Treatment Of Diabetic Nephropathy Research Articles

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.

#1642 Influence of potassium intake on the renoprotective response to sodium restriction and hydrochlorothiazide in patients with diabetic nephropathy

Abstract Background and Aims Both salt restriction and hydrochlorothiazide (HCT) potentiate the antihypertensive and antiproteinuric effects of renin-angiotensin-aldosterone-system inhibitors (RAASi) in chronic kidney disease (CKD). Potassium intake is another dietary component that influences blood pressure (BP) and albuminuria. The influence of potassium intake on the response to sodium restriction during RAASi treatment in diabetic nephropathy is unknown. Method We performed a post-hoc analysis of a randomised, double blind, placebo-controlled cross-over trial (n = 43) investigating the combined and separate effects of low sodium (LS; aim 50 mmol Na+/d) and HCT (50 mg/d) on BP and albuminuria during background ACE inhibition (ACEi; lisinopril 40 mg/d) in patients with diabetic nephropathy. Each treatment (normal sodium (NS), LS, NS+HCT, LS+HCT) period consisted of six weeks. Participants were categorised as above or below median 24-hour urinary potassium excretion (UKV) at baseline, stratified by sex. Effects on BP and albuminuria were defined as % reduction from baseline systolic BP (SBP) and urinary albumin-creatinine ratio (ACR). Changes over time within both UKV subgroups were compared to baseline using repeated measures ANOVA (SBP) or paired Wilcoxon rank sum analysis (log-transformed ACR). Post-hoc between-group comparison was performed using Bonferroni testing. Results 43 patients (6 female; mean age 64.9±1.4 yrs) had UKV data available and were included in analysis. 33 patients had complete ACR data. Mean estimated glomerular filtration rate (eGFR) was 65.2 (±3.9), mean SBP was 146.6±2.4 mmHg and median albuminuria 648.6 [251.2 - 1883.0] mg/24 h. Median UKV in the high and low potassium groups was 64 [IQR 49-71] and 94 [90 – 111] mmol/24 u, respectively (p<0.0001). Mean baseline sodium excretion was higher in the high potassium group (191 vs. 260 mmol/d; P = .002), but percentual reduction in sodium excretion at SR was comparable between the two groups. There were no significant differences in baseline SBP, ACR, age and estimated glomerular filtration rate between the groups. LS led to a significant reduction of ACR in the high potassium group (P = .011), whereas in the low potassium group the ACR reduction was not significant (P = .058; Fig. 1). Similarly, addition of HCT to background ACEi therapy without salt restriction reduced ACR compared to ACEi monotherapy in the high potassium group (P < .0001), not the low potassium group (P = .211). LS+HCT combined led to a reduction in ACR in both high (P < .0001) and low potassium (P = .034) groups. A post-hoc between-group analysis showed a significantly larger ACR reduction for the high potassium group (P = .01) upon HCT therapy, and a trend towards larger reduction for HCT+LS (P = .05). The effect of LS alone was similar between high and low potassium groups (P = .485). During LS, within-group analysis showed a significant reduction in SBP compared to baseline for the low potassium group (P = .003), but not for the high potassium group (P = .208). In all further conditions, SBP was significantly reduced from baseline in both groups. Post-hoc analysis showed no significant differences in SBP reduction between high and low potassium groups, although there was a trend towards larger SBP reduction in the low potassium group during LS (P = .07). Conclusion Higher baseline potassium excretion is associated with stronger albuminuria lowering effects of salt restriction and HCT in patients with diabetic nephropathy on background ACEi therapy. These effects were not driven by similar effects on BP.

Indoxyl sulfate aggravates podocyte damage through the TGF-β1/Smad/ROS signaling pathway.

Hyperglycaemia induces the production of a large quantity of reactive oxygen species (ROS) and activates the transforming growth factor β1(TGF-β1)/Smad signalling pathway, which is the main initiating factor in the formation of diabetic nephropathy. Indoxyl sulfate (IS) is a protein-binding gut-derived uraemic toxin that localizes to podocytes, induces oxidative stress and inflames podocytes. The involvement of podocyte damage in diabetic nephropathy through the TGF-β1/) signalling pathway is still unclear. In this study, we cultured differentiated rat podocytes in vitro and measured the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a and α-SMA by quantitative real-time PCR (qRT‒PCR) and western blotting after siRNA-mediated TGF-β1 silencing, TGF-β1 overexpression and the presence of the ROS inhibitor acetylcysteine. We detected the expression levels of nephrin, synaptopodin, CD2AP, SRGAP2a, SRGAP2a in the Smad2/3, phosphorylated-Smad2/3 (p-Smad2/3), Smad7, NADPH oxidase 4 (NOX4), and ROS levels under high glucose (HG) and IS conditions. The results indicated that nephrin, synaptopodin, CD2AP and SRGAP2a expressions were significantly upregulated and α-SMA expression was significantly downregulated in the presence of HG under siRNA-mediated TGF-β1 silencing or after the addition of acetylcysteine. However, in the presence of HG, the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a were significantly downregulated, and the expression of α-SMA was significantly upregulated with the overexpression of TGF-β1. IS supplementation under HG conditions further significantly reduced the expressions of nephrin, synaptopodin, CD2AP and SRGAP2a; altered the expressions of Smad2/3, p-Smad2/3, Smad7 and NOX4; and increased ROS production in podocytes. This study suggests that IS may modulate the expression of nephrin, synaptopodin, CD2AP and SRGAP2a by regulating the ROS and TGF-β1/Smad signalling pathways, providing new theoretical support for the treatment of diabetic nephropathy.

Network Pharmacology, Molecular Docking, and Experimental Verification to Reveal the Mitophagy-Associated Mechanism of Tangshen Formula in the Treatment of Diabetic Nephropathy [Retraction

Network Pharmacology, Molecular Docking, and Experimental Verification to Reveal the Mitophagy-Associated Mechanism of Tangshen Formula in the Treatment of Diabetic Nephropathy [Retraction

Discovery of a SUCNR1 antagonist for potential treatment of diabetic nephropathy: In silico and in vitro studies

Diabetic nephropathy (DN) is one of the most severe complications of diabetes mellitus. Succinate Receptor 1 (SUCNR1), a member of the G-protein-coupled receptor (GPCR) family, represents a potential target for treatment of DN. Here, utilizing multi-strategy in silico virtual screening methods containing AlphaFold2 modelling, molecular dynamics (MD) simulation, ligand-based pharmacophore screening, molecular docking and machine learning-based similarity clustering, we successfully identified a novel antagonist of SUCNR1, AK-968/12117473 (Cpd3). Through extensive in vitro experiments, including dual-luciferase reporter assay, cellular thermal shift assay, immunofluorescence, and western blotting, we substantiated that Cpd3 could specifically target SUCNR1, inhibit the activation of NF-κB pathway, and ameliorate epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition in renal tubular epithelial cells (NRK-52E) under high glucose conditions. Further in silico simulations revealed the molecular basis of the SUCNR1-Cpd3 interaction, and the in vitro metabolic stability assay indicated favorable drug-like pharmacokinetic properties of Cpd3. This work not only successfully pinpointed Cpd3 as a specific antagonist of SUCNR1 to serve as a promising candidate in the realm of therapeutic interventions for DN, but also provides a paradigm of dry-wet combined discovery strategies for GPCR-based therapeutics.

Application and design considerations of ROS-based nanomaterials in diabetic kidney disease.

Diabetic nephropathy (DKD) is a common chronic complication of diabetes mellitus and an important cause of cardiovascular-related death. Oxidative stress is a key mechanism leading to diabetic nephropathy. However, the current main therapeutic approach remains combination therapy and lacks specific therapies targeting oxidative stress. With the development of nanotechnology targeting ROS, therapeutic fluids regarding their treatment of diabetic nephropathy have attracted attention. In this review, we provide a brief overview of various ROS-based nanomaterials for DKD, including ROS-scavenging nanomaterials, ROS-associated nanodelivery materials, and ROS-responsive nanomaterials. In addition, we summarize and discuss key factors that should be considered when designing ROS-based nanomaterials, such as biosafety, efficacy, targeting, and detection and monitoring of ROS.

Astragalus polysaccharide attenuates diabetic nephropathy by reducing apoptosis and enhancing autophagy through activation of Sirt1/FoxO1 pathway.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in diabetic patients. Astragalus polysaccharide (APS) is a natural active ingredient in Astragalus membranaceus with anti-hypertensive and anti-oxidative properties. This study aimed to explore the protective roles of APS and its underlying mechanisms in DN. After the establishment of a rat model of DN by a high-fat diet and treatment with 30mg/kg streptozotocin (STZ), the effects of 100mg/kg APS on the levels of serum creatinine, blood urea nitrogen, blood glucose, and urinary albumin-to-creatinine ratio were measured. Histopathological alterations in renal tissues, renal cell apoptosis, renal inflammation, and oxidative stress were examined. The impacts of 0-200μg/mL APS on the viability and apoptosis in high glucose (HG)-stimulated podocytes were measured by Cell Counting Kit-8 assays and flow cytometry, respectively. The expression of genes was tested by immunoblotting, quantitative real-time PCR, and immunofluorescence staining. APS enhanced the expression of podocin and nephrin, increased viability, and reduced apoptosis in HG-induced podocytes. APS treatment abrogated high glucose-mediate suppression of autophagy in podocytes by activating the Sirt1/FoxO1 pathway. The Sirt1 inhibitor EX-527 eliminated the ameliorative effects of APS on renal dysfunction and renal tissue damage, as well as the inhibitory effects of APS on oxidative stress, inflammation, and apoptosis in DN rats. Moreover, EX-527 inhibited APS-induced autophagy activation in DN rats. APS mitigated DN under hyperglycemic conditions by activating the Sirt1/FoxO1 autophagy pathway, suggesting that APS is a promising agent for DN treatment.

Eriocitrin in the Treatment of Diabetic Nephropathy: Amelioration Against Oxidative Burst and Inflammation Approach

Background: Diabetes mellitus (DM) induces hyperglycemia and oxidative stress in the kidneys and may cause kidney dysfunction. Diabetic nephropathy (DN) is a prolonged problem of DM with limited treatment. Purpose: In this work, we planned to investigate the beneficial effects of eriocitrin, a natural flavanol found in citrus fruits, against DM-induced DN in rats. Materials and methods: For the induction of DN, animals were fed a high-fat diet and were administered with streptozotocin (35 mg/kg). After induction, eriocitrin (50 or 100 mg/kg) was administered to the DM rats, and their changes in feed intake, body weight, blood glucose levels, and blood samples were monitored on a daily basis. The oxidative stress markers were estimated by using standard protocols. The renal function markers such as the activity of lactate dehydrogenase (LDH), creatinine, and blood urea nitrogen levels were investigated by using kits. The kidney injury molecule (KIM-1) and pro-inflammatory markers were determined by using commercial kits. The kidney tissues were studied histopathologically. Results: Eriocitrin considerably reduced the body weight and food consumption in DM-induced rats. Furthermore, eriocitrin restored the values of biochemical parameters such as glucose, glycated hemoglobin, urea, creatinine, LDH, serum cholesterol, and triglycerides to near-normal levels. Moreover, the antioxidant properties of eriocitrin markedly suppressed the oxidative and inflammatory markers by continuing the antioxidant/reactive oxygen species balance. Furthermore, the biochemical parameters are well correlated with histopathological examination. Conclusion: Our results provide valuable scientific information, that supports the therapeutic role of eriocitrin and its protective effects in DM and its complications (DN).

Tanshinone IIA suppresses ferroptosis to attenuate renal podocyte injury in diabetic nephropathy through the embryonic lethal abnormal visual-like protein 1 and acyl-coenzyme A synthetase long-chain family member 4 signaling pathway.

Tanshinone IIA (TIIA) is one of the main components of the root of the red-rooted Salvia miltiorrhiza Bunge. However, the molecular mechanisms underlying TIIA-mediated protective effects in diabetic nephropathy (DN) are still unclear. High glucose (HG)-induced mouse podocyte cell line (MPC5) cells were used as the in vitro model of DN and treated with TIIA. Cell viability, proliferation and apoptosis were detected using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide, 5-ethynyl-2'-deoxyuridine and flow cytometry assays. The protein levels were assessed using western blot assay. The levels of inflammatory factors were deleted by enzyme-linked immunoassay. Fe+ level, reactive oxygen species, malondialdehyde and glutathione products were detected using special assay kits. After ENCORI prediction, the interaction between embryonic lethal abnormal visual-like protein 1 (ELAVL1) and acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) was verified using co-immunoprecipitation assay and dual-luciferase reporter assays. ACSL4 messenger ribonucleic acid expression was measured using real-time quantitative polymerase chain reaction. TIIA repressed HG-induced MPC5 cell apoptosis, inflammatory response and ferroptosis. ACSL4 upregulation relieved the repression of TIIA on HG-mediated MPC5 cell injury and ferroptosis. ELAVL1 is bound with ACSL4 to positively regulate the stability of ACSL4 messenger ribonucleic acid. TIIA hindered HG-triggered MPC5 cell injury and ferroptosis by regulating the ELAVL1-ACSL4 pathway. TIIA blocked DN progression in in vivo research. TIIA treatment restrained HG-caused MPC5 cell injury and ferroptosis partly through targeting the ELAVL1-ACSL4 axis, providing a promising therapeutic target for DN treatment.

Nephroprotective Effect of Hibiscus Sabdariffa Leaf Flavonoid Extracts via KIM-1 and TGF-1β Signaling Pathways in Streptozotocin-Induced Rats.

Diabetes-induced kidney damage represents a substantial health hazard, emphasizing the imperative to explore potential therapeutic interventions. This study investigates the nephroprotective activity of flavonoid-rich extracts from Hibiscus sabdariffa leaves in streptozotocin-induced diabetic rats. The flavonoid-rich extracts of H. sabdariffa leaves was obtained using a standard procedure. The animals were induced with streptozotocin and thereafter treated with both low (LDHSFL) and high doses (HDHSFL) of flavonoid-rich extracts from H. sabdariffa leaves and metformin (MET), and other groups are diabetic control (DC) and normal control (NC). The study assesses diverse renal parameters, encompassing kidney redox stress biomarkers, serum electrolyte levels, kidney inflammatory biomarkers, serum concentrations of creatinine, urea, and uric acid, kidney phosphatase activities, renal histopathology, and relative gene expressions of kidney injury molecule-1 (KIM-1) and transforming growth factor beta-1 (TGF-1β), comparing these measurements with normal and diabetic control groups (NC and DC). The findings indicate that the use of extracts from H. sabdariffa leaves markedly (p < 0.05) enhanced renal well-being by mitigating nephropathy, as demonstrated through the adjustment of various biochemical and gene expression biomarkers, indicating a pronounced antioxidative and anti-inflammatory effect, improved kidney morphology, and mitigation of renal dysfunction. These findings suggest that H. sabdariffa leaf flavonoid extracts exhibit nephroprotective properties, presenting a potential natural therapeutic approach for the treatment of diabetic nephropathy.

WCN24-2086 Demethylzeylasteral serum concentration was proved as Tripterygium Glycosides effects Biomarker on diabetic nephropathy treatment

WCN24-2086 Demethylzeylasteral serum concentration was proved as Tripterygium Glycosides effects Biomarker on diabetic nephropathy treatment

Exploration on the Mechanism of Jinkui Shenqi Pill in the Treatment of Diabetic Nephropathy

Exploration on the Mechanism of Jinkui Shenqi Pill in the Treatment of Diabetic Nephropathy

Research Progress on Traditional Chinese Medicine Targeting the Wnt/β-catenin Signaling Pathway in the Treatment of Diabetic Nephropathy

Research Progress on Traditional Chinese Medicine Targeting the Wnt/β-catenin Signaling Pathway in the Treatment of Diabetic Nephropathy

Analysis of clinical evidence on traditional Chinese medicine for the treatment of diabetic nephropathy: a comprehensive review with evidence mapping.

This study aims to map evidence from Randomized Controlled Trials (RCTs) and systematic reviews/Meta-analyses concerning the treatment of Diabetic Nephropathy (DN) with Traditional Chinese Medicine (TCM), understand the distribution of evidence in this field, and summarize the efficacy and existing problems of TCM in treating DN. The intention is to provide evidence-based data for TCM in preventing and treating DN and to offer a reference for defining future research directions. Comprehensive searches of major databases were performed, spanning from January 2016 to May 2023, to include clinical RCTs and systematic reviews/Meta-analyses of TCM in treating DN. The analysis encompasses the publishing trend of clinical studies, the staging of research subjects, TCM syndrome differentiation, study scale, intervention plans, and outcome indicators. Methodological quality of systematic reviews was evaluated using the AMSTAR (Assessment of Multiple Systematic Reviews) checklist, and evidence distribution characteristics were analyzed using a combination of text and charts. A total of 1926 RCTs and 110 systematic reviews/Meta-analyses were included. The majority of studies focused on stage III DN, with Qi-Yin deficiency being the predominant syndrome type, and sample sizes most commonly ranging from 60 to 100. The TCM intervention durations were primarily between 12-24 weeks. Therapeutic measures mainly consisted of Chinese herbal decoctions and patented Chinese medicines, with a substantial focus on clinical efficacy rate, TCM symptomatology, and renal function indicators, while attention to quality of life, dosage of Western medicine, and disease progression was inadequate. Systematic reviews mostly scored between 5 and 8 on the AMSTAR scale, and evidence from 94 studies indicated potential positive effects. DN represents a significant health challenge, particularly for the elderly, with TCM showing promise in symptom alleviation and renal protection. Yet, the field is marred by research inconsistencies and methodological shortcomings. Future investigations should prioritize the development of standardized outcome sets tailored to DN, carefully select evaluation indicators that reflect TCM's unique intervention strategies, and aim to improve the robustness of clinical evidence. Emphasizing TCM's foundational theories while incorporating advanced scientific technologies will be essential for innovating research methodologies and uncovering the mechanisms underlying TCM's efficacy in DN management.

Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.

TFP5 is a Cdk5 inhibitor peptide, which could restore insulin production. However, the role of TFP5 in diabetic nephropathy (DN) is still unclear. This study aims to characterize the transcriptome profiles of mRNA and lncRNA in TFP5-treated DN mice to mine key lncRNAs associated with TFP5 efficacy. We evaluated the role of TFP5 in DN pathology and performed RNA sequencing in C57BL/6Jcontrol mice, C57BL/6J db/db model mice, and TFP5 treatment C57BL/6J db/db model mice. The differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were analyzed. WGCNA was used to screen hub-gene of TFP5 in treatment of DN. Our results showed that TFP5 therapy ameliorated renal tubular injury in DN mice. In addition, compared with the control group, the expression profile of lncRNAs in the model group was significantly disordered, while TFP5 alleviated the abnormal expression of lncRNAs. A total of 67 DElncRNAs shared among the three groups, 39 DElncRNAs showed a trend of increasing in the DN group and decreasing after TFP treatment, while the remaining 28 showed the opposite trend. DElncRNAs were enriched in glycosphingolipid biosynthesis signaling pathways, NF-κB signaling pathways, and complement activation signaling pathways. There were 1028 up-regulated and 1117 down-regulated DEmRNAs inthe model group compared to control group, and 123 up-regulated and 153 down-regulated DEmRNAs in theTFP5 group compared to themodel group. The DEmRNAs were involved in PPAR and MAPK signaling pathway. We confirmed that MSTRG.28304.1 is a key DElncRNA for TFP5 treatment of DN. TFP5 ameliorated DN maybe by inhibiting MSTRG.28304.1 through regulating the insulin resistance and PPAR signaling pathway. The qRT-PCR results confirmed the reliability of the sequencing data through verifying the expression of ENSMUST00000211209, MSTRG.31814.5, MSTRG.28304.1, and MSTRG.45642.14. Overall, the present study provides novel insights into molecular mechanisms of TFP5 treatment in DN.

The Effect of Natural Polysaccharides in Treatment of Diabetic Nephropathy: A Review

AbstractDiabetic nephropathy is a serious metabolic disease that is usually caused by diabetes mellitus and ends in chronic kidney disease and renal failure. Many drugs used to treat diabetic nephropathy have limitations and side effects. There is an urgent need to find safe and effective new drugs for the treatment of diabetic nephropathy. The polysaccharides from natural sources, including plants, fungi, and algae, have good protective effects on diabetic nephropathy without side effects. In this paper, the natural sources, chemical composition, and structural characteristics of polysaccharides are reviewed. In addition, the study summarizes the different mechanisms that polysaccharides improve diabetic nephropathy, such as antioxidative stress, regulation of inflammation, inhibition of apoptosis, and renal fibrosis. This review provides theoretical support for the protective effect of polysaccharides and reveals potential therapeutic methods for diabetic nephropathy.

Jian-Pi-Gu-Shen-Hua-Yu Decoction Alleviated Diabetic Nephropathy in Mice through Reducing Ferroptosis.

Diabetic nephropathy (DN), one of the most frequent complications of diabetes mellitus, is a leading cause of end-stage renal disease. However, the current treatment methods still cannot effectively halt the progression of DN. Jian-Pi-Gu-Shen-Hua-Yu (JPGS) decoction can be used for the treatment of chronic kidney diseases such as DN, but the specific mechanism of action has not been fully elucidated yet. The aim of this study is to clarify whether JPGS alleviates the progression of diabetic nephropathy by inhibiting ferroptosis. We established a DN mouse model to investigate the therapeutic effect of JPGS in a DN mouse model. Subsequently, we examined the effects of JPGS on ferroptosis- and glutathione peroxidase 4 (GPX4) pathway-related indices. Finally, we validated whether JPGS inhibited ferroptosis in DN mice via the GPX4 pathway using GPX4 inhibitor and ferroptosis inhibitors. The results indicate that JPGS has a therapeutic effect on DN mice by improving kidney function and reducing inflammation. Additionally, JPGS treatment decreased iron overload and oxidative stress levels while upregulating the expression of GPX4 pathway-related proteins. Moreover, JPGS demonstrated a similar therapeutic effect as Fer-1 in the context of DN treatment, and RSL3 was able to counteract the therapeutic effect of JPGS and antiferroptotic effect. JPGS has significant therapeutic and anti-inflammatory effects on DN mice, and its mechanism is mainly achieved by upregulating the expression of GPX4 pathway-related proteins, thereby alleviating iron overload and ultimately reducing ferroptosis.

Research Progress of Flavonoids in The Treatment of Diabetic Nephropathy

The advantages of traditional Chinese medicine in the treatment of diabetes mellitus are stable efficacy, fewer adverse reactions, and multi-target effects. Flavonoids, as active ingredients widely distributed in plants, play an important role in the prevention and treatment of diabetes and its complications. During the past few years, domestic and foreign research have founded the application prospect of flavonoids for diabetes mellitus, which offers a new way of researching in this field. This article reviews the research on flavonoids in the treatment of diabetic nephropathy at home and abroad.

Multiomic study of the protective mechanism of Persicaria capitata (Buch.-Ham. ex D.Don) H.Gross against streptozotocin-induced diabetic nephropathy in Guizhou miniature pigs

BackgroundPersicaria capitata (Buch.-Ham. ex D.Don) H.Gross (P. capitata, PCB), a traditional drug of the Miao people in China, is potential traditional drug used for the treatment of diabetic nephropathy (DN). PurposeThe purpose of this study is to investigate the function of P. capitata and clarify its protective mechanism against DN. MethodsWe induced DN in the Guizhou miniature pig with injections of streptozotocin, and P. capitata was added to the pigs’ diet to treat DN. In week 16, all the animals were slaughtered, samples were collected, and the relative DN indices were measured. 16S rRNA sequencing, metagenomics, metabolomics, RNA sequencing, and proteomics were used to explore the protective mechanism of P. capitata against DN. ResultsDietary supplementation with P. capitata significantly reduced the extent of the disease, not only in term of the relative disease indices but also in hematoxylin-eosin-stained tissues. A multiomic analysis showed that two microbes (Clostridium baratii and Escherichia coli), five metabolites (oleic acid, linoleic acid, 4-phenylbutyric acid, 18-β-glycyrrhetinic acid, and ergosterol peroxide), four proteins (ENTPD5, EPHX1, ARVCF and TREH), four important mRNAs (encoding ENTPD5, EPHX1, ARVCF, and TREH), six lncRNAs (TCONS_00024194, TCONS_00085825, TCONS_00006937, TCONS_00070981, TCONS_00074099, and TCONS_00097913), and two circRNAs (novel_circ_0001514 and novel_circ_0017507) are all involved in the protective mechanism of P. capitata against DN. ConclusionsOur results provide multidimensional theoretical support for the study and application of P. capitata.

Pharmacokinetic and Pharmacodynamic Evaluation of Telmisartan-loaded Novel Curcumin-tagged Solid Nanodispersion for the Treatment of Diabetic Nephropathy in an Animal Model

Aim: This study aimed to evaluate the therapeutic efficacy of telmisartan-loaded novel curcumin-tagged solid nanodispersion in streptozotocin-nicotinamide-induced diabetic nephropathy in Wistar rats. Objective: The objective of this study was to perform a comprehensive pharmacokinetic and pharmacodynamic evaluation of a novel curcumin-tagged solid nanodispersion loaded with telmisartan, with the aim of assessing its potential as a treatment for diabetic nephropathy in an animal model. Specifically, the following objectives will be addressed: formulation and character-ization, in vitro evaluation, pharmacokinetics and pharmacodynamics evaluation, and compara-tive analysis. Materials and Methods: Telmisartan-loaded curcumin-tagged solid nanodispersion was prepared using the emulsion solvent evaporation method. The optimized formulation was evaluated for pharmacokinetic and pharmacodynamic parameters in an animal model. Wistar rats were divided into 5 groups, with 6 animals in each group. Diabetes was induced using nicotinamide (240 mg/kg) and streptozotocin (55 mg/kg, i.p.) injections in the animals. After 30 to 45 days of intro-duction, diabetic nephropathy was manifested. The kidneys and pancreas were used for histological analysis and renal and pancreatic damage assessment. Results: In-vivo studies showed better bioavailability with the t1/2 and Cmax of TLS-15 was 14.92 ± 0.47 hours and 0.32 ± 0.009, respectively, within 2 hours as compared to the t1/2 and Cmax of MP was 4.38 ± 0.19 hours and 0.19 ± 0.008 owing to the better dissolution due to solubility improvement. When compared to the commercially available product, TLS-15 was found to have blood glucose and body weight that were, respectively, 1.01 and 1.03 times higher. Kidney measures, such as serum urea and creatinine, were found to be 0.71 and 1.16 times lower for TLS-15, respectively, and albumin had a value that was 1.13 times higher than for the commercial formulation. Urine indicators, urine albumin, and creatinine estimations, as well as cytokine estimations, revealed that TLS-15 had creatinine levels that were 1.17 times higher and IL-6 lev-els that were 0.77 times higher than those of a commercial batch. Conclusion: The findings strongly support the renoprotective and pancreatic protective effects of TLS and Cur (SND-Solid Nanodispersion) combined by lowering levels of cytokines factor (IL-6), kidney, and lipid parameters. The postulated mechanism might be the combined inhibitory action of TLS and Cur.