Treatment Of Diabetic Nephropathy Research Articles

Plant natural products: A lead for nephroprotection

An extremely dangerous side effect of type I and type II diabetes is diabetic nephropathy (DN). From the early microproteinuria to end-stage renal failure, it progresses. About one in three diabetics in the US suffer from diabetic nephropathy. Chronic hyperglycemia is the primary cause of diabetic ketoacidosis. Hyperglycemia (HG) has the potential to cause humoral mediators and cytokines to be produced by both resident and non-resident renal cells. These substances may interfere with cell growth, alter renal cell and tissue phenotype and function, interact with proteins, produce advanced glycation end products (AGEs), damage tubules and glomeruli, and ultimately cause kidney disease. Poor blood glucose management is thus a significant risk factor for the onset of DN. An alternate course of treatment for DN may use extracts from herbal remedies. Medicinal plants' bioactive components stop DN from progressing. Attention has to be paid to the role that traditional herbs and medications play in the treatment of diabetic nephropathy, particularly in India where several fruits and herbs are believed to provide health benefits. Natural compounds influence the KEAP1/Nrf2/ARE and NFB pathways in addition to having antioxidant and anti-inflammatory properties. The efficacy of entire herbs, plants, or seeds, together with their active components, in treating diabetic nephropathy was investigated in preclinical research. Natural compounds are biologically active substances that come from natural sources and are beneficial for treating specific illnesses. Numerous natural substances, such as glycosides, polysaccharides, terpenoids, alkaloids, flavonoids, and polyphenols, have been shown to enhance DN. The exorbitant expenses associated with contemporary medications suggest that other approaches are necessary for improved DN treatment. Future research on herbal remedies may provide a natural key to open a pharmacy for diabetologists. Keywords: Diabetic nephropathy; nephroprotective plant; herbal compounds, bioactive compound

Chemical and pharmacological studies of cornus officinalis

This article reviews the chemical components and pharmacological effects of Cornus officinalis Sieb.et Zucc., a traditional Chinese medicinal herb that contains a variety of active ingredients, including iridoid glycosides, flavonoids, organic acids, and tannins. These components endow Cornus officinalis with multiple pharmacological actions, such as neuroprotection, anti-diabetes and its complications, cardioprotection, anti-tumor, and antioxidant effects. In particular, the paper discusses the impact of Cornus officinalis iridoid glycosides on learning and memory ability after cerebral ischemia, as well as their potential mechanisms in the treatment of diabetic nephropathy. Additionally, the application of Cornus officinalis methanol extract in promoting melanin synthesis and its anti-inflammatory, anti-fatigue, antibacterial, anti-osteoporotic, and hepato- and reno-protective effects are also discussed. Although progress has been made in existing research, the specific roles and mechanisms of some newly discovered compounds in Cornus officinalis still require further investigation. This paper aims to provide a reference for in-depth research and clinical application of Cornus officinalis.

Repurposing Niclosamide to Modulate Renal RNA-Binding Protein HuR for the Treatment of Diabetic Nephropathy in db/db Mice.

Hu antigen R (HuR) plays a key role in regulating genes critical to the pathogenesis of diabetic nephropathy (DN). This study investigates the therapeutic potential of niclosamide (NCS) as an HuR inhibitor in DN. Uninephrectomized mice were assigned to four groups: normal control; untreated db/db mice terminated at 14 and 22 weeks, respectively; and db/db mice treated with NCS (20 mg/kg daily via i.p.) from weeks 18 to 22. Increased HuR expression was observed in diabetic kidneys from db/db mice, which was mitigated by NCS treatment. Untreated db/db mice exhibited obesity, progressive hyperglycemia, albuminuria, kidney hypertrophy and glomerular mesangial matrix expansion, increased renal production of fibronectin and a-smooth muscle actin, and decreased glomerular WT-1+-podocytes and nephrin expression. NCS treatment did not affect mouse body weight, but reduced blood glucose and HbA1c levels and halted the DN progression observed in untreated db/db mice. Renal production of inflammatory and oxidative stress markers (NF-κBp65, TNF-a, MCP-1) and urine MDA levels increased during disease progression in db/db mice but were halted by NCS treatment. Additionally, the Wnt1-signaling-pathway downstream factor, Wisp1, was identified as a key downstream mediator of HuR-dependent action and found to be markedly increased in db/db mouse kidneys, which was normalized by NCS treatment. These findings suggest that inhibition of HuR with NCS is therapeutic for DN by improving hyperglycemia, renal inflammation, and oxidative stress. The reduction in renal Wisp1 expression also contributes to its renoprotective effects. This study supports the potential of repurposing HuR inhibitors as a novel therapy for DN.

Network Pharmacology and Experimental Analysis to Explore the Effect and Mechanism of Modified Buyang Huanwu Decoction in the Treatment of Diabetic Nephropathy.

Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN. Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD. A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson's staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1. mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.

Effect and Mechanisms of Huangqi-Shanzhuyu in the Treatment of Diabetic Nephropathy based on Network Pharmacology and In Vitro Experiments.

Huangqi-Shanzhuyu (HS), a classic combination of Chinese herbal formulae, has been widely used for the treatment of diabetic nephropathy (DN). However, its pharmacological mechanism of action is still unclear. The active ingredients of HS and their potential targets were identified through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the DN-related targets were determined from GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGkb, and Therapeutic Target Database (TTD). The Cytoscape software was used to construct a herb-disease-target network and screen core genes. STRING was employed to generate a protein-protein interaction (PPI) network. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the mechanism of action of HS in DN. Animal experiments and molecular docking were used to verify the potential mechanism. In total, 40 active ingredients and 180 effective targets of HS in DN were identified and 1115 DN-related targets were retrieved. From the PPI network, VEGFA, AKT1, IL6, IL1B, TP53, MMP9, PTGS2, CASP3, EGF and EGFR were identified as core genes. The anti-DN mechanism mainly involved multiple signaling pathways such as AGEs-RAGE. Animal experiments and molecular docking analysis confirmed that HS downregulated the expression of IL-1 and IL-6 via kaempferol-mediated inhibition of JNK1 phosphorylation. HS exhibits a therapeutic effect in DN through its multiple ingredients that act on several targets and multiple signaling pathways, including AGEs-RAGE.

Potential of Bauhinia variegata leaves in the management of diabetic nephropathy

The present study was carried out to explore the potential of aqueous extract of leaves of Bauhinia variegata (AE) in the treatment of streptozotocin-induced diabetic nephropathy in rats. Diabetes was induced in male Sprague Dawley rats with streptozotocin (STZ) at a dose of 55 mg/kg (i.p.). Four weeks after induction of diabetes animals were treated with the extract at a dose of 250, 500 and 1000 mg/kg for 28 days. On the 28th day, biochemical parameters (glucose, glycosylated haemoglobin, total protein, albumin, creatinine, blood urea nitrogen) and urine parameters (total protein, creatinine) were evaluated. After completion of 28 days of treatment, animals were sacrificed and kidneys were isolated. Histopathological evaluation of kidney tissue was carried out by staining the tissue sections with hematoxylin and eosin (HE) stain, Periodic acid–Schiff (PAS) stain and Trichrome stain. Treatment with AE to diabetic rats for 28 days showed a significant decrease in fasting blood glucose, glycosylated haemoglobin, and biochemical parameter like albumin, total protein, creatinine, and blood urea nitrogen (BUN) which is an important marker for the progression of diabetic nephropathy. AE treatment also improved the urine parameters and histological changes in kidney tissue of STZ induced diabetic rats after 28 days of treatment. In-vitro advanced glycation end product inhibitory assay showed that AE possesses AGE inhibitory activity which can play important role in the prevention of DN progression. Present studies proved the potential of aqueous extract of Bauhinia variegata leaves and open a new alternative treatment approach for diabetic nephropathy.

Effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy.

To explore the effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy (DN). Clinical data from 153 patients with early DN, admitted to Huzhou Central Hospital from January 2020 to December 2022, was retrospectively selected. Patients were divided into two groups based on the treatment they received: patients received Irbesartan treatment alone were assigned to Irbesartan group (n=74); patients received Irbesartan combined with Atorvastatin were assigned to combined group (n=79). Levels of renal function indicators, renal fibrosis indicators, micro inflammatory status indicators, and incidence of adverse reactions were compared between the two groups before and after the treatment. After the treatment, indicators of renal function, renal fibrosis and micro-inflammation in both groups significantly decreased compared to pretreatment levels (P<0.05), and were significantly lower in the combined group compared to Irbesartan group (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). Compared with Irbesartan alone, Atorvastatin combined with Irbesartan is more effective in the treatment of early DN. Combined treatment regimen is able to effectively reduces the micro-inflammatory state, improve renal function and fibrosis, and is not associated with the increased risk of adverse reactions.

Design, Synthesis, and Biological Evaluation of Quinoline (Quinolinone) Derivatives as NADPH Oxidase (NOX) Inhibitors.

NADPH oxidases (NOXs) are the sole enzyme in the human body that can directly produce reactive oxygen species. Recent studies have shown that NOXs is a very promising target for the treatment of diabetic nephropathy (DN). Here, a series of quinoline(quinolinone) derivatives have been designed based on pharmacophore strategy, synthesized and evaluated. Among them, 19d exhibits potent antiproliferative and NOXs inhibitory activities, and is worthy for further investigation.

Effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease.

To investigate the effects of Bifidobacterium bifidum tetragonum tablets and Jin Gui Ren Qi Pill on intestinal flora and metabolism in patients with diabetic kidney disease. In the study conducted at Heping Hospital of Changzhi Medical College from March 2021 to December 2022, 30 cases of patients diagnosed with diabetic nephropathy were meticulously selected as study subjects. Employing a double-blind randomized table method, these patients were randomly allocated into three groups: the control group (n = 10), the Bifidobacterium bifidum tetragonum tablets group (n = 10), and the Jin Gui Ren Qi Pill group (n = 10). The control group received standard western medical treatments for diabetic nephropathy, including serum glucose, blood lipids, blood pressure management, and other conventional therapies. In addition to the standard treatments, the Bifidobacterium bifidum tetragonum tablets group received Bifidobacterium bifidum tetragonum tablets, while the Jin Gui Ren Qi Pill group received Jin Gui Ren Qi Pill. Before and after a 4-week treatment period, various baseline parameters were assessed, including fasting blood glucose, 2-h postprandial blood glucose, triglycerides, serum total cholesterol, serum low-density lipoprotein cholesterol, serum high-density lipoprotein cholesterol, random urine microalbumin/creatinine ratio (ACR), blood creatinine (SCr), and traditional Chinese medicine evidence scores. Stool specimens were collected from all three groups before and after treatment for 16S rDNA high-throughput sequencing, followed by comprehensive analyses including OUT clustering, Alpha diversity, Beta diversity, species composition analysis, LEfSe analysis, and KEGG function prediction. Spearman correlation analysis was employed to explore the relationship between intestinal flora and clinical indicators. Furthermore, fasting peripheral venous blood was collected from patients in the Bifidobacterium tetrapunctate tablets group and the control group before and after intervention to measure the optical density values of tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), and interleukin-6 (IL-6) using the Beijing Biolite ELISA kit. This study was conducted with the approval of the Ethics Committee of Changzhi Medical College. 1. The 2hPBG, total cholesterol and LDL levels were observed among patients with diabetic kidney disease (DKD) across all groups: the Jin Gui Ren Qi Pill group, the Bifidobacterium bifidum tetragonum tablets group, and the control group (p < 0.05). 2. The Jin Gui Ren Qi Pill demonstrated superior efficacy in alleviating TCM symptoms and reducing the ACR compared to both the Bifidobacterium bifidum tetragonum tablets group and the control group. Conversely, Bifidobacterium bifidum tetragonum tablets exhibited a more pronounced reduction in TC levels compared to both the Jin Gui Ren Qi Pill and control groups. Notably, Bifidobacterium bifidum tetragonum tablets effectively decreased (IL-2) levels in patients with DKD. 3. Bifidobacterium bifidum tetragonum tablets also demonstrated efficacy in reducing IL-2 levels in DKD patients. 4. Analysis of intestinal microorganism abundance and diversity before and after the intervention, as well as among the three groups, revealed no significant alterations. Similarly, comparisons of ACE, Chao, Simpson, and Shannon indices showed no statistically significant differences (p > 0.05). 5. Qualitative analysis of intestinal microorganisms before and after intervention, as well as among the three groups, indicated no significant differences. Anosim test results also did not reveal qualitative distinctions (Anosim test R = 0.021, p = 0.215). 6. LEfSe analysis unveiled a noteworthy increase in Prevotella_7 abundance within the Jin Gui Ren Qi Pill group post-intervention (p < 0.05). 7. Furthermore, Chinese medicine evidence scores, body mass index, TC, and LDL levels correlated positively with the relative abundance of Tyzzerella_3 bacterial flora. Conversely, age, disease duration, and 2hPBG correlated positively with the relative abundance of Christensenellaceae_R_7 flora, while TC and LDL levels displayed a negative correlation with the relative abundance of Christensenellaceae_R_7 flora. The combination of Jin Gui Ren Qi Pill with western medical treatment exhibited superior efficacy in ameliorating clinical symptoms and reducing the ACR in patients with DKD compared to western medical treatment alone. Furthermore, this combination therapy led to an increase in the abundance of Prevotella_7 within the intestinal flora of patients, suggesting a potential enhancement in carbohydrate metabolism by the intestinal microbiota. On the other hand, Bifidobacterium bifidum tetragonum tablets bacterial tablets combined with western medical treatment demonstrated enhanced efficacy in reducing TC levels in DKD patients compared to western medical treatment alone. Additionally, this combination therapy effectively reduced the levels of IL-2 in DKD patients, thus mitigating inflammation in these individuals.

Myricetin alleviates renal tubular epithelial-mesenchymal transition via NOX4/NF-κB/snail axis in diabetic nephropathy based on network pharmacology analysis

Diabetic nephropathy (DN), a leading cause of end-stage renal disease, remains a formidable challenge in diabetes management due to the complex nature of its pathogenesis, particularly the epithelial-mesenchymal transition (EMT) process. Our innovative study leverages network pharmacology to explore the therapeutic potentials of Myricetin, a natural flavonoid, focusing on its effects against NOX4, a critical mediator in DN progression. This investigation marks a pioneering approach by integrating network pharmacology to predict and elucidate the inhibitory relationship between Myricetin and NOX4. Utilizing a high-fat diet/streptozotocin (HFD/STZ) induced DN mouse model, we delved into the effects of Myricetin on renal EMT processes. Through network pharmacology analyses coupled with molecular docking studies, we identified and confirmed Myricetin's binding efficacy to NOX4. Extensive in vitro and in vivo experiments further established Myricetin's significant impact on mitigating EMT by modulating the NOX4-NF-κB-Snail signaling pathway. Results from our research demonstrated notable improvements in renal function and reductions in tissue fibrosis among treated HFD/STZ mice. By curtailing NOX4 expression, Myricetin effectively reduced reactive oxygen species (ROS) production, thereby inhibiting NF-κB activation and subsequent Snail expression, crucial steps in the EMT pathway. Supported by both theoretical predictions and empirical validations, this study unveils the mechanism underlying Myricetin's modulation of EMT in DN through disrupting the NOX4-NF-κB-Snail axis. These findings not only contribute a new therapeutic avenue for DN treatment but also underscore the utility of network pharmacology in advancing drug discovery processes.

Magnetic ligand fishing protocol combined with HPLC-FT-ICR-MS for screening potential α-Glucosidase inhibitors from UCG and in silico analysis

Uremic Clearance Granule (UCG) is a traditional Chinese medicines (TCMs) that has been recognized as potentially effective treatment for diabetic nephropathy (DN). However, the chemical composition and the hypoglycemic ingredients of UCG remain unclear. In this experiment, a magnetic ligand fishing protocol combined with HPLC coupled Fourier transform ion cyclotron resonance mass spectrometry (HPLC-FT-ICR-MS) technology was developed to screen and identify α-Glucosidase inhibitors from UCG. First, constituents of UCG was identified by HPLC-FT-ICR-MS. Next, α-Glucosidase coated Fe3O4@SiO2@NH2 (Fe3O4@SiO2@NH2@α-Glucosidase) nano composites was synthesized. The essential parameters (concentration of Glutaraldehyde (GA), ratio of Fe3O4@SiO2@NH2 to enzyme, crosslinking time and immobilization time) were optimized to obtain maximum enzyme activity and the performance of immobilized enzyme was compared with that of free enzyme. The α-Glucosidase inhibitory activities were then evaluated using autodock and the 4-Nitrophenyl-α-D-glucopyranoside (pNPG) method. As a result, 142 compounds were identified were identified by comparing the retention time, molecular ions and fragmentation behaviors with the reference compounds or the in-house database. 20 possible α-Glucosidase activity inhibitory components were identified using HPLC-FT-ICR-MS. Molecular docking and inhibition studies showed that 4 compuunds including Limonexic acid, Sanggenol A, Glabrone, Matrine were more likely to stronger α-Glucosidase inhibitory activities than acarbose. In conclusion, the proposed approach, which combined highly specific screening with HPLC-FT-ICR-MS, provided a powerful platform for discovering bioactive components from multi-component and multi-target traditional Chinese medicines (TCMs).

Inonotus obliquus (Chaga) against HFD/STZ-induced glucolipid metabolism disorders and abnormal renal functions by regulating NOS-cGMP-PDE5 signaling pathway

Our prior investigations have established that Inonotus obliquus (Chaga) possesses hypoglycemic effects. Persistent hyperglycemia is known to precipitate renal function abnormalities. The functionality of the kidneys is intricately linked to the levels of cyclic guanosine-3',5'-monophosphate (cGMP), which are influenced by the activities of nitric oxide synthase (NOS) and phosphodiesterase (PDE). Enhanced cGMP levels can be achieved either through the upregulation of NOS activity or the downregulation of PDE activity. The objective of the current study is to elucidate the effects of Chaga on disorders of glucolipid metabolism and renal abnormalities in rats with type 2 diabetes mellitus (T2DM), while concurrently examining the NOS-cGMP-PDE5 signaling pathway. A model of T2DM was developed in rats using a high-fat diet (HFD) combined with streptozotocin (STZ) administration, followed by treatment with Chaga extracts at doses of 50 and 100 mg·kg−1 for eight weeks. The findings revealed that Chaga not only mitigated metabolic dysfunctions, evidenced by improvements in fasting blood glucose, total cholesterol, triglycerides, and insulin resistance, but also ameliorated renal function markers, including serum creatinine, urine creatinine (UCr), blood urea nitrogen, 24-h urinary protein, and estimated creatinine clearance. Additionally, enhancements in glomerular volume, GBM thickness, podocyte foot process width (FPW), and the mRNA and protein expressions of podocyte markers, such as nephrin and wilms tumor-1, were observed. Chaga was found to elevate cGMP levels in both serum and kidney tissues by increasing mRNA and protein expressions of renal endothelial NOS and neural NOS, while simultaneously reducing the expressions of renal inducible NOS and PDE5. In summary, Chaga counteracts HFD/STZ-induced glucolipid metabolism and renal function disturbances by modulating the NOS-cGMP-PDE5 signaling pathway. This research supports the potential application of Chaga in the clinical prevention and treatment of T2DM and diabetic nephropathy (DN), with cGMP serving as a potential therapeutic target.

The Generation and Treatment of Diabetic Nephropathy are Discussed from Deficiency, Blood Stasis, Dampness and Turbidity

Deficiency, stasis, dampness and turbidity are common clinical pathogenic factors, which have been confirmed in many fields for years, and many studies have shown that diabetic nephropathy is associated with the upper four diseases. This paper demonstrates the correlation and treatment with the occurrence of diabetic nephropathy from four aspects of deficiency, stasis, dampness and turbidity, as a clinical reference.

Molecular mechanisms of diabetic nephropathy: A narrative review.

Diabetic nephropathy (DN) is the predominant secondary nephropathy resulting in global end-stage renal disease. It is attracting significant attention in both domestic and international research due to its widespread occurrence, fast advancement, and limited choices for prevention and treatment. The pathophysiology of this condition is intricate and involves multiple molecular and cellular pathways at various levels. This article provides a concise overview of the molecular processes involved in the development of DN. It discusses various factors, such as signaling pathways, cytokines, inflammatory responses, oxidative stress, cellular damage, autophagy, and epigenetics. The aim is to offer clinicians a valuable reference for DN's diagnosis, treatment, and intervention.

Kidney tea [Orthosiphon aristatus (Blume) Miq.] improves diabetic nephropathy via regulating gut microbiota and ferroptosis.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. Due to its complex pathogenesis, new therapeutic agents are urgently needed. Orthosiphon aristatus (Blume) Miq., commonly known as kidney tea, is widely used in DN treatment in China. However, the mechanisms have not been fully elucidated. We used db/db mice as the DN model and evaluated the efficacy of kidney tea in DN treatment by measuring fasting blood glucose (FBG), serum inflammatory cytokines, renal injury indicators and histopathological changes. Furthermore, 16S rDNA gene sequencing, untargeted serum metabolomics, electron microscope, ELISA, qRT-PCR, and Western blotting were performed to explore the mechanisms by which kidney tea exerted therapeutic effects. Twelve polyphenols were identified from kidney tea, and its extract ameliorated FBG, inflammation and renal injury in DN mice. Moreover, kidney tea reshaped the gut microbiota, reduced the abundance of Muribaculaceae, Lachnoclostridium, Prevotellaceae_UCG-001, Corynebacterium and Akkermansia, and enriched the abundance of Alloprevotella, Blautia and Lachnospiraceae_NK4A136_group. Kidney tea altered the levels of serum metabolites in pathways such as ferroptosis, arginine biosynthesis and mTOR signaling pathway. Importantly, kidney tea improved mitochondrial damage, increased SOD activity, and decreased the levels of MDA and 4-HNE in the renal tissues of DN mice. Meanwhile, this functional tea upregulated GPX4 and FTH1 expression and downregulated ACSL4 and NCOA4 expression, indicating that it could inhibit ferroptosis in the kidneys. Our findings imply that kidney tea can attenuate DN development by modulating gut microbiota and ferroptosis, which presents a novel scientific rationale for the clinical application of kidney tea.

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal disease. Clinical studies have shown that renal inflammation is a key factor determining kidney damage during diabetes. With the development of immunological technology, many studies have shown that diabetic nephropathy is an immune complex disease, and that most patients have immune dysfunction. However, the immune response associated with diabetic nephropathy and autoimmune kidney disease, or caused by ischemia or infection with acute renal injury, is different, and has a com-plicated pathological mechanism. In this review, we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism, to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy: A PRISMA-compliant systematic review and meta-analysis.

Diabetes nephropathy (DN), as one of the common complications of diabetes, is characterized by persistent albuminuria, decreased glomerular filtration rate, and elevated arterial blood pressure. At present, Xuebijing injection is widely used in the treatment of DN. However, few systematic reviews and meta-analysis related to Xuebijing injection intervention in DN were published. In order to more systematically and objectively evaluate the clinical efficacy of Xuebijing injection intervention in DN, we conducted systematic reviews and meta-analysis to verify it. The purpose of the research was to systematically evaluate the clinical efficacy of Xuebijing injection combined with alprostadil in the treatment of diabetic nephropathy. We searched the China National Knowledge Infrastructure (CNKI), China Biomedical Database (SinoMed), Weipu Database (VIP), Wanfang Database, PubMed, The Cochrane Library, Embase, Web of Science and other databases by computer, and searched the randomized controlled trials of Xuebijing injection combined with alprostadil in the treatment of DN at home and abroad from the establishment of the database to 2022. The main outcome indicators included blood glucose, and the secondary outcome indicators included blood lipid, renal function, urinary protein, and safety. Two evaluators independently screened the literature, extracted the data and evaluated the risk of bias in the included studies. RevMan 5.3 software was used to analyze the data. A total of 14 randomized controlled trials were included, including 1233 cases, 618 cases in the treatment group and 615 cases in the control group. The results of meta-analysis demonstrated that compared with the control group, the treatment group could effectively reduce fasting plasma glucose [mean difference [MD] = -1.90, 95% CI (-2.40, -1.40), P < .00001], glycosylated hemoglobin A1c [MD = -2.38, 95% CI (-2.51, -2.25), P < .00001], 2h postprandial blood glucose [MD = -2.92, 95% CI (-3.95, -1.89), P < .00001], triacylglycerol [MD = -1.08, 95% CI (-1.66, -0.50), P = .0003], total cholesterol [MD = -1.17, 95% CI (-1.39, -0.95), P < .00001], low-density lipoprotein cholesterol [MD = -1.19, 95% CI (-1.60, -0.78), P < .00001], high-density lipoprotein cholesterol [MD = 0.32, 95% CI (0.23, 0.42), P < .00001], serum creatinine [MD = -42.95, 95% CI (-57.46, -28.43), P < .00001], blood urea nitrogen [MD = -2.24, 95%CI (-2.62,-1.86), P < .00001], blood β2 microglobulin [SMD = -1.49, 95% CI (-1.70, -1.28), P < .00001], urine β2 microglobulin [SMD = -0.81, 95% CI (-1.04, -0.58), P < .00001], 24-hour urinary protein quantification [MD = -0.20, 95% CI (-0.26, -0.14), P < .00001], urinary albumin excretion rate [SMD = -1.15, 95% CI (-1.38, -0.93), P < .00001]. Xuebijing injection combined with alprostadil has more advantages in treating DN compared to routine Western medicine.

Zn(II)-curcumin prevents cadmium-aggravated diabetic nephropathy by regulating gut microbiota and zinc homeostasis.

Background: Diabetic nephropathy (DN) is known as the most common complication of diabetes, resulting from a complex inheritance-environment interaction without effective clinical treatments. Herein, we revealed the protective effects and mechanisms of Zn(II)-curcumin, a curcumin derivative, against streptozotocin-induced DN in rats in the presence or absence of cadmium exposure. Methods: The present study focused on investigating the therapy of Zn(II)-curcumin against cadmium-aggravated DN by regulating gut microbiota, metabolism, inflammation and zinc homeostasis based on pathological changes, TLR4/NF-κB signaling pathway, inductively coupled plasma-mass spectrometry (ICP-MS), 16S rRNA gene sequencing and gas chromatography-mass spectrometer (GC-MS). Results: We found Zn(II)-curcumin significantly mitigated the cadmium-aggravated phenotypes of diabetic nephropathy, as indicated by the remission of renal dysfunction, pathological changes, inflammation and zinc dyshomeostasis in streptozotocin-treated rats exposed to cadmium. Administration of Zn(II)-curcumin significantly alleviated the dysbiosis of gut microbiota and the changes of serum metabolite profiles in rats treated with streptozotocin in combination with cadmium. Notably, fecal microbial transplantation identified the ability of Zn(II)-curcumin to regulate renal function, inflammation and zinc homeostasis was partly dependent on the gut microbiota. Conclusion: These findings revealed that Zn(II)-curcumin alleviated cadmium-aggravated diabetic nephropathy by reshaping the gut microbiota and zinc homeostasis, which provided unique insights into the mechanisms of the treatment and prevention of diabetic nephropathy.

Efficacy and safety of Huangkui capsule for diabetic nephropathy: A systematic review and meta-analysis.

To systematically evaluate the efficacy and safety of Huangkui capsule (HKC) in the treatment of diabetic nephropathy (DN). A computerized search of 8 online databases, CNKI, VIP, WANGFANG, CBM, ChiCTR, Embase, PubMed, and Cochrane Library, was conducted from the time of database construction to June 23, 2023, and randomized controlled trials of HKC for the treatment of DN were included according to the predefined screening criteria. Literature quality was evaluated with the help of Cochrane Risk of Bias Assessment Tool, and data were analyzed by STATA/MP17 and RevMan 5.3 software. A total of 1543 articles were retrieved, and 45 studies were finally included, all in Chinese, with a total sample size of 4297 cases, including 2168 cases in the experimental group and 2129 cases in the control group, and the quality of all the included studies was generally low. Meta-analysis showed that (1) efficacy: effective rate: [relative risk = 1.24, 95% confidence interval (CI) (1.20, 1.29), P < .001], SCR: [standard mean difference (SMD) = -1.19, 95% CI (-1.47, -0.91), P < .001], 24 h-UTP: [SMD = -1.27, 95% CI (-1.66, -0.88), P < .001]. Other renal function, glucose metabolism, lipid metabolism, and inflammatory factors related indicators improved compared with the control group. But in the outcome index of estimated glomerular filtration rate, the addition of HKC did not have an advantage over conventional treatment alone. Estimated glomerular filtration rate: [SMD = -0.21, 95% CI (-0.80, 0.39), P = .50]. (2) Safety: There was no statistical significance in the incidence of adverse reactions between the study group with the addition of HKC and the control group. The clinical efficacy and safety of DN treated with the combination of HKC is better than that of conventional western medicine alone, but to better evaluate the efficacy and safety of HKC as an adjunctive intervention for DN, more rigorously designed large-sample, multicenter randomized controlled trials are needed to provide evidence support in the future.

Research Progress on Podocyte Pyroptosis in Diabetic Nephropathy.

Pyroptosis is a recently discovered type of lytic-programmed cell necrosis. The process involves cells assembling an inflammasome and cleaving gasdermin (GSDM) to trigger the release of pro-inflammatory cytokines that eventually induce inflammatory cell death. Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus, which leads to end-stage renal disease. Podocyte damage or loss is an important feature of diabetic kidney injury. Pyroptosis involvement in podocyte injury is closely associated with DN progression, manifesting as increased renal fibrosis, glomerulosclerosis, and tubular injury. The study aims to elucidate the mechanism of pyroptosis and summarize the pathways and potential inhibitors related to pyroptosis activation in DN podocytes. We undertook a search of bibliographic databases for peer-reviewed research literature on various aspects of pyroptosis. Multiple different pathways mediate podocyte pyroptosis to promote DN progression. Inhibition of pyroptosis can reduce podocyte damage and improve renal function in DN, suggesting that pyroptosis may help identify potential new therapeutic targets for DN treatment.