Protective effects of Chinese traditional medicine against liver injury and liver fibrosis and mechanisms involved

Hovenia dulcis, known as the oriental raisin tree, is used for food supplements and traditional medicine for the liver after alcohol-related symptoms. However, little information exists about the use of its leaves and branches. In this study, we established a method to use the leaves and branches to develop anti-hangover treatment and elucidated the underlying mechanisms. Oxidation-treated leaves (OL) exhibited high antioxidant content comparable to that of the peduncles and showed an anti-hangover effect in male mice. The branch extract (BE) was enriched in the flavonoid catechin, approximately five times more than OL extract. The mixture of OL and BE (OLB) was formulated in a 2:1 ratio with frozen-dried extract weight and was tested for anti-hangover effects and protective properties against binge alcohol-induced liver injury. OLB showed better anti-hangover effect than OL. In addition to this anti-hangover effect, OLB protected the liver from oxidative/nitrosative damage induced by binge alcohol intake.

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The Protective Effects of Live and Pasteurized Akkermansia muciniphila and Its Extracellular Vesicles against HFD/CCl4-Induced Liver Injury

Microbiology Spectrum ◽

10.1128/spectrum.00484-21 ◽

2021 ◽

Author(s):

Shahrbanoo Keshavarz Azizi Raftar ◽

Fatemeh Ashrafian ◽

Abbas Yadegar ◽

Arezou Lari ◽

Hamid Reza Moradi ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Injury ◽

Gut Microbiota ◽

Chronic Liver Disease ◽

Liver Dysfunction ◽

Protective Effects ◽

Main Determinant ◽

Content Type ◽

Akkermansia Muciniphila

Akkermansia muciniphila , as a member of the gut microbiota, has been proposed as a next-generation probiotic. Liver fibrosis is the main determinant of liver dysfunction and mortality in patients with chronic liver disease.

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Effects and Mechanisms of Acremoniumterricola milleretal mycelium on Liver Fibrosis Induced by Carbon Tetrachloride in Rats

The American Journal of Chinese Medicine ◽

10.1142/s0192415x11009019 ◽

2011 ◽

Vol 39 (03) ◽

pp. 537-550 ◽

Cited By ~ 10

Author(s):

Xiao-Peng Tian ◽

Yan-Yan Yin ◽

Xia Li

Keyword(s):

Carbon Tetrachloride ◽

Liver Fibrosis ◽

Liver Injury ◽

Chinese Herb ◽

Immunoblot Analysis ◽

Hepatoprotective Activity ◽

Protective Effects ◽

Sprague Dawley ◽

Procollagen Type ◽

Tgf Β1

Acremoniumterricola milleretal mycelium (AMM) is one of the most precious traditional Chinese medicines. It has numerous protective effects on organs, and has been used in Chinese herb prescription to treat refractory diseases. Our preliminary studies demonstrated that AMM had hepatoprotective activity in acute liver injury. We further investigated the effects of AMM on liver fibrosis in rats induced by carbon tetrachloride ( CCl 4) and explore its possible mechanisms. The animal model was established by injection with 50% CCl 4 subcutaneously in male Sprague-Dawley rats twice a week for eight weeks. Meanwhile, AMM (175, 350 and 700 mg/kg) was administered intragastrically per day until sacrifice. We found that treatment with AMM (175, 350 and 700 mg/kg) decreased CCl 4-induced elevation of serum transaminase activities, hyaluronic acid, laminin and procollagen type III levels, and contents of hydroxyproline in liver tissues. It also restored the decreased SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during CCl 4 treatment. Moreover, AMM (350 and 700 mg/kg) decreased the elevation of TGF-β1 by 19.6% and 34.3%, respectively. In the pathological study, liver injury and the formation of liver fibrosis in rates treated by AMM were improved significantly. Immunoblot analysis showed that AMM (175, 350 and 700 mg/kg) inhibited Smad 2/3 phosphorylation, and elevated inhibitor Smad 7 expression. These results suggested that AMM could protect liver damage and inhibit the progression of hepatic fibrosis induced by CCl 4, and its mechanisms might be associated with its ability to scavenge free radicals, decrease the level of TGF-β1 and block TGF-β/Smad signaling pathway.

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Protective effects of total flavonoids of Bidens pilosa L. (TFB) on animal liver injury and liver fibrosis

Journal of Ethnopharmacology ◽

10.1016/j.jep.2008.01.010 ◽

2008 ◽

Vol 116 (3) ◽

pp. 539-546 ◽

Cited By ~ 50

Author(s):

Li-Ping Yuan ◽

Fei-Hu Chen ◽

Lu Ling ◽

Peng-Fei Dou ◽

Hu Bo ◽

...

Keyword(s):

Liver Fibrosis ◽

Liver Injury ◽

Total Flavonoids ◽

Protective Effects ◽

Bidens Pilosa ◽

Animal Liver

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Taurine Alleviates Schistosoma-Induced Liver Injury by Inhibiting the TXNIP/NLRP3 Inflammasome Signal Pathway and Pyroptosis

Infection and Immunity ◽

10.1128/iai.00732-19 ◽

2019 ◽

Vol 87 (12) ◽

Cited By ~ 5

Author(s):

Xin Liu ◽

Ya-Rong Zhang ◽

Chen Cai ◽

Xian-Qiang Ni ◽

Qing Zhu ◽

...

Keyword(s):

Liver Fibrosis ◽

Liver Injury ◽

Nlrp3 Inflammasome ◽

Organ Damage ◽

Inflammasome Activation ◽

Protective Effects ◽

Interacting Protein ◽

Content Type ◽

Pyrin Domain ◽

Hepatic Granulomas

ABSTRACT Schistosomiasis is a parasitic helminth disease that can cause severe inflammatory pathology, leading to organ damage, in humans. During a schistosomal infection, the eggs are trapped in the host liver, and products derived from eggs induce a polarized Th2 cell response, resulting in granuloma formation and eventually fibrosis. Previous studies indicated that the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome is involved in schistosomiasis-associated liver fibrosis and that taurine could ameliorate hepatic granulomas and fibrosis caused by Schistosoma japonicum infection. Nevertheless, the precise role and molecular mechanism of the NLRP3 inflammasome and the protective effects of taurine in S. japonicum infection have not been extensively studied. In this study, we investigated the role of the NLRP3 inflammasome and the hepatoprotective mechanism of taurine in schistosoma-induced liver injury in mice. NLRP3 deficiency ameliorated S. japonicum-infection-induced hepatosplenomegaly, liver dysfunction, and hepatic granulomas and fibrosis; it also reduced NLRP3-dependent liver pyroptosis. Furthermore, taurine suppressed hepatic thioredoxin-interacting protein (TXNIP)/NLRP3 inflammasome activation in mice with S. japonicum infections, thereby inhibiting the activation of downstream inflammatory mediators such as interleukin-1β and subsequent pyroptosis. Our results suggest that the TXNIP/NLRP3 inflammasome pathway and mediating pyroptosis are involved in S. japonicum-induced liver injury and may be a potential therapeutic target for schistosomiasis treatment. In addition, taurine may be useful to alleviate or to prevent the occurrence of schistosomiasis-associated liver fibrosis.

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Resolvin D1 attenuates CCl4 Induced Liver Fibrosis by Inhibiting Autophagy-Mediated HSC activation via AKT/mTOR Pathway

Frontiers in Pharmacology ◽

10.3389/fphar.2021.792414 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiahuan Li ◽

Xiaoling Deng ◽

Shuhan Wang ◽

Qianqian Jiang ◽

Keshu Xu

Keyword(s):

Liver Fibrosis ◽

Liver Injury ◽

Hepatic Fibrosis ◽

Stellate Cell ◽

Mtor Pathway ◽

Protective Effects ◽

Resolvin D1 ◽

Akt Inhibitor

Resolvin D1 (RvD1) was previously reported to relieve inflammation and liver damage in several liver diseases, but its potential role in liver fibrosis remains elusive. The aim of our study was to investigate the effects and underlying mechanisms of RvD1 in hepatic autophagy in liver fibrosis. In vivo, male C57BL/6 mice were intraperitoneally injected with 20% carbon tetrachloride (CCl4, 5 ml/kg) twice weekly for 6 weeks to establish liver fibrosis model. RvD1 (100 ng or 300 ng/mouse) was added daily in the last 2 weeks of the modeling period. In vitro, lipopolysaccharide (LPS)-activated LX-2 cells were co-treated with increasing concentrations (2.5–10 nM) of RvD1. The degree of liver injury was measured by detecting serum AST and ALT contents and H&E staining. Hepatic fibrosis was assessed by masson's trichrome staining and metavir scoring. The qRT-PCR, western blot, immunohistochemistry, and immunofluorescence were applied to liver tissues or LPS-activated LX-2 cells to explore the protective effects of RvD1 in liver fibrosis. Our findings reported that RvD1 significantly attenuated CCl4 induced liver injury and fibrosis by decreasing plasma AST and ALT levels, reducing collagen I and α-SMA accumulation and other pro-fibrotic genes (CTGF, TIMP-1 and Vimentin) expressions in mouse liver, restoring damaged histological architecture and improving hepatic fibrosis scores. In vitro, RvD1 also repressed the LPS induced LX-2 cells activation and proliferation. These significant improvements mainly attributed to the inhibiting effect of RvD1 on autophagy in the process of hepatic stellate cell (HSC) activation, as demonstrated by decreased ratio of LC3-II/I and elevated p62 after RvD1 treatment. In addition, using AZD5363 (an AKT inhibitor that activates autophagy) and AZD8055 (an mTOR inhibitor, another autophagy activator), we further verified that RvD1 suppressed autophagy-mediated HSC activation and alleviated CCl4 induced liver fibrosis partly through AKT/mTOR pathway. Overall, these results demonstrate that RvD1 treatment is expected to become a novel therapeutic strategy against liver fibrosis.

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Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondria function and mitophagy balance in rats.

Food & Function ◽

10.1039/d0fo03220d ◽

2021 ◽

Author(s):

Huichao Zhao ◽

Shuang Liu ◽

Hui Zhao ◽

Meilan Xue ◽

Huaqi Zhang ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Alcoholic Liver Disease ◽

Therapeutic Strategy ◽

Hepatic Lesion ◽

Protective Effects ◽

Regulatory Effects

For alcoholic liver disease (ALD), mitophagy was reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was to investigate the regulatory effects of...

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Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

Applied Sciences ◽

10.3390/app11010390 ◽

2021 ◽

Vol 11 (1) ◽

pp. 390

Author(s):

Beom-Rak Choi ◽

Il-Je Cho ◽

Su-Jin Jung ◽

Jae-Kwang Kim ◽

Dae-Geon Lee ◽

...

Keyword(s):

Carbon Tetrachloride ◽

Liver Injury ◽

Acute Liver Injury ◽

Antioxidant Activities ◽

Body Weight Gain ◽

Histopathological Analysis ◽

Related Factor ◽

Mrna Levels ◽

Protective Effects ◽

Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

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Possible unrecognised liver injury is associated with mortality in critically ill COVID-19 patients

Therapeutic Advances in Gastroenterology ◽

10.1177/17562848211023410 ◽

2021 ◽

Vol 14 ◽

pp. 175628482110234

Author(s):

Mario Romero-Cristóbal ◽

Ana Clemente-Sánchez ◽

Patricia Piñeiro ◽

Jamil Cedeño ◽

Laura Rayón ◽

...

Keyword(s):

Liver Disease ◽

Liver Fibrosis ◽

Liver Injury ◽

Chronic Liver Disease ◽

Critically Ill ◽

Cox Regression ◽

Chronic Liver ◽

Cox Regression Analysis ◽

Risk Of Death ◽

The Impact

Background: Coronavirus disease (COVID-19) with acute respiratory distress syndrome is a life-threatening condition. A previous diagnosis of chronic liver disease is associated with poorer outcomes. Nevertheless, the impact of silent liver injury has not been investigated. We aimed to explore the association of pre-admission liver fibrosis indices with the prognosis of critically ill COVID-19 patients. Methods: The work presented was an observational study in 214 patients with COVID-19 consecutively admitted to the intensive care unit (ICU). Pre-admission liver fibrosis indices were calculated. In-hospital mortality and predictive factors were explored with Kaplan–Meier and Cox regression analysis. Results: The mean age was 59.58 (13.79) years; 16 patients (7.48%) had previously recognised chronic liver disease. Up to 78.84% of patients according to Forns, and 45.76% according to FIB-4, had more than minimal fibrosis. Fibrosis indices were higher in non-survivors [Forns: 6.04 (1.42) versus 4.99 (1.58), p < 0.001; FIB-4: 1.77 (1.17) versus 1.41 (0.91), p = 0.020)], but no differences were found in liver biochemistry parameters. Patients with any degree of fibrosis either by Forns or FIB-4 had a higher mortality, which increased according to the severity of fibrosis ( p < 0.05 for both indexes). Both Forns [HR 1.41 (1.11–1.81); p = 0.006] and FIB-4 [HR 1.31 (0.99–1.72); p = 0.051] were independently related to survival after adjusting for the Charlson comorbidity index, APACHE II, and ferritin. Conclusion: Unrecognised liver fibrosis, assessed by serological tests prior to admission, is independently associated with a higher risk of death in patients with severe COVID-19 admitted to the ICU.

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