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Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Anxiety | Research article

A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats

Authors: Lalit Sharma, Aditi Sharma, Ashutosh Kumar Dash, Gopal Singh Bisht, Girdhari Lal Gupta

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

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Abstract

Background

Alcohol abuse is a major problem worldwide and it affects people’s health and economy. There is a relapse in alcohol intake due to alcohol withdrawal. Alcohol withdrawal anxiety-like behavior is a symptom that appears 6–24 h after the last alcohol ingestion.

Methods

The present study was designed to explore the protective effect of a standardized polyherbal preparation POL-6 in ethanol withdrawal anxiety in Wistar rats. POL-6 was prepared by mixing the dried extracts of six plants Bacopa monnieri, Hypericum perforatum, Centella asiatica, Withania somnifera, Camellia sinesis, and Ocimum sanctum in the proportion 2:1:2:2:1:2 respectively. POL-6 was subjected to phytochemical profiling through LC-MS, HPLC, and HPTLC. The effect of POL-6 on alcohol withdrawal anxiety was tested using a two-bottle choice drinking paradigm model giving animals’ free choice between alcohol and water for 15 days. Alcohol was withdrawn on the 16th day and POL-6 (20, 50, and 100 mg/kg, oral), diazepam (2 mg/kg) treatment was given on the withdrawal days. Behavioral parameters were tested using EPM and LDT. On the 18th day blood was collected from the retro-orbital sinus of the rats and alcohol markers ALT, AST, ALP, and GGT were studied. At end of the study, animals were sacrificed and the brain was isolated for exploring the influences of POL-6 on the mRNA expression of GABAA receptor subunits in the amygdala and hippocampus.

Results

Phytochemical profiling showed that POL-6 contains major phytoconstituents like withaferin A, quercetin, catechin, rutin, caeffic acid, and β-sitosterol. In-vivo studies showed that POL-6 possesses an antianxiety effect in alcohol withdrawal. Gene expression studies on the isolated brain tissues showed that POL-6 normalizes the GABAergic transmission in the amygdala and hippocampus of the rats.

Conclusion

The study concludes that POL-6 may have therapeutic potential for treating ethanol-type dependence.
Literature
2.
go back to reference Fiellin DA, Connor PGO, Holmboe ES, Horwitz RI. Risk for delirium tremens in patients with alcohol withdrawal syndrome. Subst Abus. 2002;23:83–94.PubMed Fiellin DA, Connor PGO, Holmboe ES, Horwitz RI. Risk for delirium tremens in patients with alcohol withdrawal syndrome. Subst Abus. 2002;23:83–94.PubMed
4.
go back to reference Koob GF. Alcoholism allostasis and beyond. Alcohol Clin Exp Res. 2003;l.27:232–43.CrossRef Koob GF. Alcoholism allostasis and beyond. Alcohol Clin Exp Res. 2003;l.27:232–43.CrossRef
5.
go back to reference Knapp DJ, Overstreet DH, Angel RA, Navarro M, Breese GR. The amygdala regulates the antianxiety sensitization effect of flumazenil during repeated chronic ethanol or repeated stress. Alcohol Clin Exp Res. 2007;31:1872–82.PubMedPubMedCentralCrossRef Knapp DJ, Overstreet DH, Angel RA, Navarro M, Breese GR. The amygdala regulates the antianxiety sensitization effect of flumazenil during repeated chronic ethanol or repeated stress. Alcohol Clin Exp Res. 2007;31:1872–82.PubMedPubMedCentralCrossRef
6.
go back to reference Hungund BL, Basavarajappa BS. Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol Alcohol. 2005;40:15–24.PubMedCrossRef Hungund BL, Basavarajappa BS. Role of the endocannabinoid system in the development of tolerance to alcohol. Alcohol Alcohol. 2005;40:15–24.PubMedCrossRef
7.
go back to reference Ross HE. Benzodiazepine use and anxiolytic abuse and dependence in treated alcoholics. Addiction. 1993;88:209–18.PubMedCrossRef Ross HE. Benzodiazepine use and anxiolytic abuse and dependence in treated alcoholics. Addiction. 1993;88:209–18.PubMedCrossRef
8.
go back to reference Majouli K, Hamdi A, Hlila MB. Phytochemical analysis and biological activities of Hertia cheirifolia L. roots extracts. Asian Pac J Trop Med. 2017;10:1134–9.PubMedCrossRef Majouli K, Hamdi A, Hlila MB. Phytochemical analysis and biological activities of Hertia cheirifolia L. roots extracts. Asian Pac J Trop Med. 2017;10:1134–9.PubMedCrossRef
9.
go back to reference Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr. 2007;40:163–73.PubMedPubMedCentralCrossRef Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr. 2007;40:163–73.PubMedPubMedCentralCrossRef
10.
go back to reference Barnes J, Anderson LA, Phillipson JD. St John’s wort (Hypericum perforatum L.): the review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol. 2001;53:583–600.PubMedCrossRef Barnes J, Anderson LA, Phillipson JD. St John’s wort (Hypericum perforatum L.): the review of its chemistry, pharmacology and clinical properties. J Pharm Pharmacol. 2001;53:583–600.PubMedCrossRef
12.
13.
go back to reference Gupta GL, Rana AC. Withania somnifera (Ashwagandha): the review. Pharmacogn Rev. 2007;1:129–36. Gupta GL, Rana AC. Withania somnifera (Ashwagandha): the review. Pharmacogn Rev. 2007;1:129–36.
14.
go back to reference Deo B, Nath M, Nayak PK, Dhal Y. Evaluation of antioxidant activity of Ocimum Tenuiflorum, an important medicinal herb. IJPAES. 2013;3:150–4. Deo B, Nath M, Nayak PK, Dhal Y. Evaluation of antioxidant activity of Ocimum Tenuiflorum, an important medicinal herb. IJPAES. 2013;3:150–4.
15.
go back to reference Sharangi AB. Medicinal and therapeutic potentialities of tea (Camellia sinensis L.) – a review. Food Res Int. 2009;42:529–35.CrossRef Sharangi AB. Medicinal and therapeutic potentialities of tea (Camellia sinensis L.) – a review. Food Res Int. 2009;42:529–35.CrossRef
16.
go back to reference Tewari I, Sharma L, Gupta GL. Synergistic antioxidant activity of three medicinal plants Hypericum perforatum, Bacopa monnieri, and Camellia sinensis. Indo Am J Pharm. 2014;4:2563–8. Tewari I, Sharma L, Gupta GL. Synergistic antioxidant activity of three medicinal plants Hypericum perforatum, Bacopa monnieri, and Camellia sinensis. Indo Am J Pharm. 2014;4:2563–8.
17.
go back to reference Sharma L, Sharma A, Gupta GL. Standardization of a polyherbal preparation (POL–6) for treatment of oxidative, inflammatory and immune disorders. Int J Pharm. 2016;8(3):129–34. Sharma L, Sharma A, Gupta GL. Standardization of a polyherbal preparation (POL–6) for treatment of oxidative, inflammatory and immune disorders. Int J Pharm. 2016;8(3):129–34.
18.
go back to reference Sharma L, Sharma A, Gupta GL, Bisht GS. Acute and sub-acute. “Oral toxicity assessment of a standardized Polyherbal preparation POL-6 in rats”. Nat Prod J. 2019;9(3):207–16. Sharma L, Sharma A, Gupta GL, Bisht GS. Acute and sub-acute. “Oral toxicity assessment of a standardized Polyherbal preparation POL-6 in rats”. Nat Prod J. 2019;9(3):207–16.
19.
go back to reference Mari A, Lyon D, Fragner L, Montoro P, Piacente S, Wienkoop S, et al. Phytochemical composition of Potentilla anserina L analyzed by an integrative GC-MS and LC-MS metabolomics platform. Metabolomics. 2013;9:599–607.PubMedCrossRef Mari A, Lyon D, Fragner L, Montoro P, Piacente S, Wienkoop S, et al. Phytochemical composition of Potentilla anserina L analyzed by an integrative GC-MS and LC-MS metabolomics platform. Metabolomics. 2013;9:599–607.PubMedCrossRef
20.
go back to reference Azeemuddin M, Rafiq M, Anturlikar SD, Kumar LMS, Patki PS, Babu UV, et al. Extract of a polyherbal formulation ameliorates experimental nonalcoholic steatohepatitis. J Tradit Complement Med. 2015;22:160–7. Azeemuddin M, Rafiq M, Anturlikar SD, Kumar LMS, Patki PS, Babu UV, et al. Extract of a polyherbal formulation ameliorates experimental nonalcoholic steatohepatitis. J Tradit Complement Med. 2015;22:160–7.
21.
go back to reference Bhole RP, Shinde SS, Chitlange SS, Wankhede SB. A high-performance thin layer chromatography (HPTLC) method for simultaneous determination of diphenhydramine hydrochloride and naproxen sodium in tablets. Anal Chem Insights. 2015;10:47–51.PubMedPubMedCentralCrossRef Bhole RP, Shinde SS, Chitlange SS, Wankhede SB. A high-performance thin layer chromatography (HPTLC) method for simultaneous determination of diphenhydramine hydrochloride and naproxen sodium in tablets. Anal Chem Insights. 2015;10:47–51.PubMedPubMedCentralCrossRef
22.
go back to reference Gupta GL, Rana AC. Effect of Withania somnifera dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol. 2008;46:470–5.PubMed Gupta GL, Rana AC. Effect of Withania somnifera dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol. 2008;46:470–5.PubMed
23.
go back to reference Gupta GL, Sharma L. Bacopa monnieri abrogates alcohol abstinence-induced anxiety-like behavior by regulating biochemical and Gabra1, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats. Biomed Pharmacother. 2019;111:1417–28.PubMedCrossRef Gupta GL, Sharma L. Bacopa monnieri abrogates alcohol abstinence-induced anxiety-like behavior by regulating biochemical and Gabra1, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats. Biomed Pharmacother. 2019;111:1417–28.PubMedCrossRef
24.
go back to reference Clemens KJ, Vendruscolo LF. Anxious to drink gabapentin normalizes GABAergic transmission in the central amygdala and reduces symptoms of ethanol dependence. J Neurosci. 2008;28:9087–9.PubMedPubMedCentralCrossRef Clemens KJ, Vendruscolo LF. Anxious to drink gabapentin normalizes GABAergic transmission in the central amygdala and reduces symptoms of ethanol dependence. J Neurosci. 2008;28:9087–9.PubMedPubMedCentralCrossRef
25.
go back to reference Chiu K, Lau WM, Lau HT, So KF, Chang RCC. Micro-dissection of rat brain for RNA or protein extraction from specific brain region. J Vis Exp. 2007;269:1–3. Chiu K, Lau WM, Lau HT, So KF, Chang RCC. Micro-dissection of rat brain for RNA or protein extraction from specific brain region. J Vis Exp. 2007;269:1–3.
26.
go back to reference Yawalkar R, Changotra H, Gupta GL. Protective influences of Nacetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats. Neurochem Int. 2018;118:73–81.PubMedCrossRef Yawalkar R, Changotra H, Gupta GL. Protective influences of Nacetylcysteine against alcohol abstinence-induced depression by regulating biochemical and GRIN2A, GRIN2B gene expression of NMDA receptor signaling pathway in rats. Neurochem Int. 2018;118:73–81.PubMedCrossRef
27.
go back to reference Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze a novel test of anxiety in the rat. Pharmacol Biochem Behav. 1986;24:525–9.PubMedCrossRef Pellow S, File SE. Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze a novel test of anxiety in the rat. Pharmacol Biochem Behav. 1986;24:525–9.PubMedCrossRef
28.
go back to reference Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ. Zacopride anxiolytic profile in rodent and primate models of anxiety. J Pharm Pharmacol. 1988;40:302–5.PubMedCrossRef Costall B, Domeney AM, Gerrard PA, Kelly ME, Naylor RJ. Zacopride anxiolytic profile in rodent and primate models of anxiety. J Pharm Pharmacol. 1988;40:302–5.PubMedCrossRef
29.
go back to reference Xiang Y, Kim KY, Gelernter J, Park IH, Zhang H. Ethanol upregulates NMDA receptor subunit gene expression in human embryonic stem cell-derived cortical neurons. PLoS One. 2015;10:e0134907.PubMedPubMedCentralCrossRef Xiang Y, Kim KY, Gelernter J, Park IH, Zhang H. Ethanol upregulates NMDA receptor subunit gene expression in human embryonic stem cell-derived cortical neurons. PLoS One. 2015;10:e0134907.PubMedPubMedCentralCrossRef
30.
go back to reference Dick DM, Plunkett J, Wetherill LF, Xuei X, Goate A, Hesselbrock V. Association between GABRA1 and drinking behaviors in the collaborative study on the genetics of alcoholism sample. Alcohol Clin Exp Res. 2006;30:1101–10.PubMedCrossRef Dick DM, Plunkett J, Wetherill LF, Xuei X, Goate A, Hesselbrock V. Association between GABRA1 and drinking behaviors in the collaborative study on the genetics of alcoholism sample. Alcohol Clin Exp Res. 2006;30:1101–10.PubMedCrossRef
31.
go back to reference Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.PubMedCrossRef Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25(4):402–8.PubMedCrossRef
32.
go back to reference Karole S, Shrivastava S, Thomas S, Son B, Khan S, Dubey J. Polyherbal Formulation Concept for Synergic Action: A Review. J Drug Deliv Ther. 2019;9:453–66.CrossRef Karole S, Shrivastava S, Thomas S, Son B, Khan S, Dubey J. Polyherbal Formulation Concept for Synergic Action: A Review. J Drug Deliv Ther. 2019;9:453–66.CrossRef
34.
go back to reference Sharma L, Sharma A, Gupta GL, Bisht GS. Protective effect of Ocimum sanctum Linn. Leaf extract on ethanol withdrawal syndrome in Wistar rats. Asian Pac J Trop Med. 2018;11(8):423–8. Sharma L, Sharma A, Gupta GL, Bisht GS. Protective effect of Ocimum sanctum Linn. Leaf extract on ethanol withdrawal syndrome in Wistar rats. Asian Pac J Trop Med. 2018;11(8):423–8.
35.
go back to reference Majchrowicz E. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia. 1975;43:245–54.PubMedCrossRef Majchrowicz E. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacologia. 1975;43:245–54.PubMedCrossRef
36.
go back to reference Sharma L, Sharma A, Gupta GL, Bisht GS. Pharmacological Evaluation of Bacopa monnieri Extract against Depressive like Behavior by Ethanol Withdrawal in Rats. Phcog J. 2018;10(6):s73–8.CrossRef Sharma L, Sharma A, Gupta GL, Bisht GS. Pharmacological Evaluation of Bacopa monnieri Extract against Depressive like Behavior by Ethanol Withdrawal in Rats. Phcog J. 2018;10(6):s73–8.CrossRef
37.
go back to reference Gruchow HW, Sobocinski KA, Barboriak JJ, Scheller JG. Alcohol consumption, nutrient intake and relative body weight among US adults. Am J Clin Nutr. 1985;42:289–95.PubMedCrossRef Gruchow HW, Sobocinski KA, Barboriak JJ, Scheller JG. Alcohol consumption, nutrient intake and relative body weight among US adults. Am J Clin Nutr. 1985;42:289–95.PubMedCrossRef
38.
go back to reference Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT. CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat. Psychopharmacology. 1991;103:227–32.PubMedCrossRef Baldwin HA, Rassnick S, Rivier J, Koob GF, Britton KT. CRF antagonist reverses the “anxiogenic” response to ethanol withdrawal in the rat. Psychopharmacology. 1991;103:227–32.PubMedCrossRef
39.
go back to reference Smith MF. Pharmacological Management of Alcohol Withdrawal A meta-analysis and evidence-based practice guideline American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997;278:144–51.CrossRef Smith MF. Pharmacological Management of Alcohol Withdrawal A meta-analysis and evidence-based practice guideline American Society of Addiction Medicine Working Group on Pharmacological Management of Alcohol Withdrawal. JAMA. 1997;278:144–51.CrossRef
40.
go back to reference Gerhard VH. Drug Discovery and Evaluation: Pharmacological Assays. 2nd ed. Berlin: Springer; 2002. p. 434–696. Gerhard VH. Drug Discovery and Evaluation: Pharmacological Assays. 2nd ed. Berlin: Springer; 2002. p. 434–696.
41.
go back to reference Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003;63:53–64.PubMedCrossRef Cagetti E, Liang J, Spigelman I, Olsen RW. Withdrawal from chronic intermittent ethanol treatment changes subunit composition, reduces synaptic function, and decreases behavioral responses to positive allosteric modulators of GABAA receptors. Mol Pharmacol. 2003;63:53–64.PubMedCrossRef
42.
go back to reference Shah LP, Patil SP, Patil J. Observations on clinical evaluation of indigenous herbal drugs in the treatment of mental illnesses. Indian J Pharm. 1997;29(5):s347–9. Shah LP, Patil SP, Patil J. Observations on clinical evaluation of indigenous herbal drugs in the treatment of mental illnesses. Indian J Pharm. 1997;29(5):s347–9.
43.
go back to reference Mohan L, Rao USC, Gopalakrishna HN, Nair V. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats. Evid Based Complement Alternat Med. 2011;327160:7. Mohan L, Rao USC, Gopalakrishna HN, Nair V. Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats. Evid Based Complement Alternat Med. 2011;327160:7.
44.
go back to reference Vidya TJ, Kulkarni KS. Beneficial effect of green tea with special reference to neuropathy: review and pilot trial. Anc Sci Life. 2002;22:41–7.PubMedPubMedCentral Vidya TJ, Kulkarni KS. Beneficial effect of green tea with special reference to neuropathy: review and pilot trial. Anc Sci Life. 2002;22:41–7.PubMedPubMedCentral
45.
go back to reference Sen P, Maiti PC, Puri S, Ray A, Audulov NA, Valdman AV. Mechanism of anti-stress activity of Ocimum sanctum Linn, Eugenol and Tinospora malabarica in experimental animals. Indian J Exp Biol. 1992;30(7):592–6.PubMed Sen P, Maiti PC, Puri S, Ray A, Audulov NA, Valdman AV. Mechanism of anti-stress activity of Ocimum sanctum Linn, Eugenol and Tinospora malabarica in experimental animals. Indian J Exp Biol. 1992;30(7):592–6.PubMed
46.
go back to reference Conigrave KM, Davies P, Haber P, Whitfield JB. Traditional markers of excessive alcohol use. Addiction. 2003;98:31–43.PubMedCrossRef Conigrave KM, Davies P, Haber P, Whitfield JB. Traditional markers of excessive alcohol use. Addiction. 2003;98:31–43.PubMedCrossRef
47.
go back to reference Dixit S, Singh P. Usefulness of gamma Glutamyl Transferase as reliable biological marker in objective corroboration of relapse in alcohol dependent patients. J Clin Diagn Res. 2015;9(12):4. Dixit S, Singh P. Usefulness of gamma Glutamyl Transferase as reliable biological marker in objective corroboration of relapse in alcohol dependent patients. J Clin Diagn Res. 2015;9(12):4.
48.
go back to reference Davies M. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci. 2003;28:263–74.PubMedPubMedCentral Davies M. The role of GABAA receptors in mediating the effects of alcohol in the central nervous system. J Psychiatry Neurosci. 2003;28:263–74.PubMedPubMedCentral
49.
50.
go back to reference Yin H, Cho DH, Park SJ, Han SK. GABA-mimetic actions of Withania somnifera on Substantia Gelatinosa neurons of the trigeminal subnucleus Caudalis in mice. Am J Chinese Med. 2013;41:1043–51.CrossRef Yin H, Cho DH, Park SJ, Han SK. GABA-mimetic actions of Withania somnifera on Substantia Gelatinosa neurons of the trigeminal subnucleus Caudalis in mice. Am J Chinese Med. 2013;41:1043–51.CrossRef
51.
go back to reference Langosch JM, Zhou XY, Heinen M, Kupferschmid S, Chatterjee SS, Nöldner M. St John's wort (Hypericum perforatum) modulates evoked potentials in Guinea pig hippocampal slices via AMPA and GABA receptors. Eur Neuropsychopharmacol. 2002;12(3):209–16.PubMedCrossRef Langosch JM, Zhou XY, Heinen M, Kupferschmid S, Chatterjee SS, Nöldner M. St John's wort (Hypericum perforatum) modulates evoked potentials in Guinea pig hippocampal slices via AMPA and GABA receptors. Eur Neuropsychopharmacol. 2002;12(3):209–16.PubMedCrossRef
52.
go back to reference Liao J, Wu X, Xing Z, Li Q, Duan Y, Fang W, Zhu X. γ-Aminobutyric acid (GABA) accumulation in tea (Camellia sinensis L.) through the GABA shunt and polyamine degradation pathways under anoxia. J Agric Food Chem. 2017;65:3013–8.PubMedCrossRef Liao J, Wu X, Xing Z, Li Q, Duan Y, Fang W, Zhu X. γ-Aminobutyric acid (GABA) accumulation in tea (Camellia sinensis L.) through the GABA shunt and polyamine degradation pathways under anoxia. J Agric Food Chem. 2017;65:3013–8.PubMedCrossRef
53.
go back to reference Fan HR, Du WF, Zhu T, Wu YJ, Liu YM, Wang Q. Quercetin reduces cortical GABAergic transmission and alleviates MK-801-induced hyperactivity. E BioMedicine. 2018;34:201–13. Fan HR, Du WF, Zhu T, Wu YJ, Liu YM, Wang Q. Quercetin reduces cortical GABAergic transmission and alleviates MK-801-induced hyperactivity. E BioMedicine. 2018;34:201–13.
54.
go back to reference Leon AH, Trujano MEG, Guasti AF. The anxiolytic-like effect of rutin in rats involves GABAA receptors in the basolateral amygdala. Behav Pharmacol. 2017;28:303–12.CrossRef Leon AH, Trujano MEG, Guasti AF. The anxiolytic-like effect of rutin in rats involves GABAA receptors in the basolateral amygdala. Behav Pharmacol. 2017;28:303–12.CrossRef
55.
go back to reference Candelario M, Cuellar E, Reyes-Ruiz JM, Darabedian N, Feimeng Z, Miledi R. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol. 2015;171:264–72.PubMedCrossRef Candelario M, Cuellar E, Reyes-Ruiz JM, Darabedian N, Feimeng Z, Miledi R. Direct evidence for GABAergic activity of Withania somnifera on mammalian ionotropic GABAA and GABAρ receptors. J Ethnopharmacol. 2015;171:264–72.PubMedCrossRef
56.
go back to reference Wang YX, Engelmann T, Xu YF, Schwarz W. Catechins from green tea modulate neurotransmitter transporter activity in Xenopus oocytes. Cogent Biology. 2019;2:1–9. Wang YX, Engelmann T, Xu YF, Schwarz W. Catechins from green tea modulate neurotransmitter transporter activity in Xenopus oocytes. Cogent Biology. 2019;2:1–9.
Metadata
Title
A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats
Authors
Lalit Sharma
Aditi Sharma
Ashutosh Kumar Dash
Gopal Singh Bisht
Girdhari Lal Gupta
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/s12906-020-03181-2

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