Ethyl acetate fraction of the root of rubia cordifolia L. inhibits keratinocyte proliferation in vitro and promotes keratinocyte differentiation in vivo: potential application for psoriasis treatment
2010
Lin, Z.X. | Jiao, B.W. | Che, C.T. | Zuo, Z. | Mok, C.F. | Zhao, M. | Ho, W.K.K. | Tse, W.P. | Lam, K.Y. | Fan, R.Q. | Yang, Z.J. | Cheng, C.H.K.
Psoriasis is a skin disease associated with hyperproliferation and aberrant differentiation of keratinocytes. Our previous studies have identified the root of Rubia cordifolia L. as a potent antiproliferative and apoptogenic agent in cultured HaCaT cells (IC₅₀ 1.4 μg/ml). In the present study, ethanolic extract of Radix Rubiae was fractioned sequentially with hexane, ethyl acetate (EA), n-butanol and water. EA fraction was found to possess most potent antiproliferative action on HaCaT cells (IC₅₀ 0.9 μg/ml). Mechanistic study revealed that EA fraction induced apoptosis on HaCaT cells, as it was capable of inducing apoptotic morphological changes. Annexin V-PI staining assay also demonstrated that EA fraction significantly augmented HaCaT apoptosis. In addition, EA fraction decreased mitochondrial membrane potential in a concentration- and time-dependent manner. The standardized EA fraction was formulated into topical gel and its keratinocyte-modulating action was tested on mouse tail model. EA fraction dose-dependently increased the number and thickness of granular layer and epidermal thickness on mouse tail skin, indicative of the keratinocyte differentiation-inducing activity. Taking the in vitro and in vivo findings together, the present preclinical study confirms that EA fraction is a promising antipsoriatic agent warranting further development for psoriasis treatment.
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