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Antitumor activities and tumor necrosis factor (TNF) producibility of traditional Chinese medicine and crude drugs
357
"THERAPEUTIC EFFECTS OF AMINISTRATION OF FATTY-ACID SUPPLE~NTED DIET ON THE COURSE OF DISEASE IN 4 MONTH OLD SPONTANEOUS AUTOI~43NE MRL-mp-lpr/lpr mice" D.G. Godfrey, J. Watson, W.H. Stimson, 3&G. Belch , R.D. Sturrock . Dept. of Biochemistry, University of Strathclyde, The Todd Centre, Glasgow. Dept. of Medicine, The Royal Infirmary, Glasgow, Scotland. The MRL/lpr mouse model of autoimmunity develops a form of systemic lupus erythematosus (SLE) similar to that of the (NZB x NZW)F mouse, hence it was of interest to determine whether dietary manipulation after the clinical onset of the disease could in any way ameliorate the severity of the symptoms and serological parameters observed. In this preliminary study, various fatty acid-containing oil eg. olive, sunflower, evening primrose (EPO), fish and fish/evening primrose oil mixture were added (5% w/w) to "fat-free" diet. The animals (aged 4 months st the initiation of the experiment) were monitored fortnightly for weight, proteinuria, survival and serologicslly for heterophile rheumatoid factor and anti-double stranded DNA antibodies by an ELISA technique. Those preparations containing higher proportions of unsaturated fatty acids showed a beneficial effect in prolonging the lifespan of the mice compared with the olive oil fed control mice and those animals on normal diet. However, the group which showed the best improvement in levels of autoantibody concomitant with an increase in survival was that group receiving evening primrose oil-supplemented diet. Therefore dietary manipulation employing EPO may prove to be of relevance in consideration of appropriate therapy far human patients. EFFECTS OF S H I - Q U A N - D A - B U - T A N G ( J T X : T R A D I T I O N A L CELLS IN MICE
CHINESE MEDICINE)
7
ON IMMUNE COMPETENT
Y.Komatsu, M.Aburada, H . T s u c h i y a , N . T a k e m o t o , H . M a r u y a m a and E.Hosoya Tsumura Research Institute for Pharmacology, Tsumura Juntendo Co. Ltd., 3586 Yoshiwara Ami, Inashiki, Ibaraki, Japan 300-11 Effects of traditional chinese medicines on immune responses have been studied. We reporte here effects of JTX on immune competent cells in mice. BDF I female mice(7-8wk) were given JTX orally. F o l l o w i n g e x p e r i m e n t s were performed:l) a n t i - s h e e p RBC antibody formation in spleen cells(SPC),2) p h a g o c y t i c activity of bone marrow cells(BMC),SPC and p e r i t o n e a l resident cells(PRC) using Candida p a l a p s i l o s i s , 3 ) g r a n u l o - m o n o c y t e ( G M ) colony formation of BMC and 4)mitogenic activity o f JTX on SPC. JTX( 2.0g/kg/day, Do, for 7days) increased a number of a n t i b o d y forming cells in SPC more than 50%. This increase was dose-dependent. JTX also a u g u m e n t e d I) phagocytic a c t i v i t y of BMC, SPC and PRC, 2)responsiveness of BMC to GM-CSF(L-929 cell c o n d i t i o n e d medium) and 3) incorporation of 3H-thymidine in SPC. This thymidine up-take in SPC r e q u i r e d p l a s t i c dish adherent cells. The r ~ u ~ ' show l ~ s i hilities that JTX m a y influence macrophages and then the o t h e r immune competent cells m a y be affected by cytokines released from activated macrophages. ANTITUMOR A C T I V I T I E S AND T U M O R NECROSIS FACTOR (TNF) PRODUCIBILITY OF TRADITIONAL CHINESE MEDICINE AND CRUDE DRUGS K. Haranaka, R. Haranaka*, N. Okada*, H. Kosoto*, N. Satomi, A. Sakurai, M. Kobayashi* Department of Internal Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan, *Department of Biochemistry, Nihon University School of Medicine, Tokyo, Japan. The antitumor activities and TNF producibility of traditional Chinese herbal preparations and crude drugs were investigated. Drugs were given to DDY mice in the drinking water before and after transplantation of Ehrlich tumors, and the development of the intradermally transplanted Ehrlich tumors and survival rate were observed. A high survival rate and good inhibition of transplanted Ehrlich tumors were observed in the groups administered Bupleuri Radix, Angelica Radix, C i n n a m o m u m Cortex or Shi-quan-da-bu-tang. To examine the TNF producibility, these drugs were given to DDY mice orally as first stimulating agents prior to LPS injection. Significant differences in TNF producibility were observed among the drugs. Relatively high levels of TNF activity were noted in the group given Xiao-chai-hu-tang, Zhu-ling-tang, Wu-ling-san, B u - z h o n g - y i - g i - t a n g or Shi-quan-dabu-tang. No TNF p r o d u c i b i l i t y in the groups given Polyporus, Hoelen or Pinelliae Tuber. The TNF p r o d u c i b i l i t y broadly p a r a l l e l e d the degree of survival rate in the mice transplanted with E h r l i c h tumors. Based on our findings, it is considered that one of mechanism u n d e r l y i n g the antitumor activities of these drugs is the induction of a hostm e d i a t e d factor like TNF as a stimulant of RES.
9
"THERAPEUTIC EFFECTS OF AMINISTRATION OF FATTY-ACID SUPPLE~NTED DIET ON THE COURSE OF DISEASE IN 4 MONTH OLD SPONTANEOUS AUTOI~43NE MRL-mp-lpr/lpr mice" D.G. Godfrey, J. Watson, W.H. Stimson, 3&G. Belch , R.D. Sturrock . Dept. of Biochemistry, University of Strathclyde, The Todd Centre, Glasgow. Dept. of Medicine, The Royal Infirmary, Glasgow, Scotland. The MRL/lpr mouse model of autoimmunity develops a form of systemic lupus erythematosus (SLE) similar to that of the (NZB x NZW)F mouse, hence it was of interest to determine whether dietary manipulation after the clinical onset of the disease could in any way ameliorate the severity of the symptoms and serological parameters observed. In this preliminary study, various fatty acid-containing oil eg. olive, sunflower, evening primrose (EPO), fish and fish/evening primrose oil mixture were added (5% w/w) to "fat-free" diet. The animals (aged 4 months st the initiation of the experiment) were monitored fortnightly for weight, proteinuria, survival and serologicslly for heterophile rheumatoid factor and anti-double stranded DNA antibodies by an ELISA technique. Those preparations containing higher proportions of unsaturated fatty acids showed a beneficial effect in prolonging the lifespan of the mice compared with the olive oil fed control mice and those animals on normal diet. However, the group which showed the best improvement in levels of autoantibody concomitant with an increase in survival was that group receiving evening primrose oil-supplemented diet. Therefore dietary manipulation employing EPO may prove to be of relevance in consideration of appropriate therapy far human patients. EFFECTS OF S H I - Q U A N - D A - B U - T A N G ( J T X : T R A D I T I O N A L CELLS IN MICE
CHINESE MEDICINE)
7
ON IMMUNE COMPETENT
Y.Komatsu, M.Aburada, H . T s u c h i y a , N . T a k e m o t o , H . M a r u y a m a and E.Hosoya Tsumura Research Institute for Pharmacology, Tsumura Juntendo Co. Ltd., 3586 Yoshiwara Ami, Inashiki, Ibaraki, Japan 300-11 Effects of traditional chinese medicines on immune responses have been studied. We reporte here effects of JTX on immune competent cells in mice. BDF I female mice(7-8wk) were given JTX orally. F o l l o w i n g e x p e r i m e n t s were performed:l) a n t i - s h e e p RBC antibody formation in spleen cells(SPC),2) p h a g o c y t i c activity of bone marrow cells(BMC),SPC and p e r i t o n e a l resident cells(PRC) using Candida p a l a p s i l o s i s , 3 ) g r a n u l o - m o n o c y t e ( G M ) colony formation of BMC and 4)mitogenic activity o f JTX on SPC. JTX( 2.0g/kg/day, Do, for 7days) increased a number of a n t i b o d y forming cells in SPC more than 50%. This increase was dose-dependent. JTX also a u g u m e n t e d I) phagocytic a c t i v i t y of BMC, SPC and PRC, 2)responsiveness of BMC to GM-CSF(L-929 cell c o n d i t i o n e d medium) and 3) incorporation of 3H-thymidine in SPC. This thymidine up-take in SPC r e q u i r e d p l a s t i c dish adherent cells. The r ~ u ~ ' show l ~ s i hilities that JTX m a y influence macrophages and then the o t h e r immune competent cells m a y be affected by cytokines released from activated macrophages. ANTITUMOR A C T I V I T I E S AND T U M O R NECROSIS FACTOR (TNF) PRODUCIBILITY OF TRADITIONAL CHINESE MEDICINE AND CRUDE DRUGS K. Haranaka, R. Haranaka*, N. Okada*, H. Kosoto*, N. Satomi, A. Sakurai, M. Kobayashi* Department of Internal Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan, *Department of Biochemistry, Nihon University School of Medicine, Tokyo, Japan. The antitumor activities and TNF producibility of traditional Chinese herbal preparations and crude drugs were investigated. Drugs were given to DDY mice in the drinking water before and after transplantation of Ehrlich tumors, and the development of the intradermally transplanted Ehrlich tumors and survival rate were observed. A high survival rate and good inhibition of transplanted Ehrlich tumors were observed in the groups administered Bupleuri Radix, Angelica Radix, C i n n a m o m u m Cortex or Shi-quan-da-bu-tang. To examine the TNF producibility, these drugs were given to DDY mice orally as first stimulating agents prior to LPS injection. Significant differences in TNF producibility were observed among the drugs. Relatively high levels of TNF activity were noted in the group given Xiao-chai-hu-tang, Zhu-ling-tang, Wu-ling-san, B u - z h o n g - y i - g i - t a n g or Shi-quan-dabu-tang. No TNF p r o d u c i b i l i t y in the groups given Polyporus, Hoelen or Pinelliae Tuber. The TNF p r o d u c i b i l i t y broadly p a r a l l e l e d the degree of survival rate in the mice transplanted with E h r l i c h tumors. Based on our findings, it is considered that one of mechanism u n d e r l y i n g the antitumor activities of these drugs is the induction of a hostm e d i a t e d factor like TNF as a stimulant of RES.
9