaris in folk medicine for dermatophytic and leishmaniasis infections. In addition, further studies are required to elucidate the exact effects of these extracts and berberine in animal models as well as volunteer human subjects as a new therapeutic agent.
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