Study on toxicity of 999 Ganmaoling grain and influence of diet on hepatic toxicity / 中国中药杂志

This paper was aimed to compare the acute toxicity of 999 Ganmaoling grain and its different ingredients, and investigate the influence of routine diet on the hepatic toxicity induced by Ganmaoling in mice, so as to provide experimental basis for the clinical safety evaluation. Mice were given a single dose of Ganmaoling grain or its different ingredients respectively by gavage, and then observed for 14 days. LD₅₀ values of Ganmaoling grain or its chemical ingredient and the maximal tolerated dose of its herb ingredient were determined. Mice were divided into starvation and diet group, a single dose of Ganmaoling grain was administered by gavage. LD₅₀ values were estimated after 14 day observation. Mice were divided into starvation and diet group. At the same time,control group was set up for each. A single dose of Ganmaoling grain was given. Serum biochemical indexes were detected, liver weight index was calculated and liver tissue morphological change was observed after 6 h. LD₅₀ values were 4.42, 0.64 g•kg⁻¹ for Ganmaoling grain group and chemical ingredient group, respectively. The maximal tolerated dose of the herb ingredient group was close to 24.24 g•kg⁻¹. The toxic symptom was basically similar in the Ganmaoling grain and the chemical ingredient group. The body weight and food intake were decreased to a certain extent in both groups. There were pathological changes of liver and heart tissue in some of the surviving animals. The animals in the Ganmaoling grain group exhibited a lighter toxicity and recovered faster than that in the chemical ingredient group. LD₅₀ values of Ganmaoling grain were 2.56, 6.93 g•kg⁻¹ for starvation and diet group respectively. TD₅₀ values were 1.29, 6.31 g•kg⁻¹ for starvation and diet group respectively. The toxicity of 999 Ganmaoling was less, which may be related to the reduction of toxicity after the combination of herb and chemical ingredients. Compared with starvation group, the values of LD₅₀ and TD₅₀ of diet group was significantly increased, and toxicity was decreased. From the point of view of safety, it is safer to use Ganmaoling in the absence of hunger or after meal. The above tests provide experimental basis for the clinical safety use of Ganmaoling.

Comparative study on hepatic toxicity of gardeniae fructus and Huanglian Jiedu decoction / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the effect of ingredients in Huanglian Jiedu decoction (HLJDT) combined with Gardeniae Fructus on the hepatic toxicity of Gardeniae Fructus and its mechanism.</p><p><b>METHOD</b>Rats were given Gardeniae Fructus and HLJDT decoction at the dose of 10 times of clinical dosage for 3 days. Their ALT AST, ALP, TBA were detected, and their liver weight index was calculated. SOD activity, MDA content, GSH-PX activity, TNF-alpha content in hepatic tissues were determined. The cell apoptosis in liver tissue was determined by TUNEL, and the expressions of apoptosis related proteins Bax, Bcl-2 were measured by immunohistochemical method.</p><p><b>RESULT</b>Compared with the normal control group, the Gardeniae Fructus group showed significant increase in the liver weight index, ALT, AST, TBA and ALP, notable decrease in SOD, SOD/MDA and GSH-PX, and remarkable rise in MDA, TNF-a concentration, accumulated optical density, apoptosis index, Bax and Bax/Bcl-2. Compare with that in the Gardeniae Fructus group, the liver index, ALT, AST, TBA, ALP reduced obviously; SOD, SOD/MDA and GSH-PX markedly increased; MDA and TNF-alpha significantly reduced; the accumulated optical density and apoptosis index significantly reduced; and Bax/Bcl-2 was much lower in HLJDT group.</p><p><b>CONCLUSION</b>The hepatic toxicity caused by Gardeniae Fructus may be related to inflammation, oxidative stress-induced hepatocyte necrosis and apoptosis. Other ingredients in HLJDT, apart from Gardeniae Fructus, can decrease the hepatic toxicity caused by Gardeniae Fructus by increasing the enzyme activity eliminating radicals and inhibiting hepatocyte injury caused by inflammatory reaction against Gardeniae Fructus.</p>

Study on early change features of microRNA in the peripheral blood of Sophorae tonkinensis radix et rhizoma induced liver injury rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study early change features of microRNA (miRNA) in the peripheral blood of Sophorae Tonkinensis Radix et Rhizoma induced liver injury rats, and to look for the miRNA biomarkers in the peripheral blood of early liver injury.</p><p><b>METHODS</b>Sixty Wistar rats were randomly divided into the control group and the Sophorae Tonkinensis Radix et Rhizoma (abbreviated as STRR) group, 30 in each group. Rats in the STRR group was administered with STRR decoction at 12 g/kg (2 mL/100 g), while equal volume of the distilled water was given to those in the control group. Rats were anesthetized on day 3, 7, 14, and 28, and 28 days after withdrawal. The serum samples were withdrawn. The alanine aminotransferase (ALT), aspartate transaminase (AST), total bile (TBIL), alkaline phosphatase (ALP), total protein (TP), and albumin (ALB) were detected. The globulin (GLO) level was calculated. HE staining was performed on the liver tissue to observe the pathomorphological changes. The whole blood was collected on day 7, 14, and 28 to perform the microarray test. The differentially expressed miRNAs were screened and verified by RT-PCR.</p><p><b>RESULTS</b>The ALT activity obviously increased on day 7 - 28 in the STRR group (P <0.05). The histopathological results showed the degeneration and swelling of the liver cells on day 28. In the microarray test, there were 11, 22, and 13 up regulated expressed miRNAs on day 7, 14, and 28, respectively. There were 1, 13, 2 down regulated expressed miRNAs on day 7, 14, and 28, respectively. By target gene prediction and pathway analysis of differentially expressed miRNA on day 7, 14, and 28, they involved in regulating and controlling signal transduction, cellular interaction, cytoskeleton. Differentially expressed miRNA might possibly participate in the process of liver injury. The RT-PCR result of the expression of miR-291a-5p with the peak time efficiency on day 7 showed that the expressions of miR-291a-5p in the peripheral blood and the liver tissue were basically identical.</p><p><b>CONCLUSION</b>miR-291a-5p could early indicate the liver injury, which could be taken as one of an early marker in STRR induced liver injury.</p>

Characteristics of changes in urinary NGAL, KIM-1 and IL-18 in Phytolaccae Radix-induced renal injury in rats and significance of combined detection / 中国中药杂志

<p><b>OBJECTIVE</b>To explore the characteristics of changes in neutrophil gelatinase-associated lipocalcin (NGAL), kidney injury molecule-1 (KIM-1) and interleukin-18 (IL-18) in Phytolaccae Radix-induced kidney injury in rats and the significance of the combined detection.</p><p><b>METHOD</b>Wistar rats were divided into three groups: high and low dose (crude drug 40, 20 g x kg(-1) x d(-1)) Phytolaccae Radix decoction groups and the control group, and orally administrated with distilled water or equal volume of Phytolaccae Radix decoction for 35 consecutive days. Their blood and urine samples were collected on day 7, 14, 21, 28, 35,42. The anatomical analysis was conducted for each group. The contents of serum total protein (TP), albumin (ALB), blood urea nitrogen (BUN), creatinine (CR) and urinary TP and ALB were detected-by means of biochemical analyzer. The concentrations of urinary NGAL, KIM-1 and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). The morphological changes of renal pathology were observed by light or electron microscopy. The curve areas of various serum or urine indexes and the combined detection were compared by receiver operating characteristic curve (ROC curve).</p><p><b>RESULT</b>Rats were given Phytolaccae Radix decoction at the doses of 40, 20 g crude drug/kg daily for 35 consecutive days to induce kidney injury characterized by the degeneration of renal tubular epithelial cell and protein cast. The injury was partially reversible during the recovery period. Compared with the control group, the content of serum BUN, CR and urinary TP in each dose group mostly showed a downward trend. On day 21, the content of urinary ALB obviously increased till the end of administration. The contents of urinary NGAL, KIM-1 and IL-18 began increasing on day 7. Since day 14, high and low dose groups showed significant difference (P<0.01). The high dose group even showed notable changes during the recovery period. According to ROC analysis, the curve areas of NGAL, KIM-1 and IL-18 were 0.846, 0.837 and 0.863 (P <0.01), respectively, much higher than that of BUN and CR. The area of the combined detection was up to 0.947.</p><p><b>CONCLUSION</b>Urinary NGAL, IL-18 and KIM-1 could forecast and indicate the occurrence and development of renal injury to some degree, and show higher sensitivity and site specificity. The combined detection could further improve the test efficiency.</p>

Mechanism studies on hepatotoxicity of rats induced by fructus toosendan / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects on SOD, MDA, gamma-GT, GSH-Px and inflammatory factor (TNF-alpha, NF-kappaB, ICAM-1) in rats that induced by fructus toosendan, and to search for the hepatotoxicity mechanism of rats that induced by fructus toosendan.</p><p><b>METHOD</b>The SD rats were given fructus toosendan 120 g x kg(-1) by orally for 45 days, then take the liver tissue of control and fructus toosendan group to prepare liver homogenate. The activities of SOD, the content of MDA, the ratio of SOD and MDA, the content of gamma-GT and glutathione peroxidase (GSH-Px) were detected according to the methods of kit. The tumor necosis factor-alpha (TNF-alpha) was detected by ABC-ELISA. The expression of NF-kappaB p65 and ICAM-1 were detected by immunohistochemistry.</p><p><b>RESULT</b>The rats were given fructus toosendan 120 g x kg(-1) by orally for 45days, the SOD and GSH-Px activities in liver tissue decreased, the content of MDA increased, the ratio of SOD and MDA decreased, the content of gamma-GT and TNF-alpha, the masculine expression of NF-kappaB p65 and ICAM-1 increased.</p><p><b>CONCLUSION</b>After the rats were given fructus toosendan, the liver can be damaged obviously, and the mechanism of hepatotoxicity perhaps related to free radical and inflammatory factor.</p>

Effect of components of dang-gui-bu-xue decoction on hematopenia / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the effects and the related mechanisms of the components of Dang-Gui-Bu-Xue decoction (DGBXD) on improving blood deficiency.</p><p><b>METHOD</b>The effects of promoting hematopoietic function were observed with the blood difficient model mice, by giving components of DGBXD. RBC, WBC, reticulocytes and bone marrow nucleated cells (BMNC) were determined. The components of DGBXD on proliferation of BMNC and on clony forming unit (CFU) were also determined.</p><p><b>RESULT</b>The components of DGBXD remarkably increased the quantity of RBC, WBC, and BMNC. Some of the components promoted the proliferation of BMNC and increased the quantity of CFU-Mix. Among them, polysaccharide of angelica was most potent.</p><p><b>CONCLUSION</b>The studies show that the extracts and some components of DGBXD can promote the hemopoietic function system of the model mice, and they exert the effects in a comprehensive way.</p>