In vivo hepatoprotective effect of <i>Morinda elliptica</i> stem extract against liver fibrosis induced by thioacetamide

Bradosty, Sarwan W.; Agha, Nabaz Fisal Shakir; Shaikh, Faiyaz K.; Nanakali, Nadir Mustafa Qadir; Aziz, Peshawa Yunis; Salehen, Nur'Ain; Süzergöz, Faruk; Abdulla, Mahmood Ameen

doi:10.1002/tox.23353

Cited by 10 publications

(7 citation statements)

References 49 publications

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“…The increase in liver function biomarkers imitates hepatocellular dysfunction. With the consistence of the results of current study increased in liver markers activities and bilirubin level in hepatotoxic group were previously reported by several researchers [18,35,43,46].…”

Section: Discussionsupporting

confidence: 85%

“…With the agreement of the results of our investigation enormous numbers of scientists displayed that rat's gavage silymarin or various plant extracts brought the albumin and protein to almost normal levels [15,20,21,25,46,50,51] reported that ethanolic leave extracts of Garuga pinnata can serve as promising herbal medicine for the treatment of both acute and chronic hepatotoxicity due to the presence of avonoids rutin, Outcomes of the existing research showed a decline collagen deposition in pinostrobin fed groups in tissue sections stained with Masson's trichrome dye. Analogous to the results of current study many investigators used innumerable plant extracts con rmed reduction of collagen bers compared to TAA control group [14,16,21,38,41].…”

Section: Discussionsupporting

confidence: 83%

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Hepatoprotective effect of Pinostrobin against Thioacetamide-induced liver cirrhosis in rats

Jabbar

Abdulla

2022

Preprint

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Pinostrobin was used in traditional medication for management of numerous syndromes. In the current study, histology, immunohistochemistry, and hepatoprotection effects of Pinostrobin were assessed against thioacetamide (TAA) hepatotoxicity in rats. Thirty rats were arbitrarily separated into five groups. Group 1 was intraperitoneally (i.p) injected with distilled water 3 times/week and fed (po) daily with 10% Tween 20 for 2 months. Group 2–5 were i.p. injected with 200 mg/kg TAA thrice weekly for 8 weeks and fed with 10% Tween 20, 50 mg/kg silymarin, 30 and 60 mg/kg of Pinostrobin daily for 8 weeks, respectively. Experimental groups fed groups showed that Pinostrobin significant reduction in liver index and hepatocyte proliferation with much lesser cell injury. These groups were significantly down-regulated the PCNA and α-SMA. The liver homogenate exhibited increased antioxidant enzymes (SOD and CAT) activities accompanied with decline in malondialdehyde (MDA) level. The serum level of bilirubin, total protein, albumin and liver enzymes (ALP, ALT, and AST) were restored to normal and were comparable to that normal control and silymarin with TAA treated groups. The hepatotoxic group showed a significant rise in serum liver biochemical markers together with a considerable decrease in protein and albumin level compared to the normal group. The hepatotoxic group displayed decreased catalase and superoxide dismutase activities while increased lipid peroxidation. Pinostrobin decreased level of TNF-a, IL-6 and increased the level of IL-10. Acute toxicity with a higher dose of 500 mg/kg Pinostrobin did not manifest any toxicological signs in rats. Macroscopy of hepatotoxic liver exhibited irregular, rough surface with micro and macro nodule. Histopathology stained by Hematoxylin and Eosin, and Masson Trichrome showed there was inflammation and infiltration of lymphocytes, focal necrosis, fibrosis, and bile duct propagation. Pinostrobin fed group had expressively reduced TAA toxicity in gross and histology as designated by fewer disturbances of hepatic tissue, slight fibrosis, and low-grade cells infiltration. Immunohistochemical staining designated that pinostrobin significantly down-regulated the expression of proliferation cellular nucleus antigen (PCNA) and alpha-smooth muscle actin (α-SMA) in the liver. Thus, the findings of this study presented that the hepatoprotective effect of this plant may be due to a reduction in toxicity, inhibition of hepatocytes proliferation, down-regulation of PCNA and α-SMA, decreased enzyme markersand increased protein and albumin increased endogenous enzymes and reduced lipid peroxidation level.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 83%

Hepatoprotective effect of Pinostrobin against Thioacetamide-induced liver cirrhosis in rats

Jabbar

Abdulla

2022

Preprint

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“…This study speculates that EVs may play an important role in the treatment of liver injury by liver stem cells. From the results, we found that the treatment of EVs could inhibit the process of liver fibrosis to a certain extent 10,34–36 . These data prove that LSCs could treat liver fibrosis through EVs.…”

Section: Discussionmentioning

confidence: 55%

“…From the results, we found that the treatment of EVs could inhibit the process of liver fibrosis to a certain extent. 10,[34][35][36] These data prove that LSCs could treat liver fibrosis through EVs. Macrophages are important effector cells of the body's immune response and play an important role in many diseases including tumors, immune system diseases and fibrosis.…”

Section: Discussionmentioning

confidence: 61%

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Zhao

Jiang

et al. 2023

Environmental Toxicology

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Background This study aims to explore the effect of liver stem cells (LSCs)‐derived exosomes and the miR‐142a‐5p carried by them on the process of fibrosis by regulating macrophages polarization. Methods In this study, CCL4 was used to establish liver fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB) and nanoparticle tracing analysis (NTA). Real‐time quantitative PCR (qRT‐PCR), WB and enzyme‐linked immunoadsorption (ELISA) were used to detect liver fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co‐culture model and liver fibrosis model were constructed to verify the expression of miR‐142a‐5p and ctsb. Results Immunofluorescence of LSCs markers CK‐18, epithelial cell adhesion molecule (EpCam), and AFP showed that these markers were up‐regulated in LSCs. In addition, we evaluated the ability of LSCs to excrete EVs by labeling LSCs‐EVs with PKH67. We found that CCL4 and EVs were simultaneously treated at 50 and 100 μg doses, and both doses of EVs could reduce the degree of liver fibrosis in mice. We tested markers of M1 or M2 macrophage polarization and found that EVs reduced M1 marker expression and promoted M2 marker expression. Further, ELISA was used to detect the secreted factors related to M1 and M2 in tissue lysates, which also verified the above views. Further analysis showed that the expression of miR‐142a‐5p increased significantly with the increase of EVs treatment concentration and time. Further, in vitro and in vivo LSCs‐EVs regulate macrophage polarization through miR‐142a‐5p/ctsb pathway and affect the process of liver fibrosis. Conclusion Our data suggest that EVs‐derived miR‐142‐5p from LSCs improves the progression of liver fibrosis by regulating macrophage polarization through ctsb.

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“…Finally, we detected the indicators of autophagy and macrophage polarization and found that when autophagy was inhibited, the expression of M1-type markers was inflammatory responses in liver tissue. 6,11,25 Autophagy is a regulated, dynamic, multistep process aimed at maintaining cellular homeostasis.…”

Section: In Vivo Assays To Verify the Effects Of Macrophage Evs And A...mentioning

confidence: 99%

Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion

Chen

Yan

et al. 2023

Environmental Toxicology

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Background: In this study, the role of autophagy in hepatic fibrosis and its effects on macrophage polarization and exosomes (EVs) were verified by establishing hepatic fibrosis model and co-culture model, providing evidence for treatment. Methods: In this study, CCL 4 was used to establish hepatic fibrosis model. The morphology and purity of exosomes (EVs) were verified by transmission electron microscopy, western blotting (WB), and nanoparticle tracing analysis (NTA). Real-time quantitative PCR (qRT-PCR), WB and enzyme-linked immunoadsorption (ELISA) were used to detect hepatic fibrosis markers, macrophage polarization markers and liver injury markers. Histopathological assays were used to verify the liver injury morphology in different groups. The cell co-culture model and hepatic fibrosis model were constructed to verify the expression of miR-423-5p.Results: Hepatic fibrosis model showed that CCL 4 promoted early autophagy increase but inhibited autophagy flux in liver. mRFP-GFP-LC3 detection showed that both LPS group and Baf group inhibited autophagy flux. This inhibitory effect was reversed by Rap combination therapy. The M1/M2 markers of macrophage polarization were further tested, and it was found that LPS and Baf could promote M1 polarization and inhibit M2 polarization. Rap processing reverses this phenomenon. These data suggest that autophagy can regulate the polarization process of liver macrophages. WB and NTA showed that LPS induced EVs generation. In addition, LPSinduced EVs could promote HSC proliferation, cell cycle, migration, and the expression of fibrosis markers. Macrophage-EVs could affect the fibrosis process of stellate cells through the secretion of miR-423a-5p expression. The hepatic fibrosis model Shengning Zhang and Li Li have contributed equally to this work.

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In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide

Cited by 10 publications

References 49 publications

Hepatoprotective effect of Pinostrobin against Thioacetamide-induced liver cirrhosis in rats

Hepatoprotective effect of Pinostrobin against Thioacetamide-induced liver cirrhosis in rats

Exosome‐derived miR‐142‐5p from liver stem cells improves the progression of liver fibrosis by regulating macrophage polarization through CTSB

Autophagy affects hepatic fibrosis progression by regulating macrophage polarization and exosome secretion

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