Thymol alleviates AGEs-induced podocyte injury by a pleiotropic effect via NF-κB-mediated by RhoA/ROCK signalling pathway

Zhou

Journal of Diabetes Research

et al. 2021

Objective. Abnormal signaling pathways play a crucial role in the mechanisms of podocyte injury in diabetic nephropathy. They also affect the recovery of podocytes after islet transplantation (IT). However, the specific signaling abnormalities that affect the therapeutic effect of IT on podocytes remains unclear. The purpose of this study was to assess whether the RhoA/ROCK/NF-κB signaling pathway is related to podocyte restoration after IT. Methods. A mouse model of diabetic nephropathy was established in vivo using streptozotocin. The mice were then subsequently reared for 4 weeks after islet transplantation to determine the effect of IT. Islet cells, CCG-1423 (RhoA Inhibitor), and fasudil (ROCK inhibitor) were then cocultured with podocytes in vitro to assess their protective effects on podocyte injury induced by high glucose (HG). Protein expression levels of RhoA, ROCK1, synaptopodin, IL-6, and MCP-1 in kidney tissues were then measured using immunohistochemistry and Western blotting techniques. Results. Islet transplantation reduced the expression levels of RhoA/ROCK1 and that of related inflammatory factors such as IL-6 and MCP-1 in the kidney podocytes of diabetic nephropathy. In the same line, islet cells reduced the expression of RhoA, ROCK1, and pp65 in immortalized podocytes under high glucose (35.0 mmol/L glucose) conditions. Conclusions. Islet transplantation can reverse podocyte injury in diabetes nephropathy by inhibiting the RhoA/ROCK1 signaling pathway. Islet cells have a strong protective effect on podocytes treated with high glucose (35.0 mmol/L glucose). Discovery of signaling pathways affecting podocyte recovery is helpful for individualized efficacy evaluation and targeted therapy of islet transplantation patients.

Section: Discussionsupporting

confidence: 93%

Islet Transplantation Reverses Podocyte Injury in Diabetic Nephropathy or Induced by High Glucose via Inhibiting RhoA/ROCK/NF-κB Signaling Pathway

Zhou

Journal of Diabetes Research

et al. 2021

Advances in Pharmacological and Pharmaceutical Sciences

“…In western blot analysis, thymol indicated that it could restore the expression of RhoA, ROCK, vimentin, nephrin, and podocin and phosphorylation of p65 and IκBα. In addition, si-RhoA also suppressed the expression of proinfammatory cytokines, ROCK, and vimentin and the phosphorylation of p65 and IκBα [53].…”

Section: Catalpolmentioning

confidence: 93%

Use of Monoterpenes as Potential Therapeutics in Diabetes Mellitus: A Prospective Review

Sousa,

Viana,

Coêlho

et al. 2023

Monoterpenes are secondary metabolites of plants belonging to the terpenoid class of natural products. They are the most abundant components of essential oils that are generally considered to have various pharmacological properties. These compounds are reported to have antidiabetic effects in recent years. Due to nature’s complex biosynthetic machinery, they also exhibit a reasonable degree of structural complexity/diversity for further analysis in structure-activity studies. Therefore, monoterpenes as antidiabetic agents have been investigated by recent in vitro and in vivo studies extensively reported in the scientific literature and claimed by patent documents. The purpose of this survey is to provide a comprehensive and prospective review concerning the potential applications of monoterpenes in the treatment of diabetes. The data for this research were collected through the specialized databases PubMed, Scopus, Web of Science, and ScienceDirect between the years 2014 and 2022, as well as the patent databases EPO, WIPO, and USPTO. The research used 76 articles published in the leading journals in the field. The main effect observed was the antidiabetic activity of monoterpenes. This review showed that monoterpenes can be considered promising agents for prevention and/or treatment of diabetes as well as have a marked pharmaceutical potential for the development of bioproducts for therapeutics applications.

“…After recording the kidney weight (KW) and morphological examination, the kidneys were fixed immediately in 10% formalin and embedded in paraffin. For general histology, specimens were cut into 2 μm sections and stained with hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining as described in a previous study [ 20 ]. The quantitative results of renal interstitial damage were calculated as follows: 20 random high-power fields for each kidney slide of every rat in each group were examined to calculate the percentage of damaged renal tubules in the total renal tubules ( n = 8 per group).…”

Section: Methodsmentioning

confidence: 99%

“…Western blotting was performed according to methods previously described [ 20 ]. Briefly, 20 µg of total lysate from kidney tissue was subjected to 10–12% SDS-PAGE, and the separated proteins were transferred to polyvinylidene fluoride (PVDF) membranes.…”

Section: Methodsmentioning

confidence: 99%

“…In kidney injury models, thymol showed protective effects against cisplatin-induced renal tubular necrosis and in STZ-induced diabetic rats by suppressing renal oxidative stress [ 18 , 19 ]. In our previous research, we found that thymol alleviates the lipopolysaccharide-stimulated inflammatory response via downregulation of the RhoA-mediated NF-κB signaling pathway in human peritoneal mesothelial cells [ 20 ]. Given its important role in anti-inflammatory and antioxidant stress, in this study, we aimed to clarify the protective effect of thymol in RM-induced AKI and further elucidate the potential mechanisms through which thymol exerts its various effects.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Protective effect of thymol on glycerol-induced acute kidney injury

Wang

Zhou

et al. 2023

Renal Failure

Self Cite

Acute kidney injury (AKI) is a syndrome characterized by an accelerating decrease in renal function in a short time. Thymol is one of the main components of thyme species and has a variety of pharmacological effects. Here, we investigated whether thymol could ameliorate rhabdomyolysis (RM)-induced AKI and its related mechanism. Glycerol was used to induce RM-associated AKI in rats. Rats received thymol (20 mg/kg/day or 40 mg/kg/day) gavage 24 h before glycerol injection until 72 h after injection daily. Kidney injury was identified by measuring serum creatinine (Scr) and urea levels and by H&E and PAS staining and immunohistochemistry (the expression of proliferating cell nuclear antigen (PCNA)). Renal superoxide dismutase (SOD), malondialdehyde (MDA), and oxidative stress-related Nrf2/HO-1 signaling pathways were measured. The expression of the inflammatory markers TNF-α, IL-6, MCP-1, and NF-κB was assessed by ELISA and western blotting. Finally, the expression of the PI3K/Akt signaling pathway was detected by western blotting. Glycerol administration induced obvious renal histologic damage and increased Scr, urea, and PCNA expression. Notably, thymol treatment attenuated these structural and functional changes and prevented renal oxidative stress, inflammatory damage and PI3K/Akt pathway downregulation associated with glycerol-induced AKI. In conclusion, thymol might have potential applications in the amelioration of AKI via its antioxidant and anti-inflammatory effects and upregulation of the PI3K/Akt signaling pathway.