Protective Effects and Mechanism of Polysaccharides from Edible Medicinal Plants in Alcoholic Liver Injury: A Review.

Alcohol use accounts for a large variety of diseases, among which alcoholic liver injury (ALI) poses a serious threat to human health. In order to overcome the limitations of chemotherapeutic agents, some natural constituents, especially polysaccharides from edible medicinal plants (PEMPs), have been applied for the prevention and treatment of ALI. In this review, the protective effects of PEMPs on acute, subacute, subchronic, and chronic ALI are summarized. The pathogenesis of alcoholic liver injury is analyzed. The structure-activity relationship (SAR) and safety of PEMPs are discussed. In addition, the mechanism underlying the hepatoprotective activity of polysaccharides from edible medicinal plants is explored. PEMPs with hepatoprotective activities mainly belong to the families Orchidaceae, Solanaceae, and Liliaceae. The possible mechanisms of PEMPs include activating enzymes related to alcohol metabolism, attenuating damage from oxidative stress, regulating cytokines, inhibiting the apoptosis of hepatocytes, improving mitochondrial function, and regulating the gut microbiota. Strategies for further research into the practical application of PEMPs for ALI are proposed. Future studies on the mechanism of action of PEMPs will need to focus more on the utilization of multi-omics approaches, such as proteomics, epigenomics, and lipidomics.

Hepatoprotective Effects of Rosmarinic Acid on Ovalbumin-Induced Intestinal Food Allergy Mouse Model.

Rosmarinic acid (RA) has been proven to exert antianaphylaxis in atopic dermatitis, asthma, and allergic rhinitis. The aim of this study was to determine the hepatoprotective effects of RA on ovalbumin (OVA) challenge-induced intestinal allergy. The results exhibited that RA could relieve anaphylactic symptoms, decrease diarrhea, and prevent hypothermia in allergic mice. Moreover, the elevation of OVA specific IgE (OVA-sIgE), histamine, and mouse mast cell proteinases (mMCP-1) in the serum of OVA challenged mice were remarkably inhibited by RA. OVA challenge resulted in notable increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, liver malondialdehyde (MDA) and nitic oxide (NO) levels, and a remarkable decrease in liver superoxide dismutase (SOD) activity and glutathione (GSH) level. RA treatments succeeded in improving these biochemical parameters and promote the redox homeostasis. Cytokine expression evaluation showed that RA effectively enhanced the expression of anti-inflammatory cytokines (IL-10 and FOXP-3) in the liver of OVA-challenged mice. Meanwhile, the elevation of pro-inflammatory cytokines (TNF-α, IL-4, IL-6, mMCP-1, and iNOS) were remarkably inhibited by RA. These findings suggest that RA possesses hepatoprotective effects on OVA challenge-induced liver injury. The anti-oxidative and anti-inflammatory activities of RA potentially play vital roles in this process.

A Novel PTP1B Inhibitor-Phosphate of Polymannuronic Acid Ameliorates Insulin Resistance by Regulating IRS-1/Akt Signaling.

Protein tyrosine phosphatase 1B (PTP1B) is a critical negative modulator of insulin signaling and has attracted considerable attention in treating type 2 diabetes mellitus (T2DM). Low-molecular-weight polymannuronic acid phosphate (LPMP) was found to be a selective PTP1B inhibitor with an IC50 of 1.02 ± 0.17 µM. Cellular glucose consumption was significantly elevated in insulin-resistant HepG2 cells after LPMP treatment. LPMP could alleviate oxidative stress and endoplasmic reticulum stress, which are associated with the development of insulin resistance. Western blot and polymerase chain reaction (PCR) analysis demonstrated that LPMP could enhance insulin sensitivity through the PTP1B/IRS/Akt transduction pathway. Furthermore, animal study confirmed that LPMP could decrease blood glucose, alleviate insulin resistance, and exert hepatoprotective effects in diabetic mice. Taken together, LPMP can effectively inhibit insulin resistance and has high potential as an anti-diabetic drug candidate to be further developed.

Hepatoprotective Effects of Bioflavonoid Luteolin Using Self-Nanoemulsifying Drug Delivery System.

Luteolin (LUT) is a natural pharmaceutical compound that is weakly water soluble and has low bioavailability when taken orally. As a result, the goal of this research was to create self-nanoemulsifying drug delivery systems (SNEDDS) for LUT in an attempt to improve its in vitro dissolution and hepatoprotective effects, resulting in increased oral bioavailability. Using the aqueous phase titration approach and the creation of pseudo-ternary phase diagrams with Capryol-PGMC (oil phase), Tween-80 (surfactant), and Transcutol-HP (co-emulsifier), various SNEDDS of LUT were generated. SNEDDS were assessed for droplet size, polydispersity index (PDI), zeta potential (ZP), refractive index (RI), and percent of transmittance (percent T) after undergoing several thermodynamic stability and self-nanoemulsification experiments. When compared to LUT suspension, the developed SNEDDS revealed considerable LUT release from all SNEDDS. Droplet size was 40 nm, PDI was <0.3, ZP was -30.58 mV, RI was 1.40, percent T was >98 percent, and drug release profile was >96 percent in optimized SNEDDS of LUT. For in vivo hepatoprotective testing in rats, optimized SNEDDS was chosen. When compared to LUT suspension, hepatoprotective tests showed that optimized LUT SNEDDS had a substantial hepatoprotective impact. The findings of this investigation suggested that SNEDDS could improve bioflavonoid LUT dissolution rate and therapeutic efficacy.

Hepatoprotective Constituents of Total Dibenzocyclooctadiene Lignans from Schisandra chinensis Based on the Spectrum-Effect Relationship.

To scientifically clarify the hepatoprotective constituents of Fructus Schizandrae chinensis, eleven batches samples of total dibenzocyclooctadiene lignans (TDL) from Schisandra chinensis were prepared by using the optimum extraction technique. Characteristic high-performance liquid chromatography (HPLC) chromatograms were obtained through HPLC analysis technology, and the hepatoprotective effects of the eleven batches of TDL were evaluated by MTT assay. Based on the chemical and biological activity results, the spectrum-effect relationship between the characteristic HPLC fingerprints and the hepatoprotective effect of TDL was established using Minitab 16.0 data analysis software. On the basis of the spectrum-effect relationship, thirteen compounds (1-13) were obtained from the TDL by chemical natural product chemical separation and purification technology, and their structures were identified on the basis of the spectral data and the literature. Based on these compounds, thirteen common peaks among the thirty-three chromatographic peaks in the above HPLC fingerprints were identified. Our findings showed that some components, including, schisandrin B (2), schisandrin A (3), and schisandrol B (7) had significant roles in promoting hepatoprotective activity. Preliminary verification of the spectrum-effect relationship of TDL from S. chinensis was carried out, and the results confirmed that the activity of a composite of these three key components in optimal ratios was better than that of any individual compound, which potentially confirmed the reliability of the spectrum-effect relationship and the synergistic effects of traditional Chinese medicine.

Brassica rapa Polysaccharides Ameliorate CCl4 -Induced Acute Liver Injury in Mice through Inhibiting Inflammatory Apoptotic Response and Oxidative Stress.

Brassica rapa L., also called NIUMA, is used empirically in Tibetan medicine for its antioxidant, anti-inflammatory and antiradiation activities. This study explored the hepatoprotective effects of B. rapa polysaccharides (BRPs) on acute liver injury induced by carbon tetrachloride (CCl4 ) in mice and the underlying mechanisms. Mice were treated with CCl4 after the oral administration of BRPs (55, 110 and 220 mg/kg) or bifendate (100 mg/kg) for 7 days. Blood and liver samples of mice were collected for analysis after 24 h. The ALP, ALT and AST levels and the biological activities of SOD, MDA and GSH-Px were measured. Histopathological changes in the liver were determined through hematoxylin and eosin staining. Moreover, TNF-α, IL-1ß and IL-6 expression levels were detected by commercial reagent kits. Finally, Western blot analysis was used to check the relative expression levels of caspase-3, p-JAK2 and p-STAT3. The BRP pre-treatment significantly decreased the enzymatic activities of ALT, ALP and AST in the serum, markedly increased the activities of SOD and GSH-Px in the liver and reduced the MDA concentration in the liver. BRPs alleviated hepatocyte injury and markedly inhibited the expression of TNF-α, IL-1ß and IL-6, also downregulating the CCl4 -induced hepatic tissue expression of caspase-3. Furthermore, BRPs inhibited the JAK2/STAT3 signaling pathway in a dose-dependent manner in the liver. This study demonstrated that BRPs exert hepatoprotective effect against the CCl4 -induced liver injury via modulating the apoptotic and inflammatory responses and downregulating the JAK2/STAT3 signaling pathway. Therefore, B. rapa could be considered a hepatoprotective medicine.

New benzoic acid glycosides from Sophora flavescens.

Two new benzoic acid derivatives, sophophenoside A (1) and sophophenoside B (2), were isolated from Sophora flavescens. Their structures were elucidated by detailed spectroscopic analysis and chemical methods. Compounds 1 and 2 were assayed for their hepatoprotective activity on the cytotoxic effect of D-galactosamine on HL-7702 cells, and compound 1 exhibited a moderate hepatoprotective activity at a concentration of 10 µM.

Antioxidant Activity and Protective Effects of Enzyme-Extracted Oudemansiella radiata Polysaccharides on Alcohol-Induced Liver Injury.

This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS) on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals, and the level of reducing power. En-OPS showed hepatoprotective activities on decreasing the serum levels of aspertate aminotransferase (AST), alamine aminotransferase (ALT), and alkaline phosphatase (ALP), as well as hepatic lipid levels of total cholesterol (TC) and triacylglycerols (TG). En-OPS treatment reversed the acute impairment induced by alcohol consumption, including reactive oxygen species (ROS) generation, malondialdehyde (MAD), and lipid peroxide (LPO) elevation; and superoxide dismutase (SOD), GSH peroxide (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) impairment. The En-OPS effectively ameliorated alcohol metabolism by activating alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), and reducing cytochrome P450 2E1 (CYP2E1) levels. Furthermore, the histopathological observations also displayed that En-OPS could alleviate liver damage. These results indicated that En-OPS could be suitable to be an ingredient of preventing alcoholic liver diseases (ALD). In addition, the preliminary structure characteristics of En-OPS were also analyzed by Fourier transform infrared (FT-IR) spectroscopy and a gas chromatography-flame ionization detector (GC-FID).

Hepatoprotective Effects of Xylose-Taurine Reduced Against Hydrogen Peroxide-Induced Oxidative Stress in Cultured Hepatocytes.

In this study, Xylose-Taurine reduced (X-T-R) was synthesized to enhance biological activities. Hence, we investigated the hepatoprotective effects of X-T-R against H2O2-induced hepatocyte damage and apoptosis. The results showed that X-T-R led to the cytoprotective effect against H2O2-induced oxidative stress in cultured hepatocytes such as the improvement of cell viability and the reduction of reactive oxygen species (ROS) production. Additionally, pre-treatment with X-T-R increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase:quinone 1 (NQO1) and heme oxygenase 1 (HO-1) in cultured hepatocytes. Furthermore, X-T-R protected the cells against apoptosis via regulating the expression level of Bcl-2/Bax as well as the activation of caspase-3. According to the results obtained, X-T-R may be a bio-material for the therapy of hepatic diseases.

In Vitro Antioxidant Activities of Enzymatic Hydrolysate from Schizochytrium sp. and Its Hepatoprotective Effects on Acute Alcohol-Induced Liver Injury In Vivo.

Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180-3000 Da (52.29%). SPH was divided into two fractions by ultrafiltration: SPH-I (MW < 3 kDa) and SPH-II (MW > 3 kDa). Besides showing lipid peroxidation inhibitory activity in vitro, SPH-I exhibited high DPPH and ABTS radicals scavenging activities with IC50 of 350 µg/mL and 17.5 µg/mL, respectively. In addition, the antioxidant activity of SPH-I was estimated in vivo using the model of acute alcohol-induced liver injury in mice. For the hepatoprotective effects, oral administration of SPH-I at different concentrations (100, 300 mg/kg BW) to the mice subjected to alcohol significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA) level compared to the untreated mice. Besides, SPH-I could effectively restore the hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level. Results suggested that SPH was rich in biopeptides that could be exploited as antioxidant molecules against oxidative stress in human body.

Purification, Preliminary Characterization and Hepatoprotective Effects of Polysaccharides from Dandelion Root.

In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn't contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose. The backbone of DRP1 was mainly composed of (1→6)-linked-α-d-Glc and (1→3,4)-linked-α-d-Glc. DRP2 was mainly composed of (1→)-linked-α-d-Ara and (1→)-linked-α-d-Glc. A proof-of-concept study was performed to assess the therapeutic potential of DRP1 and DRP2 in a mouse model that mimics acetaminophen (APAP) -induced liver injury (AILI) in humans. The present study shows DRP1 and DRP2 could protect the liver from APAP-induced hepatic injury by activating the Nrf2-Keap1 pathway. These conclusions demonstrate that the DRP1 and DRP2 might be suitable as functional foods and natural drugs in preventing APAP-induced liver injury.

Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

Role of Arthrospira Platensis in Preventing and Treating High-Fat Diet-Induced Hypercholesterolemia in Adult Rats.

Hyperlipidaemia is a recognised risk factor for cardiovascular disease. In this study, the antihyperlipidaemic properties of spirulina (Arthrospira platensis, strain S2 from Serbia) were tested in adult Wistar rats before and after induction of hypercholesterolaemia by a high-fat diet (HFD) to compare the preventive with the curative effect. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) levels were measured in the blood samples. The chemical composition (lipids, proteins and cholesterol) and the content of bile acids in the faeces of the animals were also analysed. Feeding rats with an atherogenic diet for 10 weeks led to the successful development of hyperlipidaemia, as serum TC and LDL-C levels as well as lipids, cholesterol and bile acids in the animals' faeces were significantly increased. Pre- and post-treatment with spirulina led to a reduction in serum LDL, TC and ALT levels. Administration of spirulina resulted in both a significant increase in primary bile acids excretion and a decrease in bile acids metabolism, with pre-treatment being more effective than post-treatment in some cases. These results suggest that increased excretion of bile acids as well as an effect on the gut microbiota may be the mechanism responsible for the anti-hyperlipidaemic activity of the tested spirulina strain.

Network medicine-based analysis of the hepatoprotective effects of Amomum villosum Lour. on alcoholic liver disease in rats.

Alcoholic liver disease (ALD) is characterized by high morbidity and mortality, and mainly results from prolonged and excessive alcohol use. Amomum villosum Lour. (A. villosum), a well-known traditional Chinese medicine (TCM), has hepatoprotective properties. However, its ability to combat alcohol-induced liver injury has not been fully explored. The objective of this study was to investigate the hepatoprotective effects of A. villosum in a rat model of alcohol-induced liver disease, thereby establishing a scientific foundation for the potential preventive use of A. villosum in ALD. We established a Chinese liquor (Baijiu)-induced liver injury model in rats. Hematoxylin and eosin (HE) staining, in combination with biochemical tests, was used to evaluate the protective effects of A. villosum on the liver. The integration of network medicine analysis with experimental validation was used to explore the hepatoprotective effects and potential mechanisms of A. villosum in rats. Our findings showed that A. villosum ameliorated alcohol-induced changes in body weight, liver index, hepatic steatosis, inflammation, blood lipid metabolism, and liver function in rats. Network proximity analysis was employed to identify 18 potentially active ingredients of A. villosum for ALD treatment. These potentially active ingredients in the blood were further identified using mass spectrometry (MS). Our results showed that A. villosum plays a hepatoprotective role by modulating the protein levels of estrogen receptor 1 (ESR1), anti-nuclear receptor subfamily 3 group C member 1 (NR3C1), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). In conclusion, the results of the current study suggested that A. villosum potentially exerts hepatoprotective effects on ALD in rats, possibly through regulating the protein levels of ESR1, NR3C1, IL-6, and TNF-α.

Effect of Niosomal Encapsulation of Quercetin and Silymarin and their Combination on Dimethylnitrosoamine-induced and Phenobarbital promoted Hepatocellular Carcinoma in Rat Model.

BACKGROUND: Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma. OBJECTIVE: The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine. METHODS: Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out. RESULTS: Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups. CONCLUSION: Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required.

Herbal Remedies for Hepatic Inflammation: Unravelling Pathways and Mechanisms for Therapeutic Intervention.

Inflammation is a universal response of mammalian tissue to harm, comprising reactions to injuries, pathogens, and foreign particles. Liver inflammation is commonly associated with hepatocyte necrosis and apoptosis. These forms of liver cell injury initiate a sequence of events independent of the etiological basis for the inflammation and can result in hepatic disorders. It is also common for liver cancer. This review fundamentally focuses on the molecular pathways involved in hepatic inflammation. This review aims to explore the molecular pathways involved in hepatic inflammation, focusing on arachidonic acid, NF-κB, MAPK, PI3K/Akt, and JAK/STAT pathways. It investigates active compounds in herbal plants and their pharmacological characteristics. The review proposes a unique therapeutic blueprint for managing hepatic inflammation and diseases by modifying these pathways with herbal remedies.

Synthesis of Ganoderic Acids Loaded Zein-Chitosan Nanoparticles and Evaluation of Their Hepatoprotective Effect on Mice Given Excessive Alcohol.

Ganoderma lucidum, used in East Asia for its health benefits, contains ganoderic acids (GA) which have various pharmacological activities but are limited by poor water solubility and low oral bioaccessibility. This study synthesized and characterized ganoderic acids loaded zein-chitosan nanoparticles (GA-NPs), and investigated its advantages in alleviating alcoholic liver injury (ALI) in mice model. The GA-NPs demonstrated high encapsulation efficiency (92.68%), small particle size (177.20 nm), and a +29.53 mV zeta potential. The experimental results of alcohol-induced liver injury mouse model showed that GA-NPs significantly improved liver metabolic function, reduced alcohol-induced liver oxidative stress in liver by decreasing lactate dehydrogenase activity and malondialdehyde level, while increasing the activities of liver antioxidant enzymes and alcohol dehydrogenase. Moreover, GA-NPs were favorable to ameliorate intestinal microbiota dysbiosis in mice exposed to alcohol by increasing the proportion of probiotics such as Romboutsia, Faecalibaculum, Bifidobacterium and Turicibacter, etc., which were highly correlated with the improvement of liver function. Furthermore, GA-NPs modulated the mRNA expression related to ethanol metabolism, oxidative stress and lipid metabolism. Conclusively, this study revealed that GA-NPs have stronger hepatoprotective effects than non-encapsulated ganoderic acids on alleviating ALI by regulating intestinal microbiota and liver metabolism.

Chemical characterisation of essential oil from Sambucus williamsii Hance leaves and its hepatoprotective effects.

This study is the first to examine the effect of leaves of Sambucus williamsii Hance essential oil on acute liver injury. According to gas chromatography-mass spectrometry analysis, the major constituents of S. williamsii essential oil (SEO)were (S)-falcarinol (62.66%), 17-pentatriacontene (7.78%) and tetrapentacontane (8.64%). Mice were pre-treated with SEO for 6 days followed by inducing liver injury with CCl4. The results indicated that SEO protected the liver against CCl4-induced injuries. Elevated levels of alanine-aminotransferase (ALT), aspartate amino-transferase (AST), alkaline phosphatase (ALP) in serum were significantly reduced on SEO pre-treatment. SEO pre-treatment significantly inhibited the oxidative stress and inflammation. Furthermore, toll-like receptor-4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathways were significantly modulated by SEO in the liver tissue. The findings demonstrate that the essential oil of S. williamsii has enhancing the resistance to CCl4-induced liver injury.

Chlorogenic acids: A pharmacological systematic review on their hepatoprotective effects.

BACKGROUND: Liver diseases have a negative impact on global health and are a leading cause of death worldwide. Chlorogenic acids (CGAs), a family of esters formed between certain trans-cinnamic acids and quinic acid, are natural polyphenols abundant in coffee, tea, and a variety of traditional Chinese medicines (TCMs). They are reported to have good hepatoprotective effects against various liver diseases. PURPOSE: This review aims to analyze the available literature on the hepatoprotective effect of CGAs, with particular emphasis on their mechanisms. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. PubMed and Web of Science databases were adopted to retrieve all relevant literature on CGAs for liver disease from 2013 to March 2023. RESULTS: Research has indicated that CGAs play a crucial role in improving different types of liver diseases, including drug-induced liver injury (DILI), alcoholic liver disease (ALD), metabolic (dysfunction)-associated fatty liver disease (MAFLD), cholestatic liver disease (CLD), liver fibrosis, and liver cancer. CGAs display remarkable antioxidant and anti-inflammatory effects by activating erythroid 2-related factor 2 (Nrf2) and inhibiting toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathways. Some important molecules such as AMP-activated protein kinase (AMPK) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), and other key physiological processes like intestinal barrier and gut microbiota have also been discovered to participate in CGAs-provided amelioration on various liver diseases. CONCLUSION: In this review, different studies indicate that CGAs have an excellent protective effect against various liver diseases associated with various signaling pathways.

Dendrobium and its active ingredients: Emerging role in liver protection.

Dendrobium is a traditional medicinal plant, which has a variety of clinical applications in China. It has been reported that Dendrobium contains various bioactive components, mainly including polysaccharides and alkaloids. Previous studies have shown that Dendrobium has pharmacological activities including antiviral, anti-inflammatory, and antioxidant effects, as well as immune regulation. Particularly, the anti-aging functions and neuroprotective effects of Dendrobium have been well characterized in a wide array of cell and animal models. In recent years, the effect of Dendrobium on the liver has emerged as a new direction to explore its therapeutic benefits and has received more and more attention. This review is focused on the beneficial effects of Dendrobium on liver toxicity and various liver disorders, which presumably are attributed to a consequence of an array of modes of action due to its multiple bioactive components, and largely lack mechanistic and pharmacokinetic characterization. A particular emphasis is placed on the potential action mechanisms related to Dendrobium's liver protection. Research perspectives in regard to the potential therapeutic application for Dendrobium are also discussed in this review.