The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy

Aghamiri, Seyed Hossein; Komlakh, Khalil; Ghaffari, Mostafa

doi:10.1007/s10787-021-00919-3

Cited by 11 publications

(6 citation statements)

References 106 publications

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“…[8,9] Based on previous reports, activation of TLRs have an critical role in diabetes-induced testicular dysfunction. [40] Karpova et al documented that the blockade of TLR4 reduced inflammation and improved diabetic testicular dysfunction by reducing oxidative stress and phospho-ERK1/2. [13] The Echinacea purpurea extract also decremented TLR4, NF-κB, IL-1β, and TNF-α in diabetes-induced male infertility.…”

Section: Discussionmentioning

confidence: 99%

Tropisetron improved testicular inflammation in the streptozotocin‐induced diabetic rats: The role of toll‐like receptor 4 (TLR4) and mir146a

Naderi

Pourheydar

Moslehi

2022

J Biochem & Molecular Tox

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As a serotonin antagonist, tropisetron positively affects blood glucose lowering, insulin synthesis, pancreas inflammation, and apoptosis in diabetes. Reproductive disorders are one of the diabetes‐induced chronic complications. The present study aimed to evaluate the effect of tropisetron on diabetes‐induced testicular inflammation, its signaling pathway, and mir146a. To this end, animals were assigned to the control, tropisetron, diabetes (DM), DM‐tropisetron, and DM‐glibenclamide groups. Streptozotocin (50 mg/kg) was intraperitoneally injected to provide diabetes. Tropisetron and glibenclamide were then administrated intraperitoneally for 2 weeks after diabetes induction. Testes histology, real‐time polymerase chain reaction, western blot analysis, ELISA, and immunohistochemistry assays were also performed. The finding revealed that tropisetron significantly improved diabetes‐induced testis damages, lowered TLR4, TRAF6, IRAK1, NF‐κB, and caspase3 protein expressions, and decreased TNF‐α and IL‐1 levels. Moreover, the mir146a expression declined following the tropisetron treatment. This study demonstrated that the significant role of tropisetron in lowering testicular inflammation and apoptosis might have been due to the inhibition of the TLR4/IRAK1/TRAF6 signaling pathway and thereby the attenuation of NF‐κB and caspase3 expression and inflammatory cytokines. Furthermore, the downregulation of mir146a, as an inflammatory microRNA interacting with TLR4, showed another pathway, through which tropisetron improved diabetes‐induced testicular injuries.

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Section: Discussionmentioning

confidence: 99%

Tropisetron improved testicular inflammation in the streptozotocin‐induced diabetic rats: The role of toll‐like receptor 4 (TLR4) and mir146a

Naderi

Pourheydar

Moslehi

2022

J Biochem & Molecular Tox

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“…In this work, two sorption models, namely the isotherm Langmuir and Freundlich, in their nonlinear forms, were applied to the equilibrium data of CR dye sorption by polymers SA-g-(PAA-co-AM)/CdS [24,25]. The Langmuir model assumes uniform energies of sorption onto the surface and no sorbate transmigration in the surface plane [26,27]. The equation non-linear of isotherm Langmuir model in Equation (3):…”

Section: Adsorption Isothermsmentioning

confidence: 99%

Untitled

2023

J. Med. Chem. Sci.

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In this paper, a new method was used to prepare the SA-g-(PAA-co-AM)/CdS, which is an environmentally friendly, inexpensive, available, and highly efficient absorbent material in the removal of Congo red dye from an aqueous solution. It was based on developing sodium alginate (SA) modified with Cds nano/mico composite and evaluating chemical properties. CdS nano/micro composite was combined with SA, and their chemical properties were evaluated by FTIR spectroscopy and X-ray diffraction, FESEM. The Freundlich and Langmuir models of adsorption isotherms were studied, and through the results, it was found that it is applied to the Freundlich model depending on the value of (R 2 =0.9895), compared with the Longmire model where the value of (R 2 =0.9415), because physical adsorption depends on heterogeneous surfaces. This work developed a simple, eco-friendly, and practical preparation of a low-cost composite CdS/alginate hydrogel which can be used for the pollutants removal.

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“… 16 , 17 TLR4 is a membrane transmembrane protein, which could recognize extracellular antigen or pathogens and transmit it into intracellular. 18 Afterwards, further activates NF-κB and up-regulates inflammatory cytokines, including IL-6 and IL-1β, subsequently trigger inflammation and leukocyte aggregation. 19 Accordingly, we hypothesise that suppressing the TLR4/NF-κB signaling pathway will contribute to help ameliorate DN renal inflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway

Guo¹,

Gao²,

Jiang³

et al. 2023

DDDT

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Background Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause of end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from the Astragalus membranaceus , was widely used in the treatment of diabetes mellitus. However, the functional roles of APS ameliorate inflammatory responses in DN, which remain poorly understood. Therefore, the purpose of this study was to explore the molecular mechanism of APS on DN in vivo and vitro models. Methods We explored the beneficial effects of APS in streptozotocin (STZ)-induced DN rat model and high glucose (HG)-treated glomerular podocyte model. The fasting blood glucose (FBG) and ratio of kidney weight to body weight were measured after 4 weeks of APS treatment. The renal injury parameters containing serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urinary protein were evaluated. The renal pathological examination was observed by hematoxylin-eosin (HE) staining. The levels of IL-1β, IL-6 and MCP-1 were evaluated by ELISA assay. The proliferation of podocytes was determined using CCK-8 assay and flow cytometry. qRT-PCR and Western blot analysis were performed to determine the amounts of TLR4/NF-κB-related gene expression. Results Our results indicated that APS effectively decreased the levels of FBG, BUN, Scr and renal pathological damage when compared with STZ-induced DN model group. Additionally, APS significantly ameliorated renal injury by reducing inflammatory cytokines IL-1β, IL-6, MCP-1 expression and inhibiting the TLR4/NF-κB pathway activity in DN rats. Consistent with the results in vitro, the HG-induced inflammatory response and proliferation of glomerular podocytes were also alleviated through APS administration. Conclusion We found that APS ameliorated DN renal injury, and the mechanisms perhaps related to relieving inflammatory responses and attenuating the TLR4/NF-κB signaling pathway.

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The crosstalk among TLR2, TLR4 and pathogenic pathways; a treasure trove for treatment of diabetic neuropathy

Cited by 11 publications

References 106 publications

Tropisetron improved testicular inflammation in the streptozotocin‐induced diabetic rats: The role of toll‐like receptor 4 (TLR4) and mir146a

Tropisetron improved testicular inflammation in the streptozotocin‐induced diabetic rats: The role of toll‐like receptor 4 (TLR4) and mir146a

Untitled

Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway

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