iridoids and Liver-Diseases

Liver disease rates are gradually increasing over the years, becoming a severe public health problem. The indiscriminate use of drugs associated with a rich fat diet, high consumption of alcoholic beverages, and exposure to viral infections and lipid peroxidative products are considered the chief factors for developing hepatic disorders. Owing to the absence of reliable hepatoprotective drugs in the therapeutic arsenal, since they present a high incidence of adverse reactions and/or lack of efficacy in some cases, liver diseases are widely treated with medicinal plants. Among them are the plants producing iridoids, which are believed to be good remedies for liver disease due to their bitter taste. The hepatoprotective effect of iridoids and extracts, rich in these compounds, has been demonstrated, both in vitro and in vivo.. This review aims to scrutinize the available literature related to the hepatoprotective activity of iridoids.. The information was obtained from scientific databases (Science Direct, PubMed, Web of Science, Scopus, ACS Publications, Wiley Online Library) until December, 2021.. A total of 63 hepatoprotective iridoids were found, including aucubin, catalpol and picroliv, a mixture of two iridoids. They are the target of a high number of studies, which revealed their protective action against different hepatotoxic agents and detailed action mechanisms.

Topics: Antioxidants; Humans; Iridoids; Liver; Liver Diseases; Plant Extracts; Plants, Medicinal

Yīn-Chén-Hāo decoction (YCHD) is a traditional Chinese medicine formula composed of capillaris (

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Antiviral Agents; Artemisia; Ascites; Chlorogenic Acid; Clinical Trials as Topic; Coumarins; Drugs, Chinese Herbal; Emodin; Fatty Liver; Gardenia; Humans; Iridoids; Liver Diseases; Plant Extracts; Rheum

Topics: Animals; Dietary Fats; Iridoid Glucosides; Iridoids; Lipid Metabolism; Liver; Liver Diseases; Male; Olea; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Rats

Secoiridoids could be used as a potential new drug for the treatment of hepatic disease. The content of secoiridoids of

Topics: China; Chromatography, High Pressure Liquid; Gentiana; Humans; Iridoid Glucosides; Iridoids; Liver Diseases; Plant Leaves; Plant Roots; Plant Stems; Pyrones; Spectroscopy, Fourier Transform Infrared

Recently, it has reported that many inflammatory bowel disease (IBD) patients were contracted secondary liver injury. Monotropein (MON), an iridoid glycoside, is demonstrated to possess protective effects on acute colitis mice due to its anti-inflammatory activities. However, it was remained unknown whether MON could inhibit secondary liver injury caused by IBD. The aim of the present study was to investigate the protective roles and mechanisms of MON on secondary liver injury in chronic colitis mice model. In this study, 2% Dextran sodium sulfate (DSS) was used to induce mice model of chronic colitis. The results showed that MON attenuated DSS-induced hepatic pathological damage, liver parameters, infiltration of macrophages and cytokines levels. Furthermore, we found that MON attenuated liver injury through suppressing the activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and down-regulating the activity of NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome. All the data indicated that MON may be an effective therapeutic reagent to attenuate secondary liver injury induced by chronic colitis.

Topics: Animals; Anti-Inflammatory Agents; Chronic Disease; Colitis; Dextran Sulfate; Disease Models, Animal; Inflammasomes; Iridoids; Liver; Liver Diseases; Macrophages; Male; Mice; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Toll-Like Receptor 4

In the present study, we investigated the protective effects of oleuropein- and hydroxytyrosol-rich extracts obtained from olive leaves against bisphenol A (BPA)-induced hyperlipidemia and liver injury in male rats. For this purpose, four groups of male rats (8 per group) were used: control group (Control), rats treated with BPA, rats treated with both BPA and oleuropein (OLE-BPA), and rats treated with both BPA and hydroxytyrosol (HYT-BPA). After 60 days of treatment, the results obtained using the DXA technique showed that treatment with BPA (10 mg per kg b.w.) increased the body weight and adipose tissue mass in male rats. Moreover, plasma levels of triglycerides, total cholesterol, LDL-cholesterol, AST, ALT, LDH, and TNF-α increased. The immunohistochemical analysis revealed a significant increase in the expression of COX-2 and p53 and a decrease in the expression of Bcl-2 related to liver inflammation. Oral administration of oleuropein and hydroxytyrosol-rich extracts obtained from olive leaves at 16 mg kg-1 reduced both the body weight and adipose tissue mass. These extracts were able to ameliorate liver damage and improve the elevated levels of TG and liver enzymes of BPA-treated rats possibly through enhancing CAT and SOD activities. Western blot results revealed that administration of the abovementioned extracts decreased the protein expression of NF-κB and TNF-α through the p38 signaling pathway. Overall, the findings suggest that the olive leaf extracts possess hypolipidemic and hepatoprotective effects against BPA-induced metabolic disorders through enhancing the antioxidative defense system and regulating the important signaling pathway activities.

Topics: Animals; Antioxidants; Benzhydryl Compounds; Humans; Iridoid Glucosides; Iridoids; Lipid Metabolism; Liver Diseases; Male; Olea; Phenols; Phenylethyl Alcohol; Plant Extracts; Plant Leaves; Rats

Hepatic ischemia and reperfusion (IR) injury is closely linked to oxidative mitochondrial damage. Since mitochondrial quality control (QC) plays a pivotal role in the recovery of impaired mitochondrial function, mitochondrial QC has emerged as a potential therapeutic target. Genipin, an iridoid compound from Gardenia jasminoides, has been showed antioxidant and anti-inflammatory properties. In this study, we investigated the hepatoprotective mechanism of genipin against IR-induced hepatic injury, particularly focusing on mitochondrial QC. Male C57BL/6 mice underwent liver ischemia for 60min, followed by reperfusion for 6h. Genipin (100mg/kg, i.p.) or vehicle (10% Tween 80 in saline) was administrated to mice 1h before ischemia. Liver and blood samples were collected 6h after reperfusion. Hepatic IR increased hepatocellular oxidative damage and induced mitochondrial dysfunction. These phenomena were ameliorated by genipin. Hepatic IR also increased the level of mitochondrial fission, such as dynamin-related protein 1 and the level of PINK1 protein expression. In contrast, hepatic IR decreased the levels of mitochondrial biogenesis related proteins (e.g., peroxisome proliferator-activated receptor gamma coactivator 1α, nuclear respiratory factor 1, and mitochondrial transcription factor A), mitophagy related proteins (e.g., Parkin), and fusion related protein (e.g., mitofusin 2). Furthermore, hepatic IR decreased the levels of sirtuin1 protein and phosphorylation of AMP-activated protein kinase. Genipin alleviated these IR-induced changes. These data indicate that genipin protects against IR-induced hepatic injury via regulating mitochondrial QC. (225/250).

Topics: AMP-Activated Protein Kinases; Animals; Cytokines; Gardenia; Iridoids; Lipid Peroxidation; Liver Diseases; Male; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Mitochondrial Swelling; Oxidative Stress; Protective Agents; Quality Control; Reperfusion Injury; Signal Transduction; Sirtuin 1

Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli including inflammation and microbial infection. Genipin, an aglycon of geniposide found in gardenia fruit, is well known to have anti-inflammatory, antibacterial and antioxidative properties. This study examined the protective mechanisms of genipin against sepsis, with particular focus on the autophagic signalling pathway.. Mice were subjected to sepsis by caecal ligation and puncture (CLP). Genipin (1, 2.5 and 5 mg·kg(-1) ) or vehicle (saline) was injected i.v. immediately (0 h) after CLP, and chloroquine (60 mg·kg(-1) ), an autophagy inhibitor, was injected i.p. 1 h before CLP. Blood and liver tissues were isolated 6 h after CLP.. Genipin improved survival rate and decreased serum levels of aminotransferases and pro-inflammatory cytokines after CLP; effects abolished by chloroquine. The liver expression of autophagy-related protein (Atg)12-Atg5 conjugate increased after CLP, and this increase was enhanced by genipin. CLP decreased Atg3 protein liver expression, and genipin attenuated this decrease. CLP impaired autophagic flux, as indicated by increased liver expression of microtubule-associated protein-1 light chain 3-II and sequestosome-1/p62 protein; this impaired autophagic flux was restored by genipin, and chloroquine abolished this effect. Genipin also attenuated the decreased expression of lysosome-associated membrane protein-2 and Rab7 protein and increased expression of calpain 1 protein induced by CLP in the liver.. Our findings suggest that genipin protects against septic injury by restoring impaired autophagic flux. Therefore, genipin might be a potential therapeutic agent for the treatment of sepsis.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Autophagy; Autophagy-Related Proteins; Chloroquine; Interleukin-6; Iridoids; Liver; Liver Diseases; Male; Mice; Mice, Inbred ICR; Microscopy, Electron, Transmission; Protective Agents; Sepsis; Tumor Necrosis Factor-alpha

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

Topics: Animals; Anthraquinones; Biomarkers; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Iridoids; Liver; Liver Diseases; Male; Medicine, Chinese Traditional; Metabolome; Metabolomics; Molecular Targeted Therapy; Proteome; Proteomics; Rats; Rats, Wistar; Umbelliferones

We investigated the effect of tetrahydroswertianolin (THS), a hepatoprotective agent from Swertia japonica, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (D-GalN) (700 mg/kg, i.p.) and lipopolysaccharide (LPS) (10 microg/kg, i.p.) in mice. Apoptotic symptoms were observed at the initial stage of liver damage. By 5 hr after intoxication, hepatic DNA fragmentation had risen to 2123%, with the value in untreated mice set at 100%, without a significant elevation of serum alanine transaminase (ALT) activity. There was a parallel increase in hepatocytes undergoing chromatin condensation and apoptotic body formation. By 8 hr after intoxication, serum ALT activity had risen to 3707 U/L. Pretreatment with THS (50 mg/kg, p.o.) at 18 and 2 hr before intoxication significantly reduced DNA fragmentation to 821% of that in untreated mice and prevented the emergence of chromatin condensation and apoptotic body formation. A significant and dose-dependent reduction in serum ALT activity at 8 hr also was observed with THS pretreatment. These effects of THS were different from those observed from pretreatment with glycyrrhizin (GCR), which is a clinically used hepatoprotective agent with membrane-stabilizing activity. GCR pretreatment (100 mg/kg, p.o.) did not inhibit hepatic DNA fragmentation (1588% of untreated mice), although this compound significantly protected against serum ALT elevation (1463 U/L). These data suggest that an inhibitory effect on the progression of hepatic apoptosis prior to liver injury may be involved in the hepatoprotective mechanisms of THS, whereas it appears that GCR affects the processes after apoptosis. In a separate experiment, we found that the concentration of serum TNF-alpha rose to 2016 pg/mL at 1 hr after intoxication of mice with D-GalN and LPS, but this increase was suppressed by THS pretreatment (10, 50, or 200 mg/kg, p.o.) to 716, 454, or 406 pg/mL, respectively. Further study with a reverse transcriptase-polymerase chain reaction method showed that THS blocked TNF-alpha production at the transcriptional level. Because TNF-alpha is a critical mediator to elicit apoptosis in this model, the property of suppressing TNF-alpha production may be of prime importance for THS inhibition of hepatic apoptosis.

Topics: Analysis of Variance; Animals; Apoptosis; Chemical and Drug Induced Liver Injury; DNA Fragmentation; Enzyme-Linked Immunosorbent Assay; Galactosamine; Glucosides; Iridoid Glucosides; Iridoids; Lipopolysaccharides; Liver Diseases; Male; Mice; Protective Agents; Tumor Necrosis Factor-alpha