Association of the dietary inflammatory index with complicated diabetic kidney disease in people with diabetes mellitus: evidence from NHANES 2009-2018.

AIMS: Diabetic kidney disease (DKD) significantly impairs quality of life in individuals with diabetes mellitus (DM). The influence of the Dietary Inflammatory Index (DII) on DKD, which is associated with adverse health outcomes, is not well-understood. METHODS: We analyzed 2712 subjects from the National Health and Nutrition Examination Survey (NHANES) spanning 2011-2018, aiming to elucidate the relationship between DII and DKD. RESULTS: DKD was diagnosed in 1016 participants (37.46%). Elevated DII levels were significantly associated with an increased DKD risk, as evidenced by multivariate logistic regression (Odds Ratio [OR] = 1.40, 95% Confidence Interval [CI] 1.12-1.75, P < 0.05). Further analysis after adjusting for covariates highlighted a notable non-linear correlation between DII and DKD risk, at DII values below 0.45, the risk of DKD increases with higher DII levels, whereas it stabilizes beyond this point. Subgroup analysis additionally revealed that diabetic men have a significantly higher DKD risk compared to women (P < 0.05). CONCLUSION: Our study indicates a pronounced link between higher DII scores and increased risk of DKD among DM patients. These findings underscore the paramount importance of dietary management in DM treatment, stressing the need for interventions focused on reducing dietary inflammation to decelerate DKD progression.

Unlocking renal Restoration: Mesaconine from Aconitum plants restore mitochondrial function to halt cell apoptosis in acute kidney injury.

Acute kidney injury (AKI) is characterized by a sudden decline in renal function. Traditional Chinese medicine has employed Fuzi for kidney diseases; however, concerns about neurotoxicity and cardiotoxicity have constrained its clinical use. This study explored mesaconine, derived from processed Fuzi, as a promising low-toxicity alternative for AKI treatment. In this study, we assessed the protective effects of mesaconine in gentamicin (GM)-induced NRK-52E cells and AKI rat models in vitro and in vivo, respectively. Mesaconine promotes the proliferation of damaged NRK-52E cells and down-regulates intracellular transforming growth factor ß1 (TGF-ß1) and kidney injury molecule 1 (KIM-1) to promote renal cell repair. Concurrently, mesaconine restored mitochondrial morphology and permeability transition pores, reversed the decrease in mitochondrial membrane potential, mitigated mitochondrial dysfunction, decreased ATP production, inhibited inflammatory factor release, and reduced early apoptosis rates. In vivo, GM-induced AKI rat models exhibited elevated AKI biomarkers, in which mesaconine was effectively reduced, indicating improved renal function. Mesaconine enhanced superoxide dismutase activity, reduced malondialdehyde content, alleviated inflammatory infiltrate, mitigated tubular and glomerular lesions, and downregulated NF-κB (nuclear factor-κb) p65 expression, leading to decreased tumor necrosis factor-α (TNF-α) and IL-1ß (interleukin-1ß) levels in GM-induced AKI animals. Furthermore, mesaconine inhibited the expression of renal pro-apoptotic proteins (Bax, cytochrome c, cleaved-caspase 9, and cleaved-caspase 3) and induced the release of the anti-apoptotic protein bcl-2, further suppressing apoptosis. This study highlighted the therapeutic potential of mesaconine in GM-induced AKI. Its multifaceted mechanisms, including the restoration of mitochondrial dysfunction, anti-inflammatory and antioxidant effects, and apoptosis mitigation, make mesaconine a promising candidate for further exploration in AKI management.

The protective effect and mechanism of piperazine ferulate in rats with 5/6 nephrectomy-caused chronic kidney disease.

Chronic kidney disease (CKD) is a type of chronic disease in which multiple factors are responsible for the structural and functional disorders of the kidney. Piperazine ferulate (PF) has anti-platelet and anti-fibrotic effects, and its mechanism of action remains to be elucidated. This study aimed to investigate the protective effect of PF against CKD in rats and to determine its mechanism of action. Network pharmacology was used to predict potential PF action targets in the treatment of CKD and to further validate them. A rat model of CKD was established; blood was collected, etc., for the assessment of the renal function; renal pathologic damage was examined using hematoxylin and eosin (HE) staining and Masson staining; changes in the levels of TGF-ß1 and α-SMA were determined with ELISA; EPOR, FN, and COL I expression were detected utilizing immunohistochemistry; and HIF-1α, HIF-2α, and EPO protein molecules were analyzed deploying western blotting. PF reduces Scr, BUN, and 24 h UP levels; decreases FN and COL I expression; and attenuates renal injury. Additionally, PF inhibited TGF-ß1 and stimulated the production of HIF-1α and HIF-2α, which downregulated α-SMA and upregulated EPO. PF attenuated the progression of the CKD pathology, and the mechanism of its action is possibly associated with the promotion of HIF-1α/HIF-2α/EPO production and TGF-ß1 reduction.

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis.

Objectives: Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney. Conclusion: Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

Piperazine ferulate attenuates gentamicin-induced acute kidney injury via the NF-κB/NLRP3 pathway.

BACKGROUND: Piperazine ferulate (PF) is widely used in chronic nephritis and nephrotic syndrome in clinic. PF can improve diseases related inflammation by inhibiting the activation of nuclear factor kappa-B (NF-κB) signal. Acute kidney injury (AKI) is usually associated with the occurrence and development of renal inflammation. However, the nephroprotective effect and anti-inflammatory mechanisms of PF on AKI are not clear. PURPOSE: This study aimed to investigate the nephroprotective effects of PF on gentamicin (GM) induced AKI in rats and its potential mechanisms. METHODS: Male Sprague Dawley (SD) rats were intraperitoneally injected with GM (100 mg/kg/day) with or without PF (50 and 100 mg/kg/day) for 7 consecutive days. In vitro, the NRK-52e cells were exposed to GM (7 mg/ml) with or without PF (62.5 µg/ml) treatment. The renal injury and cell damage were assessed subsequently. RESULTS: Our findings showed that PF treatment can significantly improve renal function, reduce renal pathological changes, and attenuate inflammatory response in rats treated with gentamicin. Besides, PF could significantly reduce the cell damage and cellular inflammatory response. In terms of mechanisms, our study revealed that PF can evidently inhibit the activation of NF-κB and nod-like receptor family pyrin domain protein 3 (NLRP3) inflammasome. Meanwhile, it could down regulate the expressions of protein and gene of p-IKKα, p-IKKß, p-p65, p65, p50, p105, NLRP3 and IL-1ß. CONCLUSION: Our findings showed that PF may improve inflammation by inhibiting the NF-κB/NLRP3 pathway, so as to attenuate AKI.

Ferulic acid: A review of its pharmacology, pharmacokinetics and derivatives.

Ferulic acid, a kind of phenolic substance widely existing in plants, is an important active component of many traditional Chinese medicines. So far, it has been proved that ferulic acid has a variety of biological activities, especially in oxidative stress, inflammation, vascular endothelial injury, fibrosis, apoptosis and platelet aggregation. Many studies have shown that ferulic acid can inhibit PI3K/AKT pathway, the production of ROS and the activity of aldose reductase. The anti-inflammatory effect of ferulic acid is mainly related to the levels of PPAR γ, CAM and NF-κ B and p38 MAPK signaling pathways. Ferulic acid not only protects vascular endothelium by ERK1/2 and NO/ET-1 signal, but also plays an anti-fibrosis role by TGF-ß/Smad and MMPs/TIMPs system. Moreover, ferulic acid has ant-apoptotic and anti-platelet effects. In addition to the pharmacological effects of ferulic acid, its pharmacokinetics and derivatives were also discussed in this paper. This review provides the latest summary of the latest research on ferulic acid.