Effects of Shuanghuanglian and Qingkailing, two multi-components of traditional Chinese medicinal preparations, on human leukocyte function.
Qingkailing (QKL) and Shuanghuanglian (SHHL) are two commonly used Chinese herbal preparations with reported antiinflammatory activity. The effects of these two preparations on the capacity of staphylococcal toxic shock syndrome toxin 1 (TSST-1) to stimulate the production of cytokines (IL-1beta, IL-6, TNF-alpha, IFN-gamma) and chemokines (MIP-1alpha, MIP-1beta and MCP-1) by peripheral blood mononuclear cell (PBMC) was tested. We also evaluated their effect on LPS-stimulated NF-kappaB transcriptional activity in a THP-1 cell line, and on human monocyte chemotactic response to chemoattractants. Non-cytotoxic concentrations of QKL (0.1 to approximately 2%) and SHHL (6 to approximately 120 microg) significantly inhibited production of cytokines and chemokines in a dose-dependent manner (P < 0.05). Both, QKL at 1:100 and SHHL at 60 microg/ml, markedly inhibited RANTES, MIP-1alpha, SDF-1alpha and fMLP induced human monocyte migration (P < 0.05 or 0.01). QKL (1%) did not inhibit monocyte chemotaxis induced by super-or sub-optimal concentrations of fMLP (10(-5), 10(-6) and 10(-10) M), but only inhibited chemotaxis induced by optimal concentrations of fMLP at 10(-7), 10(-8) and 10(-9) M. QKL (0.1% or 1%) and SHHL (6 or 60 microg/ml) markedly inhibited LPS-induced NF-kappaB activity in THP-1 cells. The results suggested that the pharmacological basis for the antiinflammatory effects of QKL and SHHL is the result of suppression of NF-kappaB regulated gene transcription, leading to suppressed production of proinflammatory cytokine and chemokine. Interference with leukocyte chemotaxis also contributes to the antiinflammatory and immunomodulating effects of these medicinals. Identification of the responsible components in these two herbal preparations may yield compounds suitable for structural modification into potent novel drugs.
Chen
Xin
X
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Fort Detrick, MD, 21702-1201, USA. xinc@mail.ncifcrf.gov
Howard
O M Zack
OM
Yang
Xiaoyi
X
Wang
Lihua
L
Oppenheim
Joost J
JJ
Krakauer
Teresa
T
D001427:Bacterial Toxins; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004768:Enterotoxins / Q000633:toxicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D013211:Staphylococcus aureus; D018089:Superantigens; D014162:Transfection
D001427:Bacterial Toxins; D018932:Chemokine CCL2; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D004768:Enterotoxins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D008156:Luciferases