Coping with work-related stress 7. Helm Switzerland: Springer International Publishing35— Flavonoid bioavailability may be related Sustainable skincare options Flaavonoids binding affinity Flavonoies plasma proteins. Tsaroucha, A. Specifically, they can stimulate liver enzymes such as superoxide dismutase SOD and glutathione peroxidase GSH-Pxwhich play crucial roles in the antioxidant defense system and hepatic detoxification Yu et al.

Flavonoids and liver detoxification -

Alcohol hinders the functional aspects of various tissue components and hepatocytes in particular. Alcohol diffuses, crossing the membrane barrier, and is distributed throughout the cell and tissue system, interacting with the major proteins and cellular component present in it Li et al.

Development of toxic molecules like reactive oxygen species ROS is another negative upshot of alcohol. In addition to ROS, it also produces acetaldehyde and nitric oxides, an extremely reactive and toxic by-product that chip into tissue damage Madrigal-Santillán et al.

Nitric oxide NO is recognized as managing mitochondrial respiration and biogenesis amongst organelle. Under conditions of alcohol-mediated hepatic complications, mitochondrial respiration was hindered and, in turn, hypoxia occured. Simultaneously, nuclear factor-kappa β NF-κβ , a transcription factor activation, takes place, in which it binds to iNOS promoter, an important NO, and aggravates the expression of iNOS Figure 9 Iwakiri and Kim, ; Starkel et al.

Together, this entire environment amplifies the expression of inducible nitric oxide synthase iNOS. iNOS joins hands in inducing hepatic fibrosis and the expression of inflammatory cytokines Tacke and Zimmermann, ; Cassini-Vieira et al. iNOS increases two other factors in this process.

Hypoxia-inducible factor-1 and its gene expression aid various connected hepatic anomalies viz; inhibition of mitochondrial respiration, impairment of mitochondrial fatty acid β-oxidation, and mitochondrial DNA damage Chang et al. Figure 9. Alcohol mediated Hepatotoxicity.

Hepatotoxicity caused by increased production of ROS; due to alcohol damages antioxidant defenses and mitochondrial function as well as structure. It leads to liver inflammation, fibrosis and steatosis. Cellular responses, which are sturdily involved in Kupffer cell may also activated due to action of ROS which contribute to an increase of inflammatory responses, resulting liver injury.

Furthermore, activated Kupffer cells release ROS and cytokines that are crucial for HSC activation and inducing the pro-fibrogenic pathway. Phenolics possess immense potentials in regulating the inflammatory cytokines, which are expressed in clinical conditions such as alcoholic liver diseases Wan and Jiang, ; Xu et al.

Puerarin, a known isoflavone, can excite the AMP-activated protein kinase AMPK phosphorylation in H4IIE cell lines suppressing the m TOR target proteins and 4E-binding protein Zhao et al.

This strategy aids in ameliorating the alcohol-based hepatotoxicity. Puerarin can also alleviate the hepatic necrosis due to its role in the AMPK pathway activation, scavenging activity, and lipid peroxidation inhibition Wang et al.

A majority of the metabolic disorders and their physiology related to hepatotoxicity have been studied over the years. Where sharp and clear possible elements that are responsible for chemical-induced toxicity, enzymes and protein-induced complications are considered, yet a fair amount of diseases related to metabolism remain unidentified.

Such prognostic parameters include blood pressure, abdominal obesity, or potentially hyperglycaemia. They are collectively termed as the non-alcoholic fatty liver diseases NAFLD Chalasani et al. This clinical situation is one of the most familiar and dormant forms of liver diseases, which accounts for the preliminary stage, but when left untreated this results in inflammation and, subsequently, can even lead to serious fibrosis and hepatocellular carcinoma HCC , with high rates of mortality Chen et al.

Until now, the main drugs for the treatment of NAFLD in clinics are lipid regulating agents such as statins, which are not only toxic, but also aggravate the deposition of lipids in the liver, leading to serious liver injury Arguello et al.

Phenolics such as baicalin, epicatechin, and apigenin Figure 5 have been reported to protect the liver from NAFLD, which are associated with their effects on insulin resistance and for signaling the way to anti-inflammation as well as antioxidant action Sen and Chakraborty, ; Wan and Jiang, Phenolic compounds can significantly regulate these NAFLD conditions.

Apigenin, a flavone, is a well-studied phenolic compound that can check the lipid accumulation and oxidative stress induced by high-fat diet. It can abridge the inflammatory mediators but can simultaneously amplify various endogenous antioxidative enzymes actions like superoxide dismutase and glutathione peroxidase in the liver Feng et al.

Dihydromyricetin, another important phenolic, exhibits its therapeutic effect on the improvement of glucose and lipid metabolism in patients with NAFLD, by blocking the phosphatidyl inositol 3-kinase, NF-κβ signaling pathway Chen et al.

Liver inflammation is a state of the reaction in which the liver tissues send a constant stimulus, whether acute or chronic, in response to extrinsic and intrinsic factors hampering the liver status. Acute inflammation is a localized affair, where the liver tries to regain its previous configuration.

It is the first line of defense, but when the liver cannot check these associated level of lymphocytes, vascular proliferation and tissue destruction become chronic and ultimately lead to fibrotic condition Pawlak et al.

During such chronic conditions, specialized cells such as macrophages recruit more of the inflammatory mediators including interleukins and tumor necrosis factor TNF -α Seki and Schwabe, ; Williams et al. This amplification altogether results in such a complex state that it leads to many degenerative diseases including severe cirrhosis and hepatic carcinoma Czaja, For this reason, slowing down the inflammation process becomes essential.

Initially, non-steroidal anti-inflammatory drugs NSAIDs are prescribed but the associated side effects include mild gastritis, renal failure and at times allergy due to hypersensitivity Figure 10 Pawlak et al. Figure Protective effect of phenols in various metabolic pathways in liver diseases.

The upward arrow indicating upregulation and down arrow indicating downregulation of the enzymes. Recent information on hepatic inflammation demonstrated the role of phenolics in protecting such inflammation.

Phenolic compounds like hesperidin can act against inflammation by downregulating liver enzyme biomarkers such as aspartate amino transferase AST and alanine aminotransferase ALT primarily.

It can also hold back oxidative stress and activation of T cells, which is a prime instigator of inflammation Li et al. Hesperidin, a common Citrus flavonoid, further aids in the management of various proinflammatory recruiters viz; NF-κβ and α smooth muscle actin α-SMA.

Another well-known flavone, silymarin, is also a subclass of the family of phenolic compounds that works in patients with chronic hepatic carcinoma González-Gallego et al. The chemical nature, physical properties, and dose ratio of a particular drug, along with an individual's gene expression profile, antioxidant status, and the capacity for regeneration are also crucial for cell injury.

Several mechanisms are involved in the initiation of liver cell damage and aggravate ongoing injury processes Guan et al. Dysfunction of these vital cell organelles results in the impairment of dynamic equilibrium in homeostatic condition, thus resulting in intracellular oxidative stress with excessive formation of reactive oxygen species Cannistrà et al.

Major causes of the hepatotoxic reactions by drugs are elevated ROS generation, oxidative stress and suppressed immune responses. Hepatotoxicity remains a major cause of drug withdrawal from the market. Recent examples in the USA and Europe are ximelagatran, nefazodone, nimesulide, ebrotidine, trovafloxacin, troglitazone, bromfenac, and so forth.

Gene-metabolic networks are an advanced mode to construct a network with genes and metabolites specifically deregulated in different liver disease phenotypes.

It compactly gives an overview of genes of interest, representative gene subsets that were involved in regulated signaling pathways, including tumor necrosis factor TNF , P53, NF-κB, chemokine, peroxisome proliferator activated receptor PPAR and Toll-like receptor TLR signaling pathways associated with the physiology of various hepatic disease.

Detailed information for the clinical status and associated genes in the hepatotoxicity are summarized in gene networking model Figures 11 , Gene regulation of a few bioactive phytocompounds is discussed below in Tables 1 , 2. Gene networking showing hepatotoxicity mediated gene expression and subsequent mode of action of various natural products.

This network was generated by a software Cytoscape version 3. Gene-modeling showing various hepatic diseases and associated genes with it.

A tool named Circus on shiny Circos server generated this image. The blue band is showing various genes responsible for pathophysiological conditions, the green showing various hepatic complications and the red band shows the bioactive natural compounds possessive hepatoprotective activity.

Various shades indicating the degree of relatedness between the various bands. Table 1. List of a few potent natural phenolics and their mode of action imparting hepatoprotective activity.

Table 2. Table showing various hepatic diseases and various genes and metabolites associated with it. Apigenin, a plant flavone, can improve hepatic health during severe liver disease conditions by down-regulating Nrf2-signaling and up-regulatingBCL-2 apoptotic pathway Tsaroucha et al.

It is chemically 3,4-dihydroxycinnamic acid that occurs in a diet of fruits, green tea, wine, and coffee bean components. Caffeic acid showed potential antioxidant and anti-inflammatory properties and is effective in treating major liver hitches Kim et al.

It can modulate the expression of kelch-like ECH-associated protein-1 Keap1 , a hepatic carcinoma factor, by interacting with Nrf2 binding site and restraining it from binding to Keap1 and elevating the expressions of vital antioxidative signals like HO-1 Yang et al. Catechin from green tea extracts, selective seeds, and fruits.

It is categorized by the presence of a hydroxyl moiety at C3, C5, and C7 position of at A ring, and again in C3 and C4 of the B ring. Catechin with anti-hyperlipidemic property helps in treating diverse clinical conditions associated with non-alcoholic fatty liver diseases where abnormalities in protein and lipid metabolism play the prime role in pathophysiology of the liver Sun et al.

It exerts its protective and therapeutic effects in oxidative coupled liver diseases by suppressing proinflammatory cytokines, lipid peroxidation products, hepatic stellate cells, and Akt activation. Curcumin ameliorates oxidative stress induced expression of Nrf2, SOD, CAT, and GSH.

Curcumin acts as a free-radical scavenger over the activity of different kinds of ROS via its active phenolic pharmacophore, β-diketone and methoxy group Nabavi et al. It is a flavanol found in edible plant products like cocoa and other varieties of plant foods.

Epicatechin plays an important role in lipid metabolism in fatty liver condition and hypercholesterimia Cordero-Herrera et al. It can down-regulate important liver enzymes like SGPT and SGOT, which increases its liver anomalies Shanmugam et al. It is the most abundant phenolic acid in plants that has potent antioxidant ability to freeze the activity of the free radicals like NO, O 2 -.

It exhibits prevailing anticholestatic action against liver cholestasis by inhibiting extracellular matrix related gene expression and also by disruption of the Smad signaling pathways and extracellular signal-regulated kinases Gerin et al.

It sometimes activate the AMPK or the MAPK signaling pathway by enhancing lipid metabolism Cheng et al. Several reports also confirmed the mode of action of ferulic acid is mediated by regulating the expression of several physiological factors viz; PPAR-α, CPT-1α toward lipid oxidation and this action is very important in treating fatty liver diseases Kim et al.

It is a significant flavonoid that can fuel up the expression of diverse endogenous antioxidant enzymes and can quench free radicals formed during the metabolism of xenobiotics in the liver. Further, the capacity of hyperoside to regulate detoxifying enzymes phase II makes it potent as these enzymes are the prerequisite for liver during the initial round of oxidation.

It is reported from genus Epimedium and has been shown to delay the fibronectin and collagen accumulation in renal interstitial tissues and mesengial cells of rat model Algandaby et al. Several published reports confirmed its protective role in inflammation blocking TNF-α and IFN-γ signaling pathway Sinha et al.

Other important protective actions of iccarin comprises of modulating expression of toll-like receptor and inhibition of the mitogen activated protein kinase MAPK Mochizuki et al. Magnolol from Magnolia officinalis is an important phenolic compound that maintains the oxidative balance during hepatotoxicity in galactosamine-injured mice models.

Magnolin, another phenolics from same plant was reported to have ameliorating activity in lipid build up, insulin resistance and also in hepatic inflammation, when hepatocytes are exposed to free fatty acid in vitro Tian et al.

It exerts beneficial effects on metabolism by suppressing canonical NF-Kβ signaling Caselli et al. Naringenin, a natural flavonoid, possesses antioxidant, anticancer and anti-inflammatory activity Chtourou et al. Naringenin exhibits very little antioxidant action directly as a scavenger, yet it helps in upregulating of Nrf2 pathways and thus upholds the normal redox of the cell even in clinical conditions where prooxidants and reactive oxygens are formed as a of damage mechanism in hepatocytes, Esmaeili and Alilou, It can control a specialized mammalian homolog, sirtuins SIRT Andrade et al.

Over expression of this homolog helps in treating non-alcoholic related fatty liver disease by regulation lipogenesis.

Resveratrol is associated with considerable reduction in various liver enzymes, cytokines, and also transcriptional factors like nuclear factor κB. It alleviates the nuclear factor-κB NF-κB expression following the stimulation of its inhibitor IκBα Zhang et al.

It is another flavone that imparts hepatoprotective activity via different facilitating lipid metabolism by increasing oxidation process. AMPK signaling to bestow its effectiveness by various modules Wang et al.

In silico appraisal presently happens to be a pronounced method of evaluation in various biological research these days. It has the benefit of low cost, fast execution, and the most constructive face of such study is to diminish the animal usage in various toxicity screening.

PASS prediction assay Lagunin et al. Lipinski's Rule of Five Lipinski, is another method that can be applied to all the phenolic compounds to evaluate their drug likeness and pharmacological properties. Such information is very helpful in accessing the phenolic compounds as potential drug leads that can act as natural therapeutics.

Only the compounds satisfying the Lipinski's criteria are further considered for additional computational operations. Compounds that cleared the Lipinski's barrier were prepared for docking studies by their energy minimization in Marvin Sketch. Receptor-ligand interaction study using the Hex docking tool Macindoe et al.

Various amino acids of the target protein interaction with the lead compound are studied with respect to their bond length and bond angle.

Hence, the reported phenolic compounds can thus be studied as good prospective options for their use as medicine that targets various proteins for hepatic treatment. Reports of phosphorylated flavonoids i. Insilico studies have its implication in various pharmacological studies. From the initial protein, study to gene expression analysis related to any diseases can be carried out by the concept of pharmacogenomics.

Phenolic compounds as hepatoprotective have been reported in the work of Kaveri, , with insilico approach. The work was carried out on a group of newly synthesized acetylated phenolics. A good number of target proteins of hepatic anomaly have been reported when target fishing was performed Liu et al.

This mode thus supports the traditional uses for hepatic disorders and thus can suggest major bioactive phenolic compounds as contributors to produce ethnopharmacological effect. Natural products and specially plant phenolics have become a promising therapeutic alternative and prospective replacement of conventional marketed drug in practice due to their effectiveness, minimal side effects, and protective properties.

Furthermore, their dietary nature and availability is a bonus, and gives all the more reason to decline those generally available drugs that also cause toxicity to cells. Remarkable phenolics like curcumin and resveratrol are pharmacologically tested chemoprotective agents against treatment of hepatic carcinoma.

Though widely held natural products evaluated until now are generally non-toxic in nature, a few studies on toxicity regarding certain natural products are also highlighted these days. As a result, appropriate selection of the natural based drug is also obligatory.

All the important phenolics with their derivatives, though studied and well reported for, have not yet been fully analyzed for their immense therapeutic usage, as there are not enough studies available regarding them.

Components of such compounds in the diet varies with temperature and cultivation process. Furthermore, variation in the physicochemical properties could result from different modes of production of such plants, including agricultural and environmental factors.

Many pharmacological reports have demonstrated that phenols have a variety of therapeutic effects, including anti-cancer, anti-diabetic, anti-obesity, immunomodulatory, cardioprotective, hepatoprotective, and neuroprotective effects through antioxidant and anti-inflammatory activities.

However, additional studies are required to understand biological functions and compositions of many phenols, such as iccartin and morin, in more detail. Understanding biological function, composition, and therapeutic effects could help prevent adverse effects from long-term administration of phenolic compounds, and develop health promoting properties.

It is envisaged from this presented review that plant based phenolics will not only reduce the risk of hepatopathy, but will also endow a sure substitute that can be used for various hepatotoxicity mediated diseases.

PS prepared the initial draft and graphical representation for figures. AT finalized the manuscript and supervised as a whole. RN worked on the graphical representations and carried out various literature survey studies.

JS worked on gene network modeling and the gene expression study. MC worked on bioinformatics and the phenolic study in hepatic disease. SS and LN provided significant input into the chemistry part of this review, editing, and finalizing the draft.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The authors are grateful to DBT government of india sponsored institutional biotech hub and bioinformatics infrastructure facility of Assam University. Abenavoli, L.

Milk thistle Silybum marianum : a concise overview on its chemistry, pharmacological, and nutraceutical uses in liver diseases. doi: PubMed Abstract CrossRef Full Text Google Scholar. Adaramoye, O. Kolaviron, a biflavonoid fraction from Garcinia kola, protects against isoproterenol-induced injury by mitigating cardiac dysfunction and oxidative stress in rats.

Basic Clin. Adnane, L. Methods Enzymol. CrossRef Full Text Google Scholar. Ahadpour, M. Mitochondrial oxidative stress and dysfunction induced by isoniazid: study on isolated rat liver and brain mitochondria.

Drug Chem. Ahmad, N. Characterization of free and conjugated phenolic compounds in fruits of selected wild plants. Food Chem. Algandaby, M. Icariin protects against thioacetamide-induced liver fibrosis in rats: Implication of anti-angiogenic and anti-autophagic properties.

Anand, A. Approach to clinical syndrome of jaundice and encephalopathy in tropics. Andrade, J. Resveratrol attenuates hepatic steatosis in high-fat fed mice by decreasing lipogenesis and inflammation. Nutrition 30, — Arannilewa, S. Laboratory evaluation of four medicinal plants as protectants against the maize weevil, Sitophilus zeamais Mots.

Google Scholar. Arguello, G. Recent insights on the role of cholesterol in non-alcoholic fatty liver disease. et Biophys. Acta , — Arulselvan, P. Role of antioxidants and natural products in inflammation.

Aseervatham, G. Patel, R. Rajendram, and V. Preedy Academic Press , — Awogbindin, I. Viral Immunol. Baker, P. Bernstein, F. Rohr, and J. Helm Switzerland: Springer International Publishing , 35— Balderramo, D. Sorafenib for treatment of hepatocellular carcinoma: a survival analysis from the south american liver research network.

Baur, J. Therapeutic potential of resveratrol: the in vivo evidence. Drug Discov. Bhattacharyya, S. Cytochrome Ps: mechanisms and biological implications in drug metabolism and its interaction with oxidative stress. Drug Metabol. Bischoff, K. Gupta Breathitt Veterinary Center, Murray State University, Hopkinsville, KY: Elsevier , — Boari, C.

Toxic occupational liver diseases. Therapeutic effects of silymarin. PubMed Abstract Google Scholar. Bogdanska, J. Morphological and biochemical changes in wistar rat livers after clofibrate treatment.

Branco, A. Ketogenic diets: from cancer to mitochondrial diseases and beyond. Brodowska, K. Natural flavonoids: classification, potential role, and application of flavonoid analogues. Cannistrà, M. Hepatic ischemia reperfusion injury: a systematic review of literature and the role of current drugs and biomarkers.

Caselli, A. Morin: a promising natural drug. Cassini-Vieira, P. iNOS activity modulates inflammation, angiogenesis, and tissue fibrosis in polyether-polyurethane synthetic implants.

Cederbaum, A. Muriel Mexico: Elsevier , — Chalasani, N. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology 67, — Chang, W. Early activated hepatic stellate cell-derived molecules reverse acute hepatic injury.

World J. Chen, J. Inhibition of cytochrome c oxidase activity by 4-hydroxynonenal HNE : role of HNE adduct formation with the enzyme subunits.

et Biophy. Chen, S. Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Liver Dis. Dihydromyricetin improves glucose and lipid metabolism and exerts anti-inflammatory effects in nonalcoholic fatty liver disease: a randomized controlled trial.

Cheng, Q. Methyl ferulic acid attenuates ethanol-induced hepatic steatosis by regulating AMPK and FoxO1 pathways in rats and L cells. Choi, J. Protective effects of hyperoside against carbon tetrachloride-induced liver damage in mice.

Chorfa, N. An efficient method for high-purity anthocyanin isomers isolation from wild blueberries and their radical scavenging activity. Chtourou, Y. Naringenin reduces cholesterol-induced hepatic inflammation in rats by modulating matrix metalloproteinases-2, 9 via inhibition of nuclear factor κB pathway.

Chu, J. Protective effects of caffeic acid phenethyl ester against acute radiation-induced hepatic injury in rats. Cordero-Herrera, I. Cocoa and cocoa flavanol epicatechin improve hepatic lipid metabolism in in vivo and in vitro models. Role of PKCζ. Foods 17, — Cseke, L.

Natural Products from Plants. Boca Raton, FL: CRC press. Culver, A. TGF-Beta Signaling in an In Vivo Model of NASH. Spain: Taylor and Francis. Cummins, C. Luteolin-mediated inhibition of hepatic stellate cell activation via suppression of the STAT3 pathway. Czaja, A. Hepatic inflammation and progressive liver fibrosis in chronic liver disease.

De Beer, D. Phenolic compounds: a review of their possible role as in vivo antioxidants of wine. South Afr. Decker, T. A randomized phase II study of paclitaxel alone versus paclitaxel plus sorafenib in second-and third-line treatment of patients with HER2-negative metastatic breast cancer PASO.

BMC Cancer 17, Defronzo, R. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism 65, 20— Dei, A. Functional constituents of wild and cultivated Goji L. barbarum L. leaves: phytochemical characterization, biological profile, and computational studies. Enzyme Inhib.

CrossRef Full Text. Dhilleswara Rao, V. Translational approach in emerging infectious disease treatment: an update. Di Carlo, G. Flavonoids: old and new aspects of a class of natural therapeutic drugs.

Life Sci. Ding, L. Curcumin rescues high fat diet-induced obesity and insulin sensitivity in mice through regulating SREBP pathway. Domínguez-Avila, J. Gastrointestinal interactions, absorption, splanchnic metabolism and pharmacokinetics of orally ingested phenolic compounds.

Food Func. Domitrović, R. Liver fibrosis in mice induced by carbon tetrachloride and its reversion by luteolin. Dong, L. Hepatoprotective effects of kaempferolO-α-l-arabinopyranosylO-α-l-rhamnopyranoside on d-galactosamine and lipopolysaccharide caused hepatic failure in mice.

Molecules 22, Esmaeili, M. Naringenin attenuates CC l4-induced hepatic inflammation by the activation of an Nrf2-mediated pathway in rats.

Fang, S. Feng, X. Apigenin, a modulator of PPARγ, attenuates HFD-induced NAFLD by regulating hepatocyte lipid metabolism and oxidative stress via Nrf2 activation. Filannino, P. Metabolism of phenolic compounds by Lactobacillus spp. during fermentation of cherry juice and broccoli puree.

Food Microbiol. Finkelstein, E. Obesity and severe obesity forecasts through Forbes, S. Liver regeneration—mechanisms and models to clinical application. Fracanzani, A. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes.

Hepatology 48, — Frémont, L. Biological effects of resveratrol. Gao, B. Liver: an organ with predominant innate immunity.

Hepatology 47, — García-Mediavilla, V. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells.

Gerin, F. The effects of ferulic acid against oxidative stress and inflammation in formaldehyde-induced hepatotoxicity. Inflammation 39, — Ghiliyal, P.

Medicinal plants for treatment of liver disorders. Gómez-Juaristi, M. Absorption and metabolism of yerba mate phenolic compounds in humans. González-Gallego, J. González-Ponce, H. Natural dietary pigments: potential mediators against hepatic damage induced by over-the-counter non-steroidal anti-inflammatory and analgesic drugs.

Nutrients E Guan, L. Mechanisms of hepatic ischemia-reperfusion injury and protective effects of nitric oxide. Gupta, C. Antioxidant and antimutagenic effect of quercetin against DEN induced hepatotoxicity in rat.

Han, M. Hispidulin inhibits hepatocellular carcinoma growth and metastasis through AMPK and ERK signaling mediated activation of PPARγ. He, B. The small molecule nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome.

Cell Metabol. Heleno, S. Bioactivity of phenolic acids: Metabolites versus parent compounds: a review. Hernández-Aquino, E.

Beneficial effects of naringenin in liver diseases: Molecular mechanisms. Hernandez-Rodas, M. Relevant aspects of nutritional and dietary interventions in non-alcoholic fatty liver disease.

Hou, X. Suppression of inflammatory responses by dihydromyricetin, a flavonoid from ampelopsis grossedentata, via inhibiting the activation of NF-κB and MAPK signaling pathways.

Products 78, — Hu, C. Hussain, A. Cellular DNA breakage by flavonoids and other polyphenols in the presence of CU II a structure activity study. BMJ Open Gastroenterol.

Iwakiri, Y. Nitric oxide in liver diseases. Trends Pharmacol, Sci. Jain, A. Therapeutic efficacy of silymarin and naringenin in reducing arsenic-induced hepatic damage in young rats.

Jose, M. Effect of silymarin in diabetes mellitus patients with liver diseases. Ju, C. Hepatic macrophages in homeostasis and liver diseases: from pathogenesis to novel therapeutic strategies. Jung, E. AMPK activation by liquiritigenin inhibited oxidative hepatic injury and mitochondrial dysfunction induced by nutrition deprivation as mediated with induction of farnesoid X receptor.

Kashyap, D. Kaempferol—A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements. Foods 30, — Kaveri, A. PLoS ONE e Kay, C. Anthocyanins and flavanones are more bioavailable than previously perceived: a review of recent evidence. Food Sci.

Kim, H. Caffeic acid ameliorates hepatic steatosis and decreased ER stress in high fat diet-induced obese mice by regulating autophagy.

Nutrition , 63— Ferulic acid protects against carbon tetrachloride-induced liver injury in mice. Toxicology , — Kim, Y. Long-term dietary supplementation with low-dose nobiletin ameliorates hepatic steatosis, insulin resistance, and inflammation without altering fat mass in diet-induced obesity.

Food Res. Kobayashi, H. The antioxidant effect of green tea catechin ameliorates experimental liver injury. Phytomedicine 17, — Kolasani, B.

Prescribing pattern of drugs in patients with alcoholic liver disease in a tertiary care teaching hospital. Kumar, A. Protective effect of 3-O-methyl quercetin and kaempferol from Semecarpus anacardium against H 2 O 2 induced cytotoxicity in lung and liver cells.

BMC Compl. Kwon, E. Luteolin targets the toll-like receptor signaling pathway in prevention of hepatic and adipocyte fibrosis and insulin resistance in diet-induced obese mice. Nutrients Lagunin, A. PASS: prediction of activity spectra for biologically active substances.

Bioinformatics 16, — Lee, M. Antihepatotoxic activity of icariin, a major constituent of Epimedium koreanum. Planta Med. Lee, W. Leyva-López, N. Flavonoids as cytokine modulators: a possible therapy for inflammation-related diseases.

Li, G. Protective effects of hesperidin on concanavalin A-induced hepatic injury in mice. Li, M. MicroRNA ameliorates alcoholic liver injury by inhibiting the IL-6—p47phox—oxidative stress pathway in neutrophils.

Li, S. The potential and action mechanism of polyphenols in the treatment of liver diseases. Lieber, C. Silymarin retards the progression of alcohol-induced hepatic fibrosis in baboons. Lin, S. Molecular mechanisms of apoptosis induced by magnolol in colon and liver cancer cells.

Lin, Y. Screening for bioactive natural products from a compound library of Glycyrrhiza inflata. Lipinski, C. Lead-and drug-like compounds: the rule-of-five revolution.

Today Technol. Liu, A. Baicalein protects against polymicrobial sepsis-induced liver injury via inhibition of inflammation and apoptosis in mice. Liu, J. Synthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: a review.

Carbohydrate Polymers , — Locke, A. Genetic studies of body mass index yield new insights for obesity biology.

Nature Lu, Y. Icariin is a PPARα activator inducing lipid metabolic gene expression in mice. Molecules 19, — Luo, J.

The effects of modified sini decoction on liver injury and regeneration in acute liver failure induced by d-galactosamine in rats. Macindoe, G. HexServer: an FFT-based protein docking server powered by graphics processors.

Nucleic Acids Res. Madankumar, P. Madrigal-Santillán, E. Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration. Mäkilä, L. Stability of hydroxycinnamic acid derivatives, flavonol glycosides, and anthocyanins in black currant juice. Malvicini, M.

A tricin derivative from Deschampsia antarctica Desv. inhibits colorectal carcinoma growth and liver metastasis through the induction of a specific immune response. Cancer Therapeut. Mandal, B. These compounds exert protective effects by reducing inflammation, oxidative stress, and apoptosis in liver cells, thereby preserving liver structure and function Wan et al.

It is important to note that further studies are necessary to establish optimal dosage, bioavailability, and specific mechanisms of action for flavonoids in liver health Tang et al. Additionally, the effects of different types of flavonoids and their interactions with other compounds need to be explored to fully understand their hepatoprotective potential.

In conclusion, current research suggests that flavonoids possess hepatoprotective properties and offer potential applications in preventing liver diseases, supporting liver function, and mitigating liver damage Li et al.

The antioxidant, anti-inflammatory, and detoxifying properties of flavonoids contribute to their beneficial effects on liver health. However, more comprehensive studies are required to determine the specific mechanisms and clinical implications of flavonoids in liver disease prevention and treatment.

References Brunetti, C. Flavonoids as antioxidants and developmental regulators: relative significance in plants and humans. International journal of molecular sciences, 14 2 , Lee, N.

The role of the gut microbiome in liver cirrhosis treatment. International journal of molecular sciences, 22 1 , Li, H. Physicochemical, biological properties, and flavour profile of Rosa roxburghii Tratt, Pyracantha fortuneana, and Rosa laevigata Michx fruits: A comprehensive review.

Food Chemistry, ,

Flavonoids, a diverse group of natural compounds found abundantly detoxificaation fruits, vegetables, kiver other plant-based foods, Sustainable skincare options been Flavonoida for their potential hepatoprotective effects Tang et detoxificatioj. Numerous studies have Citrus fruit supplement for stress management the lFavonoids of Attention span improvement on detoxlfication health, including their ability to prevent liver diseases, support Flavonoidds function, Flavonoidz mitigate liver damage. Flafonoids suggests that flavonoids may reduce the risk of liver diseases such as non-alcoholic fatty liver disease NAFLD and liver cancer Li et al. These compounds exhibit antioxidant and anti-inflammatory properties, which contribute to the prevention of oxidative stress, inflammation, and lipid accumulation in the liver, all of which are key factors in the development and progression of liver diseases Tang et al. Specifically, they can stimulate liver enzymes such as superoxide dismutase SOD and glutathione peroxidase GSH-Pxwhich play crucial roles in the antioxidant defense system and hepatic detoxification Yu et al. The hepatoprotective effects of flavonoids also extend to mitigating liver damage caused by factors such as alcohol consumption, drug-induced toxicity, and viral infections Brunetti et al.

Flavonoids and liver detoxification -

They help your body respond to inflammation and protect the cells while also helping prevent the development of hepatic fibrosis, in which excessive connective tissue builds up in the liver.

Like other citrus fruits, grapefruits stimulate the liver, helping it turn toxins into substances that water can absorb.

Grapefruits also have vitamin B, which further reduces inflammation. B vitamins help slow down fatty liver disease and may even assist in preventing it. Olive oil is a healthy fat that positively affects your metabolic and heart health. It also offers many benefits for your liver.

Following a diet rich in olive oil reduces your risk of developing fatty liver disease , especially in older adults. It helps decrease fat accumulation in the liver while also improving the blood levels of liver enzymes. Because fat accumulation is the first step in the development of liver disease, adding olive oil to your diet goes a long way toward preventing that problem.

The flavonoids present in milk thistle supplements help with liver detoxification. The most important flavonoid in milk thistle supplements is silymarin , which has anti-inflammatory and antioxidant properties.

Milk thistle supplements protect new liver cells from alcohol damage as well as damage from other toxic substances. It can also help with symptoms of jaundice. Most nuts are excellent for liver health because of the antioxidative properties they have, but walnuts are one of the best options.

They have a higher level of antioxidant content, including the beneficial polyphenol antioxidants and glutathione, as well as a high level of omega-3 and omega-6 fatty acids. Walnuts help reduce the amount of fat in the liver. Because walnuts contain an antioxidant called arginine , they help the liver get rid of ammonia.

Vitamin E is another important nutrient walnuts have that contributes to liver health. Lee, N. The role of the gut microbiome in liver cirrhosis treatment. International journal of molecular sciences, 22 1 , Li, H. Physicochemical, biological properties, and flavour profile of Rosa roxburghii Tratt, Pyracantha fortuneana, and Rosa laevigata Michx fruits: A comprehensive review.

Food Chemistry, , Tang, Y. Liver International , 37 3 , Wan, L. Protective effects of plant-derived flavonoids on hepatic injury. Journal of Functional Foods, 44 , Yu, L. The NLRP3 inflammasome in non-alcoholic fatty liver disease and steatohepatitis: Therapeutic targets and treatment.

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Received: Oct, Manuscript No. MCA; Editor assigned: Flavonoids and liver detoxification, Pre Wnd No. MCA PQ ; Reviewed: Nov, QC No. MCA; Revised: Nov, Manuscript No. MCA R ; Published: Nov, DOI: Milk thistle Silybum marianum detoxificatiin been used for 2, years as Citrus fruit supplement for stress management herbal remedy for a variety of ailments, particularly liver, kidney, and gall bladder problems. Flavnooids scientific Citrus fruit supplement for stress management Slimming products that substances deoxification milk thistle especially a flavonoid called silymarin protect the liver from toxins, including certain drugs, such as acetaminophen Tylenolwhich can cause liver damage in high doses. Silymarin has antioxidant and anti-inflammatory properties. And it may help the liver repair itself by growing new cells. Although a number of animal studies demonstrate that milk thistle can be helpful in protecting the liver, results in human studies are mixed.

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