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Phytomedicine : International Journal... Jul 2017Human noroviruses (HuNoV), which are responsible for acute gastroenteritis, are becoming a serious public health concern worldwide. Since no effective antiviral drug or...
BACKGROUND
Human noroviruses (HuNoV), which are responsible for acute gastroenteritis, are becoming a serious public health concern worldwide. Since no effective antiviral drug or vaccine for HuNoV has been developed yet, some natural extracts and their active components have been investigated for their ability to inhibit noroviruses. However, their exact antiviral mechanisms have not been investigated.
PURPOSE
This study was performed to investigate the expression of interferon (IFN)-α, IFN-λ, tumor necrosis factor-α (TNF-α), Mx, and zinc finger CCCH type antiviral protein 1 (ZAP), 2'-5' oligo (A) synthetase (OAS), and inducible nitric oxide synthase (iNOS) in RAW 264.7 cells pre-treated with fisetin, daidzein, quercetin, epigallocatechin gallate (EGCG), and epicatechin gallate (ECG) that have anti-noroviral activity.
STUDY DESIGN
Based on the antiviral activity of the five flavonoids, recently reported by our group, the expression of antiviral factors such as IFN-α, IFN-λ, TNF-α, IL-1β, IL-6, Mx, ZAP, OAS, and iNOS was investigated in RAW 264.7 cells pre-treated with these flavonoids.
METHODS
Anti-noroviral effect was determined by performing a plaque assay on cells treated with the flavonoid. RAW 264.7 cells were treated with fisetin, daidzein, quercetin, EGCG, and ECG. Then, mRNA of IFN-α, IFN-λ, TNF-α, IL-1β, IL-6, Mx, ZAP, OAS, and iNOS were measured by real-time RT-PCR. IFN-α, TNF-α, IL-1β, and IL-6 proteins were measured by ELISA.
RESULTS
Pre-treatment with fisetin (50μM), fisetin (100μM), EGCG (100μM), quercetin (100μM), daidzein (50μM), and ECG (150μM) significantly reduced MNoV by 50.00±7.14 to 60.67±9.26%. The mRNA levels of IFN-α, IFN-λ, TNF-α, Mx, and ZAP were upregulated in RAW 264.7 cells pre-treated with fisetin, quercetin, and daidzein, but not in those pre-treated with EGCG or ECG. Regarding protein levels, IFN-α was significantly induced in cells pre-treated with fisetin, quercetin, and daidzein, whereas TNF-α was significantly induced only in cells pre-treated with daidzein.
CONCLUSION
Pre-treatment of RAW 264.7 cells with the five flavonoids inhibited MNoV by upregulating the expression of antiviral cytokines (IFN-α, IFN-λ, and TNF-α) and interferon-stimulating genes (Mx and ZAP).
Topics: Animals; Antiviral Agents; Catechin; Cell Line; Cytokines; Drug Evaluation, Preclinical; Flavonoids; Flavonols; Gene Expression Regulation; Interleukin-6; Isoflavones; Mice; Nitric Oxide Synthase Type II; Norovirus; Quercetin; Up-Regulation; Virus Replication
PubMed: 28545670
DOI: 10.1016/j.phymed.2017.04.011 -
Frontiers in Pharmacology 2021Daidzein is a plant isoflavonoid primarily isolated from Radix as the dry root of (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China....
Daidzein is a plant isoflavonoid primarily isolated from Radix as the dry root of (Wild.) Ohwi, have long been used as nutraceutical and medicinal herb in China. Despite the report that daidzein can prevent neuronal damage and improve outcome in experimental stroke, the mechanisms of this neuroprotective action have been not fully elucidated. The aim of this study was to determine whether the daidzein elicits beneficial actions in a stroke model, namely, cerebral ischemia/reperfusion (I/R) injury, and to reveal the underlying neuroprotective mechanisms associated with the regulation of Akt/mTOR/BDNF signal pathway. The results showed that I/R, daidzein treatment significantly improved neurological deficits, infarct volume, and brain edema at 20 and 30 mg/kg, respectively. Meanwhile, it was found out that the pretreatment with daidzein at 20 and 30 mg/kg evidently improved striatal dopamine and its metabolite levels. In addition, daidzein treatment reduced the cleaved Caspase-3 level but enhanced the phosphorylation of Akt, BAD and mTOR. Moreover, daidzein at 30 mg/kg treatment enhanced the expression of BDNF and CREB significantly. This protective effect of daidzein was ameliorated by inhibiting the PI3K/Akt/mTOR signaling pathway using LY294002. To sum up, our results demonstrated that daidzein could protect animals against ischemic damage through the regulation of the Akt/mTOR/BDNF channel, and the present study may facilitate the therapeutic research of stroke.
PubMed: 35095491
DOI: 10.3389/fphar.2021.772485 -
Molecules (Basel, Switzerland) Dec 2017The inclusion complexes between daidzein and three cyclodextrins (CDs), namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD, DS = 12.5) and...
The inclusion complexes between daidzein and three cyclodextrins (CDs), namely β-cyclodextrin (β-CD), methyl-β-cyclodextrin (Me-β-CD, DS = 12.5) and (2-hydroxy)propyl-β-cyclodextrin (HP-β-CD, DS = 4.2) were prepared. The effects of the inclusion behavior of daidzein with three kinds of cyclodextrins were investigated in both solution and solid state by methods of phase-solubility, XRD, DSC, SEM, ¹H-NMR and 2D ROESY methods. Furthermore, the antioxidant activities of daidzein and daidzein-CDs inclusion complexes were determined by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method. The results showed that daidzein formed a 1:1 stoichiometric inclusion complex with β-CD, Me-β-CD and HP-β-CD. The results also showed that the solubility of daidzein was improved after encapsulating by CDs. ¹H-NMR and 2D ROESY analyses show that the B ring of daidzein was the part of the molecule that was most likely inserted into the cavity of CDs, thus forming an inclusion complex. Antioxidant activity studies showed that the antioxidant performance of the inclusion complexes was enhanced in comparison to the native daidzein. It could be a potentially promising way to develop a new formulation of daidzein for herbal medicine or healthcare products.
Topics: Antioxidants; Chemistry, Pharmaceutical; Drug Carriers; Drug Liberation; Herbal Medicine; Humans; Isoflavones; Molecular Structure; Phase Transition; Solubility; Water; beta-Cyclodextrins
PubMed: 29292784
DOI: 10.3390/molecules22122183 -
Molecules (Basel, Switzerland) Aug 2021Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess...
Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s) and high (1800 s) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.
Topics: 14-3-3 Proteins; Animals; Blood Platelets; Fibrinogen; Genistein; Immobilized Proteins; Isoflavones; Male; Mice, Inbred C57BL; Platelet Aggregation; Platelet Glycoprotein GPIb-IX Complex; Signal Transduction; Glycine max; Thrombosis; Mice
PubMed: 34443497
DOI: 10.3390/molecules26164911 -
Recent Patents on Anti-cancer Drug... 2022Hepatocellular carcinoma (HCC) is one of the most common cancers, associated with a high rate of mortality. A disturbance between cell proliferation and cell death is...
BACKGROUND
Hepatocellular carcinoma (HCC) is one of the most common cancers, associated with a high rate of mortality. A disturbance between cell proliferation and cell death is one of the cancer hallmarks including HCC. Cell proliferation is mainly controlled by the cell cycle. The arrest of the cell cycle is one of the important targets of anticancer agents.
OBJECTIVES
The present study tries to clarify the exact role of some natural products such as daidzein (DAZ) and alcoholic chicory leaf extract (CE), as possible regulators of cell cycle and apoptosis.
METHODS
HCC in rats was induced using diethylnitrosamine (DENA). Ninety rats were allocated and divided equally into nine groups, treated with CE, DAZ, a combination of both, and sorafenib with non-treated control groups.
RESULTS
Treatment with CE, DAZ, and their combination significantly downregulated hepatic tissue expression of cyclin D1/CDK4 axis as well as cyclin A/CDK2 axis. The suggested therapeutic protocol inhibited the proliferation and dampened Bcl-2 expression. Furthermore, the efficiency of combining CE and DAZ demonstrated a potency comparable to sorafenib in terms of cyclin D/CDK4 axis expression, as well as; this combination protocol was more potent in revealing a potentiated inhibitory effect on cyclin A and Ki-67 expression.
CONCLUSION
Treatment with DAZ or CE alone, or in combination, could possess an inhibitory effect on hepatocarcinogenesis via cell cycle arrest, inhibition of proliferation through suppression of Ki-67 expression, and apoptosis induction, mediated by downregulation of Bcl-2.
Topics: Humans; Rats; Animals; Carcinoma, Hepatocellular; Cichorium intybus; Sorafenib; Cyclin A; Ki-67 Antigen; Liver Neoplasms; Cyclin-Dependent Kinase 4; Cell Cycle; Cell Cycle Checkpoints; Cell Proliferation; Proto-Oncogene Proteins c-bcl-2; Gene Expression; Cyclin-Dependent Kinase 2
PubMed: 35319392
DOI: 10.2174/1574892817666220321161318 -
Molecules (Basel, Switzerland) Apr 2024It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic,...
It is well known that daidzein has various significant medicinal values and health benefits, such as anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, cholesterol lowering, neuroprotective, cardioprotective and so on. To our disappointment, poor solubility, low permeability and inferior bioavailability seriously limit its clinical application and market development. To optimize the solubility, permeability and bioavailability of daidzein, the cocrystal of daidzein and piperazine was prepared through a scientific and reasonable design, which was thoroughly characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and thermogravimetric analysis. Combining single-crystal X-ray diffraction analysis with theoretical calculation, detailed structural information on the cocrystal was clarified and validated. In addition, a series of evaluations on the pharmacogenetic properties of the cocrystal were investigated. The results indicated that the cocrystal of daidzein and piperazine possessed the favorable stability, increased solubility, improved permeability and optimized bioavailability of daidzein. Compared with the parent drug, the formation of cocrystal, respectively, resulted in 3.9-, 3.1-, 4.9- and 60.8-fold enhancement in the solubility in four different media, 4.8-fold elevation in the permeability and 3.2-fold in the bioavailability of daidzein. Targeting the pharmaceutical defects of daidzein, the surprising elevation in the solubility, permeability and bioavailability of daidzein was realized by a clever cocrystal strategy, which not only devoted assistance to the market development and clinical application of daidzein but also paved a new path to address the drug-forming defects of insoluble drugs.
Topics: Solubility; Biological Availability; Isoflavones; Piperazine; Permeability; Crystallization; X-Ray Diffraction; Spectroscopy, Fourier Transform Infrared; Animals; Crystallography, X-Ray; Calorimetry, Differential Scanning; Humans
PubMed: 38675529
DOI: 10.3390/molecules29081710 -
Ultrasonics Sonochemistry Nov 2021In this study, daidzein microparticles (DMP) were prepared using an improved ultrasound-assisted antisolvent precipitation method. Preliminary experiments were conducted...
In this study, daidzein microparticles (DMP) were prepared using an improved ultrasound-assisted antisolvent precipitation method. Preliminary experiments were conducted using six single-factor experiments, and principal component analysis (PCA) was adopted to obtain the three staple elements of the ultrasonic power, solution concentration, and nozzle diameter. The response surface Box-Behnken (BBD) design was used to optimize the level of the above factors. The optimal preparation conditions of the DMP were obtained as follows: the flow rate was 4 mL/min, the concentration of the daidzein solution was 16 mg/mL, the ratio of antisolvent to solvent (liquid-to-liquid ratio) was 9, the nozzle diameter was 300 μm, the ultrasonic power was 180 W (665 W/L), and the system speed was 760 r/min. The minimum average particle size of DMP was 181 ± 2 nm. The properties of daidzein particles before and after preparation were analyzed via scanning electron microscopy, X-ray diffraction analysis, Differential scanning calorimetry and Fourier transform infrared spectroscopy, no obvious change in its chemical structure was observed, but crystallinity was reduced. Compared with daidzein powder, DMP has a higher solubility and stronger antioxidant capacity. The above results indicate that the improved method of ultrasonication combined with antisolvent can reduce the size of daidzein particles and has a great potential in practical production.
PubMed: 34624663
DOI: 10.1016/j.ultsonch.2021.105772 -
Drug Metabolism Reviews Aug 2016Cytochromes P450 (CYPs) play an important role in metabolism and clearance of most clinically utilized drugs and other xenobiotics. They are important in metabolism of... (Review)
Review
Cytochromes P450 (CYPs) play an important role in metabolism and clearance of most clinically utilized drugs and other xenobiotics. They are important in metabolism of endogenous compounds including fatty acids, sterols, steroids and lipid-soluble vitamins. Dietary factors such as phytochemicals are capable of affecting CYP expression and activity, which may be important in diet-drug interactions and in the development of fatty liver disease, cardiovascular disease and cancer. One important diet-CYP interaction is with diets containing plant proteins, particularly soy protein. Soy diets are traditionally consumed in Asian countries and are linked to lower incidence of several cancers and of cardiovascular disease in Asian populations. Soy is also an important protein source in vegetarian and vegan diets and the sole protein source in soy infant formulas. Recent studies suggest that consumption of soy can inhibit induction of CY1 enzymes by polycyclic aromatic hydrocarbons (PAHs) which may contribute to cancer prevention. In addition, there are data to suggest that soy components promiscuously activate several nuclear receptors including PXR, PPAR and LXR resulting in increased expression of CYP3As, CYP4As and CYPs involved in metabolism of cholesterol to bile acids. Such soy-CYP interactions may alter drug pharmacokinetics and therapeutic efficacy and are associated with improved lipid homeostasis and reduced risk of cardiovascular disease. The current review summarizes results from in vitro; in vivo and clinical studies of soy-CYP interactions and examines the evidence linking the effects of soy diets on CYP expression to isoflavone phytoestrogens, particularly, genistein and daidzein that are associated with soy protein.
Topics: Animals; Cytochrome P-450 Enzyme System; Diet; Gene Expression Regulation, Enzymologic; Genistein; Humans; Isoflavones; Soybean Proteins
PubMed: 27440109
DOI: 10.1080/03602532.2016.1206562 -
Archives of Toxicology Sep 2018Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by...
Daidzein, one of the major soy isoflavones, has a number of beneficial bioactivities for human health. It is mainly metabolized into 7- and/or 4'-glucuronides by UDP-glucuronosyltransferase (UGT) enzymes in mammals, including humans. The present study was conducted to examine the regioselective glucuronidation of daidzein at the 7- and 4'-hydroxyl groups in the liver and intestinal microsomes of humans, monkeys, rats, and mice. Daidzein glucuronidation activities at substrate concentrations of 1.0-200 µM were assessed, and Eadie-Hofstee plots were constructed. The kinetics for 7- and 4'-glucuronidation in the liver microsomes fit the Michaelis-Menten model, except for an atypical model for 7-glucuronidation in rats and a biphasic model for 4'-glucuronidation in monkeys. These kinetics in the intestinal microsomes followed the Michaelis-Menten model, except for a biphasic model for 7-glucuronidation in mice. The CL values for 7-glucuronidation were in the order of monkeys (49) ≫ rats (5.3) > humans (1.0) > mice (0.7) for liver microsomes, and rats (2.4) ≥ monkeys (2.2) > humans (1.0) ≥ mice (0.8) for intestinal microsomes. On the other hand, the CL values for 4'-glucuronidation were in the order of monkeys (4.0) > mice (1.0) ≈ humans (1.0) > rats (0.4) for liver microsomes, and humans (1.0) ≫ monkeys (0.08) ≥ mice (0.07) > rats (0.05) for intestinal microsomes. These results demonstrated that the metabolic abilities of UGT enzymes toward daidzein in the liver and intestines markedly differed among humans, monkeys, rats, and mice, and suggest that species and regioselective differences are closely associated with the bioactivities of soy isoflavones.
Topics: Adolescent; Adult; Aged; Animals; Glucuronosyltransferase; Humans; Intestinal Mucosa; Intestines; Isoflavones; Macaca fascicularis; Mice, Inbred Strains; Microsomes; Microsomes, Liver; Middle Aged; Rats, Sprague-Dawley
PubMed: 30014295
DOI: 10.1007/s00204-018-2265-1 -
Indian Journal of Pharmacology 2017The objective of the study was to investigate the effect of daidzein flavonoid on cisplatin (CP)-induced hematotoxicity and hepatotoxicity in experimental rats.
OBJECTIVE
The objective of the study was to investigate the effect of daidzein flavonoid on cisplatin (CP)-induced hematotoxicity and hepatotoxicity in experimental rats.
MATERIALS AND METHODS
The Wistar rats were randomly divided into four equal groups: Normal (saline 1 ml p.o.), CP (7.5 mg/kg once intraperioteneally on 16 day), test group of low dose (combination of CP and daidzein 20 mg/kg p.o. for 21 days), and test group of high dose (combination of CP and daidzein 40 mg/kg p.o. for 21 days). Blood samples were collected on 22 day from each rat and subjected for evaluation of hematological parameters such as red blood corpuscles (RBC), white blood corpuscles, hemoglobin (Hb) and platelets, and serum biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Liver of each rat was excised and subjected for antioxidants evaluation such as malonyl dialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase, and histopathological study.
RESULTS
Daidzein had a significant ( < 0.001) beneficial role in CP-induced hemotoxicity by increasing RBC, Hb, packed cell volume, and platelets. Daidzein also exhibited a significant ( < 0.001) protection against CP-induced hepatotoxicity by decreasing ALT, AST, ALP, and MDA level and by elevating the GSH, SOD, and catalase.
CONCLUSIONS
Daidzein attenuates CP-induced oxidative stress on blood cells and antioxidants in rats.
Topics: Alanine Transaminase; Animals; Antineoplastic Agents; Antioxidants; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cisplatin; Dose-Response Relationship, Drug; Female; Glutathione; Isoflavones; Male; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase
PubMed: 28458422
DOI: 10.4103/0253-7613.201022