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

• Published in: Phytotherapy research Vol. 24; no. 7; pp. 1056 - 1064
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-07-2010; Wiley
• Subjects: Acetates; Administration, Cutaneous; Animals; apoptosis; Biological and medical sciences; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Dermatologic Agents - administration & dosage; Dermatologic Agents - pharmacology; differentiation; General pharmacology; HaCaT keratinocytes; Humans; Keratinocytes - drug effects; Male; Medical sciences; Mice; Mice, Inbred BALB C; mouse tail test; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Plant Extracts - administration & dosage; Plant Extracts - pharmacology; Plant Roots - chemistry; proliferation; psoriasis; Psoriasis - drug therapy; Rubia - chemistry; Rubia cordifolia L; Asia; China; Cell proliferation; HaCaT keratinocytes; Skin disease; differentiation; Medicinal plant; mouse tail test; Folk medicine; Dicotyledones; Angiospermae; Rubiaceae; Keratinocyte; Below ground plant part; Psoriasis; Root; proliferation; Pharmacognosy; Rodentia; Nubia cordifolia L; In vitro; In vivo; Vertebrata; Dye plant; Mammalia; Treatment; Mouse; Cell death; Animal; Plant origin; Spermatophyta; Skin; Apoptosis
• ISSN: 0951-418X; 1099-1573
• DOI: 10.1002/ptr.3079

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. Copyright © 2009 John Wiley & Sons, Ltd.