The regulatory effect and mechanism of traditional Chinese medicine on the renal inflammatory signal transduction pathways in diabetic kidney disease: A review.

Inflammatory injury is a critical factor in the occurrence and development of diabetic kidney disease (DKD). Signal transduction pathways such as the nuclear factor kappa beta (NF-κB), mitogen-activated protein kinase (MAPK), NOD-like receptor protein 3, and Smads are important mechanisms of inflammatory kidney injury in DKD, and the NF-κB pathway plays a key role. The inflammatory factor network formed after activation of the NF-κB pathway connects different signaling pathways and exacerbates renal inflammatory damage. Many traditional Chinese medicine compounds, single agents, effective components and active ingredients can regulate the expression of key molecules in the signaling pathways associated with inflammatory injury, such as transforming growth factor-ß activated kinase 1, NF-κB, p38MAPK, NOD-like receptor protein 3, and Smad7. These treatments have the characteristics of multiple targets and have multiple and overlapping effects, which can treat DKD kidney inflammation and injury through multiple mechanisms and apply the "holistic concept" of traditional Chinese medicine.

Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese Medicine.

Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases (CVDs), such as diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, heart failure and hypertension. Noncoding RNAs (ncRNAs) are important regulatory factors. Many Chinese medicine (CM) compounds, including their effective components, can regulate pyroptosis and exert myocardium-protecting effects. The mechanisms underlying this protection include inhibition of inflammasome protein expression, Toll-like receptor 4-NF-κB signal pathway activation, oxidative stress, endoplasmic reticulum stress (ERS), and mixed lineage kinase 3 expression and the regulation of silent information regulator 1. The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM. Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

Establishment of a new arrhythmia model in SD rats induced by isoproterenol.

BACKGROUND: The main purpose of this study was to establish an ideal arrhythmia model using isoproterenol and explore its mechanism. METHODS: Fifty healthy male SD rats were randomly divided into the following groups: control (CON), subcutaneous injection (SC; 5 mg/kg ISO for 2 consecutive days), intraperitoneal injection (IP; ISO 5 mg/kg for 2 consecutive days), 2 + 1 (5 mg/kg ISO by SC for 2 consecutive days and then 3 mg/kg ISO by IP for 1 day), and 6 + 1 (5 mg/kg ISO by SC for 6 consecutive days and then 3 mg/kg ISO by IP for 1 day). Electrocardiograms (ECGs) were recorded using a BL-420F system, and the pathological changes in myocardial tissue were observed by HE and Masson staining. The serum cTnI, TNF-α, IL-6, and IL-1ß levels were detected by ELISA, and serum CK, LDH and oxidative stress-related indicators were detected with an automatic biochemical analyser. RESULTS: The cardiomyocytes of the rats belonging to the CON group were normal, whereas those of the rats in the other groups, particularly the 6 + 1 group, showed signs of disorder, unclear borders, and lysis and necrosis. The incidence of arrhythmia, arrhythmia score, and levels of serum myocardial enzymes, troponin, and some inflammatory factors were higher in the 2 + 1 and 6 + 1 groups than in the single injection group (p < 0.01 or p < 0.05). The indicator levels found for the 6 + 1 group were generally higher than those found for the 2 + 1 group (p < 0.01), and the 6 + 1 group exhibited a lower SOD level and higher MDA and NO levels compared with the CON group (p < 0.01 or p < 0.05). CONCLUSION: The combined mode of ISO injection (SC with IP) was more likely to induce arrhythmia than a single ISO injection. The "6 + 1" method of ISO injection can establish a more stable arrhythmia model and cardiomyocyte damage induced by oxidative stress and inflammation was an important mechanism.

Corrigendum to "Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway".

[This corrects the article DOI: 10.1155/2021/5545193.].

Mechanisms of Kidney Cell Pyroptosis in Chronic Kidney Disease and the Effects of Traditional Chinese Medicine.

Chronic kidney disease (CKD) is a major public health issue that is highly prevalent worldwide. Pyroptosis is an important pathological mechanism underlying kidney cell damage in CKD and is associated with the classic caspase-1-mediated pathway and nonclassic caspase-4/5/11-mediated pathway. The NLRP3-caspase-1-GSDMD signaling pathway is the key mechanism of kidney cell pyroptosis in CKD, and noncoding RNAs such as lncRNAs and miRNAs are important regulators of kidney cell pyroptosis in CKD. In addition, the NLRP1/AIM2-caspase-1-GSDMD and caspase-3-GSDME signaling pathways have also been shown to mediate kidney cell pyroptosis. Traditional Chinese medicine (TCM) and extracts can interfere with the occurrence and development of kidney cell pyroptosis in CKD by inhibiting the NLRP3 signaling pathway and oxidative stress, activating Nrf-2 signaling, protecting mitochondrial integrity, regulating AMPK signaling, and regulating TXNIP/NLRP3 axis, which have become increasingly prominent. It is critical to explore the effects of TCM on kidney cell pyroptosis in CKD and its mechanisms to identify targets and develop new and effective drugs.

Berberine Reduces Renal Cell Pyroptosis in Golden Hamsters with Diabetic Nephropathy through the Nrf2-NLRP3-Caspase-1-GSDMD Pathway.

Objective: To observe the effect of berberine (BBR) on kidney cell pyroptosis in golden hamsters with diabetic nephropathy (DN) and to explore the molecular mechanism of its renal protection. Methods: Fifty clean-grade male golden hamsters were randomly divided into a control group (10) and a model building group (40). The DN model was established by high-sugar and high-fat feeding and injection of a small amount of STZ. After successful establishment of the model, they were randomly divided into a model group, western medicine group, and berberine high- and low-dose groups. The western medicine group was given irbesartan 13.5 mg/kg, and the berberine high- and low-dose groups were given BBR 200 mg/kg and 100 mg/kg, respectively, for 8 consecutive weeks. An automatic biochemical analyser was used to measure blood glucose, blood lipids, kidney function, MDA, and other indicators; radioimmunoassay was used to assess serum insulin; enzyme-linked immunosorbent assay (ELISA) was used to quantify IL-1ß, IL-6, IL-18, TNF-α; HE, PAS, and Masson staining were used to observe kidney pathological tissue morphology; western blot and real-time fluorescent quantitative PCR were used to assess protein and mRNA expression of molecules, such as Nrf2, NLRP3, Caspase-1, and GSDMD; and TUNEL staining was used to detect DNA damage. SPSS statistical software was used for the data analysis. Results: The kidney tissues of golden hamsters in the control group were normal; Nrf2 was highly expressed, serum MDA level was low, NLRP3 expression in kidney tissue was not obvious, Caspase-1 and GSDMD were weakly expressed, and only a few TUNEL-positive cells were observed. Compared with the control group, the golden hamsters in the model group had obvious renal pathological damage; blood glucose, blood lipids, renal function-related indexes, insulin, and inflammatory factors IL-1ß, IL-6, IL-18, and TNF-α were increased (P < 0.05); NLRP3, Caspase-1, and GSDMD expression was increased; Nrf2 expression was decreased; MDA level was increased (P < 0.05); and the number of TUNEL-positive cells was increased. Compared with the model group, the pathological morphology of the kidney tissue of golden hamsters in the three treatment groups was significantly improved; blood glucose, blood lipids, renal function, and the expression of inflammatory factors IL-1ß and IL-6 were reduced (P < 0.05); NLRP3, Caspase-1, GSDMD, and other molecular proteins and mRNA expression were decreased; Nrf2 expression was increased; MDA level was decreased (P < 0.05); and the number of TUNEL-positive cells was decreased. Conclusion: DN golden hamster kidney NLRP3-Caspase-1-GSDMD signalling was enhanced. BBR can reduce oxidative stress damage by regulating antioxidative Nrf2 and then regulating NLRP3-Caspase-1-GSDMD signalling to inhibit pyroptosis, antagonizing DN inflammation-induced damage.