Immune reponses in human mesangial cells regulated by emodin from Polygonum hypoleucum Ohwi.
In the hope of identifying agents of therapeutic value in glomerulonephritis from Chinese herbs, we found that methanolic extracts of Polygonum hypoleucum Ohwi (P. hypoleucum Ohwi) inhibit human mesangial cells proliferation activated with interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) previously. This study was designed to identify bioactive components from P. hypoleucum Ohwi and elucidate their action mechanisms. We tested four anthraquinones emodin, emodin 1-O-beta-D-glucoside (49A), physcion (62A), and physcion 1-O-beta-D-glucoside (50A) purified from P. hypoleucum Ohwi for their effects on human mesangial cell proliferation and cytokines production in vitro. On a percentage basis, emodin had the highest suppressing activity on the human mesangial cells proliferation activated by IL-1beta and IL-6. The IC50 of emodin on human mesangial cells proliferation were 17.9+/-1.2 microM. In contrast to 49A, 50A, and 62A, emodin also decreased IL-1beta, IL-6 and tumor necrosis factor-alpha (TNF-alpha) production in human mesangial cells activated with IL-1beta and IL-6. The IC50 of emodin on IL-1beta, IL-6 and TNF-alpha production in activated human mesangial cells were 16.6+/-1.8 microM, 8.2+/-1.3 microM, and 9.5+/-1.6 microM, respectively. Moreover, IL-1beta and TNF-alpha mRNA expression in activated human mesangial cells was impaired by emodin. The intracellular free Ca2+ concentration ([Ca2+]i) in IL-1beta and IL-6 activated human mesangial cells was decreased by emodin. It is unlikely that cytotoxicity was involved because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of emodin on activated human mesangial cells proliferation may be related to the impairments of gene expression and production of cytokines and [Ca2+]i in the cells.
Laboratory of Immunology, National Research Institute of Chinese Medicine, Taipei, Taiwan. Kuo9111@cma23.nricm.edu.tw
Y C
YC
Kuo
W J
WJ
Tsai
H C
HC
Meng
W P
WP
Chen
L Y
LY
Yang
C Y
CY
Lin
D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival; D004365:Drugs, Chinese Herbal; D004642:Emodin / Q000302:isolation & purification / Q000494:pharmacology*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D004365:Drugs, Chinese Herbal; D007375:Interleukin-1; D015850:Interleukin-6; D010936:Plant Extracts; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004642:Emodin; D002118:Calcium