Diabetic kidney disease (DKD) is a prevalent and severe complications of diabetes and serves as the primary cause of end-stage kidney disease (ESKD) globally. Increasing evidence indicates that renal inflammation is critical in the pathogenesis of DKD. The nucleotide - binding oligomerization domain (NOD) - like receptor family pyrin domain containing 3 (NLRP3) inflammasome is the most extensively researched inflammasome complex and is considered a crucial regulator in the pathogenesis of DKD. The activation of NLRP3 inflammasome is regulated by various signaling pathways, including NF- κB, thioredoxin—interacting protein (TXNIP), and non-coding RNAs (ncRNA), among others. Natural products are chemicals extracted from living organisms in nature, and they typically possess pharmacological and biological activities. They are invaluable sources for drug design and development. Research has demonstrated that many natural products can alleviate DKD by targeting the NLRP3 inflammasome. In this review, we highlight the role of the NLRP3 inflammasome in DKD, and the pathways by which natural products fight against DKD via inhibiting the NLRP3 inflammasome activation, so as to provide novel insights for the treatment of DKD.

Objective. The mechanism of Panax notoginseng in treating myocardial fibrosis (MF) was investigated using network pharmacology. Methods. Effective ingredients and potential targets of Panax notoginseng were screened in relevant databases to construct a compound-target network. Targets of MF were then screened to select common targets and construct a protein-protein interaction network. This was followed by Gene Ontology and pathway enrichment analyses. Molecular docking then verified the results of network analysis. Results. A total of 14 effective ingredients and 119 potential targets for MF were predicted. Quercetin, beta-sitosterol, and gossypetin were speculated to be the main active ingredients. The mechanism of action may be related to AGE-RAGE, proteoglycans, and IL-17 signaling pathways. Five key targets (IL6, ALB, AKT1, TNF, and VEGFA) may be involved in the treatment of MF using Panax notoginseng. Conclusions. This study embodies the complex network relationship of multicomponents, multitargets, and multipathways of Panax notoginseng in treating MF and provides a novel method for further research on this herbs mechanism.

Morroniside (MOR), a cyclic enol ether terpene glycoside isolated from Cornus officinalis, has been shown to inhibit lipid accumulation, although the mechanism of action is uncertain. The aim of this study was to investigate the potential pathways by which MOR affects renal lipid deposition in diabetic nephropathy (DN). In vitro and in vivo experiments were performed using the PA-induced HK-2 cell model and a KKAy animal model, respectively. Network pharmacological analysis was used to identify potential MOR signaling pathways for DN therapy, with results verified via Western blotting and immunofluorescence experiments. The effect of MOR on lipid metabolism was investigated using BODIPY 493/503 staining. Our results indicate that MOR significantly reduces lipid accumulation both in vitro and in vivo. According to network pharmacology studies, the NF-κB/TNF-α/SREBP1c signaling pathway may be the mechanism of action of MOR in DN. MOR was found to inhibit this pathway by reducing the phosphorylation of NF-κB p65 and the expression of TNF-α and SREBP1c, similar to the effects of Bay11-7082. Additionally, MOR significantly inhibited the expression of lipid factors such as ACC, FAS, and SCD1. In conclusion, MOR can regulate the disruption of lipid metabolism in DN and reduce renal lipid deposition via suppression of the NF-κB/TNF-α/SREBP1c signaling pathway.

Diabetic nephropathy (DN) is one of the serious complications of diabetes mellitus, primarily arising from type 2 diabetes (T2DM), and can progress to chronic kidney disease (CKD) and end stage renal disease (ESRD). The pathogenesis of DN involves various factors such as hemodynamic changes, oxidative stress, inflammatory response, and lipid metabolism disorders. Increasing attention is being given to DN caused by oxidative stress in the mitochondrial pathway, prompting researchers to explore drugs that can regulate these target pathways. Chinese herbal medicine, known for its accessibility, rich historical usage, and remarkable efficacy, has shown promise in ameliorating renal injury caused by DN by modulating oxidative stress in the mitochondrial pathway. This review aims to provide a reference for the prevention and treatment of DN. Firstly, we outline the mechanisms by which mitochondrial dysfunction impairs DN, focusing on outlining the damage to mitochondria by oxidative stress. Subsequently, we describe the process by which formulas, herbs and monomeric compounds protect the kidney by ameliorating oxidative stress in the mitochondrial pathway. Finally, the rich variety of Chinese herbal medicine, combined with modern extraction techniques, has great potential, and as we gradually understand the pathogenesis of DN and research techniques are constantly updated, there will be more and more promising therapeutic targets and herbal drug candidates. This paper aims to provide a reference for the prevention and treatment of DN.

Lipid deposition is an etiology of renal damage caused by lipid metabolism disorder in diabetic nephropathy (DN). Thus, reducing lipid deposition is a feasible strategy for the treatment of DN. Morroniside (MOR), an iridoid glycoside isolated from the Chinese herb Cornus officinalis Sieb. et Zucc., is considered to be an effective drug in inhibiting oxidative stress, reducing inflammatory response, and countering apoptosis. To explore the protective mechanism of MOR in attenuating renal lipotoxicity in DN, we investigated the effect of MOR on an in vitro model of lipid metabolism disorder of DN established by stimulating mouse renal tubular epithelial cells (mRTECs) with sodium palmitate (PA) or high glucose (HG). Oil Red O and filipin cholesterol staining assays were used to determine intracellular lipid accumulation status. Results revealed that PA or HG stimulation inhibited the expressions of peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α), liver X receptors (LXR), ATP‐binding cassette subfamily A member 1 (ABCA1), ABCG1, and apolipoprotein E (ApoE) in mRTECs as evidenced by western blot and quantitative real‐time PCR, resulting in increased intracellular lipid deposition. Interestingly, MOR upregulated expressions of PGC‐1α, LXR, ABCA1, ABCG1, and ApoE, thus reducing cholesterol accumulation in mRTECs, suggesting that MOR might promote cholesterol efflux from mRTECs via the PGC‐1α/LXR pathway. Of note, silencing PGC‐1α reversed the promotive effect of MOR on PA‐ or HG‐induced cellular cholesterol accumulation. In conclusion, our results suggest that MOR has a protective effect on mRTECs under high lipid or high glucose conditions, which may be related to the promotion of intracellular cholesterol efflux mediated by PGC‐1α.