Taxifolin Treatment Research Articles

Taxifolin attenuates gentamicin-induced hepatotoxicity via modulation of oxidative stress, inflammation, and apoptosis in mice: potential involvement of Nrf2/HO-1 signaling

ABSTRACT The natural flavonoid taxifolin (TX) is known for its anti-inflammatory and antioxidant potential. Gentamicin (GEN) is a popular antibiotic agent that is associated with hepatotoxicity. The study assessed the hepatoprotective impacts of TX against GEN-linked liver injury in mice. Mice were orally administered with TX (25 and 50 mg/kg/day) for 14 days followed by GEN administration (100 mg/kg/day, i.p.) from the 8th to 14th day. GEN treatment significantly increased lactate dehydrogenase, transaminases (AST and ALT), and alkaline phosphatase levels in mouse serum, in addition to various histopathological liver changes. Higher levels of protein carbonyl and malondialdehyde and lower levels of superoxide dismutase, catalase, and glutathione were noted in the livers of GEN-administered mice. GEN administration also showed enhanced interleukins (IL-6 and IL-1β) and TNF-α levels and NF-κB p65 expression in mouse liver. TX treatment effectively ameliorated tissue injury, attenuated levels of MDA, protein carbonyl, and pro-inflammatory mediators, and improved antioxidants in GEN-treated mice. Increased caspase-3 and Bax protein expressions with decreased Bcl-2 levels were noted in the GEN-administrated mice, which were largely alleviated by TX pretreatment. Moreover, TX restored hepatic Nrf2/HO-1 signaling in GEN-administrated mice to counter GEN toxicity. These findings suggest TX as a promising adjuvant to prevent drug-associated tissue injury.

Taxifolin Attenuates Hepatic Fibrosis and Injury in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetes Mice

This study investigated the protective effects of taxifolin (TAX), a bioflavonoid, against hepatic fibrosis and injury in the type 2 diabetes mellitus (T2DM) mouse model. T2DM model was induced in male C57BL/6 mice by high-fat diet (HFD) and intraperitoneal injection for 5 consecutive days of 40 mg/kg streptozotocin (STZ). HFD-STZ groups were administered TAX (80 mg/kg/day) or vehicle daily for 12 weeks. The control or wild-type (WT) group received equal amounts of the vehicle and was fed a normal chow diet. Body weight and blood glucose were checked every 4 weeks. H&E and Masson's trichrome staining were performed to assess liver fibrosis and injury. The western blot was used to determine the expression levels of key fibrotic proteins. The data showed that taxifolin treatment significantly decreased body weight, liver weight, and blood glucose in diabetic mice. In particular, liver enzymes including alanine transaminase (ALT) and aspartate transferase (AST), and triglyceride levels were significantly higher in the non-treated diabetic group than in the WT group but markedly reduced after TAX treatment. In addition, the histological analysis revealed that TAX attenuated hepatic interstitial fibrosis. Moreover, western blot data showed downregulation of fibrotic markers including TGF-β1, Col1a1, and Smad2 in TAX group treatment indicating the molecular mechanisms through which TAX exerts its hepatoprotective effects. These findings suggest that TAX holds therapeutic potential in mitigating liver fibrosis and injury associated with T2DM, providing a promising avenue for further research and potential clinical application.

Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl4 induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl4, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl4, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.

Hepatoprotective potential of taxifolin in type 2 diabetic rats: modulation of oxidative stress and Bcl2/Bax/Caspase-3 signaling pathway.

Diabetes mellitus (DM) is a global metabolic problem. Several factors including hyperglycemia, oxidative stress, and inflammation play significant roles in the development of DM complications. Apoptosis is also an essential event in DM pathophysiology, -with B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) determining apoptotic susceptibility. The present study aimed to elucidate the protective effects of two doses of taxifolin (TXF) on liver damage in diabetic rats and explore the possible mechanisms of action. DM was induced in eighteen rats through intraperitoneal injections of 50mg/kg streptozotocin and 110mg/kg nicotinamide. Diabetic rats received daily oral intubation of 25 and 50mg/kg TXF for 3 months. In the untreated diabetic group, there was a significant increase in fasting and postprandial glucose levels, glycosylated hemoglobin A1C (HbA1c), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), while insulin and adiponectin levels decreased significantly. Both TXF doses mitigated hyperglycemia, regulated cytokine production, and increased insulin level. Gene expressions and protein levels of Bax, caspase 3, and cytochrome c were significantly increased, while Bcl-2 was significantly decreased in the livers of diabetic rats, effects that were significantly ameliorated after TXF treatment. The results of the TUNEL assay supported the apoptotic pathway. Additionally, TXF significantly decreased lipid peroxidation and enhanced antioxidant enzyme activity in diabetic rats. Liver enzymes and histopathological changes also showed improvement. TXF mitigated diabetes-associated hepatic damage by reducing hyperglycemia, oxidative stress, inflammation, and modulating anti-/pro-apoptotic genes and proteins. A dose of 50mg/kg TXF was more effective than 25mg/kg and is recommended for consumption.

Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer’s disease (AD). Taxifolin’s neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 μM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin’s mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats’ brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be −4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 μM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.

EFFECT OF TAXIFOLIN ON DOXORUBICIN-INDUCED OXIDATIVE CARDIAC DAMAGE IN RATS: A BIOCHEMICAL AND HISTOPATHOLOGICAL EVALUATION

Doxorubicin is a widely used anthracycline-derived broad-spectrum antitumoral antibiotic drug. However, cardiotoxicity due to doxorubicin treatment has warranted dose reduction or complete discontinuation in certain cases. The role of oxidative stress in the pathogenesis of doxorubicin-induced cardiotoxicity has been previously demonstrated. Against this background, this study aimed to investigate the protective effect of the potent antioxidant flavone taxifolin against possible oxidative heart damage biochemically and histopathologically induced by doxorubicin. Albino Wistar male rats were divided into three groups: healthy controls (HG), a group given doxorubicin alone (DG), and a group given taxifolin + doxorubicin (TDG). Taxifolin was administered orally at a dose of 50 mg/kg via gavage. Doxorubicin was injected intraperitoneally at a dose of 5 mg/kg. This procedure was repeated for 7 days. The results of the biochemical experiment showed that taxifolin significantly inhibited doxorubicin-induced malondialdehyde increases and glutathione decreases in heart tissues. In addition, taxifolin significantly suppressed the increases in cardiac damage markers, such as serum troponin I, creatine kinase, and creatine kinase-MB, induced by doxorubicin. Taxifolin treatment has also been histopathologically shown to alleviate doxorubicin-induced heart tissue damage. Accordingly, the results of the present study suggest that taxifolin may be useful in the treatment of doxorubicin-induced oxidative heart damage. Keywords: Antioxidant, cardiotoxicity, doxorubicin, flavonoid, taxifolin.

Taxifolin Inhibits the Proliferation of Glioblastoma Multiforme Cells via Apoptosis and Autophagy

Glioblastoma multiforme is the most malignant tumor in the central nervous system. As a result of its high recurrence rate, drug resistance, and distal metastasis, the 5-year survival rate of glioblastoma multiforme patients is only around 5%. Taxifolin, a polyphenol from traditional Chinese medicine, exerts antioxidant, anti-inflammatory, and antitumor properties. This study aimed to explore the molecular mechanisms of taxifolin on the proliferation of glioblastoma multiforme. Taxifolin mitigated the viability of GBM 8901 cells in a time- and dose-dependent manner. Flow cytometry analysis by PI alone or PI combined with Annexin V revealed that taxifolin at 200 and 400 μM significantly elevated the apoptosis population in GBM8901 cells. Western blot analysis demonstrated that taxifolin dose-dependently increased p53 expression and reduced poly ADP-ribose polymerase, B-cell lymphoma 2, and pro-caspase-3 expression. Moreover, the autophagy-related protein p62 was reduced by taxifolin. By contrast, expression of the light chain 3β protein was elevated in response to taxifolin treatment. Depletion of light chain 3β protein by short hairpin RNA significantly recovered 200 and 400 μM taxifolin-induced cell death in GBM8901 cells. Our findings indicated that taxifolin repressed the cell proliferation of glioblastoma multiforme by triggering apoptosis and autophagy. Using taxifolin to treat glioblastoma multiforme may be a potential therapy agent.

Taxifolin ameliorates IL-17A-enhanced hippocampal inflammation and oxidative stress in arsenic-exposed HT-22 cells

Arsenic (As) promotes neuronal damage in the hippocampus which is associated with cognitive function. Taxifolin, a flavonol with strong anti-oxidative and anti-inflammatory properties, is known to have beneficial properties in neurodegeneration, but its effect on As-induced hippocampal damage is unknown. Here, we explored whether taxifolin has therapeutic potential in ameliorating as causing toxicity in mouse hippocampal HT-22 cells, hypothesizing that inhibiting oxido-inflammation stress may reverse As-associated damage through several pathways. Findings indicate that pretreatment with taxifolin reversed the reduction of sodium arsenite (NaAsO2) induced cell death. In addition, taxifolin ameliorated NaAsO2-related oxidative stress as measured by the formation of ROS, MDA level and GSH content. Moreover, we revealed the taxifolin treatment resulted in a reduction of IL-17A level and subsequent diminished activation of TNF-α, IL-1β, and IL-6 concentrations in HT-22 cells treated with NaAsO2. These findings imply when considered collectively, HT-22 cells are shielded by taxifolin from NaAsO2-evoked oxidative cell death and neuroinflammation. Thus, our report indicates that has a protective role in hippocampal cell culture systems.

Hepatoprotective effect of taxifolin on cyclophosphamide-induced oxidative stress, inflammation, and apoptosis in mice: Involvement of Nrf2/HO-1 signaling.

Taxifolin (TA) is a natural flavonoid found in many foods and medicinal plants with well-documented antioxidant and anti-inflammatory properties. Cyclophosphamide (CP) is an effective antineoplastic and immunosuppressive agent; however, it is associated with numerous adverse events, including hepatotoxicity. Herein, we aimed to investigate the potential protective effects of TA using a mouse model of CP-induced hepatotoxicity. Mice were co-treated with TA (25 and 50 mg/kg, orally) and CP (30 mg/kg, i.p.) for 10 consecutive days and sacrificed 24 hours later. CP induced increased transaminases (ALT and AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) paralleled with pronounced histopathological alterations in the liver. Moreover, hepatic tissues of CP-injected mice showed increased malondialdehyde (MDA), protein carbonyl, and nitric oxide (NO) levels, accompanied by decreased antioxidant defenses (glutathione [GSH], superoxide dismutase [SOD], and catalase [CAT]). Livers of CP-injected mice also showed increased inflammatory response (nuclear transcription factor kappa-B [NF-κB] p65 activation, increased levels of proinflammatory cytokines tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL-1β], and IL-6) and apoptosis (decreased Bcl-2 and increased Bax and caspase-3 expression levels). Remarkably, TA ameliorated markers of liver injury and histological damage in CP-injected mice. TA treatment also attenuated numerous markers of oxidative stress, inflammation, and apoptosis in the liver of CP-injected mice. This was accompanied by increased nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) expression in the liver tissues of CP-injected mice. Taken together, this study indicates that TA may represent a promising new avenue to prevent/treat CP-induced hepatotoxicity and perhaps other liver diseases associated with oxidative stress and inflammation.

Taxifolin ameliorates cigarette smoke-induced chronic obstructive pulmonary disease via inhibiting inflammation and apoptosis.

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide and is characterized by chronic airway inflammation and lung parenchymal cell apoptosis. Cigarette smoke is the major risk factor for the occurrence and development of COPD. Taxifolin (TAX) showed promising pharmacological effects in the management of inflammation, oxidative stress, and apoptosis. In the present study, our results demonstrated that TAX significantly alleviated cigarette smoke-induced inflammation and apoptosis both in vivo and in vitro. TAX notably lowered the elevated total cell count in mouse BALF compared with that in the COPD group. The cigarette smoke-induced emphysematous changes were remarkably reversed by TAX. In addition, treatment with TAX suppressed the elevated mRNA and protein levels of IL-1β, IL-6 and TNF-α in COPD mouse lung tissue and cigarette smoke extract (CSE)-treated human bronchial epithelial cells (HBECs). Additionally, TAX significantly decreased the ratios of p-iκB to iκB and p-p65 to p65 compared with the COPD group and CSE-treated HBECs. Moreover, the results of the TUNEL assay and flow cytometry also demonstrated the anti-apoptotic effect of TAX in mouse lung tissue and HBECs. Furthermore, the elevated Bax and CCP3 levels and decreased Bcl-2 levels induced by cigarette smoke were significantly reversed by TAX treatment in vivo and in vitro. Our results highlight the ameliorating effects of TAX against cigarette smoke-induced inflammation and apoptosis in the pathogenesis of COPD.

Novel Therapeutic Potentials of Taxifolin for Obesity-Induced Hepatic Steatosis, Fibrogenesis, and Tumorigenesis.

The molecular pathogenesis of nonalcoholic steatohepatitis (NASH) includes a complex interaction of metabolic stress and inflammatory stimuli. Considering the therapeutic goals of NASH, it is important to determine whether the treatment can prevent the progression from NASH to hepatocellular carcinoma. Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid with antioxidant and anti-inflammatory properties commonly found in various foods and health supplement products. In this study, we demonstrated that Taxifolin treatment markedly prevented the development of hepatic steatosis, chronic inflammation, and liver fibrosis in a murine model of NASH. Its mechanisms include a direct action on hepatocytes to inhibit lipid accumulation. Taxifolin also increased brown adipose tissue activity and suppressed body weight gain through at least two distinct pathways: direct action on brown adipocytes and indirect action via fibroblast growth factor 21 production in the liver. Notably, the Taxifolin treatment after NASH development could effectively prevent the development of liver tumors. Collectively, this study provides evidence that Taxifolin shows pleiotropic effects for the treatment of the NASH continuum. Our data also provide insight into the novel mechanisms of action of Taxifolin, which has been widely used as a health supplement with high safety.

Effects of Taxifolin in Spontaneously Hypertensive Rats with a Focus on Erythrocyte Quality.

Oxidative stress and multiple erythrocyte abnormalities have been observed in hypertension. We focused on the effects of angiotensin-converting enzyme 2 (ACE2) inhibition by MLN-4760 inhibitor on angiotensin peptides, oxidative stress parameters, and selected erythrocyte quality markers in spontaneously hypertensive rats (SHR). We also investigated the potential effects of polyphenolic antioxidant taxifolin when applied in vivo and in vitro following its incubation with erythrocytes. SHRs were divided into four groups: control, taxifolin-treated, MLN-4760-treated, and MLN-4760 with taxifolin. MLN-4760 administration increased the blood pressure rise independent of taxifolin treatment, whereas taxifolin decreased it in control SHRs. Body weight gain was also higher in ACE2-inhibited animals and normalized after taxifolin treatment. However, taxifolin did not induce any change in angiotensin peptide concentrations nor a clear antioxidant effect. We documented an increase in Na,K-ATPase enzyme activity in erythrocyte membranes of ACE2-inhibited SHRs after taxifolin treatment. In conclusion, ACE2 inhibition deteriorated some selected RBC properties in SHRs. Although taxifolin treatment did not improve oxidative stress markers, our data confirmed the blood pressure-lowering potential, anti-obesogenic effect, and some "erythroprotective" effects of this compound in both control and ACE2-inhibited SHRs. In vitro investigations documenting different effects of taxifolin on erythrocyte properties from control and ACE2-inhibited SHRs accentuated the irreplaceability of in vivo studies.

Effects of taxifolin from enzymatic hydrolysis of Rhododendron mucrotulatum on hair growth promotion.

Flavonoid aglycones possess biological activities, such as antioxidant and antidiabetic activities compared to glycosides. Taxifolin, a flavonoid aglycones, is detected only in trace amounts in nature and is not easily observed. Therefore, in this study, to investigate the hair tonic and hair loss inhibitors effect of taxifolin, high content of taxifolin aglycone extract was prepared by enzymatic hydrolysis. Taxifolin effectively regulates the apoptosis of dermal papilla cells, which is associated with hair loss, based on its strong antioxidant activities. However, inhibition of dihydrotestosterone (DHT), which is a major cause of male pattern hair loss, was significantly reduced with taxifolin treatment compared with minoxidil, as a positive control. It was also confirmed that a representative factor for promoting hair growth, IGF-1, was significantly increased, and that TGF-β1, a representative biomarker for hair loss, was significantly reduced with taxifolin treatment. These results suggest that taxifolin from enzymatic hydrolysis of RM is a potential treatment for hair loss and a hair growth enhancer.

Taxifolin delays the degradation of chlorophyll in pakchoi (Brassica rapa L subsp. chinensis) by regulating the ascorbate-glutathione cycle

The effects of taxifolin (TF) treatment on chlorophyll (Chl) degradation and the ascorbate-glutathione (AsA-GSH) cycle were evaluated in pakchoi. Compared with a control and other treatment concentrations, 1000 mg L −1 TF treatment had the greatest green retention effect on pakchoi. This treatment delayed the degradation of Chl and its derivatives and inhibited the activities of chlorophyllase, Mg-dechelatase, pheophytinase, and pheophorbide a oxygenase. The expression of Chl degradation ( BrNYC1 , BrNOL , BrCLH , BrSGR1 , BrSGR2 , BrPPH , BrPAO , and BrRCCR ) and senescence ( BrSAG12 ) related-genes was also suppressed, leading to better quality pakchoi. In addition, TF treatment alleviated decreases in total ascorbic acid, reduced ascorbic acid, dehydroascorbic acid, total glutathione, reduced glutathione, and oxidized glutathione, while enhancing the activities of ascorbic acid peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and glutathione reductase. This contributed to maintained high free radical scavenging ability and lower membrane lipid peroxidation. These results demonstrate that TF can regulate the AsA-GSH cycle and maintain the activity to scavenge reactive oxygen species, thus reducing membrane lipid oxidation and ultimately reducing nutrient loss and Chl degradation in pakchoi. • TF treatment delayed chlorophyll degradation and maintained quality of pakchoi. • TF treatment regulated AsA-GSH cycle products, substrate, and enzymes. • TF treatment reduced ROS accumulation and inhibited membrane lipid peroxidation. • TF may slow down the yellowing of pakchoi by regulating the AsA-GSH cycle.

Taxifolin Modulates Transcriptomic Response to Heat Stress in Rainbow Trout, Oncorhynchus mykiss.

Simple SummaryCultivated rainbow trout face with multiple stressors that impact their viability, growth, and welfare. Heat stress provoked by summer temperature rise leads to increased mortality and accelerated transmission of bacterial and parasite pathogens in fish population. Feed supplements of plant-origin could alleviate stress in fish presumably via stimulation of their defense systems. To understand the mechanism of beneficial effects of taxifolin, an antioxidant extracted from larix wood, we compared transcriptomic responses to both temperature rise and flatworm infection in rainbow trout individuals fed either a standard ration or supplemented with taxifolin. Dietary taxifolin has been shown to mitigate some heat-induced responses in fish, such as biosynthesis of sterols, heat-shock proteins, and cell death regulators, while it does not interfere with temperature-dependent antioxidant induction. Interestingly, no transcriptomic response was induced due to Gyrodactylus infestation in trout, whereas parasite load was diminished due to heat treatment. Thus, the plant-origin supplementation of fish diet could be an easy way to improve the health of fish and promote their ability to tolerate stresses under intensive production.Taxifolin is a natural flavonoid known for its antioxidant, anti-inflammatory, and antiproliferative effects on animals. In this work, we have studied the effect of this compound on rainbow trout, Oncorhynchus mykiss, a major object of aquaculture, under slowly increasing ambient temperature and Gyrodactylus flatworm infection. Transcriptomic profiling of liver samples performed by using the Illumina HiSeq 2500 sequencing platform shows that a combined taxifolin/heat treatment, unlike heat treatment alone, downregulates the production of isopentenyl diphosphate, likely affecting the production of cholesterol and other sterols. Taxifolin treatment also modulates multiple apoptosis regulators and affects the expression of HSPs in response to increasing temperature. On the other hand, the expression of antioxidant enzymes in response to heat is not significantly affected by taxifolin. As for the Gyrodactylus infection, the parasite load is not affected by taxifolin treatment, although it was lower in the high-temperature group. Parasite load also did not induce a statistically significant transcriptomic response within the no heat/no taxifolin group.

Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats.

This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200mg/kg i.p.) thioacetamide and taxifolin (50 and 100mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1β, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments.

Taxifolin Alleviates DSS-Induced Ulcerative Colitis by Acting on Gut Microbiome to Produce Butyric Acid.

Taxifolin is a bioflavonoid which has been used to treat Inflammatory Bowel Disease. However, taxifolin on DSS-induced colitis and gut health is still unclear. Here, we studied the effect of taxifolin on DSS-induced intestinal mucositis in mice. We measured the degree of intestinal mucosal injury and inflammatory response in DSS treated mice with or without taxifolin administration and studied the changes of fecal metabolites and intestinal microflora using 16S rRNA. The mechanism was further explored by fecal microbiota transplantation. The results showed that the weight loss and diarrhea score of the mice treated with taxifolin decreased in DSS-induced mice and longer colon length was displayed after taxifolin supplementation. Meanwhile, the expression of GPR41 and GPR43 in the colon was significantly increased by taxifolin treatment. Moreover, the expression of TNF-α, IL-1β, and IL-6 in colon tissue was inhibited by taxifolin treatment. The fecal metabolism pattern changed significantly after DSS treatment, which was reversed by taxifolin treatment. Importantly, taxifolin significantly increased the levels of butyric acid and isobutyric acid in the feces of DSS-treated mice. In terms of gut flora, taxifolin reversed the changes of Akkermansia, and further decreased uncultured_bacterium_f_Muribaculaceae. Fecal transplantation from taxifolin-treated mice showed a lower diarrhea score, reduced inflammatory response in the colon, and reduced intestinal mucosal damage, which may be related to the increased level of butyric acid in fecal metabolites. In conclusion, this study provides evidence that taxifolin can ameliorate DSS-induced colitis by altering gut microbiota to increase the production of SCFAs.

Taxifolin ameliorates sepsis-induced lung capillary leak through inhibiting the JAK/STAT3 pathway

As a systemic inflammatory reaction, sepsis is associated with various organ dysfunctions. The capillary leakage and the imbalance between T helper 17 and regulatory T (Th17/Treg) cells are associated with sepsis-induced lung injury. Taxifolin (TXL) has been found to play a vital role in regulating this diverse disease. However, the detailed functioning and mechanism of TXL in regulating sepsis-induced lung capillary leak remain elusive. Balb/c mice were used to establish sepsis-induced lung injury model through administration of lipopolysaccharide (LPS). The structure of lung tissues was observed by using hematoxylin & eosin staining. Protein level and total cells in bronchoalveolar lavage fluid (BALF) were measured by bicinchoninic acid (BCA) protein assay kit and hematimetry assay, respectively. Quantitative real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were employed to detect the level of inflammatory cytokines. The content of Th17 and Treg cells were measured by flow cytometry analysis. Western blot assay was used to determine the protein level of retinoid-related orphan receptor-γt (RORγt), Forkhead box P3 (Foxp3), Janus kinase 2 (JAK2), phospho(p)-JAK2, signal transducer and activator of transcription 3 (STAT3), and phospho(p)-STAT3. Taxifolin effectively prolonged the survival period of sepsis mice and alleviated LPS-induced lung injury in a dose-dependent manner. Moreover, TXL reduced LPS-induced increase in protein levels and T cell content in BALF, and effectively restored the wet:dry ratio of lung tissue and tissue permeability. Treating with TXL notably inhibited the production of pro-inflammatory cytokines induced by sepsis and influenced the balance between Th17 and Treg cells. Furthermore, TXL treatment suppressed the activation of JAK/STAT3 signaling pathway in a dose-dependent manner. Our findings revealed that TXL alleviated sepsis-induced capillary leak in the lungs of mice by regulating JAK/STAT3 signaling pathway.

O efeito preventivo da taxifolina em danos cardíacos induzidos por acrilamida em ratos

ABSTRACT Objective Acrylamide is a toxic compound widely used in industrial sectors. Acrylamide causes reactive oxygen species formation and the subsequent lipid peroxidation reaction, which plays an important role in the pathogenesis of oxidative damage. Taxifolin is a flavonoid with antioxidant properties that inhibit reactive oxygen species formation. In this study, we aimed to investigate the preventive effect of taxifolin on acrylamide-induced oxidative heart damage. Methods The rats were divided into three groups: Acrylamide, Acrylamide+Taxifolin , and Healthy group. Water and food intake and body weight alterations were recorded daily. Malondialdehyde, total glutathione, nuclear factor kappa-B, total oxidant status, and total antioxidant status levels were analyzed from the heart tissue. Troponin-I levels, the parameter known as a cardiac biomarker, were analyzed from the blood sample. The cardiac histopathologic examination was also performed. Results In the Acrylamide group animals, the malondialdehyde, nuclear factor kappa-B, total oxidant status, and troponin-I levels were significantly higher compared to the ones of Acrylamide+Taxifolin and Healthy groups. The levels of total glutathione and total antioxidant status were significantly lower compared to Acrylamide+Taxifolin and Healthy groups’. Additionally, in the Acrylamide group, body weight gain, food and water intake, significantly declined compared to the Acrylamide+Taxifolin and Healthy groups. However, in the Acrylamide+Taxifolin group, taxifolin supplementation brought these values close to Healthy group ones. Furthermore, taxifolin treatment ameliorated structural myocardial damage signs induced by acrylamide. Conclusion Acrylamide exposure significantly induced oxidative damage to rat heart tissue. Taxifolin was able to improve the toxic consequences of acrylamide biochemically and histopathologically, possibly due to its antioxidant properties.

Effect of Taxifolin on Ischemia/Reperfusion-Induced Oxidative Injury of Sciatic Nerve in Rats

Ischemia is a condition in which blood flow to tissues is decreased or entirely stopped for various reasons. The reperfusion process exacerbates damage caused by ischemia in the organs and tissues. Reactive oxygen species (ROS) are mainly responsible for ischemia-reperfusion (IR) damage. ROS increase results in lipid peroxidation (LPO) and oxidative stress. In the literature, taxifolin reportedly suppresses ROS production. This study aimed to determine the effect of taxifolin, which is a flavonoid, on IR injury of the sciatic nerve in rats. This study divided 30 albino Wistar rats into 3 groups: IR without medication (IR) group, taxifolin applied IR (TAX+IR) group, and only dissection made to the sciatic nerve sham group (SHAM). Sciatic nerve injury was induced by applying 2 hours of ischemia and 3 hours of reperfusion to the abdominal aorta and iliolumbar arteries. Biochemical and histopathologic investigations then were performed on sciatic nerve tissues. Malondialdehyde, total glutathione, glutathione reductase, and glutathione peroxidase were analyzed as oxidative stress markers, and tumor necrosis factor-α and interleukin-1β levels were evaluated as inflammatory stress markers in biochemical tests. The IR group has statistically significantly high oxidant and cytokine levels and low antioxidant levels compared with the TAX+IR group. Taxifolin treatment was also shown to cause significant histopathologic improvement. We suggest that taxifolin may be effective in preventing IR injury of the sciatic nerve.