INTERNATIONAL UROLOGY AND NEPHROLOGY
·
2015
·Vol. 48
·期 2
·213-221
·
IF 1.519
Wang Zhi-shun,Qiu Tao,Liu Xiu-heng,Zhou Jiang-qiao,Chen Zhong-bao,Wang Lei,Zhang Long,Shen Ye,Zhang Lu
Background
Ischemia–reperfusion (I/R) injury to the kidney occurs commonly in organ transplantation from donation after cardiac death, involving many pathologic processes. In this study, we used rat model to assess whether tripterysium glycosides (TG) preconditioning could exert protective effects in renal I/R injury. Materials and methods All male SD rats were randomly divided into four groups (6 each): sham group, TG group, I/R group and TG + I/R group. Groups TG and TG + I/R were pretreated with TG at 0.1 mg/kg for 14 days; groups sham and I/R were administered with the same dosage of normal saline. Groups TG + I/R and I/R underwent 45 min of renal ischemia of left kidney after right nephrectomy, and then, they were subjected to 72-h reperfusion. Groups sham and TG were only received right nephrectomy. The indicators of apoptosis, fibrosis and inflammation were analyzed to evaluate the effect of tripterysium glycosides preconditioning on renal I/R injury. Results Pretreatment with TG significantly inhibited the levels of serum creatine and blood urea nitrogen and improved histologic lesions induced by I/R injury. Moreover, for the apoptosis signal pathway, pretreatment with TG markedly decreased the expression of caspase-3 and Bax and increased the level of Bcl-2. HMGB1, which was regarded as one of inflammation marker molecule, it was inhibited in the TG + I/R group. For the fibrosis signal pathway, the pretreatment with TG before I/R could down-regulate the expression level of typical molecules of fibrosis (TGF-β1, Smad3, p-Smad3). Conclusions Pretreatment with tripterysium glycosides exhibited protective effect on kidney ischemia/reperfusion injury, which might be related to the alleviation of inflammation, fibrosis and the reduction in apoptosis.
研究领域:
药理学
·
肾脏病学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 4
·591
·
IF 4.7
Xi Peng,Kai Liu,Xing Hu,Deming Gong,Guowen Zhang
Background: Hyperuricaemia (HUA) is a disorder of purine metabolism in the body. We previously synthesized a hesperitin (Hsp)-Cu(II) complex and found that the complex possessed strong uric acid (UA)-reducing activity in vitro. In this study we further explored the complex’s UA-lowering and nephroprotective effects in vivo. Methods: A mouse with HUA was used to investigate the complex’s hypouricemic and nephroprotective effects via biochemical analysis, RT-PCR, and Western blot. Results: Hsp-Cu(II) complex markedly decreased the serum UA level and restored kidney tissue damage to normal in HUA mice. Meanwhile, the complex inhibited liver adenosine deaminase (ADA) and xanthine oxidase (XO) activities to reduce UA synthesis and modulated the protein expression of urate transporters to promote UA excretion. Hsp-Cu(II) treatment significantly suppressed oxidative stress and inflammatory in the kidney, reduced the contents of cytokines and inhibited the activation of the nucleotide-binding oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory pathway. Conclusions: Hsp-Cu(II) complex reduced serum UA and protected kidneys from renal inflammatory damage and oxidative stress by modulating the NLRP3 pathway. Hsp-Cu(II) complex may be a promising dietary supplement or nutraceutical for the therapy of hyperuricemia.
研究领域:
药理学
·
生物化学
·
分子生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2025
·
IF 4.5
Huijia Mao,Yang Fan,Fang Tan,Xingyao Long
Objective: The present study aimed to investigate the uric acid-lowering effects of Bifidobacterium animalis QC08 and explore its underlying mechanisms.Methods: Hyperuricemia (HUA) model in mice was established using potassium oxonate (250 mg/kg) and yeast extract (15 g/kg). The serum levels of uric acid (UA), blood urea nitrogen (BUN), creatinine (Cr), and liver xanthine oxidase (XO) were measured in four groups, including normal group, control group, allopurinol group (5 mg/kg), and Bifidobacterium animalis QC08 group (1010 CFU/kg) using enzyme colorimetry. Additionally, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assay (ELISA). Pathological changes in renal tissue were examined through hematoxylin–eosin (HE) staining.Results: In vivo experimental results indicated that compared with the normal group, the serum UA, Cr, and BUN levels, as well as the levels of inflammatory factors (TNF-α and IL-1β), and the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly elevated in the control group (p < 0.05). The expression levels of uric acid transport-related genes (UAT, ABCG2, and OAT1) in kidney tissue were significantly downregulated (p < 0.05), and evident kidney damage was found. In contrast, compared with the control group, the Bifidobacterium animalis QC08 group exhibited a significant decrease in serum UA, BUN, Cr, TNF-α, and IL-6 levels, along with reduced hepatic XOD and ADA activities (p < 0.05). Additionally, Bifidobacterium animalis QC08 was found to regulate the mRNA transcription of renal uric acid transporters, leading to significantly upregulation of the expression levels of UAT, ABCG2, and OAT1 genes (p < 0.05).Conclusion: Bifidobacterium animalis QC08 demonstrates certain uric acid-lowering, anti-inflammatory, and renal protective effects, which are associated with the inhibition of XOD activity and the modulation of the expression levels of uric acid transporter genes (UAT, ABCG2, and OAT1).
研究领域:
医学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL BIOLOGY
·
2021
·
IF 3.503
Danling Liang,Tianqiao Yong,Xue Diao,Shaodan Chen,Diling Chen,Chun Xiao,Dan Zuo,Yizhen Xie,Xinxin Zhou,Huiping Hu
Context Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action.Objective To examine hypouricaemic action of Poria coco.Materials and methods Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed.Results P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 μmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 μmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 μmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate.Discussion and conclusions This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.
研究领域:
药理学
·
分子生物学
·
中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2022
·
IF 6.819
Wenhao Xu,Jinli Yang,Xiangyang Gu,Wenjing Su,Faxiang Pu,Zhangfu Xie,Kongliang Jin,Weike Su,Lichan Mao
Ibuprofen (IBU) was a widely used NSAID (a type of nonsteroidal anti-inflammatory drug) worldwide, and many drug deliveries had been reported to enhance bioavailability. However, higher bioavailability would increase the danger of renal injury caused by oxidative stress. This study prepared IBU-Polygonatum sibiricum polysaccharide (IBU-PSP) drug delivery system via mechanochemical method. Due to drug delivery and renal protection effect of Polygonatum sibiricum polysaccharide (PSP), the solubility of IBU-PSP was increased 8.22 times, and the bioavailability was increased 2.52 times compared with IBU, carrageenin-induced rat paw edema test also increased. Meanwhile, short-term and long-term renal injuries induced by IBU were notable decreases. In conclusion, IBU-PSP was a multifunctional drug delivery system with superior anti-inflammatory and renal protection effects. It will benefit from developing high-efficiency NADIs preparations with safer clinical applications while providing an efficient and energy-saving technology for polysaccharide drug delivery.
研究领域:
药理学
·
药物递送
·
药物化学
·
肾病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Shuhui Zhou,Liping Zheng,Tingxuan Zheng,Haiyan Zhan,Qiuyuan Lin,Jiaoao Wei,Yong Huang
Background: Nephrotic syndrome has a significant impact on global health, often leading to cardiovascular disease and high mortality due to limited effective treatments. This study investigates the efficacy of Shensu IV in a puromycin aminonucleoside (PAN)-induced rat model of nephropathy.Methods: Rat models and in vitro podocyte PAN nephropathy models were established with PAN and treated with Shensu IV. Renal function was evaluated by measuring urine output and protein content, while hydrogen sulfide (H2S) and oxidative stress markers were quantified in serum and podocyte lysates. We conducted histological examination on kidney tissues and analyzed molecular markers (CD2AP, nephrin, and PI3K/AKT pathway) using RT-qPCR and Western blot.Results: Shensu IV significantly improved urine output and proteinuria, and attenuated glomerular damage, fibrosis, and mitochondrial swelling in PAN-treated rats. Mechanistically, Shensu IV enhanced endogenous H2S production, reducing oxidative stress and activating the PI3K/AKT pathway in vivo and in vitro. This facilitated the upregulation of the target genes CD2AP and nephrin, which are critical for maintaining glomerular integrity and improving renal function in PAN nephropathy models.Conclusion: Shensu IV and NaHS confer renal protection primarily by modulating oxidative stress and restoring the integrity of the glomerular filtration barrier through mechanisms involving the enhancement of the PI3K/AKT pathway and modulation of H2S levels. These findings suggest a promising therapeutic potential for these metabolites in the treatment of nephrotic syndrome.
研究领域:
药理学
·
肾病学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 4
·551-560
·
IF 2.571
Xu Wen-hao,Wang Han-tao,Sun Ying,Xue Zhen-cheng,Liang Ming-li,Su Wei-ke
ObjectivesTo investigate the antihyperuricemia and nephroprotective effects of Orthosiphon stamineus extracts on hyperuricemia (HUA) mice and explore the potential mechanisms.MethodsOrthosiphon stamineus extracts were extracted using 50% ethanol and enriched using ethyl acetate, and characterised utilising UPLC/ESI-MS. A potassium oxonate (PO) induced hyperuricemic mouse model was used to evaluate antihyperuricemia and nephroprotective effects of O. stamineus ethyl acetate extracts (OSE).Key findingsEight constituents from OSE were identified and OSE treatment ameliorated HUA by regulating key indicators of kidney dysfunction and xanthine oxidase, adenosine deaminase activity and urate transporters in hyperuricemic mice. Moreover, in renal histopathology analysis, OSE significantly alleviated kidney injury.ConclusionsThese findings demonstrate that OSE has antihyperuricemic and nephroprotective effects on PO-induced HUA mice and those results indicate that OSE could be a safe and effective agent or functional ingredient for treating HUA.
研究领域:
药理学
·
肾病学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2023
·
IF 3.4
Mei Dong,Cheng Zhao,Yongfang Huang,Ke Zheng,Guanhu Bao,Fenglin Hu,Fan Peng,Mingjun Chen,Zengzhi Li,Ruili Lu
ABSTRACT Cordyceps chanhua on artificial media has been approved as a medicine food homology product. However, the metabolites have not been extensively studied. HPLC-HRMS analysis showed that there were 11 main metabolites in the EtOAc extract including 4 probable unknown compounds. Fumosoroseain A with anti-aging effects is the most abundant known compound and was identified from C. chanhua for the first time. The second abundant compound is N 6 -(2-Hydroxyethyl) adenosine, a typical metabolite of C. chanhua . All the known compounds have consistent health function with that of the fungus. HRMS, 1D and 2D NMR analyses revealed that compounds 2 , 3, and 4 are new nucleosides named as chanhuanosides A, B, and C. Compound 1 is the known compound cordyrrole B isolated from C. chanhua for the first time whose structure is firstly confirmed by single crystal X-ray analysis. Bioactivity analysis revealed that 1 - 4 significantly inhibited pancreatic lipase acitivty, and strongly promoted the proliferation of RAW264.7 and 293 T cells, suggesting that they might have ant-obesity, immunoregulation, and renal protection functions. Structure-bioactivity analysis revealed that the esterification on ribose can increase their bioactivity. Present metabolites study suggests that C. chanhua cultured on the artificial medium is a promising health food.
研究领域:
药用植物学
·
生物化学
·
药物化学
·
免疫学
·
功能性食品
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Cai Feng,Zongling Xiong,Xianting Sun,Hao Zhou,Tianming Wang,Ying Wang,Harrison X. Bai,Peng Lei,Weihua Liao
It is a challenging task to develop a contrast agent that not only provides excellent image contrast but also protects impaired kidneys from oxidative-related stress during angiography. Clinically approved iodinated CT contrast media are associated with potential renal toxicity, making it necessary to develop a renoprotective contrast agent. Here, we develop a CeO 2 nanoparticles (NPs)-mediated three-in-one renoprotective imaging strategy, namely, i) renal clearable CeO 2 NPs serve as a one-stone-two-birds antioxidative contrast agent, ii) low contrast media dose, and iii) spectral CT, for in vivo CT angiography (CTA). Benefiting from the merits of advanced sensitivity of spectral CT and K-edge energy of Cerium (Ce, 40.4 keV), an improved image quality of in vivo CTA is successfully achieved with a 10 times reduction of contrast agent dosage. In parallel, the sizes of CeO 2 NPs and broad catalytic activities are suitable to be filtered via glomerulus thus directly alleviating the oxidative stress and the accompanying inflammatory injury of the kidney tubules. In addition, the low dosage of CeO 2 NPs reduces the hypoperfusion stress of renal tubules induced by concentrated contrast agents used in angiography. This three-in-one renoprotective imaging strategy helps prevent kidney injury from being worsened during the CTA examination.
研究领域:
医学影像
·
纳米技术
·
放射学
·
肾病学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Zhiwei Huang,Changju Chun,Xinze Li
The management of acute kidney injury (AKI) imposes a significant medical burden. Due to the lack of effective drug transport vehicles, the administration of therapeutic agents for AKI cannot obtain the desired therapeutic effects. Kidney-targeted nanoparticles for renal delivery of drugs have shown promising potential as an emerging strategy for AKI therapy. However, these exogenous nanoparticles are rapidly cleared in the body and fail to achieve the expected renal targeting efficiency. Herein, we prepared the kidney targeting peptide-modified renal tubular epithelial cell membrane to coat zeolite imidazolate framework-8 nanoparticles for FGF21 delivery ( [email protected] ) for AKI treatment. [email protected] could be efficiently internalized by renal cells and exhibited antioxidative, antiapoptotic and anti-inflammatory effects. A septic AKI murine model was established to assess the in vivo performance of [email protected] The results showed that injected [email protected] specifically accumulated in the injured kidney and exerted good renoprotective effects. This study provides an innovative thread for precise drug delivery in the treatment of various renal diseases.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
肾脏生理学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Zhihao Liu,Qixiang Shang,Haimeng Li,Daozheng Fang,Zhuohuan Li,Yuqi Huang,Mimi Zhang,Kam Ming Ko,Jihang Chen
Background Diabetic kidney disease (DKD) is one of the major chronic microvascular complications of diabetes and the main cause of end-stage renal failure. Zhenwu Decoction (ZWD), an ancient classic herbal formula in Chinese medicine, has been clinically used for the treatment of kidney disease in China for many years. However, there is currently limited research investigating the application of ZWD in the treatment of DKD and the underlying chemical and biochemical mechanisms involved. Therefore, in the present study, we aimed to identify active components in ZWD and unravel the possible mechanism(s) of action for ZWD in treating DKD. Methods The protective effect of ZWD against DKD was evaluated utilizing an in vitro model of diabetic renal proximal tubulopathy. The major chemical components from ZWD were identified by LC-MS/MS. Drug targets were predicted by submitting the SMILES (Simplified Molecular Input Line Entry System) of the compounds to SEA (Similarity Ensemble Approach) search server and SwissTargetPrediction. The differentially expressed genes (DEGs) of the disease were collected and integrated from GeneCards. The constructions of “Compounds-potential targets interaction” (CTI) network and Protein-Protein Interaction (PPI) network, as well as topology analysis were conducted by Cytoscape. Gene Ontology (GO)-enrichment and Metacore pathway enrichment analysis were also performed. Lastly, molecular docking and experimental studies were adopted to validate the core target and identify an active component(s) of ZWD. Results We demonstrated that the ZWD extract could significantly rescue the palmitic acid (PA) and high glucose-induced apoptotic cell death in HK-2 cells, and the cytoprotection was accompanied by decreases in the extent of reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ATP depletion. Fifty-seven compounds in the aqueous extract of ZWD were identified by LC-MS. The results of PPI analysis showed that top hub genes involved epidermal growth factor receptor (EGFR), Signal Transducer and Activator of Transcription 3 (STAT3), Serine/Threonine Kinase 1 (AKT1), Vascular Endothelial Growth Factor A (VEGFA) and Fibroblast Growth Factor 2 (FGF2). Pathway enrichment analysis revealed the involvement of S1P1 receptor signaling and EGFR pathways. The results of molecular docking analysis showed that albiflorin has a high binding affinity to EGFR. Albiflorin could also exert protective effects in an HK-2 cell model of DKD, which may be related to the inhibition of the high glucose/high lipid-induced EGFR and Akt phosphorylation. Conclusion ZWD has been shown to be effective in ameliorating cell death in an experimental model of DKD. The beneficial effect of ZWD against DKD was associated with the interactions between the active ingredients and the hub genes, such as EGFR, STAT3, AKT1, and VEGF-A. Albiflorin may be one of the active components responsible for the nephroprotective effect in ZWD.
研究领域:
药理学
·
分子生物学
·
中医
·
糖尿病
·
肾病学
·
生物信息学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）