Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2021 | Research

Protective effect of Glechoma hederacea extract against gallstone formation in rodent models

Authors: Min Xiao, Mengbi Yang, Xiaoyu Ji, Dan Li, Yuning Xie, Yuanfeng Lyu, Zhong Zuo

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

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.

Available only for authorised users

Lammert F, Gurusamy K, Ko CW, Miquel J, Mendez-Sanchez N, et al. Gallstones. Nat Rev Dis Primers. 2016;2(1):16024. https://doi.org/10.1038/nrdp.2016.24.CrossRefPubMed

Maurer KJ, Carey MC, Fox JG. Roles of infection, inflammation, and the immune system in cholesterol gallstone formation. Gastroenterology. 2009;136(2):425–40. https://doi.org/10.1053/j.gastro.2008.12.031.CrossRefPubMed

Portincasa P, Moschetta A, Palasciano G. Cholesterol gallstone disease. Lancet. 2006;368(9531):230–9. https://doi.org/10.1016/S0140-6736(06)69044-2.CrossRefPubMed

Portincasa P, Ciaula AD, Bonfrate L, Wang DQ. Therapy of gallstone disease: what it was, what it is, what it will be. World J Gastrointest Pharmacol Ther. 2012;3(2):7–20. https://doi.org/10.4292/wjgpt.v3.i2.7.CrossRefPubMedPubMedCentral

Chen G, Wu S. Role of Baicalin and Liver X Receptor Alpha in the Formation of Cholesterol Gallstones in Mice. Gastroenterol Res Pract. 2020;1343969. https://doi.org/10.1155/2020/1343969.

Chou ST, Lin TH, Peng HY, Chao WW. Phytochemical profile of hot water extract of Glechoma hederacea and its antioxidant, and anti-inflammatory activities. Life Sci. 2019;231:116519. https://doi.org/10.1016/j.lfs.2019.05.075.

Kitani K, Kanai S, Ivy G, Carrillo MC. Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy. Mech Ageing Dev. 1999;111(2–3):211–21. https://doi.org/10.1016/S0047-6374(99)00065-2.CrossRefPubMed

Podda M, Zuin M, Battezzati PM, Ghezzi C, Fazio DC, Dioguardi ML. Efficacy and safety of a combination of chenodeoxycholic acid and ursodeoxycholic acid for gallstone dissolution: a comparison with ursodeoxycholic acid alone. Gastroenterology. 1989;96(1):222–9. https://doi.org/10.1016/0016-5085(89)90784-1.CrossRefPubMed

Xiong X, Chen W, Cui J, Yi S, Zhang Z, Li K. Effects of ursolic acid on liver-protection and bile secretion. Zhong Yao Cai. 2003;26(8):578–81.PubMed

10.

Chen P, Li J, Fan X, Zeng H, Deng R, Li D, et al. Oleanolic acid attenuates obstructive cholestasis in bile duct-ligated mice, possibly via activation of NRF2-MRPs and FXR antagonism. Eur J Pharmacol. 2015;765:131–9. https://doi.org/10.1016/j.ejphar.2015.08.029.CrossRefPubMed

11.

Hu G, Yuan X, Zhang S, Wang R, Yang M, Wu C, et al. Research on choleretic effect of menthol, menthone, pluegone, isomenthone, and limonene in DanShu capsule. Int Immunopharmacol. 2015;24(2):191–7. https://doi.org/10.1016/j.intimp.2014.12.001.CrossRefPubMed

12.

An HJ, Jeong HJ, Um JY, Kim HM, Hong SH. Glechoma hederacea inhibits inflammatory mediator release in IFN-gamma and LPS-stimulated mouse peritoneal macrophages. J Ethnopharmacol. 2006;106(3):418–24. https://doi.org/10.1016/j.jep.2006.01.024.CrossRefPubMed

13.

Bergendorff O, Franzén C, Jeppsson AB, Sterner O, Waldeck B. Screening of some European medicinal plants for spasmolytic activity on isolated Guinea-pig trachea. Int J Pharmacol. 1995;33(4):356–8.

14.

Wang YY, Lin SY, Chen WY, Liao SL, Wu CC, Pan PH, et al. Glechoma hederacea extracts attenuate cholestatic liver injury in a bile duct-ligated rat model. J Ethnopharmacol. 2017;204:58–66. https://doi.org/10.1016/j.jep.2017.04.011.CrossRefPubMed

15.

Casey HJ. Efficacy study on gallstones remedy, vegetable extract II, final report of the study 1976; ref. no.11/7606, Pharmazeutische Fabrik Evers & Co GmbH.

16.

Milovanovic M, Zivkovic D, Vucelic-Radovic B. Antioxidant effects of Glechoma hederacea as a food additive. Nat Prod Commun. 2010;5(1):61–3.PubMed

17.

Kumarasamy Y, Cox PJ, Jaspars M, Nahar L, Sarker SD. Biological activity of Glechoma hederacea. Fitoterapia. 2002;73(7–8):721–3. https://doi.org/10.1016/S0367-326X(02)00237-X.CrossRefPubMed

18.

Ohigashi H, Takamura H, Koshimizu K, Tokuda H, Ito Y. Search for possible antitumor promoters by inhibition of 12-O-tetradecanoylphorbol-13-acetate-induced Epstein-Barr virus activation; Ursolic acid and oleanolic acid from an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L. Cancer Lett. 1986;30(2):151.CrossRef

19.

Fuchs-Algrim J, Lorenz H. Efficacy and tolerability of Hitrechol® in the dissolution of cholesterol gallstones and the treatment of accompanying complaints. 2003 Integrated final report of study IBP 312001/93.

20.

Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB, et al. Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. J Hepatol. 2014;59(2):661–70. https://doi.org/10.1002/hep.26709.CrossRef

21.

Cheng S, Zou M, Liu Q, Kuang J, Shen J, Pu J, et al. Activation of constitutive androstane receptor prevents cholesterol gallstone formation. Am J Pathol. 2017;187(4):808–18. https://doi.org/10.1016/j.ajpath.2016.12.013.CrossRefPubMed

22.

Carey MC. Critical tables for calculating the cholesterol saturation of native bile. J Lipid Res. 1978;19(8):945–55. https://doi.org/10.1016/S0022-2275(20)40677-7.CrossRefPubMed

23.

Huang J, Sai PR, Bathena IL, Csanaky YA. Simultaneous characterization of bile acids and their sulfate metabolites in mouse liver, plasma, bile, and urine using LC–MS/MS. J Pharm Biomed Anal. 2011;55(5):1111–9. https://doi.org/10.1016/j.jpba.2011.03.035.CrossRefPubMed

24.

Rassias G. Kestin M Nestel PJ linoleic acid lowers LDL cholesterol without a proportionate displacement of saturated fatty acid. Eur J Clin Nutr. 1991;45(6):315–20.PubMed

25.

Moschetta A, van Berge-Henegouwen GP, Portincasa P, van Erpecum KJ GP. Cholesterol crystallization in model biles: effects of bile salt and phospholipid species composition. J. Lipid Res. 2001;8:1273–81.CrossRef

26.

Zhao H, Zhou M, Duan L, Wang W, Zhang J, Wang D, et al. Efficient synthesis and anti-fungal activity of oleanolic acid oxime esters. Molecules. 2013;18(3):3615–29. https://doi.org/10.3390/molecules18033615.CrossRefPubMedPubMedCentral

27.

Ayeleso TB, Matumba MG, Mukwevho E. Oleanolic acid and its derivatives: biological activities and therapeutic potential in chronic diseases. Molecules. 2017;22(11):1915. https://doi.org/10.3390/molecules22111915.CrossRefPubMedCentral

28.

Percie du SN, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. PLoS Biol. 2020; 18(7): e3000410.

Title: Protective effect of Glechoma hederacea extract against gallstone formation in rodent models
Authors: Min Xiao
Mengbi Yang
Xiaoyu Ji
Dan Li
Yuning Xie
Yuanfeng Lyu
Zhong Zuo
Publication date: 01-12-2021
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-021-03368-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Protective effect of Glechoma hederacea extract against gallstone formation in rodent models

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Anti-influenza A virus activity of two Newtonia species and the isolated compound myricetin-3-o-rhamnoside

Efficacy of a curcumin extract (Curcugen™) on gastrointestinal symptoms and intestinal microbiota in adults with self-reported digestive complaints: a randomised, double-blind, placebo-controlled study

Effect of Shuangdan Mingmu capsule, a Chinese herbal formula, on oxidative stress-induced apoptosis of pericytes through PARP/GAPDH pathway

Antimicrobial activity of the volatile substances from essential oils

Oral magnesium supplementation for insomnia in older adults: a Systematic Review & Meta-Analysis

Community education and health promotion activities of naturopathic practitioners: results of an international cross-sectional survey