Dihydroquercetin improves the proliferation of porcine intestinal epithelial cells via the Wnt/ß-catenin pathway.

Dihydroquercetin (DHQ), also known as Taxifolin (TA), is a flavanonol with various biological activities, such as anticancer, anti-inflammatory, and antioxidative properties. It has been found to effectively increase the viability of porcine intestinal epithelial cells (IPEC-J2). However, the precise mechanism by which DHQ increases the proliferation of IPEC-J2 cells is not entirely understood. This study aimed to explore the potential pathways through which DHQ encourages the proliferation of IPEC-J2 cells. The findings indicated that DHQ significantly improved the protein expression of tight junction proteins (ZO-1, Occludin, and Claudin1) and a molecular biomarker of proliferation (PCNA) in IPEC-J2 cells. Furthermore, DHQ was found to increase the Wnt/ß-catenin pathway-associated ß-catenin, c-Myc, and cyclin D1 mRNA expression, and promote the protein expression of ß-catenin and TCF4. To confirm the involvement of the Wnt/ß-catenin signaling pathway in the DHQ-promoted proliferation of IPEC-J2 cells, the inhibitor LF3, which targets ß-catenin/TCF4 interaction, was used. It was found that LF3 inhibited the protein expressions upregulated by DHQ and blocked the promotion of cell proliferation. These results indicate that DHQ positively regulates IPEC-J2 cell proliferation through the Wnt/ß-catenin pathway, providing constructive insights into the role of DHQ in regulating intestine development.

Pharmacokinetics of Dihydroquercetin after Single and Repeated Administration to Rats.

The pharmacokinetic properties of dihydroquercetin (DHQ) were studied after single and repeated (for 3 days) administration to rats in the form of a starch suspension at a dose of 25 mg/kg. Blood samples were collected using a permanent catheter in the jugular vein in 2, 5, 10, 20, and 30 min and in 1, 2, 4, and 6 h after administration. Before the repeated administration (5 min), blood sample was collected to assess the concentration of DHQ at the zero time point. Quantitative analysis was carried out by HPLC-tandem mass spectrometry. DHQ was very quickly absorbed by the gastrointestinal tract and quickly eliminated from the body. Repeated administration of DHQ did not lead to its accumulation in the body but had an effect on the enzymatic system with a subsequent increase in DHQ exposure (accumulation factor >1 by AUC after repeated administration).

Taxifolin inhibits NETosis through activation of Nrf2 and provides protective effects in models of lupus and antiphospholipid syndrome.

OBJECTIVES: Taxifolin (dihydroquercetin) is a bioactive plant flavonoid that exhibits anti-inflammatory and anti-oxidative properties. We hypothesized that taxifolin might be an effective dietary supplement to ameliorate symptoms arising from thrombo-inflammatory diseases such as lupus and antiphospholipid syndrome (APS). METHODS: We used in vitro assays and a mouse model to determine mechanisms by which taxifolin inhibits neutrophil extracellular trap (NET) formation (i.e., NETosis) and venous thrombosis in lupus and APS. RESULTS: At doses ranging from 0.1 to 1 µg/ml, taxifolin inhibited NETosis from control neutrophils stimulated with autoantibodies isolated from lupus and APS patients, and its suppressive effects were mitigated by blocking the antioxidant transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). Furthermore, taxifolin at a dose as low as 20 mg/kg/day reduced in vivo NETosis in thrombo-inflammatory mouse models of lupus and APS while also significantly attenuating autoantibody formation, inflammatory cytokine production, and large-vein thrombosis. CONCLUSION: Our study is the first to demonstrate the protective effects of taxifolin in the context of lupus and APS. Importantly, our study also suggests a therapeutic potential to neutralize neutrophil hyperactivity and NETosis that could have relevance to a variety of thrombo-inflammatory diseases.

Dihydroquercetin (DHQ) ameliorates LPS-induced acute lung injury by regulating macrophage M2 polarization through IRF4/miR-132-3p/FBXW7 axis.

BACKGROUND: Acute lung injury (ALI) is a common complication of sepsis. Dihydroquercetin (DHQ) has been found to attenuate lipopolysaccharide (LPS)-induced inflammation. However, the effect of DHQ on LPS-challenged ALI remains unclear. METHODS: Pulmonary HE and TUNEL staining and lung wet/dry ratio were detected in LPS-treated Balb/c mice. IL-1ß, IL-6 and TNF-α levels were determined utilizing ELISA assay. RAW264.7 cell apoptosis and macrophage markers (CD86, CD206) were tested using flow cytometry. TC-1 viability was analyzed by MTT assay. Western blot measured protein expression of macrophage markers. Interactions of miR-132-3p, IRF4 and FBXW7 were explored utilizing ChIP, RNA pull-down and dual luciferase reporter assays. RESULTS: DHQ alleviated histopathological change, pulmonary edema and apoptosis in LPS-treated mice. DHQ affected LPS-induced M2 macrophage polarization and TC-1 cell injury-related indicators, such as decreased cell activity, decreased LDH levels, and increased apoptosis. LPS inhibited IRF4 and miR-132-3p expression, activated Notch pathway and increased FBXW7 level, which were overturned by DHQ. IRF4 transcriptionally activated miR-132-3p expression. FBXW7 was a downstream target of miR-132-3p. CONCLUSION: DHQ alleviated LPS-induced lung injury through promoting macrophage M2 polarization via IRF4/miR-132-3p/FBXW7 axis, which provides a new therapeutic strategy for ALI.

Unraveling the Antioxidant Activity of 2R,3R-dihydroquercetin.

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in 'biotargeting' quercetin.

Taxifolin Reduces Blood Pressure via Improvement of Vascular Function and Mitigating the Vascular Inflammatory Response in Spontaneously Hypertensive Rats.

The effect of a 10-day-long treatment with taxifolin (TAX, 20 mg/kg/day p.o.) was investigated on spontaneously hypertensive rats (SHRs) with a focus on the vascular functions of isolated femoral arteries and thoracic aortas. TAX reduced blood pressure in SHRs. In femoral arteries, TAX increased acetylcholine-induced relaxation, reduced the maximal NA-induced contraction, and reduced acetylcholine-induced endothelium-dependent contraction (EDC); however, TAX had no effect on the vascular reactivity of isolated thoracic aortas. In addition, TAX elevated the total nitric oxide synthase (NOS) activity and iNOS protein expression but reduced cyclooxygenase-2 (COX2) protein expression in the tissue of the abdominal aorta without changes in Nos2 and Ptgs2 gene expressions. TAX also increased the gene expression of the anti-inflammatory interleukin-10 (Il10). In addition, in vitro studies showed that TAX has both electron donor and H atom donor properties. However, TAX failed to reduce superoxide production in the tissue of the abdominal aorta after oral administration. In conclusion, our results show that a decrease in the blood pressure in TAX-treated SHRs might be attributed to improved endothelium-dependent relaxation and reduced endothelium-dependent contraction. In addition, the results suggest that the effect of TAX on blood pressure regulation also involves the attenuation of COX2-mediated pro-inflammation and elevation of anti-inflammatory pathways.

Research Progress of Dihydroquercetin in the Treatment of Skin Diseases.

Skin is a barrier to maintaining the stability of the human environment and preventing the invasion of pathogens. When skin tissue is exposed to the external environment, it will inevitably develop defects due to trauma, injury, burns, ulcers, surgery, and chronic diseases. Rapid skin repair is the key to reducing infection, relieving pain, and improving quality of life. Dihydroquercetin is a kind of flavonoid that has a wide range of pharmacological activities and can improve skin repair, skin inflammation, skin cancer, and so on. In this paper, the application of dihydroquercetin in medical dressings and the research progress in the treatment of skin-related diseases are reviewed, so as to provide reference for further developing dihydroquercetin as a drug for the treatment of skin diseases.

Production of phenylpropanoids and flavonolignans from glycerol by metabolically engineered Escherichia coli.

Phenylpropanoids are a group of plant natural products with medicinal importance derived from aromatic amino acids. Here, we report the production of two representative phenylpropanoids-coniferyl alcohol (CA) and dihydroquercetin (DHQ)-from glycerol by engineered Escherichia coli. First, an E. coli strain capable of producing 187.7 mg/L of CA from glycerol was constructed by the introduction of hpaBC from E. coli and OMT1, 4CL4, and CCR1 from Arabidopsis thaliana to the p-coumaric acid producer. Next, an E. coli strain capable of producing 239.4 mg/L of DHQ from glycerol was constructed by the introduction of F3H, TT7, and CPR from A. thaliana to the naringenin producer, followed by engineering the signal peptide of a cytochrome P450 TT7. Furthermore, to demonstrate the production of flavonolignans, a group of heterodimeric phenylpropanoids, from glycerol, ascorbate peroxidase 1 from Silybum marianum was employed and engineered to produce 0.04 µg/L of silybin and 1.29 µg/L of isosilybin from glycerol by stepwise culture. Finally, a single strain harboring all the 16 necessary genes was constructed, resulting in 0.12 µg/L of isosilybin production directly from glycerol. The strategies described here will be useful for the production of pharmaceutically important yet complex natural products.

Engineering Saccharomyces cerevisiae for the production of dihydroquercetin from naringenin.

BACKGROUND: Dihydroquercetin (DHQ), a powerful bioflavonoid, has a number of health-promoting qualities and shows potential as a treatment for a number of disorders. Dihydroquercetin biosynthesis is a promising solution to meet the rising demand for dihydroquercetin. However, due to the significant accumulation of eriodietyol (ERI), naringenin (NAR), dihydrokaempferol (DHK), and other metabolites, the yield of DHQ biosynthesis is low. As a result, this is the hindrance to the biosynthesis of DHQ. RESULTS: In this study, we proposed several strategies to enhance the product formation and reduce the metabolites in accumulation. The flavonoid 3'-hydroxylase (F3'H) and cytochrome P450 reductase from different species were co-expressed in S. cerevisiae, and the best strain expressing the P450-reductase enzyme complex (SmF3'H/ScCPR) yielded 435.7 ± 7.6 mg/L of ERI from NAR in the deepwell microplate. The product conversion rate was improved further by mutating the predicted potential ubiquitination sites to improve SmF3'H stability, resulting in a 12.8% increase in titre using the mutant SmF3'H (K290R). Besides, different F3Hs from various sources and promoters were tested for the improved DHQ production, with the best strain producing 381.2 ± 10.7 mg/L of DHQ from 1 g/L of NAR, suggesting the temporal regulation the expression of F3H is important for maximization the function of F3'H and F3H. CONCLUSION: This study offers effective strategies for improving DHQ production from NAR and could be used as a reference for related research.

Dihydroquercetin improves rotenone-induced Parkinsonism by regulating NF-κB-mediated inflammation pathway in rats.

This study examined the effect of dihydroquercetin (DHQ), also knofigurewn as taxifolin, on rotenone-induced Parkinsonism in rats. Male Wistar rats were administered 1.5 mg/kg rotenone for 10 days and subsequently treated with 0.25-1.0 mg/kg DHQ for 3 days followed by the assessment of parkinsonian symptoms. Brain striatal redox stress and neurochemical dysfunction markers were assessed spectrophotometrically. Histopathological evaluation of the striatum was done by hematoxylin and eosin staining technique. The expression of genes involved in the activation of NF-κB signaling pathway (IL-1ß, TNF-α, NF-κB and IκKB), and the p53 gene in the striatum were determined by RT-qPCR. DHQ attenuated parkinsonian symptoms as well as striatal redox stress, neurochemical dysfunction, and histological alterations occasioned by rotenone toxicity. Importantly, DHQ significantly suppressed the rotenone-induced upregulation of IL-1ß, NF-κB, and IκKB expression (p < 0.05) in the striatum of parkinsonian rats. DHQ demonstrated notable neurotherapeutic potential against rotenone-induced Parkinsonism in rats by improving parkinsonian symptoms (bradykinesia, catalepsy, postural instability, impaired locomotor behavior, and tremor) and neurochemical dysfunctions via modulation of genes involved in the activation of the canonical pathway of NF-κB-mediated inflammation.

A Three-Reagent "Green" Paper-Based Analytical Device for Solid-Phase Spectrometric and Colorimetric Determination of Dihydroquercetin.

Microfluidic paper-based analytical devices (µPADs) represent one of the promising green analytical strategies for low-cost and simple determination of various analytes. The actual task is the development of such devices for quantitation of antioxidants, e.g., flavonoids. In this paper, possibilities of a novel three-reagent µPAD including silver nitrate, 4-nitrophenyldiazonium tetrafluoroborate, and iron(III) chloride as reagents are assessed with respect to the determination of dihydroquercetin. It is shown that all the three reagents produce different colorimetric responses that can be detected by a mini-spectrophotometer-monitor calibrator or by a smartphone. The method is applicable to direct measuring high contents of dihydroquercetin (the linearity range is 0.026-1 mg mL-1, and the limit of detection is 7.7 µg mL-1), which is favorable for many dietary supplements. The analysis of a food supplement was possible with the relative standard deviations of 9-26%, which is satisfactory for quantitative and semiquantitative determinations. It was found that plotting a calibration graph in 3D space of the three reagents' responses allows us to distinguish dihydroquercetin from its close structural analogue, quercetin.

Modeling of the structure and forecasting properties of dihydroquercetin derivatives.

AIMS: To study new chemical compounds with the potential cure proper, and to develop modifications of the preferred structure of dihydroquercetin. BACKGROUND: Producing the new drugs needs the study of the cure properties of the chemical composes first of all, and computer modeling can make this process more informative and easy. OBJECTIVE: Computer projection of the chemical compounds' potential cure properties. METHODS: The reactivity of the studied models was evaluated by comparing the energies of the boundary molecular orbitals (HOMO and LUMO), as well as the difference in their values. The reaction center of the model molecules was determined via the analysis of the charge characteristics of atoms in each of them. RESULTS: A theoretical model of new chemical compounds with the potential properties of drugs was substantiated and modifications of the preferred structure of dihydroquercetin have been developed. The concept of new compounds has been expanded and opportunities for the modification of compounds with high pharmacological activity have been discussed. Using the AM1, PM3, and RM1 methods spatial characteristics were calculated. The results of quantum-chemical studies of model derivatives of dihydroquercetin via the RM1 method were carried out. CONCLUSIONS: Calculation of the enthalpies of formation of model molecules allowed evaluating their thermodynamic stability. An analysis of the electric dipole moments made a possibility to determine the preferred (polar) nature of the solvents for the studied model molecular systems.

Solubility Enhancement of Dihydroquercetin via "Green" Phase Modification.

Dihydroquercetin (DHQ) is a promising antioxidant for medical applications. The poor water solubility of this flavanonol at ambient conditions inhibits its implementation in clinical practice as an injectable dosage form. Thus, increasing water solubility is a critical step toward solving this problem. Herein we attempted to deal with this problem via DHQ phase modification while at the same time adhering to the principles of green chemistry as much as possible. Lyophilization is an appropriate method to achieve phase modification in an environment-friendly way. This method was employed to generate new phase modifications of DHQ that were then characterized. Mixtures of water with ethanol or acetonitrile were used as solvents for the preparation of the lyophilizates, DHQE, and DHQA, respectively. The results of dissolution testing of the obtained DHQE and DHQA demonstrated that the lyophilization increased water solubility at least 30-fold times. These new DHQ modifications were studied by scanning electron microscopy, mass-spectrometry, nuclear magnetic resonance spectroscopy, infrared spectroscopy, X-ray powder diffraction, and thermal analysis. Their solid-state phases were confirmed to differ from the initial DHQ substance without any changes in the molecular structure. Both DHQE and DHQA showed as high antioxidant activity as the initial DHQ. These data demonstrate the potential of DHQE and DHQA as active pharmaceutical ingredients for injectable dosage forms.

Crystal Structure of an SSB Protein from Salmonella enterica and Its Inhibition by Flavanonol Taxifolin.

Single-stranded DNA (ssDNA)-binding proteins (SSBs) play a central role in cells by participating in DNA metabolism, including replication, repair, recombination, and replication fork restart. SSBs are essential for cell survival and thus an attractive target for potential anti-pathogen chemotherapy. In this study, we determined the crystal structure and examined the size of the ssDNA-binding site of an SSB from Salmonella enterica serovar Typhimurium LT2 (SeSSB), a ubiquitous opportunistic pathogen which is highly resistant to antibiotics. The crystal structure was solved at a resolution of 2.8 Å (PDB ID 7F25), indicating that the SeSSB monomer possesses an oligonucleotide/oligosaccharide-binding (OB) fold domain at its N-terminus and a flexible tail at its C-terminus. The core of the OB-fold in the SeSSB is made of a six-stranded ß-barrel capped by an α-helix. The crystal structure of the SeSSB contained two monomers per asymmetric unit, which may indicate the formation of a dimer. However, the gel-filtration chromatography analysis showed that the SeSSB forms a tetramer in solution. Through an electrophoretic mobility shift analysis, we characterized the stoichiometry of the SeSSB complexed with a series of ssDNA dA homopolymers, and the size of the ssDNA-binding site was determined to be around 22 nt. We also found the flavanonol taxifolin, also known as dihydroquercetin, capable of inhibiting the ssDNA-binding activity of the SeSSB. Thus, this result extended the SSB interactome to include taxifolin, a natural product with a wide range of promising pharmacological activities.

Feeding dihydroquercetin in wheat-based diets to laying hens: impact on egg production and quality of fresh and stored eggs.

1. This study assessed the impact of dietary dihydroquercetin (DHQ) in wheat-based diets on egg production, composition and quality when fed to laying hens. A total of 80 Hy-Line Brown hens were allocated to 20 enriched layer cages, over two tiers, in groups of four birds.2. Two wheat-based diets were used in the study. A basal diet, meeting the nutrient requirement of the hens, containing 11.56 MJ/kg AME and 172 g/kg crude protein, was mixed and split into two parts. One part was fed as prepared to the control group of birds. The second diet was made by adding 1.5 g DHQ per kg basal diet and fed to the treatment group of birds. This level was relatively high and extended the data on levels normally fed. The diets were fed in a meal form and did not contain any coccidiostat, antimicrobial growth promoters or other similar additives. Each diet was fed to hens in 10 replicate cages for 4 weeks, from 22 to 26 weeks of age, following randomisation.3. Subsequently, eggs were investigated to determine the impact of dietary DHQ on the quality variables of fresh and 28-d stored eggs.4. Overall, feeding 1.5 g/kg dietary DHQ for 4 weeks did not affect (P > 0.05) egg production or the quality of fresh and stored eggs. Any observed egg quality changes (P < 0.05) confirmed the expected effects of egg storage.

The antihypertensive potential of flavonoids from Chinese Herbal Medicine: A review.

With the coming of the era of the aging population, hypertension has become a global health burden to be dealt with. Although there are multiple drugs and procedures to control the symptoms of hypertension, the management of it is still a long-term process, and the side effects of conventional drugs pose a burden on patients. Flavonoids, common compounds found in fruits and vegetables as secondary metabolites, are active components in Chinese Herbal Medicine. The flavonoids are proved to have cardiovascular benefits based on a plethora of animal experiments over the last decade. Thus, the flavonoids or flavonoid-rich plant extracts endowed with anti-hypertension activities and probable mechanisms were reviewed. It has been found that flavonoids may affect blood pressure in various ways. Moreover, despite the substantial evidence of the potential for flavonoids in the control of hypertension, it is not sufficient to support the clinical application of flavonoids as an adjuvant or core drug. So the synergistic effects of flavonoids with other drugs, pharmacokinetic studies, clinical trials and the safety of flavonoids are also incorporated in the discussion. It is believed that more breakthrough studies are needed. Overall, this review may shed some new light on the explicit recognition of the mechanisms of anti-hypertension actions of flavonoids, pointing out the limitations of relevant research at the current stage and the aspects that should be strengthened in future researches.

Comparative Study of Wound-Healing Activity of Dihydroquercetin Pseudopolymorphic Modifications.

Wound-healing activity of the crystalline form of dihydroquercetin and its microtubular pseudopolymorphic modification obtained by crystal engineering was compared using the rat model of IIIA degree burn. The rate of wound healing in the group treated with microtubular pseudopolymorphic modification of dihydroquercetin was 4.8±0.1%, which was higher by 11.6% than in the group treated with crystalline form (4.3±0.1%). Bioavailability analysis on MDCK cell culture showed that the apparent permeability coefficient of microtubular pseudopolymorphic modification was higher than that of crystalline form by 31.1% (19.4±0.2×10-4 and 14.8±0.3×10-4 cm/sec, respectively). It was proven that the use of crystal engineering improved the biopharmaceutical parameters of dihydroquercetin and increased its pharmacological efficiency.

[Dihydroquercetin influence on clinical and biochemical blood parameters of pigs under conditions of stress load].

In modern society, distress has become a widespread condition that negatively affects the functioning of all systems of the human organism. The study of biological mechanisms and changes in the organism under the influence of stress, as well as methods of their leveling, are relevant in medicine, animal science and veterinary medicine. Pigs are an excellent biological model that is closest to humans. The aim of the research was to study the hematological and biochemical parameters of pigs out of and under stress, including against the background of daily consumption of the flavonoid dihydroquercetin (DHQ) with feed. Material and methods. The research was conducted in the experimental yard of the L.K. Ernst Federal Science Center for Animal Husbandry on 3 groups of pigs [F2 hybrid (large white×Landrace)×Duroc] with an initial body weight of 30-35 kg (n=27). Group 1K consisted of control animals not exposed to stress (n=9); group 2K - control animals subjected to simulated stress by the rearrangement of animals (n=9); group 3O - experimental animals subjected to simulated stress and fed throughout the entire experiment DHQ (32 mg per 1 kg of feed) (n=9). On days 0, 42, and 76, blood was collected from the animals and their hematological and biochemical parameters were studied using conventional methods. Results. The positive effect of using DHQ in pigs' nutrition on enhancing the oxidizing function of blood, metabolic intensity, and increasing the endurance of animals under stress conditions has been manifested in maintaining leukocyte level with a higher content of erythrocytes and hematocrit. In animals fed DHQ, alanine aminotransferase activity was lower than in animals not receiving DHQ. Stress led to a significant increase in lactate dehydrogenase activity in group 2K on the 46th day, which was not observed in animals treated with DHQ. Conclusion. Long-term intake DHQ (up to 72 days inclusive) against the background of stress contributed to the preservation of blood values at the control level (without stress), within the physiological norm.

[Effect of per os administration of dihydroquercetin aqueous form on energy exchange in blood lymphocytes of rats with experimental cardiomyopathy].

Cardiomyopathies are among the most severe myocardial pathologies, which are characterized by resistance to therapy and high mortality due to increasing heart failure and arrhythmia. Cardiomyocyte pathological changes upon cardiomyopathies are associated with mitochondrial dysfunction, leading to excessive formation of reactive oxygen species and the development of oxidative stress. In this regard, the study of the therapeutic potential of antioxidants in cardiomyopathies, as well as the mechanisms of their action on the functioning of mitochondria, is relevant and of high practical importance. The aim of this study was to determine the effect of oral 14-day administration of dihydroquercetin in a water-soluble form (DHQWF) on the activity of the key marker of mitochondrial respiration [succinate dehydrogenase (SDH)] and the cytoplasmic marker of glycolysis [lactate dehydrogenase (LDH)] in blood lymphocytes, as well as on the serum level of lipid peroxidation (LPO) in control rats and rats with experimental cardiomyopathy. Material and methods. Adult male Wistar rats (body weight 220-240 g) were used for the study. Isoprenaline hydrochloride was used to induce cardiomyopathy (IIC) in animals (twice subcutaneous injection at a dose of 150 mg/kg body weight, with a break of 24 hours). DHQ-WF was added to the drinking water for 14 days at the dose of 15 or 30 mg/kg body weight. SDH and LDH activity in lymphocytes was measured using a highly sensitive cytobiochemical method on a blood smear according to the reduction of nitrotetrazolium blue chloride to diformazan of dark blue color. The content of malone dialdehyde (MDA) in the blood serum, heart and liver mitochondria was determined spectrophotometrically using thiobarbituric acid. Mitochondria were isolated from rat tissues by the conventional method of differential centrifugation. Mitochondrial respiration was recorded using a polarographic method. Results. Experimental cardiomyopathy in rats was accompanied by a twofold increase in blood serum MDA level, as well as by a significant increase in SDH and LDH activity in blood lymphocytes. The oral administration of DHQ-WF in cardiomyopathy at a dose of 15 mg/kg body weight led to a significant decrease in serum MDA level, but did not reduce the activity of SDH and LDH in blood lymphocytes, compared with animals with cardiomyopathy that did not receive DHQ-WF. In the control group of animals, the use of DHQ-WF at a dose of 15 mg/kg body weight significantly increased blood lymphocyte LDH activity, but did not have a statistically significant effect on SDH activity and the parameters of mitochondrial respiration and oxidative phosphorylation, the level of MDA in heart and liver mitochondria. Increasing the dose of DHQ-WF administered to 30 mg/kg had less effect on changes in these parameters in control animals. Conclusion. The data obtained indicate that in experimental cardiomyopathy in rats, the course application of DHQ-WF at a dose of 15 mg/kg of body weight acts as an effective antioxidant that prevents the development of lipid peroxidation in blood serum, and can modulate energy metabolism towards the enhancement of glycolysis in blood lymphocytes in control animals.

Dihydroquercetin attenuates lipopolysaccharide-induced acute lung injury through modulating FOXO3-mediated NF-κB signaling via miR-132-3p.

BACKGROUND: Dihydroquercetin (DHQ) is a potent flavonoid which has been demonstrated to have multiple biological activities including anti-inflammation activity, antioxidant activity as well as anti-cancer activity etc. Recently, many studies have focused on the antioxidant activity of DHQ. However, the use of the anti-inflammation activity of DHQ in acute lung injury (ALI) has not been reported. METHODS: Cell viability was examined by CCK-8 assay. The relative expression of miR-132-3p, FOXO3 were detected by qPCR. The levels of TNF-α, IL-6 and IL-1ß were detected using enzyme-linked immunosorbent assay. The amount of apoptosis cells was detected by flow cytometry. The protein levels of Bcl-2, Bax, p-p65 and p-IκBα were measured by western blot. RESULTS: We found that DHQ-induced the expression of miR-132-3p in LPS-induced ALI. Overexpression of miR-132-3p resulted in the inhibition of FOXO3 expression and then suppressed FOXO3-activated NF-κB pathway, attenuating LPS-induced inflammatory response and apoptosis. CONCLUSION: We demonstrated FOXO3 to be a target of miR-132-3p, and DHQ could induce the expression of miR-132-3p, relieving LPS-induced ALI via miR-132-3p/FOXO3/NF-κB axis, providing a promising therapeutic target for ALI.