ABSTRACT
<b>Objective::To investigate the effect of Aconiti Lateralis Praeparata Radix combined with Glycyrrhizae Radix et Rhizoma on mRNA expression of cytochrome P450 (CYP450) enzymes in rat' s heart. <b>Method::Male Sprague Dawley rats were randomly divided into the control group, the inducer group (0.08 g·kg<sup>-1</sup>·d<sup>-1</sup>), the aconite group (0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>), the licorice group (0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>) and the compatibility group (aconite and licorice group 0.5 g·kg<sup>-1</sup>·d<sup>-1</sup>), with 6 rats in each group. In each group, the serum concentrations of aspartate transaminase (AST), creatine kinase (CK) andlactate dehydrogenase (LDH) were respectively measured. Hematoxylin-eosin(HE) staining was used to detect the pathologic changes in the heart tissue of the rats. The expression of several CYP genes were measured. <b>Result::After combination, the contents of AST, CK and LDH were lower than those of the aconite group. At the same time, the pathological results showed cardiac injury in rats in the aconite group, and licorice could alleviate the cardiac injury caused by aconite. At the level of gene transcription, the glycyrrhizae group could up-regulate the expressions of CYP2C11 and CYP2J3 to different degrees (<italic>P</italic><0.05), and the combination of licorice and aconite could up-regulate the expression of CYP2B1, CYP2C11 and CYP2J3 family (<italic>P</italic><0.05). It suggested that the combination could promote the formation of EETs in arachidonic acid(AA) metabolism, and the aconite could up-regulate the expressions of CYP4A1, CYP4A3, CYP4F5 and CYP4F6 in CYP4 family (<italic>P</italic><0.05), promote the formation of 20-hydroxyeicosatetraenoic acid(20-HETE). The combination of aconite and licorice can weaken the ability of aconite, down-regulate the expression of CYP4A3, CYP4F1, CYP4F5 and CYP4F6 family mRNA (<italic>P</italic><0.05), inhibit the formation of 20-HETE and reduce the cardiotoxicity caused by aconite. <b>Conclusion::The combination of licorice and aconite can regulate the expression of CYP450 enzyme in the heart, increase the production of EETs and the content of 20-HETE, and finally play a role in reducing toxicity.
ABSTRACT
After reviewing literature, this paper will briefly introduce the research progress on toxicity-reducing and efficacy-enhancing through compatibility of Radix Aconiti Lateralis Praeparata in recent years. It includes five parts:modern basic study of Radix Aconiti Lateralis Praeparata; research on toxicity-reducing and efficacy-enhancing of complete or separate prescription of Sini Tang; research of the herb-pair in compatible prescription; studying the efficacy of herbal prescription of Radix Aconiti Lateralis Praeparata by utilizing complex biological networks; further research of Radix Aconiti Lateralis Praeparata and its prospect.
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This article was aimed to study the acute toxicities on intragastric administration of differentRadix Aconiti Lateralis Praeparataprocessed products to Beagle dogs. A total of 16 healthy and qualified Beagle dogs were randomly divided into the blank group,Pao-Fu-Pian(PFP) group,Pao-Tian-Xiong(PTX) group andHei-Shun-Pian(HSP) group according to the body weight. The intragastric administration of 4 g crude herb per kg was given. Before medication, 1 h, 24 h, and 3, 7, 14 days after medication, the body weight, food consumption, rectal temperature, electrocardiogram, blood routine and blood biochemistry were measured. The results showed that after medication, all dogs in three experimental groups were depressed. And there were significant differences in the electrolytes of blood. Among them, the HSP group was the most obvious one. The red blood cells, blood sugar and triglycerides of dogs in the PFP group had significant difference. The lymphocytes and blood sugar had significant difference of dogs in the PTX group. However, after the medication of HSP, the lymphocytes of the dogs were decreased significantly. It was concluded that the toxicity of three processed products followed the order of HSP > PFP > PTX.
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OBJECTIVE To study the mitochondrial toxicity effect of Radix Aconiti Lateralis Praepa?rata(Fuzi)on H9c2 cardiomyocytes. METHODS H9c2 cells were exposed to Fuzi decoction 6.25, 12.5,25,50 and 100 g·L-1 for 24 h. Fluorescence staining and CCK-8 assay were used to detect cell viability. H9c2 cells were exposed to Fuzi decoction 6.25,12.5 and 25 g · L-1 for 24 h,while the effect on mitochondrial membrane potential and reactive oxygen species(ROS)was detected by flow cytometry. The fluorescence molecular probe and laser scanning confocal microscope were used to observe the effect on Ca2+ in cells,Ca2+ and superoxide in mitochondria. The effect on ATP concentration in cells was detected via firefly luciferin and the expression of Pgc-1α,Bcl-2 and Bax mRNA evaluated by real-time PCR,while the expression of Pgc-1α protein was measured by Western blotting. RESULTS H9c2 cell viability was significantly inhibited by Fuzi decoction 12.5-100 g · L-1(P<0.05,P<0.01). The IC50 value was 47.4669 g · L-1,while the 95%confidence limit was 32.5997-69.1145 g · L-1. After treatment with Fuzi decoction 25 g · L-1 ,the fluorescence intensity of ROS in the normal control group increased from 204±67 to 454±78(P<0.05),that of mitochondrial superoxide increased from 5.4±1.8 to 26.8±8.5 (P<0.01),mitochondrial membrane potential decreased from 1.7±0.5 to 0.8±0.4(P<0.05),the fluores?cence intensity of intracellular Ca2+increased from 7.8±0.8 to 22.1±0.5(P<0.05)while that of mitochon?drial Ca2+decreased from 38.0±4.3 to 9.2±1.6(P<0.01),and intracellular ATP concentration decreased from (10.6 ± 0.4)μmol · g-1 to (5.3 ± 1.1)μmol · g-1 protein (P<0.05). qPCR and Western blotting test results showed that compared with the normal control group ,Pgc-1αand Bcl-2 mRNA relative expression level in Fuzi decoction 25 g·L-1 group was decreased from 1.00±0.10 and 1.00±0.10 to 0.09±0.06(P<0.01)and 0.43±0.06(P<0.01),respectively, while the relative expression of Bax mRNA was increased from 1.00 ± 0.03 to 1.17 ± 0.06 (P<0.05),and the expression of Pgc-1α protein was decreased from 0.906±0.034 to 0.541±0.003(P<0.01). CONCLUSION Fuzi has some mitochondrial toxicity to cardiomy?opathy. This effect arises from the combined action of different mechanisms. Mitochondrial toxicity of myocytes may account for the cardiac toxicity of Fuzi.
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AIM: To compare the effects of Yuxingcao(Herba houttuyniae),Paojiang(Radix aconiti lateralis praeparata) and Fuzi(Rhizoma Zingiberis recens(blastfried)) on ventricular remodeling induced by high pressure in rats. METHODS: Ventricular remodeling model was induced by constriction of abdominal aorta in rats.After 1 week,the model rats were divided randomly into 5 groups,such as model control,captopril,Yuxingcao,Paojiang and Fuzi.In addition,a sham-operated group was designed.The rats were given per oral captopril,Yuxingcao,Paojiang and Fuzi respectively for consecutive 3 weeks.Rats in sham-operated group and model control group were treated with distilled water.The blood pressure was measured.The ratio of LVW/BW,HW/BW was calculated as an index indicating the grade of ventricular hypertrophy.The contents of AngⅡ,ET in heart tissue and blood level of aldosterone(ALD) were determined by radio-immunoassay.The myocardium collagen volume fraction(CVF),perivascular circumferential area(PVCA) and the content of type Ⅰ and Ⅲ collagen were determined by histological assay using the picric acid/sirius red stain.The expression of protein kinase C(PKC) was determined by immunohistochemical analysis. RESULTS: Yuxingcao could lower the blood pressure and the ratio of LVW/BW,HW/BW;reduce the level of AngⅡ,ET in myocardium and ALD in blood serum,decrease myocardium CVF,PVCA and the content of type Ⅰ,Ⅲ collagen,and inhibit the expression of PKC.Paojiang did not show obvious effects mentioned above,neither did Fuzi,except that it decreased the level of AngⅡ in myocardium. CONCLUSION: Yuxingcao,the herb with cool nature,can attenuate the ventricular remodeling,and inhibit the over-activity of neuroendocrine factor release.Paojiang and Fuzi,the herbs with hot nature,fail to show that.