Potent hepatoprotective activity of common rattan ( <i>Calamus rotang</i> L.) leaf extract and its molecular mechanism

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Calamus rotang L. (CR) is an Indian shrub. The leaves and other organs of the plant are traditionally used in India for treatment of various diseases. The in vitro antioxidant property of the leaves extract was previously established. Thus, the current study aimed to evaluate the antioxidant and hepatoprotective effects of CR ethyl acetate extract at a dose of 350 mg/kg on CCl ₄ induced hepatotoxic rats through different mechanisms.

Methods

Histopathological examination of the treated rats’ group in comparison with positive and negative controls were performed. Quantitative measuring of the proinflammatory cytokines (TNF α), inflammatory regulators (Arginase, PPAR α) and the antiapoptotic protein Bcl-2 in comparison with positive and negative control groups was achieved using immunohistochemical examination. HPLC profiling of the polyphenol contents and molecular docking of the identified compounds against BH3 proapoptotic protein were correspondingly studied to evaluate the potential antiapoptotic property.

Results

The CR extract greatly protects the liver tissue through the suppression of TNF α, arginase and PPAR α induced by CCl ₄ as well as its enhancement of the antiapoptotic Bcl-2 protein. Fourteen polyphenols of different classes were identified in CR extract and tested via molecular docking for their potential antiapoptotic activities against BH3 protein. Naringin, rutin, 7-hydroxy flavone, and ellagic acid compounds exhibit the highest affinity and potential inhibition of pro-apoptotic protein BH3 via molecular docking study.

Conclusions

The ethyl acetate fraction of the leaves of C. rotang is rich in polyphenols that exhibited potent hepatoprotective effect on CCl ₄ induced hepatotoxic rats through its antioxidant, anti-inflammatory, anti-steatosis and antiapoptotic properties.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12906-023-03853-9.

Related collections

Most cited references 48

Record: found
Abstract: found
Article: not found

AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.

Oleg Trott, Arthur J Olson (2010)

AutoDock Vina, a new program for molecular docking and virtual screening, is presented. AutoDock Vina achieves an approximately two orders of magnitude speed-up compared with the molecular docking software previously developed in our lab (AutoDock 4), while also significantly improving the accuracy of the binding mode predictions, judging by our tests on the training set used in AutoDock 4 development. Further speed-up is achieved from parallelism, by using multithreading on multicore machines. AutoDock Vina automatically calculates the grid maps and clusters the results in a way transparent to the user. Copyright 2009 Wiley Periodicals, Inc.

0 comments Cited 5582 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Liver inflammation and fibrosis.

Yukinori Koyama, David A. Brenner (2017)

Chronic liver inflammation leads to fibrosis and cirrhosis, which is the 12th leading cause of death in the United States. Hepatocyte steatosis is a component of metabolic syndrome and insulin resistance. Hepatic steatosis may be benign or progress to hepatocyte injury and the initiation of inflammation, which activates immune cells. While Kupffer cells are the resident macrophage in the liver, inflammatory cells such as infiltrating macrophages, T lymphocytes, neutrophils, and DCs all contribute to liver inflammation. The inflammatory cells activate hepatic stellate cells, which are the major source of myofibroblasts in the liver. Here we review the initiation of inflammation in the liver, the liver inflammatory cells, and their crosstalk with myofibroblasts.

0 comments Cited 391 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

Lutz Weber, Meinrad Boll, Andreas Stampfl (2003)

The use of many halogenated alkanes such as carbon tetrachloride (CCl4), chloroform (CHCl3) or iodoform (CHI3), has been banned or severely restricted because of their distinct toxicity. Yet CCl4 continues to provide an important service today as a model substance to elucidate the mechanisms of action of hepatotoxic effects such as fatty degeneration, fibrosis, hepatocellular death, and carcinogenicity. In a matter of dose,exposure time, presence of potentiating agents, or age of the affected organism, regeneration can take place and lead to full recovery from liver damage. CCl4 is activated by cytochrome (CYP)2E1, CYP2B1 or CYP2B2, and possibly CYP3A, to form the trichloromethyl radical, CCl3*. This radical can bind to cellular molecules (nucleic acid, protein, lipid), impairing crucial cellular processes such as lipid metabolism, with the potential outcome of fatty degeneration (steatosis). Adduct formation between CCl3* and DNA is thought to function as initiator of hepatic cancer. This radical can also react with oxygen to form the trichloromethylperoxy radical CCl3OO*, a highly reactive species. CCl3OO* initiates the chain reaction of lipid peroxidation, which attacks and destroys polyunsaturated fatty acids, in particular those associated with phospholipids. This affects the permeabilities of mitochondrial, endoplasmic reticulum, and plasma membranes, resulting in the loss of cellular calcium sequestration and homeostasis, which can contribute heavily to subsequent cell damage. Among the degradation products of fatty acids are reactive aldehydes, especially 4-hydroxynonenal, which bind easily to functional groups of proteins and inhibit important enzyme activities. CCl4 intoxication also leads to hypomethylation of cellular components; in the case of RNA the outcome is thought to be inhibition of protein synthesis, in the case of phospholipids it plays a role in the inhibition of lipoprotein secretion. None of these processes per se is considered the ultimate cause of CCl4-induced cell death; it is by cooperation that they achieve a fatal outcome, provided the toxicant acts in a high single dose, or over longer periods of time at low doses. At the molecular level CCl4 activates tumor necrosis factor (TNF)alpha, nitric oxide (NO), and transforming growth factors (TGF)-alpha and -beta in the cell, processes that appear to direct the cell primarily toward (self-)destruction or fibrosis. TNFalpha pushes toward apoptosis, whereas the TGFs appear to direct toward fibrosis. Interleukin (IL)-6, although induced by TNFalpha, has a clearly antiapoptotic effect, and IL-10 also counteracts TNFalpha action. Thus, both interleukins have the potential to initiate recovery of the CCl4-damaged hepatocyte. Several of the above-mentioned toxication processes can be specifically interrupted with the use of antioxidants and mitogens, respectively, by restoring cellular methylation, or by preserving calcium sequestration. Chemicals that induce cytochromes that metabolize CCl4, or delay tissue regeneration when co-administered with CCl4 will potentiate its toxicity thoroughly, while appropriate CYP450 inhibitors will alleviate much of the toxicity. Oxygen partial pressure can also direct the course of CCl4 hepatotoxicity. Pressures between 5 and 35 mmHg favor lipid peroxidation, whereas absence of oxygen, as well as a partial pressure above 100 mmHg, both prevent lipid peroxidation entirely. Consequently, the location of CCl4-induced damage mirrors the oxygen gradient across the liver lobule. Mixed halogenated methanes and ethanes, found as so-called disinfection byproducts at low concentration in drinking water, elicit symptoms of toxicity very similar to carbon tetrachloride, including carcinogenicity.

0 comments Cited 390 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Ahmed M. Zaher: ahmedshaekhon@aun.edu.eg

Journal

Journal ID (nlm-ta): BMC Complement Med Ther

Journal ID (iso-abbrev): BMC Complement Med Ther

Title: BMC Complementary Medicine and Therapies

Publisher: BioMed Central (London )

ISSN (Electronic): 2662-7671

Publication date (Electronic): 30 January 2023

Publication date PMC-release: 30 January 2023

Publication date Collection: 2023

Volume: 23

Electronic Location Identifier: 24

Affiliations

[1 ]Department of Pharmacognosy, Faculty of Pharmacy, Merit University, New Sohag, Egypt

[2 ]GRID grid.252487.e, ISNI 0000 0000 8632 679X, Department of Anatomy and Embryology, Faculty of Vet. Medicine, , Assiut University, ; Assiut, Egypt

[3 ]GRID grid.252487.e, ISNI 0000 0000 8632 679X, Biochemistry Laboratory, Chemistry Department, Faculty of Science, , Assiut University, ; Assiut, Egypt

[4 ]GRID grid.412707.7, ISNI 0000 0004 0621 7833, Department of Pharmacognosy, Faculty of Pharmacy, , South Valley University, ; Qena, Egypt

Article

Publisher ID: 3853

DOI: 10.1186/s12906-023-03853-9

PMC ID: 9885597

PubMed ID: 36717906

SO-VID: f7ab6fb5-9743-4f07-8558-3a3dbc1d385a

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 20 November 2022

Date accepted : 20 January 2023

Funding

Funded by: Assiut University

Open Access :

Open access funding provided by The Science, Technology & Innovation Funding Authority (STDF) in cooperation with The Egyptian Knowledge Bank (EKB).

Custom metadata

Keywords: calamus rotang,hepatoprotective,molecular docking,apoptosis,hplc,metabolite profiling

Data availability:

Keywords: calamus rotang, hepatoprotective, molecular docking, apoptosis, hplc, metabolite profiling

Potent hepatoprotective activity of common rattan ( Calamus rotang L.) leaf extract and its molecular mechanism

Read this article at

Abstract

Background

Methods

Results

Conclusions

Supplementary Information

Related collections

Fandom activity

Most cited references 48

AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.

Liver inflammation and fibrosis.

Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model.

Author and article information

Contributors

Journal

Affiliations

Article

History

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 118

Cited by 2

Most referenced authors 3,571