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Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study eval...

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Autores principales: Sharma, Ruchi, Jadhav, Mangala, Choudhary, Neha, Kumar, Arun, Rauf, Abdur, Gundamaraju, Rohit, AlAsmari, Abdullah F., Ali, Nemat, Singla, Rajeev K., Sharma, Rohit, Shen, Bairong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709420/
https://www.ncbi.nlm.nih.gov/pubmed/36466417
http://dx.doi.org/10.3389/fnut.2022.1063118
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author Sharma, Ruchi
Jadhav, Mangala
Choudhary, Neha
Kumar, Arun
Rauf, Abdur
Gundamaraju, Rohit
AlAsmari, Abdullah F.
Ali, Nemat
Singla, Rajeev K.
Sharma, Rohit
Shen, Bairong
author_facet Sharma, Ruchi
Jadhav, Mangala
Choudhary, Neha
Kumar, Arun
Rauf, Abdur
Gundamaraju, Rohit
AlAsmari, Abdullah F.
Ali, Nemat
Singla, Rajeev K.
Sharma, Rohit
Shen, Bairong
author_sort Sharma, Ruchi
collection PubMed
description Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.
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spelling pubmed-97094202022-12-01 Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation Sharma, Ruchi Jadhav, Mangala Choudhary, Neha Kumar, Arun Rauf, Abdur Gundamaraju, Rohit AlAsmari, Abdullah F. Ali, Nemat Singla, Rajeev K. Sharma, Rohit Shen, Bairong Front Nutr Nutrition Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms. Frontiers Media S.A. 2022-11-16 /pmc/articles/PMC9709420/ /pubmed/36466417 http://dx.doi.org/10.3389/fnut.2022.1063118 Text en Copyright © 2022 Sharma, Jadhav, Choudhary, Kumar, Rauf, Gundamaraju, AlAsmari, Ali, Singla, Sharma and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Sharma, Ruchi
Jadhav, Mangala
Choudhary, Neha
Kumar, Arun
Rauf, Abdur
Gundamaraju, Rohit
AlAsmari, Abdullah F.
Ali, Nemat
Singla, Rajeev K.
Sharma, Rohit
Shen, Bairong
Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title_full Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title_fullStr Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title_full_unstemmed Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title_short Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
title_sort deciphering the impact and mechanism of trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9709420/
https://www.ncbi.nlm.nih.gov/pubmed/36466417
http://dx.doi.org/10.3389/fnut.2022.1063118
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