BACKGROUND:One function of papaver nudicaule L is its analgesic effect. Previous studies showed that total alkaloid,extracted from papaver nudicaule,possesses observable analgesic effects. Nudicauline,separated from the total alkaloid of papaver nudicaule,is a new kind of alkaloid.OBJECTIVE:To study the analgesic effect of nudicauline and its mechanism of action.DESIGN:A randomized controlled study based on the experimental animals.SETTING:Institute of Traditional Chinese Medicine ,Chengde Medical Colege.MATERIALS:The experiment was conducted in the Institute of Traditional Chinese Medicine of Chengde Medical College (Key Laboratory for Research and Exploitation of Traditional Chinese Medicine) from August 2001 to December 2003.Totally 140 mice were included and randomly divided into 14 groups with 10 mice in each group in this experiment.METHODS: ① Study of the analgesic effect.The animals were randomly assigned to 5 groups:saline control group,and nudicauline 2.5,5.0 and 10.0 mg/kg groups as well as morphine group. ② relation with endor-phin.The animals were divided into 5 groups:saline control group,nudicauline +naloxone group,morphine group,and morphine +naloxone group. ③relation with nitrogen monoxide.The animals were divided into 4 groups:saline group,nudicauline group,nudicauline +L-arginine 400 mg/kg group,and n-nitro-L-arginine methyl ester (L-NAME) 37.5 mg/kg group.Totally 20 μL 10 g/L formalin was injected into the right hindlimbs of the mice. The pain observation item:walking freely was 0 point;being lame,could stand on the floor without moving was 1 point;could lift their feet was 2 point;could shake or lick their feet was 3 points.The observation fell into 2 phases:0 to 10 minutes after pain induction was set as the first phase,and 20 to 30minutes was set as the second phase.MAIN OUTCOME MEASURES:The pain response scores of the mice in each group under the effect of different drugs.RESULTS: ① Nudicauline reduced significantly the score of response to the pain induced by formalin in the second phase(P ＜ 0.05-0.01).The higher dosage of nudicauine had certain inhibitory effect on the pain reaction in the first phase (P ＜ 0.05).Morphine had significant inhibitory effect on the pain reaction in both phases(P ＜ 0.01). ② Naloxone could completely inhibit the analgesic effect of morphine,but had no influence on the analgesic effect of nudicauline. ③ The analgesic effect of nudicauline was partially blocked by L-arginine in the second phase and enhanced by L-NAME.CONCLUSION:Nudicauline has obvious analgesic effects,whereas opium antagonist naloxone can completely inhibit the analgesic effect of morphine,but cannot alter the effect of nudicauline,which indicates that the analgesic effect is not related to the endogenous opioid system. L-arginine can partially inhibit the analgesic effect of nudicauline while L-NAME can increase the analgesic effect of nudicauline,suggesting that the analgesic effect of nudicauline may be partially associated with the production and release of nitrogen monoxide.

BACKGROUND: The effective fraction of stem and leaf of Scutellaria baicalensis, total flavones from stem and leaf of Scutellaria baicalensis (SSTF) can improve blood flow of coronary artery and cerebral blood flow,prolong the time of cruor and prothrombin and decrease blood lipid.OBJECTIVE: To observe the effect of SSTF on blood pressure of normal rats and rat models of renal artery stenosis.DESIGN: A completely randomized and controlled experiment.SETTING: Institute of Traditional Chinese Medicine, Chengde Medical College (Key Laboratory of Research and Exploiture of Traditional Chinese Medicine in Hebei Province) MATERIALS: Totally 70 Wistar rats, aged 2 months old , of clean degree, with body mass of (250±50) g, male and female in half, with permission number of 01-3003 , were provided by the Experimental Animal Research Institute, Chinese Academy of Medical Sciences. SSTF was provided by the phytochemical laboratory of Institute of Traditional Chinese Medicine, Chengde Medical College; Niuhuangjiangya pian was produced by Shiyitang Pharmaceutical Factory, Hayao Company (batch number:9802304).METHODS: The experiment was conducted in Institute of Traditional Chinese Medicine, Chengde Medical College from January to October 1999. The rats were raised in the environment of (22±1) ℃, with relative humidity of 50%-55%, of daylight and darkness for 12 hours for each. ①In the experiment 1, we studied the effect of SSTF on the blood pressure of normal rats. Totally 30 Wistar rats were randomly divided into SSTF group of 100 mg/kg (n=10, 100 mg/kg SSTF), SSTF group of 50 mg/kg (n=10, 50 mg/kg SSTF), and normal saline control group (n=10, 0.5 mL /100 g normal saline). Before being administrated, rats were anaesthetized by intraperitoneal injection of pentobarbital sodium. Blood pressure was recorded by MecLab/4e four-channel physiologic instrument. Then intragastric administration of SSTF and normal saline were performed on the rats in SSTF groups and normal saline control group respectively. Thirty minutes later, the changes of blood pressure of rats in each group were observed successively. ②In the experiment 2, we studied the effect of SSTF on the blood pressure of model rats with hypertension induced by renal artery stenosis. The rest 40 Wistar rats were randomly divided into SSTF group of high dosage, SSTF group of low dosage, normal saline control group, Niuhuangjiangya pian group, with 10 rats in each group. Rats in each group were created into rat models with hypertension induced by renal artery stenosis according to methods from the literatures. Two weeks after operation, intragastric administration of 100 mg/kg SSTF, 50 mg/kg SSTF, 0.5 mL/100 g normal saline and 1 200 mg/kg Niuhuangjiangya pian were daily performed on the rats in four groups respectively for one month successively. Carotid blood pressure of rats in all groups was measured.MAIN OUTCOME MEASURES: ① The effect of SSTF on the blood pressure of normal rats. ②The effect of SSTF on the blood pressure of model rats with hypertension induced by arteria renalis stenosis.RESULTS: ① Effect of SSTF on the blood pressure of normal rats: Blood pressure of SSTF group of 50 mg/kg and SSTF group of 100 mg/kg presented a little decrease compared with before administration. There was no significant difference when compared with normal saline control group (P ＞ 0.05). ②Effeet of SSTF on the blood pressure of model rats with hypertension induced by arteria renalis stenosis: Blood pressure of rats with hypertension in normal saline control group was significantly increased after modeling; Blood pressure of rats with hypertension in SSTF group of 50 mg/kg , SSTF group of 100 mg/kg and Niuhuangjiangya pian group was significantly lower than that in the normal saline control group, especially significantly in SSTF group of 100 mg/kg [(126.3±14.5),(120.2±15.9),(127.8 ±23.4 ) ,(139.6±15.8) mm Hg; P ＜ 0.05-0.01].CONCLUSION: SSTF has the significant hypotensive effect on model rats with hypertension; it does not have obvious effect on normal rats.

BACKGROUND: Yishen jiangu granule is one of sheer traditional Chinese drugs, which has good effect of tonifying kidney, strengthening bone, reinforcing the spleen, nourishing qi and improving the body condition, mainly used to prevent the lassitude, rickets, osteomalacia and calcium-deficiency induced by kidney-deficiency.OBJECTIVE: To observe the preventive effect of yishen jiangu granule on the reproductive organs, physical strength as well as the ability of stress, and compare with the effect of longmu zhuanggu preparation which was characterized by invigorating spleen and replenishing qi, and tonifying kidney and replenishing essence.DESIGN: Completely randomized controlled design.SETTING: Institute of Traditional Chinese Medicine, Chengde Medical CollegeMATERIALS: A total of 180 Kunming mice, weighing 25-30 g, of half gender, of clean grade, were selected in this study. Longmu zhuanggu granule, which was composed of root of tangshen, tuckahoe, rhizome of lagehead atractylodes, huai yam, astragalus root, schisandra fruit, keel,oyster shell, tortoise plastron, dwarf lilyturf, Chinese date, licorice root,vitamin D, etc., was provided by Wuhan Jianmin Pharmaceutical Factory (batch number: 960618). Yishen jiangu granule, which was composed of 6 kinds of traditional Chinese medicine such as dark plum, Chinese wolfberry, oyster shell, etc., was manufactured by Institute of Traditional Chinese Medicine of Chengde Medical College (batch number: 950510).Hydrocortisone injection was produced by Bohai Pharmaceutical Factory of Tangshan city (batch number: 940303).METHODS: The experiment was completed in Institute of Traditional Chinese Medicine, Chengde Medical College from January to October 1997. ① A total of 180 mice were randomly divided into 6 groups with 30 in each group: normal group (5.0 mL/kg saline, muscle injection); model group (25 mg/kg hydrocortisone for the mice model with kidney-yang deficiency, muscle injection); longmu zhuanggu granule group (5.0 g/kg longmu zhuanggu granule, and 25 mg/kg hydrocortisone); three groups of yishen jiangu granule at different dosages (perfused respectively with yishenjiangu granule at the dosages of 1.25 g/kg, 2.5 g/kg and 5.0 g/kg;meanwhile, 25 mg/kg hydrocortisone, muscle injection). The mice were administered successively for 14 days. ② In 12 hours after giving the last medicine, each group was divided into 3 parts to go on with the following 3 sub-experiments: Firstly, the spermary and uterus of mice were taken out to determine their weight, then calculate the indexes (mass of uterus/body mass of mice); secondly, the mice were put into the water [water depth:30 cm, water temperature: (20±0.5) ℃], burden of tail of mice was weighed 10% of the body mass, then timed immediately, when the mice could not immerge from the water after their heads sank into the water for 10 seconds.It showed that they were exhausted (the time was regarded as the swimming time of mice); thirdly, 10 g sodalime was added into each bottle with wide neck whose volume was 150 mL, then one mouse was put into each of them,covered them and timed immediately. The breath of the mice was observed until they stopped breathing, then timing was over. This was the bearing time of mice on anoxia under normal pressure. ③ Difference of statistical significance between groups was determined by t-test.MAIN OUTCOME MEASURES: The mass indexes of reproductive organs, swimming time and the bearing time on anoxia under normal pressure of the mice in all groups.RESULTS: A total of 180 mice were all involved in result analysis. ① The mass indexes of spermary in mice in normal group, longmu zhuanggu granule group and yishen jiangu groups at high and middle dosages were significantly higher than those in model group (P ＜ 0.05-0.01); the mass indexes of uterus in mice in normal group, longmu zhuanggu granule group and yishenjiangu groups at high dosage were significantly higher than those in model group (P ＜ 0.01). ② The swimming time of the mice in model group was significantly shorter than that in the other 5 groups (P ＜ 0.01). ③The bearing time on anoxia under normal pressure of the mice in model group were significantly shorter than that in the other 5 groups (P ＜ 0.01).CONCLUSION: Yishen jiangu granule has the remarkable effect on kidney-tonifying. It can remarkably relieve the reproductive organ atrophy of the mice with kidney-yang deficiency, has remarkable effect on antifatigue, and also can increase the ability of stress.

Objective To investigate the effects of Additive Foshousan(AFSS) on the serum levels of estradiol and progesterone in rats with primary dysmenorrhea. Methods SD rats were divided into six groups, each 10. Group 1 was normal control , groups 2,3 and 4 were treated with low, middle and high dose of AFSS(0.75, 1.5 and 3.0 g/kg) respectively, group 5 as positive controls was treated with Yuanhuzhitong tablets (1 mg/kg)and group 6 served as model control. Except the normal control group, all rats were injected diethylstilbestrol and oxytocin to establish primary dysmenorrhea model. The levels of estradiol(E2)and progesterone(P) in rats serum was determined by ELISA method and the ratio of E2/P was calculated. Results In middle and high dose of AFSS groups, the level of E2(48.27±6.42)pg/L,(47.51±7.03)pg/L respectively were lower than that in model group(54.47±9.12)pg/L and the difference was statistically significant(P<0.05). In low dose of AFSS group, the level of E2 was(50.83±6.26)pg/L and the difference was no statistically significant compared with model group. In all doses of AFSS groups,The content of P(687.41±21.14)ng/L, (720.47±41.03)ng/L, (719.78±32.01)ng/L respectively were higher than that in the model control group (667.32±46.51)ng/L and the difference was statistically significant(P<0.05 or<0.01). In middle and high dose of AFSS groups, the content of P were higher than that of Yuanhu-Zhitong tablets group(699.31±36.31)and the difference was statistically significant(P<0.05). Conclusion To reduce the content of E2, increase of P the content and decrease ratio of E2/P is one of the mechanism for AFSS to treat primary dysmenorrhea.

Objective To study the analgesic sites and mechanism of total alkaloids in Papaver nudicaule (TAPN). Methods The sites of analgesic action of TAPN were observed by adopting Formalin test and two different routes of intracerebroventricular (icv), intrathecal (ith) in mice and rats and comparing ED 50 of TAPN in writhing reaction in mice induced by acetic acid by ip and iv administration. Results TAPN significantly lowered pain score of the early and late phase of Formalin response and was more sensitive in the late phase. Inhibition of TAPN at the same dose by ip administration in writhing reaction in mice induced by acetic acid was stronger than that by iv. The ED 50 value of TAPN at any time by ip administration was lower than that by iv administration. By means of central microinjection, TAPN by icv administration induced remarkable analgesic effect in mice, but TAPN by ith administration had no significant analgesic effect. Conclusion The sites of analgesic action of TAPN are mainly at periphery. TAPN has also central analgesic effect, and the site may be at the level above the spinal cord.

Objective To study the relationship between analgesic effect of total alkaloids in Papaver nudicaule(TAPN) and prostaglandins(PGs) with opium receptors.Methods The analgesic effect of TAPN was studied by hot-plate, writhing,electric-evoked methods of mice.The analgesic mechanisms of TAPN and PGs with opium receptors were studied by the writhing numbers induced by different substances(Ach,AA,MgSO_4),the PGE_2 level in celiac fluid in mice after treated by AA writhing test and the antagonistic experiment of Naloxone.Results The inhibitory effect of TAPN on the writhing induced by Ach and AA in mice was stronger than that induced by MgSO_4.TAPN could also lower the PGE_2 level in celiac fluid.In the antagonistic experiment of Naloxone,no antagonism to the analgesic effect of TAPN had been found by ip or icv Naloxone.Conclusion It may be the mainly peripheral analgesic mechanism that TAPN could lower the PGE_2 level in celiac fluid.Its central analgesic mechanisms are not related to opium receptors.

BACKGROUND: Qinggong changchun dan (QGCCD) capsule has efficacy in profiting kidney-yang and bettering muscle or bone, it could treat debility, deficiency of energy, forgettery and tiredness and the ache of waist or knee in clinic.OBJECTIVE: To study the effect of QGCCD capsule on stress capability of mice with kidney-yang deficiency.DESIGN: Completely randomized controlled trial.SETTING: Institute of Traditional Chinese Medicine, Chengde Medical College (Key Laboratory of Research and Exploiture of Traditional Chinese Medicine in Hebei Province).MATERIALS: Totally 60 stirp Kunming mice, weighting 19-21 g, of either gender, of grade Ⅱ, were selected in this study.METHODS: The experiment was conducted in the Department of Pharmacology and Toxicology, Institute of Traditional Chinese Medicine of Chengde Medical College from February 2002 to December 2002. Totally 160 Kunming mice of either gender were randomly divided into three groups:Swimming endurance group (n=60), tolerance of hypoxia at normal pressure group (n=50) and single macrophage function group (n=50); and mice in each group were divided into 5 subgroups, including 0.25, 0.5,1.0 g/kg QGCCD groups, model control group and normal control group.Mice were fasted for 12 hours and injected with 25 mg/kg hydrocortisone for 7 successive days to establish yang-deficiency model. Various dosages of QGCCD were given with the same volume of 20 mL/kg for 7 successive days. Mice in model control group were treated with the same volume of saline. Forty minutes later, testes of swimming tolerance, tolerance time of anoxia and engulfment capability of macrophage were performed on mice [To take 20 μL blood in the eyepit vein plexus after the mice were injected 2 minutes and 10 minutes later respectively, and to count the charcoal particle expurgation index (K) of macrophage] to observe effect of various dosages of QGCCD on swimming tolerance, tolerance time of anoxia and engulfment capability of macrophage.RESULTS: Data of totally 160 mice was entered the final analysis without normal control group were longer than those of mice in model control group [(10.94±3.79), (13.68±5.62), (14.58±5.49), (16.12±2.35), (6.45±4.87) minutes;ia of mice in 0.25, 0.5, 1.0 g/kg QGCCD groups and normal control group were longer than those of mice in model control group [(19.45 ±4.63),(21.18±4.25), (22.58±5.21), (23.12±4.78), (12.35±4.89) minutes; t=1.566,macrophage and K index of mice in 0.25, 0.5, 1.0 g/kg QGCCD groups and normal control group were higher than those of mice in model control group (0.023 6±0.010 6, 0.029 1±0.0092, 0.030 8±0.008 6, 0.031 8±0.010 1, 0.012 5±0.008 1; t=2.63, 4.282, 4.898, 4.714, P ＜ 0.05-0.01).CONCLUSION: QGCCD can prolong the swimming time of mice obviously, prolong tolerance time of anoxia according to dosage dependence,increase engulfment capability of macrophags, and strengthen stress capability of mice with kidney-yang deficiency.

BACKGROUND:The Scutellaria baicalensis is a traditional Chinese herb frequently used. Only its root is used, and its stem and leaf are abandoned in traditional custom. Inorder to make full use of medicinal material resource, the chemical component and pharmacological effects of the stem and leaf have been studied. OBJECTIVE: To observe the preventive effect of total flavones from stem and leaf of scutellaria baicalensis on experimental hyperlipidemia in rats. DESIGN: Randomized controlled trial. SETTING: Institute of Traditional Chinese Medicine, Chengde Medical College MATERIALS: The experiment was conducted in the Institute of Traditional Chinese Medicine, Chengde Medical College from March 1999 to January 2000. Totally 60 male Wistar rats with beginning body mass(200±10)g were provided by Experimental Animal Research Institute, Chinese Academy of Medical Science (Qualification No.01-3008). INTERVENTIONS: Sixty rats were randomly divided into 6 groups:normal control group, high-lipid model group, the groups of 12.5, 25 and 50 mg/kg of total flavonoids (TF group) and clofibrate group (25 mg/kg),with 10 rats in each group. The rats in the normal control group were fed with basic feed. The rats in the high-lipid model group were fed with highlipid feed.Rats in the TF group and clofibrate group were fed synchronously with high-lipid feed and total flavonoids or clofibrate for consecutive 30 days. The change of blood lipid was observed. MAIN OUTCOME MEASURES: The levels of total cholesterol (TC),triglyceride (TG), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) in the serum of all the rats were measured with CL-7200 type automatic biochemistry analytical instrument at the end of the experiment, and the atherosclerosis indexes (AI) were calculated (AI=TC-HDL-C/HDL-C).RESULTS: Totally 60 rats entered the result analysis. ① Level of TC in the serum of rats: The level in the high-lipid model group was significantly higher than that in the normal control group[(5.01 ±1.05,2.33±0.35)mmol/L, (P ＜ 0.01 )]; The level in the groups of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of TF was (4.15±1.12, 3.03±0.31,2.98±0.56)mmol/L, there was no significant difference between group of 12.5 mg/kg of TF and model group (t=1.74, P ＞ 0.05), but there was significant difference between groups of 25 mg/kg and 50 mg/kg of TF and model group (t=5.66-5.23, P ＜ 0.01). ②Level of TG in the serum of rats: The level in the groups of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of TF was (1.22±0.56)mmol/L,(1.56±0.41)mmol/L,(1.24 ±0.45)mmol/L respectively, compared with model group(2.14±0.74) mmol/L, there was significant difference (t =2.19-3.45, P ＜ 0.05-0.01). ③ LDL-C level of the serum in the rats: The level in the groups of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of TF was (2.67 ±0.45) mmol/L, (1.41 ±0.23)mmol/L, (1.29±0.23) mmol/Lrespcrtively,compared with model group[(3.94±0.42)mmol/L, there was significant difference (t=5.77-12.71, P ＜ 0.05-0.01). ④ HDL-C level of the serum in the rats: the level in the groups of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of TF was (0.72±0.23)mmol/L,( 0.91±0.32)mmoL/L,(1.05±0.23)mmoL/L respectively, there was no significant difference between group of 12.5 mg/kg of TF and model group[(0.56±0.21)mmol/L, but there was significant difference between groups of 25 mg/kg and 50 mg/kg of TF and model group (t=2.92-4.38,0.05 ,P ＜ 0.05-0.01).⑤AI: the level in the groups of 12.5 mg/kg, 25 mg/kg and 50 mg/kg of TF was(2.96 ±1.35), (2.10±0.97), (1.55±0.41)respectively, compared with model group (4.23±0.65) , there was significant difference (t =3.54-9.49 ,P ＜ 0.01). CONCLUSION: TF has significantly inhibitory effect on the increase of TC, TG and LDL-C in the serum of the rats induced by high-lipid feed; it can also increase the level of HDL-C, indicating TF has obviously preventive effect on experimental hyperlipidemia in rats.

OBJECTIVE:To investigate the effect of total saponins of Man medicine Thladiantha dubia root(TSTR)on the ex-pressions of CD3+,CD4+and CD8+ in spleen tissue of rats with type Ⅱ collagen-induced arthritis (CIA),and explore its mecha-nism in the treatment of rheumatoid arthritis(RA). METHODS:8 rats were taken as normal control group(NC group),the others 72 rats were injected mixture of bovine type Ⅱ collagen and Freund's complete adjuvant in tail and back to induce CIA model. The 50 modeled rats were randomly divided into model group(MC group),tripterygium polyglycoside(TG)group(12 mg/kg,posi-tive control),TSTR low-dose,medium-dose,high-dose groups (20,40,80 mg/kg),10 in each group. Rats in medicine groups were intragastrically administrated for 35 d,once a day;rats in NC group and MC group were intragastrically administrated equal volume of distilled water. Ankle swelling degree of rats was determined,arthritis indexes were calculated,HE staining was used to observe the lesions in synovial tissue,and immunohistochemistry was used to detect the expressions of CD3+,CD4+,CD8+ in spleen tissue of rats. RESULTS:After 35 d of administration,ankle swelling degree,arthritis indexes,CD4+ expression in spleen tissue,and CD4+/CD8+ ratio in MC group were significantly higher than NC group (P<0.05 or P<0.01),expressions of CD3+, CD8+were significantly lower than NC group(P<0.05);and there was congestion and massive inflammatory cell infiltration in sy-novial tissue. The ankle swelling degree,arthritis indexes,expression of CD4+ in spleen tissue,and CD4+/CD8+ ratio in administra-tion groups were significantly lower than MC group(P<0.05);the expressions of CD3+,CD8+ in spleen tissue in administration groups were significantly higher than MC group (P<0.05);TG group,TSTR medium-dose and high-dose groups showed mild congestion and a small amount of inflammatory cell infiltration in synovial tissue of rats,and TSTR low-dose group showed no ob-vious congestion or inflammatory cell infiltration. CONCLUSIONS:Up-regulating the expressions of CD3+,CD8+ and down-regu-lating the expression of CD4+ may be one of the mechanisms of TSTR in the treatment of RA;and with best efficacy when the TSTR dose of 20 mg/kg.