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.
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 (IC(50) 1.4 microg/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 (IC(50) 0.9 microg/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.
Lin
Z X
ZX
School of Chinese Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. linzx@cuhk.edu.hk
Jiao
B W
BW
Che
C T
CT
Zuo
Z
Z
Mok
C F
CF
Zhao
M
M
Ho
W K K
WK
Tse
W P
WP
Lam
K Y
KY
Fan
R Q
RQ
Yang
Z J
ZJ
Cheng
C H K
CH
D000085:Acetates; D000279:Administration, Cutaneous; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D011565:Psoriasis / Q000188:drug therapy; D045470:Rubia / Q000737:chemistry*
D000085:Acetates; D003879:Dermatologic Agents; D010936:Plant Extracts; C007650:ethyl acetate