Min-Kyung Choi

Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride-induced chronic hepatic fibrosis animal model.

ETHNOPHARMACOLOGICAL RELEVANCE Artemisia capillaris and Artemisia iwayomogi, both members of the Compositae family, have been indiscriminately used for various liver disorders as traditional hepatotherapeutic medicines in Korea for many years. AIM OF THE STUDY In this study, the anti-hepatofibrotic effects of Artemisia capillaris and Artemisia iwayomogi were comparatively analyzed using a carbon tetrachloride (CCl(4))-induced liver fibrosis rat model. MATERIALS AND METHODS Hepatic fibrosis was induced via a 10-week course of intraperitoneal CCl(4) injections (50% dissolved in olive oil, 2mL/kg, twice per week). Water extract of Artemisia capillaris (AC) or Artemisia iwayomogi (AI) was orally administered six times per week from the 5th to the 10th week. RESULTS AI (50mg/kg) significantly attenuated the CCl(4)-induced excessive release of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) in serum (p<0.05), and hydroxyproline and malondialdehyde (MDA) contents in liver tissue (p<0.05). Further, AI markedly ameliorated the depletion of total antioxidant capacity (TAC), glutathione (GSH), and superoxide dismutase (SOD) in liver tissue (p<0.01). Unexpectedly, AC did not exert any effects on the above parameters. Histopathological and immunohistochemical analyses revealed that AI drastically reduced inflammation, necrosis, fatty infiltration, collagen accumulation, and activation of hepatic satellite cells in liver tissue. These changes were not observed with AC treatment. Several critical genes of fibrosis-related cytokines including transforming growth factor beta (TGF-β), platelet-derived growth factor beta (PDGF-β), and alpha smooth muscle actin (α-SMA) were more prominently downregulated by AI compared to AC treatment. CONCLUSION Our results show that AI exerts greater hepatoprotective and anti-fibrotic effects as compared with AC via enhancing antioxidant capacity and downregulating fibrogentic cytokines.

Aqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic liver fibrosis in a rat model of bile duct ligation

Cholestatic liver fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins, is associated with bile acid-induced oxidative stress and lipid peroxidation. We evaluated the therapeutic or protective effect of an aqueous extract of Artemisia iwayomogi Kitamura (WAI) in a rat bile duct ligation (BDL)-induced hepatic fibrogenesis model. After BDL, rats were treated once daily with 25 or 50 mg/kg of WAI for 2weeks. The serum bilirubin, aspartate transaminase, alanine transaminase, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group. WAI administration significantly reduced these markers and restored BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAI treatment, and these changes were paralleled by significantly suppressed gene and protein expression of fibrogenic factors, including hepatic alphasmooth muscle actin, platelet-derived growth factor, and transforming growth factor β. Our data suggest that WAI may have antifibrotic properties via both improvement of antioxidant activities and inhibition of ECM protein production in the rat model of BDL.

Anti-atherosclerosis and hyperlipidemia effects of herbal mixture, Artemisia iwayomogi Kitamura and Curcuma longa Linne, in apolipoprotein E-deficient mice.

ETHNOPHARMACOLGICAL RELEVANCE Artemisiaiwayomogi Kitamura and Curcuma longa Linne. (ACE) has been popularly used to treat atherosclerosis as well as hyperlipidemia in the Asian countries. OBJECTIVE Antiatherosclerotic and anti-hyperlipidemic effects of ACE were evaluated at protein and gene expression level by using apoE(-/-) mice. METHOD Apoprotein E deficient (apoE(-/-)) mice were randomly divided into five groups and fed freely Western diet (WD) which contained ACE (50, 100 and 200mg/kg) or curcumin (50mg/kg). The C57/BLJ mice were used as normal and which were fed the WD. After 10 weeks of being fed the WD, the atherosclerosis related mediators and hyperlipidemia induced hepatic steatosis were analyzed in serum, aorta tissue or hepatic tissues. RESULTS Ten-week feeding of WD considerably increased the serum lipid profiles including total cholesterol (TC), low density lipoprotein, high density lipoprotein (HDL), triglyceride, TC/HDL ratio and glucose, and also elevated the total reactive oxygen species (ROS) and inflammatory cytokines (tumor necrosis factor-α, TNF-α; and interlukin-6, IL-6) in the serum levels. ACE treatment significantly resolved these alterations. The aortic lesion formation was significantly decreased as were lipid formations by ACE treatment. Moreover, ACE not only caused significant decreases of the lipid drops on the hepatic tissues, but also restored the antioxidant components. The gene expression levels including SREBP-1c, FAS, SCD-1, PPAR-α, CPT-1, IL-6, IL-1β and TNF-α in hepatic tissue were altered by Western diet fed in apoE(-/-) mice, while ACE treatment significantly normalized those alterations. CONCLUSIONS The ACE treatment is beneficial for atherosclerosis in arterial area and hyperlipidemia induced hepatic tissue steatosis.

An herbal fruit, Amomum xanthoides, ameliorates thioacetamide-induced hepatic fibrosis in rat via antioxidative system

AIM OF THE STUDY Amomum xanthoides is a well-known traditional herbal medicine mainly for diverse digestive system disorders in Asia for a long time. In the present study, we investigate the effects and action mechanism of methanol fraction of Amomum xanthoides (MFAX) on thioacetamide (TAA)-induced liver fibrosis in rat model. MATERIALS AND METHODS TAA (200mg/kg, ip on twice a week for 14 weeks) treated rats were orally administered with MFAX (25, 50 or 100mg/kg) once a day from the 7th week until 14th week. RESULT Significantly elevated serum bilirubin, liver tissue hydroxyproline and malondialdehyde (MDA) in liver fibrosis were ameliorated by MFAX treatment. Further, MFAX treatment attenuated the reactive oxygen species (ROS) levels and restored glutathione (GSH) content and glutathione-peroxidase (GPx) activity. Histopathological data showed that MFAX treatment inhibited collagen accumulation and activation of hepatocyte stellate cells (HSCs) in the liver tissue. Compared to the TAA group, activation of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), platelet-derived growth factor beta (PDGF-β) mRNAs and the level of pro-fibrotic cytokines PDGF-β and connective tissue growth factor (CTGF) in the liver tissue were attenuated in MFAX treated groups. CONCLUSION The above evidences collectively indicate that MFAX is a potential herb which can be used as an anti-hepatofibrotic remedy.

Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats

Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-β). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.

Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model.

In the present study, we investigate the effect of Korean ginseng root extract (KG) on cisplatin-induced pica in a rat model. Rats were treated with KG before (25, 50, and 100 mg/kg) or after (12.5, 25, and 50 mg/kg) a single intraperitoneal injection of cisplatin (7 and 6 mg/kg, respectively). We examined intake of kaolin and normal food as an indicator of the emetic stimulus every 24 h for 120 h. Changes in body weight, haematology and histopathology were additionally assessed. Pre-treatment with KG (25 and 50 mg/kg) significantly attenuated cisplatin-induced kaolin intake (24, 48, and 72 h) and markedly improved intake of normal food by rats at 48, 72, 96, and 120 h. Cisplatin-induced kaolin intake was markedly decreased upon post-treatment of rats with KG (12.5, 25, and 50 mg/kg) at 24 h. Notably, post-treatment with the lowest KG dose resulted in a significant anti-pica effect and improved food intake until 72 h. The magnitude of body weight reduction was significantly diminished in rats pre-treated/post-treated with 25, 50, and 12.5 mg/kg KG. The anti-pica effects of KG were further confirmed with haematological and histopathological findings. Our findings collectively indicate that KG improves the resistance of rats against emesis.

Hepatoprotective effect of Amomum xanthoides against dimethylnitrosamine-induced sub-chronic liver injury in a rat model

Abstract Context: Amomum xanthioides Wall. ex Baker (Zingiberaceae) is a tropical medicinal plant that is commonly utilized in the treatment of digestive system disorders in Asia for a long time. Objective: This study aimed to evaluate the hepatoprotective effect and related mechanisms of A. xanthoides. Materials and methods: Sub-chronic liver injury was induced by dimethylnitrosamine (DMN, 10 mg/kg, three times per week for 3 weeks, i.p.) in rats. Water extract of A. xanthoides (WAX, 50 and 100 mg/kg) was given once a day for 3 weeks. Results and conclusion: WAX (100 mg/kg) significantly attenuated the DMN-induced excessive release of alanine aminotransferase (123.6 IU/L), aspartate aminotransferase (227.9 IU/L), alkaline phosphatase (820.9 IU/L) and total bilirubin (0.50 g/dL) in serum (p < 0.01), and hydroxyproline (30.5 mg/g tissue) and malondialdehyde (MDA) (53.6 μM/g tissue) contents (p < 0.01) in liver tissue. Furthermore, WAX significantly ameliorated the depletion of total antioxidant capacity (2.54 μM/mg tissue), superoxide dismutase (0.30 U/mg tissue), glutathione (2.10 μM/mg tissue) and catalase (605.0 U/mg tissue) activities (p < 0.05 or p < 0.01) in liver tissue. Histopathological and immunohistochemical analyses indicated that WAX markedly reduced inflammation, necrosis, collagen accumulation and activation of hepatic satellite cells in the liver. Our findings demonstrated that A. xanthoides exerts favorable hepatoprotective effects via positive regulation of the antioxidative system.

Hepatoprotective Effect of Terminalia chebula against t-BHP-Induced Acute Liver Injury in C57/BL6 Mice.

We aimed to identify the hepatoprotective effects of Terminalia chebula water extract (TCW) and its corresponding pharmacological actions using C57/BL6 mice model of tert-butylhydroperoxide-(t-BHP-) induced acute liver injury. Mice were orally administered with TCW (0, 50, 100, or 200 mg/kg) or gallic acid (100 mg/kg) for 5 days before t-BHP (2.5 mM/kg) injection. Liver enzymes, histopathology, oxidative stress parameters, antioxidant components, and inflammatory cytokines were examined 18 h after t-BHP injection. t-BHP injection caused dramatic elevation of serum AST, ALT, and LDH level, while TCW pretreatment notably attenuated these elevations. Inflammatory cytokines including TNF-α, IL-1β, and IL-6 were notably increased in hepatic tissues, and then these were efficiently attenuated by TCW pretreatment. t-BHP injection notably increased malondialdehyde, total reactive oxygen species, and nitric oxide in the liver tissue, while it markedly dropped the antioxidant activities including total antioxidant capacity, total glutathione contents, glutathione peroxidase, superoxide dismutase, and catalase. TCW pretreatment remarkably ameliorated these alterations, and these effects were relevant to gene expressions. Histopathological examinations supported the above findings. Collectively, these findings well prove that TCW beneficially prevents acute and severe liver injury and clarify its corresponding mechanisms involved in the inhibition of oxidative stress and inflammatory cytokines.

Uwhangchungsimwon, a traditional herbal medicine, protects brain against oxidative injury via modulation of hypothalamus-pituitary-adrenal (HPA) response in a chronic restraint mice model.

ETHNOPHARMACOLOGICAL RELEVANCE Uwhangchungsimwon (UCW) is a representative traditional herbal medicine for central nervous system disorders in East Asia countries over thousand years. To evaluate the pharmacological effects of UCW against oxidative brain injury in a chronic restraint stress mice model. METHODS AND MATERIALS C57BL/6 male mice underwent daily oral administration of distilled water, UCW or ascorbic acid 1h before induction of restraint stress (5h of immobilization daily for 14 days). Nitric oxide (NO), total reactive oxygen species (ROS) levels, malondialdehyde, protein carbonyl contents, and activities of antioxidant enzymes, and concentrations of corticosterone, adrenaline, noradrenaline, and dopamine, were measured in brain tissues or sera. RESULTS Restraint stress notably increased NO and ROS levels, malondialdehyde and protein carbonyl contents in brain tissues, but decreased activities of catalase, glutathione reductase and glutathione peroxidase. These alterations were significantly ameliorated by UCW. UCW significantly attenuated the elevated serum concentrations of corticosterone, adrenaline and noradrenaline. UCW also significantly normalized the gene expressions in brain tissues altered by restraint stress; up-regulation of phenylethanolamine N-methyltransferase (PNMT) and N-methyl-d-aspartate type 1 receptor (NMDAR1), and down-regulation of gamma-Aminobutyric acid type A receptor (GABAAR), glutamate decarboxylase 1 (GAD 67), and glutamate decarboxylase 2 (GAD 65), respectively. Moreover, UCW considerably restored neurogenesis in the hippocampal regions which was disturbed by chronic restraint stress. CONCLUSIONS These results evidenced that UCW has pharmacological properties for brain protection and neurogenesis in status of stress-associated oxidative damage, and the underlying mechanisms involve the regulation of HPA axis in stress responses.

Myelophil attenuates brain oxidative damage by modulating the hypothalamus-pituitary-adrenal (HPA) axis in a chronic cold-stress mouse model

ETHNOPHARMACOLOGICAL RELEVANCE Myelophil is composed of Astragali Radix and Salviae Miltiorrhizae Radix, according to the long traditional pharmacological practices, and it has been used for patients with chronic fatigue-associated symptoms including concentration problem or memory loss. AIM OF THE STUDY This study aimed to evaluate the clinical relevance of Myelophil on brain oxidative damage using a chronic cold stress mice model. MATERIAL AND METHODS Balb/c mice were subjected to cold stress (4°C for 4h) six times per week for 2 weeks with or without oral administration of Myelophil (50, 100, or 200mg/kg), or ascorbic acid (50mg/kg). RESULTS Chronic cold stress induced histopathological hippocampal apoptosis with drastically increased serum levels of total reactive oxygen species and nitric oxide, as well as brain lipid peroxidation levels, protein carbonyl, and caspase-3/7 activity. These alterations were significantly ameliorated by Myelophil treatment. Myelophil administration significantly recovered the depleted glutathione and its enzymes, superoxide dismutase activity, and catalase protein and gene expression levels. Serum levels of corticosterone, dopamine, and adrenaline were notably altered by chronic cold stress but were significantly ameliorated by Myelophil treatment. Myelophil also normalized alterations in tumor necrosis factor-α, interleukin (IL)-1β, and IL-10 gene expression and protein levels. Chronic cold stress up-regulated gene expression levels of phenylethanolamine N-methyltransferase and monoamine oxidase-B, and glucocorticoid receptors in the hypothalamus and hippocampus, respectively, whereas Myelophil treatment completely normalized these levels. CONCLUSIONS These results suggest that Myelophil has potent pharmaceutical effects against chronic cold-stress-induced brain damage by relieving oxidative stress and inflammation and regulating stress hormones in mice.