[A study on anti-inflammatory and analgesic effects of alkaloids of Toddalia asiatica].

OBJECTIVE: To study the pharmacological activities and toxicity of the crude alkaloids of Toddalia asiatica and to provide pharmacological data for the further development of this herbal medicine. METHODS: We observed the anti-inflammatory effects of the crude alkaloids of Toddalia asiatica, using xylol and agra to induce the turgidness and sodium carboxymethyl cellulose (CMC-Na) to induce leucocyte strolling in the rats. The analgesic effects were observed by body-distortion methods. The effects of alkaloids of Toddalia asiatica on hepatic function were observed by testing the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum and calculating the liver index. The LD 50 and 95% creditability were calculated with developed Karber Method. RESULTS: The administration of alkaloids of Toddalia asiatica had the function of inhibiting the auricle swelling caused by xylol and joint swelling caused by agar and leucocyte migration caused by CMC-Na, decreasing the body-distortion of the rats. After two weeks administration, the contents of ALT and AST showed that there was no obvious difference between administered group and control group. The LD50 of the crude alkaloids of Toddalia asiatica was 1.622 g/kg and the 95% creditability was 1.29-2.03 g/kg. CONCLUSION: Toddalia asiatica has anti-inflammatory and analgesic effects, and there is no injury to the liver after long-term administration in rats.

Effect of Maotai liquor on the liver: an experimental study.

BACKGROUND: Epidemiology investigation showed that no worker drunk Maotai liquor for nearly 30 years died of hepatic diseases, and no obvious hepatic fibrosis and cirrhosis were found in 99 workers who had drunk Maotai liquor for a long period by epidemiology investigation and needle biopsy. The same finding was detected in rats that were drunk by Maotai liquor continued for 56 days. This study was to investigate the effects of Maotai liquor on the liver and its mechanism of preventing hepatic fibrosis. METHODS: After ingestion of Maotai for 56 consecutive days, male SD rats were killed for detecting the levels of metallothionein and malondialdehyde (MDA) in liver tissues. Rat hepatic stellate cells (HSCs) and human HSCs were cultured in vitro to observe the effect of Maotai on HSCs proliferation and collagen synthesis. After ingestion of Maotai for 14 consecutive weeks, the livers of male SD rats were harvested for pathohistological examination. RESULTS: The level of metallothionein in the liver of Maotai-induced rats increased by 22 folds, whereas the levels of hepatic lipid peroxide and MDA was decreased significantly (P<0.05) in Maotai-induced animals suffering from CCl4. Maotai demonstrated obvious inhibitory effect on proliferation of HSCs and the inhibition was concentration-dependent. Gene expression and protein secretion of collagens could also be inhibited by Maotai. In alcoholic group, typical liver cirrhosis was observed. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of the interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found. CONCLUSION: It might be an important mechanism of interfering the progress of hepatic fibrosis that Maotai increases the level of metallothionein in the liver and inhibits the activation of HSCs and the synthesis of collagen proteins.

[An experimental study on the effect of Maotai liquor on the liver].

OBJECTIVE: To explore the effect on liver and the mechanism of preventing hepatic fibrosis by drinking Kweichow Moutai liquor (Maotai). METHODS: (1) After ingested with Maotai for 56 days consecutively, the male SD rats were decollated for detecting metallothioneins and MDA content in liver tissues; (2) Culturing rat hepatic stellate cell (HSC) and human HSC in vitro, observing the effect of Maotai on HSC's proliferation and collagen synthesis; (3) After male SD rats were ingested with Maotai for 14 weeks consecutively, the livers were harvested for pathohistological examination. RESULTS: (1) Metallothioneins content in the liver of Maotai-induced rats increased by 22 folds, the production of hepatic lipid peroxide, MDA was significantly decreased (P < 0.05) in Maotai-induced animals suffering from CCL4; (2) Maotai demonstrate obvious inhibitory effect against proliferation of HSC, and the inhibition was concentration-dependent. gene expression and protein secretion of collagens could also be inhibited by Maotai; (3) In control alcoholic group, typical cirrhosis of liver was shaped. In Maotai group, however, though fatty degeneration of hepatocytes and mild fibrosis of interstitium were observed, no obvious hepatic fibrosis and cirrhosis were found. CONCLUSION: It might be an important mechanism of interfering hepatic fibrosis progressing that Maotai induces the increase of metallothioneins content in the liver, inhibits the activation HSC and the synthesis of collagen protein.

Effect of Maotai liquor in inducing metallothioneins and on hepatic stellate cells.

AIM: To explore the possible mechanism why drinking Maotai liquor dose not cause hepatic fibrosis. METHODS: After being fed with Maotai for 56 days consecutively, the male SD rats were decollated for detecting the biological indexes, and the livers were harvested to examine the liver indexes and the level of hepatic metallothioneins (MT). Hepatic stellate cells (HSC) proliferation and collagen generation were also observed. RESULTS: Hepatic MT contents were 216.0 ng.g(-1)+/-10.8 ng.g(-1) in the rats of Maotai group and 10.0 ng.g(-1)+/-2.8 ng.g(-1) in the normal control group, which was increased obviously in Maotain group (P<0.05). In the rats with grade CCL(2) poisoning induced by Maotai, hepatic MT content was 304.8 ng.g(-1)+/-12.1 ng.g(-1) whereas in the controls with grade CCL(4) poisoning, it was 126.4 ng.g(-1)+/-4.8 ng.g(-1) (P<0.05). MDA was 102.0 nmol.g(-1)+/-3.4 nmol.g(-1) in Maotai group and 150.8 nmol.g(-1)+/-6.7 nmol.g(-1) in the control group (P<0.05). When both of the groups were suffering from grade CCL(4) poisoning, hepatic MT contents was negatively correlated with MDA (r=-0.8023, n=20, P<0.01). The 570 nmA values of each tube with HSC regeneration at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai were 0.818, 0.742, 0.736, 0.72, 0.682, and 0.604, respectively. From the concentration of 10 g.L(-1), Maotai began to show obvious inhibitory effects against HSC, and the inhibition was concentration-dependent (P<0.05, P<0.01). Type I collagen contents in HSC were 61.4, 59.9, 50.1, 49.2, 48.7, 34.4 microg.g(-1) at concentrations of 0, 10, 50, 100, and 200 g.L(-1) of Maotai. At the concentration of 100-200 g.L(-1), Maotai had obvious inhibitory effect against the secretion of type I collagen (P<0.05). Gene expression analysis was conducted on cells with Maotai concentrations of 0, 50, 100g.L(-1) respectively and the ash values of beta-actin gene expression were 0.88, 0.74, and 0.59, respectively,suggesting that at the concentration of 100g.L(-1), Maotai could obviously inhibit gene expression of type I procollagen (P<0.05), but the effect was not obvious at the concentration of 50 g.L(-1) (P>0.05). At the concentration of 10 g.L(-1), HSC growth in vitro inhibition rates were 16.4+/-2.3 in Maotai group and -8.4+/-2.3 in the control group (P<0.05). CONCLUSION: Maotai liquor can increase metallothioneins in the liver and inhibit the activation of HSC and the synthesis of collagen in many aspects, which might be the mechanism that Maotai liquor interferes in the hepatic fibrosis.

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases.

AIM: To explore the relevance of Maotai liquor and liver diseases. METHODS: Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor. Experimental histopathological study was conducted as follows: sixty male Wistar rats were divided into 3 groups randomly and fed with Maotai liquor, ordinary white wine, and physiological saline respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches, then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to measure the liver indexes, GSH, and MDA. Histopathological examinations were also performed. Another eighty mice were randomly divided into 4 groups and fed with Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and physiological saline. The animals were sacrificed after 4 weeks and serum ALT was determined. Then the livers were harvested and liver indexes and MDA were measured. RESULTS: The incidence rate of hepatic symptoms, splenomegaly, liver function impairment, reversal of Albumin/Globulin and increased diameter of portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively. There was no significant difference between the Maotai group and the non-alcoholic control group P>0.05 . Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was no obvious hepatic fibrosis or cirrhosis. A comparison was made between the Maotai liquor group and the ordinary white wine group. It was found that hepatic MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had an obvious decrease in the Maotai liquor group (P<0.05); hepatic GSH were 0.12 mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/-0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai liquor group (P<0.05). After the 20 rats had been fed with ordinary white wine for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of hepatocytes, and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed; after 12 weeks, the fibrous tissue proliferation continued and early cirrhosis appeared. Compared with the ordinary white wine group, fatty infiltration was observed in the 8-week and 12-week groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor group (P<0.05). CONCLUSION: Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.