scholarly journals Lycium Barbarum Polysaccharides and Wolfberry Juice Prevent DEHP-Induced Hepatotoxicity via PXR-Regulated Detoxification Pathway

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 859
Author(s):  
Huan Liu ◽  
Xiong Zhou ◽  
Shaowen Huang ◽  
Jie Yang ◽  
Ruijing Liu ◽  
...  
Keyword(s):  
Pregnane X Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Glutathione S Transferase ◽  
Lycium Barbarum ◽  
Cytochrome P4502e1 ◽  
Exposure Experiment ◽  
Retinoid X Receptor Alpha ◽  
Dehp Exposure ◽  
Lycium Barbarum Polysaccharides

Environmental di(2-Ethylhexyl) phthalate (DEHP) is widely used in various industries as a plasticizer, and has been reported to induce reproductive and developmental toxicities in organisms. The purpose of this study was to evaluate the detoxification capacity of Lycium barbarum polysaccharides (LBP) and wolfberry juice (WJ) against DEHP-induced hepatotoxicity. Two groups of rats were purchased to study two different intervention method experiments: LBP (50, 100, 200 mg/kg·bw) intervention before DEHP (2000 mg/kg·bw) exposure, and LBP (200 mg/kg·bw) or WJ (8 mL/kg·bw) intervention after DEHP (3000 mg/kg·bw) exposure. The rats were exposed to DEHP once, while the intervention lasted for seven days. At the end of the intervention, enzyme-linked immunosorbent assay (ELISA) was used to measure the related index. The LBP intervention before DEHP exposure experiment (the first experimental method) found that LBP group rats showed a strong capacity toward DEHP detoxification, evidenced by the significant upregulation of activities and concentrations of the partner retinoid, X receptor alpha (RXRα), and downstream regulators Cytochrome P4502E1 (CYP2E1), Cytochrome P4503A1 (CYP3A1), Glutathione S-Transferase Pi (GSTpi), and UDP-glucuronosyltransferase 1 (UGT1) in a dose-dependent manner. The LBP and WJ intervention after DEHP exposure experiment (the second intervention experiment) found that WJ could downregulate pregnane X receptor (PXR), and upregulate downstream regulators, CYP2E1, CYP3A1, and Glutathione S-Transferase (GST) with the extension of intervention time, to alleviate the toxicity of DEHP. However, the intervention effect of WJ was more obvious than that of LBP. These results suggested that LBP and WJ might be effective detoxification agents against DEHP-induced toxic effects, by activating PXR and PXR-related detoxifying enzymes.

scholarly journals Protective Effect of Lycium Barbarum Polysaccharides on Anti-Tuberculosis Drug-Induced Injury to Human Hepatocytes and Its Mechanism

2021 ◽  
Author(s):  
Jianteng Wei ◽  
Yongsheng Li ◽  
Han Wang ◽  
Dong Pei ◽  
Ningli Wang ◽  
...  
Keyword(s):  
Liver Injury ◽  
Protective Effect ◽  
Underlying Mechanism ◽  
Dependent Manner ◽  
Lycium Barbarum ◽  
Drug Induced ◽  
Nrf2 Signaling Pathway ◽  
Induced Apoptosis ◽  
Dose Dependent ◽  
Lycium Barbarum Polysaccharides

Abstract Studies have shown that Lycium barbarum polysaccharides (LBPs) have a protective effect on liver injury, but the mechanism is not fully understood. In this work, the effect of LBPs on L-02 cells exposed to anti-tuberculosis drug was investigated and the potential molecular mechanism was explored. Results showed that LBPs significantly prevented anti-tuberculosis drug-induced hepatotoxicity in a dose-dependent manner, as indicated by cell viability and diagnostic indicators of liver injury. The anti-tuberculosis drug promoted the production of reactive oxygen species and enhanced the oxidative stress, as evidenced by an increase in the malondialdehyde level and a decrease in the antioxidant enzyme levels in the liver. These effects were suppressed by treatment with LBPs. Furthermore, exploration of the underlying mechanism of LBPs revealed that the caspase-3 activity was markedly inhibited by the treatment with LBPs in the liver of anti-tuberculosis drug-treated mice. LBPs increased the expression level of Nrf2, thereby inactivating proapoptotic signaling events and restoring the balance between proapoptotic Bax and antiapoptotic Bcl-2 proteins in the cell of anti-tuberculosis drug-treated mice. In conclusion, LBPs inhibited anti-tuberculosis drug-induced apoptosis partly due to its antioxidant and antiapoptosis activities via the Nrf2 signaling pathway.

scholarly journals The Effect of Lycium barbarum Polysaccharides on Pyroptosis-Associated Amyloid β1-40 Oligomers-Induced Adult Retinal Pigment Epithelium 19 Cell Damage

2020 ◽  
Vol 21 (13) ◽  
pp. 4658 ◽  
Author(s):  
Ming Yang ◽  
Kwok-Fai So ◽  
Amy Cheuk Yin Lo ◽  
Wai Ching Lam
Keyword(s):  
Retinal Pigment Epithelium ◽  
Cell Viability ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Morphological Characteristics ◽  
Age Related Macular Degeneration ◽  
Dependent Manner ◽  
Lycium Barbarum ◽  
Age Related ◽  
Lycium Barbarum Polysaccharides

Age-related macular degeneration (AMD) is a sight-threatening disease with limited treatment options. We investigated whether amyloid β1-40 (Aβ1-40) could cause pyroptosis and evaluated the effects of Lycium barbarum polysaccharides (LBP) on Aβ1-40 oligomers-induced retinal pigment epithelium 19 (ARPE-19) damage, which is an in vitro AMD model. Aβ1-40 oligomers verified by Western blot were added to ARPE-19 cells with or without 24 h LBP treatment. Aβ1-40 oligomers significantly decreased ARPE-19 cell viability with obvious morphological changes under light microscopy. SEM revealed swollen cells with a bubbling appearance and ruptured cell membrane, which are morphological characteristics of pyroptosis. ELISA results showed increased expression of IL-1β and IL-18, which are the final products of pyroptosis. LBP administration for 24 h had no toxic effects on ARPE-19 cells and improved cell viability and morphology while disrupting Aβ1-40 oligomerization in a dose-dependent manner. Furthermore, Aβ1-40 oligomers up-regulated the cellular immunoreactivity of pyroptosis markers including NOD-like receptors protein 3 (NLRP3), caspase-1, and membrane N-terminal cleavage product of GSDMD (GSDMD-N), which could be reversed by LBP treatment. Taken together, this study showed that LBP effectively protects the Aβ1-40 oligomers-induced pyroptotic ARPE-19 cell damages by its anti-Aβ1-40 oligomerization properties and its anti-pyroptotic effects.

scholarly journals Inhibition of binding of anti-PLA1 antibodies to platelets with monoclonal antibody LK-4. Evidence for multiple PLA1 receptor sites on platelet GPIIIa

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3601-3607 ◽  
Author(s):  
LX Liu ◽  
MA Nardi ◽  
JF Casella ◽  
S Karpatkin
Keyword(s):  
Monoclonal Antibody ◽  
Flow Cytometry ◽  
Solid Phase ◽  
Fusion Peptide ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Glutathione S Transferase ◽  
Receptor Sites ◽  
Resistant Group ◽  
Sensitive Group

The PLA1 epitope on platelet GPIIIa has a sulfhydryl-dependent conformation and is dependent on a leucine 33/proline33 polymorphism. Monoclonal antibody LK-4 differentiates PLA1/PLA1 from PLA2/PLA2 platelet lysates on solid phase enzyme-linked immunosorbent assay (ELISA), as well as immunoblot. To determine whether LK-4 reacts at or near the binding site(s) for human anti-PLA1, nine such antibodies (Abs) (six neonatal; three posttransfusion) were examined in the presence and absence of LK-4 for binding to platelets, as well as rGPIIIa 1–66, a recombinant glutathione S-transferase fusion peptide. All nine human Abs bound to rGPIIIa 1–66, as well as platelets, in a saturation-dependent manner, employing both solid phase ELISA, as well as flow cytometry. Binding of all nine Abs to rGPIIIa 1–66 or platelets was inhibited by LK-4. IC50′s for inhibition of binding of anti-PLA1 to rGPIIIa 1–66 varied from 8 to 160 micrograms/mL (5 x 10(-8)- 1 x 10(-6) mol/L). However, IC50′s for LK-4 inhibition of binding to platelets was strikingly different. Six of the nine Abs had IC50′s of 1 to 10 micrograms/mL (8-fold to 16-fold greater inhibition than with rGPIIIa 1–66), whereas three neonatal Abs had IC50′s of 380 to 1,013 micrograms/mL (6-fold to 48-fold less inhibition than with rGPIIIa 1–66). Similar results were noted with intact GPIIIa, rGPIIIa 1–66 blocked the binding of anti-PLA1 Abs to platelets and served to segregate the nine patients into two groups: a sensitive group of anti-PLA1 Abs from six patients in which binding to platelets was progressively inhibited by increasing concentrations of rGPIIIa 1–66 with inhibition at 1 micrograms/mL of 18% and inhibition at 256 micrograms/mL of 78%; a second resistant group of three anti-PLA1 Abs from three patients in which inhibition was first noted at 16 micrograms/mL of 4% with 35% inhibition at 256 micrograms/mL. Thus, LK-4 binds to GPIIIa at the 1–66 N-terminal region, inhibits binding of anti-PLA1 Ab to platelets, and segregates, anti-PLA1 Abs into two groups. These data are compatible with two or more receptor sites for anti-PLA1 Ab: one that is present on rGPIIIa 1–66 and sensitive to LK-4 inhibition, another that is present on rGPIIIa 1–66, as well as other site(s) on platelet GPIIIa and insensitive to inhibition.

scholarly journals Role of MDA5 in regulating CXCL10 expression induced by TLR3 signaling in human rheumatoid fibroblast-like synoviocytes

2021 ◽  
Author(s):  
Tatsuro Saruga ◽  
Tadaatsu Imaizumi ◽  
Shogo Kawaguchi ◽  
Kazuhiko Seya ◽  
Tomoh Matsumiya ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Neutralizing Antibody ◽  
Poly I:C ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Inflammatory Reactions ◽  
Polyinosinic:Polycytidylic Acid ◽  
Tlr3 Signaling ◽  
Fibroblast Like Synoviocytes

AbstractC-X-C motif chemokine 10 (CXCL10) is an inflammatory chemokine and a key molecule in the pathogenesis of rheumatoid arthritis (RA). Melanoma differentiation-associated gene 5 (MDA5) is an RNA helicase that plays a role in innate immune and inflammatory reactions. The details of the regulatory mechanisms of CXCL10 production and the precise role of MDA5 in RA synovitis have not been fully elucidated. The aim of this study was to examine the role of MDA5 in regulating CXCL10 expression in cultured human rheumatoid fibroblast-like synoviocytes (RFLS). RFLS was stimulated with Toll-like receptor 3 (TLR3) ligand polyinosinic:polycytidylic acid (poly I:C), a synthetic double-stranded RNA mimetic. Expression of interferon beta (IFN-β), MDA5, and CXCL10 was measured by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), western blotting, and enzyme-linked immunosorbent assay. A neutralizing antibody of IFN-β and siRNA-mediated MDA5 knockdown were used to determine the role of these molecules in regulating CXCL10 expression downstream of TLR3 signaling in RFLS. Poly I:C induced IFN-β, MDA5, and CXCL10 expression in a concentration- and time-dependent manner. IFN-β neutralizing antibody suppressed the expression of MDA5 and CXCL10, and knockdown of MDA5 decreased a part of CXCL10 expression (p < 0.001). The TLR3/IFN-β/CXCL10 axis may play a crucial role in the inflammatory responses in RA synovium, and MDA5 may be partially involved in this axis.

Mechanism of Lycium barbarum polysaccharides on primary cultured rat hippocampal neurons

2017 ◽  
Vol 369 (3) ◽  
pp. 455-465 ◽  
Author(s):  
Peng Zhao ◽  
Ning-Tian Ma ◽  
Ren-Yuan Chang ◽  
Yu-Xiang Li ◽  
Yin-Ju Hao ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Lycium Barbarum ◽  
Lycium Barbarum Polysaccharides

scholarly journals Inhibition of Fungal Appressorium Formation by Pepper (Capsicum annuum) Esterase

2001 ◽  
Vol 14 (1) ◽  
pp. 80-85 ◽  
Author(s):  
Young Soon Kim ◽  
Hyun Hwa Lee ◽  
Moon Kyung Ko ◽  
Chae Eun Song ◽  
Cheol-Yong Bae ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Capsicum Annuum ◽  
Magnaporthe Grisea ◽  
Dependent Manner ◽  
Appressorium Formation ◽  
Glutathione S Transferase ◽  
Porcine Liver ◽  
Esterase Gene ◽  
Dose Dependent ◽  
Dependent Signaling Pathway

A pepper esterase gene (PepEST) that is highly expressed during an incompatible interaction between pepper (Capsicum annuum) and the anthracnose fungus Colletotrichum gloeosporioides has been previously cloned. Glutathione-S-transferase-tagged recombinant PepEST protein expressed in Escherichia coli showed substrate specificity for p-nitrophenyl esters. Inoculation of compatible unripe pepper fruits with C. gloeosporioides spores amended with the recombinant protein did not cause anthracnose symptoms on the fruit. The recombinant protein has no fungicidal activity, but it significantly inhibits appressorium formation of the anthracnose fungus in a dose-dependent manner. An esterase from porcine liver also inhibited appressorium formation, and the recombinant protein inhibited appressorium formation in the rice blast fungus, Magnaporthe grisea. Inhibition of appressorium formation in M. grisea by the recombinant protein was reversible by treatment with cyclic AMP (cAMP) or 1,16-hexadecanediol. The results suggest that the recombinant protein regulates appressorium formation by modulating the cAMP-dependent signaling pathway in this fungus. Taken together, the PepEST esterase activity can inhibit appressorium formation of C. gloeosporioides, which may result in protection of the unripe fruit against the fungus.

Lycium barbarum polysaccharides reduce intestinal ischemia/reperfusion injuries in rats

2013 ◽  
Vol 204 (3) ◽  
pp. 166-172 ◽  
Author(s):  
Xuekang Yang ◽  
Hua Bai ◽  
Weixia Cai ◽  
Jun Li ◽  
Qin Zhou ◽  
...  
Keyword(s):  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Lycium Barbarum ◽  
Intestinal Ischemia Reperfusion ◽  
Lycium Barbarum Polysaccharides

scholarly journals Human Articular Chondrocytes Induce Interleukin-2 Nonresponsiveness to Allogeneic Lymphocytes

Cartilage ◽  
2016 ◽  
Vol 8 (3) ◽  
pp. 300-306 ◽  
Author(s):  
Satomi Abe ◽  
Hitoshi Nochi ◽  
Hiroshi Ito
Keyword(s):  
T Cells ◽  
Articular Chondrocytes ◽  
Interleukin 2 ◽  
Flow Cytometric Analysis ◽  
Third Party ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Activated T Cells ◽  
Allogeneic Lymphocytes

Introduction We previously showed that articular chondrocytes (ACs) have immune privilege and immunomodulatory functions like those of mesenchymal stem cells. To elucidate these mechanisms, we focused on interleukin-2 (IL-2), which plays critical roles in lymphocyte mitogenic activity. The purpose of this study was to explore whether ACs affect the role of IL-2 underlying immunomodulatory functions. Material and Methods Irradiated human ACs from osteoarthritis donors were used. Third-party ACs were added to the mixed lymphocyte reaction (MLR) with or without recombinant human IL-2 (rhIL-2), and the levels of IL-2 and the soluble form of the IL-2 receptor α (sIL-2Rα) protein in supernatant were measured by enzyme-linked immunosorbent assay. Recombinant human IL-2 (rhIL-2) was also added to the MLR. To detect the expression of IL-2 receptor α (CD25) on lymphocytes in the MLR, flow cytometric analysis was performed. Last, ACs and allogeneic activated CD4+ T cell were co-cultured, and the expression of CD25 on activated T cells was examined by flow cytometry. Results Third-party ACs significantly inhibited the MLR and reduced the level of sIL-2Rα in a dose-dependent manner, but did not affect the concentration of IL-2. Exogenous rhIL-2 accelerated MLR but did not rescue the inhibitory effect of ACs. ACs inhibited the expression of CD25 on activated CD4+ T cells. Discussion Our results showed that third-party ACs inhibited the proliferation of allogeneic activated lymphocytes, thereby inhibiting production sIL-2Rα, although ACs did not affect IL-2 secretion from lymphocytes. Also, ACs inhibited CD25 expression on activated CD4+ T cells. Thus, ACs inhibited the immune response of allogeneic lymphocytes by inducing IL-2 nonresponsiveness.

Sign in / Sign up

Export Citation Format

Share Document