Abstract
Objective
To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro.
Methods
In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA).
Results
GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71–1.24), 0.34 (0.29–0.41) and 0.15 (0.11–0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil.
Conclusions
GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.
Similar content being viewed by others
References
Ukeermu K, Shatal K, Xue Q, Deng LJ, Xu XY. Effects of Zirike Granule on diarrhea and small intestine propulsion in mice. Chin Pharmacol (Clin) 2012;28:158–161.
Chen HZ, Lin GW, eds. Practical internal medicine. 13th edition. Beijing: People’s Medical Publishing House; 2009:1948–1949.
Thapar N, Sanderson IR. Diarrhoea in children: an interface between developing and developed countries. Lancet 2004;363:641–653.
Wang WP, ed. Pediatrics. 8th edition. Beijing: People’s Medical Publishing House; 2013:1286–1287.
Han YF, Wang YL, Li JX. Research progress on pathogenesis and intervention of diarrhea-predominant irritable bowel syndrome. Liaoning Univ Tradit Chin Med (Chin) 2018;20:114–117.
Kosek M, Bernm C, Guerrant RL. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ 2003;81:197–204.
Zhang SS, Wang CJ, Li YF, Wang N. Expert consensus on diagnosis and treatment of diarrhea in traditional Chinese medicine. J Tradit Chin Med (Chin) 2017;58:1256–1260.
Chinese Pharmacopoeia Commission. The Chinese Pharmacopoeia. Beijing: China Medical and Technology Press; 2020:88.
Deng TM, Peng C, Peng DY, Yu NJ, Chen WD, Wang L. Research progress on chemical constituents and pharmacological effects of Glycyrrhizae Radix et Rhizoma and discussion of Q-markers. China J Chin Mater Med (Chin) 2021;46:2660–2676.
Zhang Z, Yang L, Hou J. Molecular mechanisms underlying the anticancer activities of licorice flavonoids. J Ethnopharmacol 2021;267:113635.
Zhang Q, Ye M. Chemical analysis of the Chinese herbal medicine Gan-Cao (licorice). J Chromatogr A 2009;1216:1954–1969.
Li J. Clinical observation on 37 cases of functional abdominal pain treated by Shaoyao Gancao Decoction. Chin J Ethnomed Ethnopharm (Chin) 2020;29:62–64.
Zhou ZH, Ji JB, Wang ZC. Effects of Shaoyao Gancao Decoction on visceral hypersensitivity of irritable bowel syndrome rats. Chin J Integr Tradit West Med (Chin) 2017;37:575–578.
Wu B, Chang ZP, Deng GF, Shao YY. Intervention effect and mechanism of Shaoyao Gancao Decoction on post-inflammatory irritable bowel syndrome in rats. J Shanxi Med Univer (Chin) 2021;52:605–611.
Zheng JQ. Preliminary study on pharmaceutical mechanism of total flavonoids from Eupatorium Odoratum Linn. against E. Coli diarrhea in mice [dissertation]. Zhanjiang: Guangdong Ocean University; 2016.
Liu DN. Flavonoids in Fructus Aurantii Immaturus: ultrasound-assisted deep eutectic solvent extraction and effects on 5-FU induce diarrhea mice [dissertation]. Chongqing: Southwest University; 2020.
Wu LF, Li YT, Tang YZ. Research progress on chemical constituents and pharmacological activities of Shaoyao Gancao Decoction. Drug Eval Res (Chin) 2021;44:7.
Chen Y, Wu MX, Liu J, Ma XJ, Shi JL, Wang SN, et al. Acute and sub-acute oral toxicity studies of the aqueous extract from radix, radix with cortex and cortex of Psammosilene tunicoides in mice and rats. J Ethnopharmacol 2018;213:199–209.
Li Y, Li J, Liu X. Antidiarrheal activity of methanol extract of Sophora tonkinensis in mice and spasmolytic effect on smooth muscle contraction of isolated jejunum in rabbits. Pharm Biol 2019;57:477–484.
Gong XP, Sun YY, Chen W. Anti-diarrheal and anti-inflammatory activities of aqueous extract of the aerial part of Rubia cordifolia. BMC Complement Altern Med 2017;17:20.
Tadesse WT, Hailu AE, Gurmu AE. Experimental assessment of antidiarrheal and antisecretory activity of 80% methanolic leaf extract of Zehneriascabra in mice. BMC Complement Altern Med 2014;14:460.
Alani’s AD, Calzada F, Cervantes JA. Antibacterial properties of some plants used in Mexican traditional medicine for the treatment of gastrointestinal disorders. J Ethnopharmacol 2005;100:153–157.
Velázquez C, Calzada F, Torres J, González F, Ceballos G. Antisecretory activity of plants used to treat gastrointestinal disorders in Mexico. J Ethnopharmacol 2006;103:66–70.
Palombo EA. Phytochemicals from traditional medicinal plants used in the treatment of diarrhoea: modes of action and effects on intestinal function. Phytother Res 2006;20:717–724.
Piper BJ, Alinea AA, Wroblewski JR, Graham SM, Chung DY, McCutcheon LRM, et al. A quantitative and narrative evaluation of Goodman and Gilman’s pharmacological basis of therapeutics. Pharmacy (Basel) 2020;8:1–20.
Wambe H, Noubissi PA, Fokam Tagne MA, Fankem GO, Kamtchouing L, Ngakou MJ, et al. Anti-shigellosis activity of cola anomala water/ethanol pods extract on Shigella flexneri-induced diarrhea in rats. Biomed Res Int 2019;6706230.
Samuel ES, Dalia GM, Patricia CE, Francisco AC, Juan CSS. Spasmolytic effect of Mentha pulegium L. involves ionic flux regulation in rat ileum strips. J Smooth Muscle Res 2010;46:107–177.
Aleem A, Janbaz KH. Dual mechanisms of anti-muscarinic and Ca2+ antagonistic activities to validate the folkloric uses of Cyperus niveus Retz. as antispasmodic and antidiarrheal. J Ethnopharmacol 2018;213:138–148.
Guo H, Zhang J, Gao W. Gastrointestinal effect of methanol extract of Radix Aucklandiae and selected active substances on the transit activity of rat isolated intestinal strips. Pharm Biol 2014;52:1141–1149.
Guo H, Zhang J, Gao W. Anti-diarrhoeal activity of methanol extract of Santalum album L. in mice and gastrointestinal effect on the contraction of isolated jejunal in rats. J Ethnopharmacol 2014;154:704–710.
Kase S. Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active componentes. Phytother Res 1999;13:468–473.
Mahmood H, Chaudhry MA, Masood Z, Saeed MA, Adnan S. A mechanistic evaluation of the traditional uses of Nepeta ruderalis in gastrointestinal and airway disorders. J Pharm Biol 2017;55:1017–1021.
Polyanna SN, Douglas SC, Valdelânia GS, Izabela BCL, Daniel BN, Francisca BMS, et al. Antidiarrheal activity of a -terpineol in mice. Biomed Pharmacother 2019;110:631–640.
Wei YY, Sun LL, Fu ST. HEF-19-induced relaxation of colonic smooth muscles and the underlying mechanisms. World J Gastroenterol 2013;19:5314–5319.
Salud PG, Maria M, Daniel ZM, Laura G, Miguel ZS. Antispasmodic effects and action mechanism of essential oil of Chrysactinia mexicana A. gray on rabbit Ileum. Molecules 2016;21:783–795.
Zhang J, Shao ZW, Gao Y, Wang QY. Diastolic effect of quercetin on isolated intestinal smooth muscle of rabbits and its mechanism. Chin J App Physiol (Chin) 2013;29:162–165.
Xu J, Zhang L, Hou XH, Li TW, Gao QH, Zhang SY, et al. Effects of Lianpo Drink on gastric motility of functional dyspepsia rats. China J Tradit Chin Med Pharm (Chin) 2022;2:1018–1021.
Tezuka A, Ishihata A, Aita T, Katano Y. Aging-related alterations in the contractile responses to acetylcholine, muscarinic cholinoceptors and cholinesterase activities in jejunum and colon of the male Fischer 344 rats. Exp Gerontol 2004;39:91–100.
Gilani AH, Shah AJ, Yaeesh S. Presence of cholinergic and calcium antagonist constituents in Saussurea lappa explains its use in constipation and spasm. Phytother Res 2007;21:541–544.
Ali MZ, Mehmood MH, Saleem M, Gilani AH. The use of Euphorbia hirta L. (Euphorbiaceae) in diarrhea and constipation involves calcium antagonism and cholinergic mechanisms. BMC Complement Alternat Med 2020;20:14–30.
Author information
Authors and Affiliations
Contributions
Zhang JW contributed to conception of the study and perform the analysis with constructive discussions. Wen J and Wei Y contributed to the phytochemical study and performed the data analyses and wrote the manuscript. Deng KX and Chen HX performed the experiment and revised the manuscript. Lyu YX and Zhang H performed the experiment and analysis with constructive discussions.
Corresponding author
Additional information
Conflict of Interest
The authors declare no conflicts of interest in this work.
Supported by Innovation and Entrepreneurship Training Program for College Students in Sichuan Province (No. S201910634082, 202110634018), Nanchong Government-Municipal Colleges and Universities Cooperative Scientific Research Project (No. 19SXHZ0231), and Doctor Initiation Fund of North Sichuan Medical College (No. CBY19-QD07)
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Wen, J., Zhang, Jw., Lyu, Yx. et al. Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum. Chin. J. Integr. Med. 29, 325–332 (2023). https://doi.org/10.1007/s11655-022-3536-5
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11655-022-3536-5