scholarly journals Protective Effect of Glechoma Hederacea Extract Against Gallstone Formation in Rodent Models

Author(s):  
Min Xiao ◽  
Mengbi Yang ◽  
Xiaoyu Ji ◽  
Dan Li ◽  
Yuning Xie ◽  
...  

Abstract Background: Our current study aimed to evaluate the effect of an Glechoma Hederacea extract (Hitrechol ®) in normal rats and gallstone diseased mice to explore its underlying mechanisms. Normal rats and C57BL/6 mice with/without cholesterol gallstone were used in this study. Methods: To monitor the effect of Hitrechol ®️ on bile secretion, bile flow rates at 15 min interval until 2 hours post-dosing in normal rats treated with vehicle and Hitrechol ®️ were compared using multiple t-test with a p<0.05 considered as statistically significant different. To further evaluate the effect of Hitrechol ®️ against the development of gallstone, mice were treated with vehicle or Hitrechol (QD-once daily or TID-three times daily) for 3 weeks followed by comparing the levels of bile composition among the treatment groups. In addition, the anti-oxidative biomarkers in liver and anti-inflammatory biomarker in serum were detected and compared among all the treatment groups to evaluate the hepato-protective effect of Hitrechol ®️. The obtained levels of biomarkers and bile composition were compared among different treatment groups using one-way ANOVA tests followed by Tukey’s mutiple comparisons with p<0.05 considered as statistically significant. Results: Despite no significant impact on the bile flow rate, Hitrechol TID treatment dramatically decreased size and amount of gallstone crystals and total cholesterol level (p<0.05), as well as total bile acid (p<0.05) and several types of bile acid (p<0.05) levels in gallstone diseased model mice. Hitrechol ®️ TID treatment could significantly decrease the frequencies of hepatocyte necrosis and lipid aggregation notably as well as increase the antioxidant enzymes level (p<0.05) in liver. Conclusions: Our findings for the first time demonstrated the beneficial effect of Hitrechol ®️ against gallstone via its litholytic, liver-protective and antioxidant activities.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Min Xiao ◽  
Mengbi Yang ◽  
Xiaoyu Ji ◽  
Dan Li ◽  
Yuning Xie ◽  
...  

Abstract Background Our current study aimed to evaluate the effect of an Glechoma hederacea extract (Hitrechol®) in normal rats and gallstone diseased mice to explore its underlying mechanisms. Normal rats and C57BL/6 mice with/without cholesterol gallstone were used in this study. Methods To monitor the effect of Hitrechol® on bile secretion, bile flow rates at 15 min interval until 2 h post-dosing in normal rats treated with vehicle and Hitrechol® were compared using multiple t-test with a p < 0.05 considered as statistically significant different. To further evaluate the effect of Hitrechol® against the development of gallstone in lithogenic diet treated mice, mice were treated with vehicle or Hitrechol® (QD-once daily or TID-three times daily) for 3 weeks followed by comparing the levels of bile composition among the treatment groups. In addition, the anti-oxidative biomarkers in liver and anti-inflammatory biomarkers in serum were detected and compared among all the treatment groups to evaluate the hepato-protective effect of Hitrechol®. The obtained levels of biomarkers and bile composition were compared among different treatment groups using one-way ANOVA tests followed by Tukey’s multiple comparisons with p < 0.05 considered as statistically significant. Results Despite no significant impact on the bile flow rate, Hitrechol® TID treatment dramatically decreased size and amount of gallstone crystals and total cholesterol level (p < 0.05), as well as total bile acid (p < 0.05) and several types of bile acid (p < 0.05) levels in gallstone disease model mice. Hitrechol® TID treatment could significantly decrease the frequencies of hepatocyte necrosis and lipid aggregation notably as well as increase the antioxidant enzyme level (p < 0.05) in the liver. Conclusions Our findings for the first time demonstrated the beneficial effect of Hitrechol® against gallstone via its litholytic, liver-protective and antioxidant activities.


2000 ◽  
Vol 278 (6) ◽  
pp. R1674-R1684 ◽  
Author(s):  
M. Grosell ◽  
M. J. O'Donnell ◽  
C. M. Wood

Ion and water transport across the teleost Oncorhynchus mykiss gallbladder were studied in vivo by comparing flow and composition of hepatic bile, collected by chronic catheter, to volume and composition of terminally collected gallbladder bile. Differences in composition were comparable with those of other vertebrates, whereas bile flow (75 μl ⋅ kg− 1 ⋅ h− 1) was below values reported for endothermic vertebrates. The gallbladder concentrates bile acids five- to sevenfold and exhibits higher net Cl− than Na+ transport in vivo, in contrast to the 1:1 transport ratio from gallbladders under saline/saline conditions. Transepithelial potential (TEP) in the presence of bile, at the apical surface, was −13 mV (bile side negative) but +1.5 mV in the presence of saline. Bile acid in the apical saline reversed the TEP, presumably by a Donnan effect. We propose that ion transport across the gallbladder in vivo involves backflux of Na+ from blood to bile resulting in higher net Cl− than Na+ flux. This Na+backflux is driven by a bile side negative TEP and low Na+activity in bile due to the complexing effects of bile acids.


1989 ◽  
Vol 256 (1) ◽  
pp. G22-G30 ◽  
Author(s):  
N. Ballatori ◽  
A. T. Truong

Glutathione efflux into bile of the fluorocarbon-perfused isolated rat liver was altered with eight different agents (L-buthionine-[S,R]-sulfoximine, cefamandole, sodium arsenite, phenobarbital, furosemide, nitrofurantoin, aminopyrine, and benzylamine), and correlations were established between bile flow and biliary excretion of 1) glutathione, 2) endogenous bile acids, and 3) glutathione plus bile acids. Biliary efflux of endogenous bile acids was relatively low (0.5-5 nmol.min-1.g liver-1) and was minimally affected by these agents. Biliary glutathione excretion in control livers was between 4 and 9 nmol.min-1.g-1 and in treated livers ranged from 1 to 21 nmol.min-1.g-1. For each of the various interventions, an increase or decrease in glutathione excretion was always accompanied by a change in bile flow in the same direction; however, these changes were not always directly proportional when comparisons were made between treatment groups. Nevertheless, when bile flow (microliter.min-1.g-1; ordinate) was plotted against glutathione excretion into bile for the pooled data, a significant correlation was observed that was adequately described by a straight line: y = 0.071 chi + 0.72 (r2 = 0.62, P less than 0.001). A similar function described the relation between bile flow and the sum of bile acids and glutathione in bile: y = 0.077 chi + 0.55 (r2 = 0.62, P less than 0.001). In contrast, the taurocholate- or glycocholate-induced choleresis had only minimal effects on glutathione efflux. These findings support the hypothesis that glutathione is one of the osmotic driving forces in bile acid-independent bile formation.(ABSTRACT TRUNCATED AT 250 WORDS)


2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jing Lin ◽  
Ming Lu ◽  
Wei-qing Shao ◽  
Zong-you Chen ◽  
Wen-wei Zhu ◽  
...  

Abstract The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments.


1990 ◽  
Vol 269 (3) ◽  
pp. 781-788 ◽  
Author(s):  
M J Smit ◽  
A M Temmerman ◽  
R Havinga ◽  
F Kuipers ◽  
R J Vonk

The present study concerns short- and long-term effects of interruption of the enterohepatic circulation (EHC) on hepatic cholesterol metabolism and biliary secretion in rats. For this purpose, we employed a technique that allows reversible interruption of the EHC, during normal feeding conditions, and excludes effects of anaesthesia and surgical trauma. [3H]Cholesteryl oleate-labelled human low-density lipoprotein (LDL) was injected intravenously in rats with (1) chronically (8 days) interrupted EHC, (2) interrupted EHC at the time of LDL injection and (3) intact EHC. During the first 3 h after interruption of the EHC, bile flow decreased to 50% and biliary bile acid, phospholipid and cholesterol secretion to 5%, 11% and 19% of their initial values respectively. After 8 days of bile diversion, biliary cholesterol output and bile flow were at that same level, but bile acid output was increased 2-3-fold and phospholipid output was about 2 times lower. The total amount of cholesterol in the liver decreased after interruption of the EHC, which was mainly due to a decrease in the amount of cholesteryl ester. Plasma disappearance of LDL was not affected by interruption of the EHC. Biliary secretion of LDL-derived radioactivity occurred 2-4 times faster in chronically interrupted rats as compared with the excretion immediately after interruption of the EHC. Radioactivity was mainly in the form of bile acids under both conditions. This study demonstrates the very rapid changes that occur in cholesterol metabolism and biliary lipid composition after interruption of the EHC. These changes must be taken into account in studies concerning hepatic metabolism of lipoprotein cholesterol and subsequent secretion into bile.


1990 ◽  
Vol 63 (1-5) ◽  
pp. 120-126 ◽  
Author(s):  
M. Kirchgessner ◽  
M. Schliack ◽  
R. Löser ◽  
K. Seibel ◽  
W. Kulig ◽  
...  
Keyword(s):  

1986 ◽  
Vol 35 (15) ◽  
pp. 2625-2628 ◽  
Author(s):  
Cristina E. Carnovale ◽  
Raúl A. Marinelli ◽  
E.A.Rodrlguez Garay
Keyword(s):  

2018 ◽  
Vol 103 (2) ◽  
pp. 917-927 ◽  
Author(s):  
Jun An ◽  
Cui Yang ◽  
Zuming Li ◽  
Patricia W. Finn ◽  
David L. Perkins ◽  
...  

2017 ◽  
Vol 11 (1-2) ◽  
pp. 19 ◽  
Author(s):  
Gokhun Ozmerdiven ◽  
Burhan Coskun ◽  
Onur Kaygisiz ◽  
Berna Aytac Vuruskan ◽  
Burak Asiltas ◽  
...  

Introduction: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for preventionof the ischemia reperfusion injury after testis torsion in rats.Methods: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue.Spermatogenesis was evaluated with Johnsen’s score.Results: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group inipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen’s score of the I/Rgroup was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The meanJohnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05).Conclusions: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion.


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