Sophocarpine and matrine inhibit the production of TNF-alpha and IL-6 in murine macrophages and prevent cachexia-related symptoms induced by colon26 adenocarcinoma in mice.
The present study aims to access the effects of sophora alkaloids on the production of pro-inflammatory cytokines and evaluate their therapeutic efficiency on cachexia. The comparative study showed that all sophora alkaloids tested here, including matrine, oxymatrine, sophocarpine, sophoramine, and sophoridine, inhibited TNF-alpha and IL-6 production in both RAW264.7 cells and murine primary macrophages, and sophocarpine showed the most potent inhibitory effect among them. Quantification of TNF-alpha and IL-6 mRNA in RAW264.7 cells by real-time RT-PCR revealed that both sophocarpine and matrine suppressed TNF-alpha and IL-6 expression and sophocarpine has stronger suppressing potency than matrine. Inoculation (s.c.) of colon26 adenocarcinoma cells into BALB/c mice induced cachexia, as evidenced by progressive weight loss, reduction in food intake, wasting of gastrocnemius muscle and epididymal fat, and increase in serum levels of TNF-alpha and IL-6. Administration of 50 mg/kg/d sophocarpine or matrine for 5 days from the onset of cachexia did not inhibit the tumor growth but resulted in attenuation of cachexia symptoms. Furthermore, sophocarpine and matrine decreased the serum levels of TNF-alpha and IL-6, and sophocarpine showed a better therapeutic effect than matrine. These results suggest that sophocarpine and matrine exert anti-cachectic effects probably through inhibition of TNF-alpha and IL-6.
Zhang
Yuefan
Y
Department of Biochemical Pharmacy, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
Wang
Shaozhan
S
Li
Yuanyuan
Y
Xiao
Zhenyu
Z
Hu
Zhenlin
Z
Zhang
Junping
J
D000230:Adenocarcinoma / Q000150:complications*; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002100:Cachexia / Q000209:etiology / Q000517:prevention & control*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000150:complications*; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood; D000093842:Matrines; D000093242:Interleukin-6 Inhibitors
D000470:Alkaloids; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011807:Quinolizines; D014409:Tumor Necrosis Factor-alpha; D000093842:Matrines; D000093242:Interleukin-6 Inhibitors; C035933:sophocarpine; C055681:sophoramine; C037573:oxymatrine