Berberine chloride nanoemulgel enriched with clove oil attenuated monobenzone-induced experimental vitiligo in C57BL/6 mice: Pharmaceutical, molecular modeling, biochemical, protein, and mRNA expression analysis.

Vitiligo causes progressive loss of pigmentation owing to the destruction of melanocytes. Berberine chloride (BRB) protects melanocytes from oxidative stress and enhances melanophores. However, BRB exhibited reduced skin permeation efficiency due to poor (pKa-2.47 and 15.7; log P--1.5) physicochemical attributes. Therefore, in the present investigation, berberine chloride nanoemulsion (BRB-NE) enriched with clove oil, a well-known source of eugenol (EUG), was prepared with a droplet size of 20.50 ± 0.10 nm and a Polydispersity index (PDI) of 0.178 ± 0.022. Later, BRB-NE was transformed into berberine chloride nanoemulgel (BRB-NEG) using 1 % carbopol Ultrez 10 NF, a biodegradable polymer. The flux of BRB from BRB-GEL (Berberine chloride gel) and BRB-NEG was observed to be 8.38 ± 1.99 μg/cm2/h and 14.25 ± 6.82 μg/cm2/h, respectively. JAK1 and JAK3 play a significant role in the progression of vitiligo. We observed that JAK1, JAK3, TNF-α, IL-6, and IFN-γ mRNA levels were significantly (P < 0.001; P < 0.01) elevated in the experimental vitiligo designated as the positive control (PC) group as compared to the normal control (NC) group. Interestingly, BRB-NEG significantly (P < 0.01) decreased the IL-6 and IFN-γ expression compared to the PC group. The TNF-α, JAK1, and JAK3 levels were also significantly (P < 0.001) reduced in the BRB-NEG-treated group compared to the PC group. Western blot analysis also demonstrated the reduced expression of JAK1 in the BRB-NEG-treated group as compared to the PC group. Thus, BRB-NEG mitigated vitiligo progression by synergistically suppressing inflammatory mediators, thereby promoting re-pigmentation. In conclusion, BRB-NEG may be a potential treatment modality for translating into a clinically viable product.