Pharmacology Research & Perspectives
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2025
·Vol. 13
·期 3
·e70094
·
IF 2.3
Lei Zhu,Mengru Ding,Lina Liu,Pingchuan Yuan,Taili Shao,Chunyan Liu,Chuanhu Xi,Jun Han,Yuyan Zhou,Donglin Zhang,Guodong Wang
Diabetic nephropathy (DN) is a common complication of diabetes mellitus, with oxidative stress playing a critical role in its development. Burdock fructooligosaccharide (BFO), a major compound in Burdock, exhibits antioxidative effects. However, its mechanisms of action and effects on diabetic nephropathy are not clear enough. This study aims to explore the mechanisms of BFO and its impact on streptozotocin-induced diabetic nephropathy in mice. Male C57BL/6J mice were randomly divided into normal control, DN, and BFO groups. Relevant serum biochemical parameters were detected using kits. Renal injury was evaluated through fluorescence microscopy, histopathology, and transmission electron microscopy. Nrf2/HO-1 signaling was analyzed via quantitative real-time PCR, western blotting, and immunohistochemistry. In DN mice, BFO significantly reduced fasting blood glucose, kidney index, urine protein, serum creatinine, blood urea nitrogen, total cholesterol, triglyceride, and low-density lipoprotein cholesterol, while significantly increasing high-density lipoprotein, SOD, and CAT levels. Additionally, BFO protected against streptozotocin-induced renal injury, restored podocyte function, increased both mRNA and protein expression of Nrf2, HO-1, and Bcl-2, and decreased those of Bax. In conclusion, BFO can be used to treat streptozotocin-induced renal injury in mice and is a promising candidate for diabetic nephropathy treatment.
研究领域:
药理学
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分子生物学
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糖尿病研究
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2018
·
IF 3.831
Zhang Zhi-Hao,Li Ming-Hua,Liu Dan,Chen Hua,Chen Dan-Qian,Tan Ning-Hua,Ma Shuang-Cheng,Zhao Ying-Yong
Tubulointerstitial fibrosis is the final common pathway for all kidney diseases leading to chronic kidney disease (CKD). TGF-β/Smad signaling pathway plays a key role in renal fibrosis. Previous studies have revealed that rhubarb extracts attenuated the increase of transforming growth factor-β 1 (TGF-β1) in CKD rats. To gain an in-depth insight into the mechanism of the anti-fibrotic activities of the rhubarb extracts, we investigated the influence of rhubarb extracts on TGF-β/Smad signaling pathway and the influence on metabolome in a rat model of CKD with adenine-induced chronic tubulointerstitial nephropathy. Male Sprague-Dawley rats were divided into four groups, including control, CKD, CKD + petroleum ether extract, CKD + ethyl acetate extract, and CKD + n-butanol extract groups. Kidneys harvested on the week three were evaluated for renal fibrosis, the expression of proteins in TGF-β/Smad signaling pathway and metabolomic study. We found rhubarb extracts suppressed TGF-β/Smad3-mediated renal fibrosis by reducing the TGF-β1, transforming growth factor-β receptor I (TGF-β RI), transforming growth factor-β receptor II (TGF-β RII), Smad2, p-Smad2, Smad3, p-Smad3, and Smad4, meanwhile increased Smad7. In addition, rhubarb extracts mitigated renal injury and dysfunction, and either fully or partially reversed the abnormalities of tissue metabolites. Thus, rebalancing the disorder of TGF-β/Smad signaling and metabolic dysfunction by treatment with rhubarb extracts may represent as an effective therapy for CKD associated with fibrosis.
研究领域:
药理学
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhang Cong,Song Yingying,Chen Liang,Chen Peng,Yuan Ming,Meng Yan,Wang Qi,Zheng Guohua,Qiu Zhenpeng
Urolithin A (UroA) is one of the primary intestinal metabolites of ellagitannins, showing translational potential as a nutritional intervention in humans. Mounting evidence suggests that fructose consumption contributes to the progression of chronic kidney disease (CKD) that manifests in hyperuricemic nephropathy, renal inflammation, and tubulointerstitial injury. Here, we investigated the efficacy of UroA in alleviating fructose-induced hyperuricemic nephropathy in mice. Uric acid-exposed human kidney-2 (HK-2) cells were utilized for in vitro mechanism validation. Histopathological staining, immunoblotting, and transmission electron microscope were performed for the mechanistic investigations. Our results revealed that UroA ameliorated fructose-induced hyperuricemic nephropathy in mice. The histopathologic assessment showed that UroA attenuated tubular hypertrophy and dilation, glomerular basement membrane thickening, and collagen deposition in the kidney of fructose-fed mice. Mechanistically, UroA treatment impaired STING-NLRP3 activation, resulting in reduced production of proinflammatory cytokines IL-1β, IL-6, and TNF-α. Notably, UroA exhibited a scavenging effect against reactive oxygen species (ROS) and restored fructose-impaired PINK1/Parkin-mediated mitophagy in nephropathic mice. Furthermore, the inhibitory effect of UroA in STING-NLRP3 activation was impaired after Parkin gene silencing in HK-2 cells. Together, this study suggests that UroA alleviates fructose-induced hyperuricemic nephropathy by promoting Parkin-dependent mitophagy, thereby suppressing STING-NLRP3 axis-mediated inflammatory response. Thus, dietary supplementation with UroA or ellagitannins-rich foods may serve as a promising intervention to prevent CKD progression.
研究领域:
药理学
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肾病学
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分子生物学
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营养学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2020
·
IF 10.652
Dong-Yang Zhang,Hengke Liu,Muhammad Rizwan Younis,Shan Lei,Chen Yang,Jing Lin,Junle Qu,Peng Huang
Acute kidney injury (AKI) is a common kidney disease with high mortality rate, while surprisingly, the supportive treatment and renal replacement are the only available clinical treatment options to date. The onset of AKI is often triggered by excessive toxic reactive oxygen/nitrogen species (RONS), and hence, the development of antioxidants with high renal accumulation and effective renal clearance is highly demanded to consume RONS in the kidneys. In this study, we developed ultrasmall polyvinylpyrrolidone-coated platinum nanoparticles (Pt NPs-PVP, ~3 nm) as multienzyme mimetics (catalase, peroxidase, and superoxide dismutase). Thanks to their excellent RONS scavenging ability, Pt NPs-PVP effectively reduced the hydrogen peroxide induced cellular damage. Analytical (inductively coupled plasma mass spectrometry) as well as imaging (photoacoustic and computed tomography) techniques revealed the preferential renal uptake and high enrichment of ultrasmall Pt NPs-PVP after intravenous administration, offering remarkable relief of the clinical symptoms of glycerol-induced AKI mice without any apparent systemic toxicity in vivo . Importantly, because of their ultrasmall size, Pt NPs-PVP exhibited rapid excretion from healthy mice, presenting relatively low toxicity and side effects. In conclusion, our work demonstrated ultrasmall Pt nanozyme as a state of the art antioxidant for dual-modal imaging guided treatment of AKI with improved treatment efficacy.
研究领域:
纳米技术
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药学
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生物医学工程
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治疗诊断学
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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
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肾病学
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分子生物学
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DOI
PubMed
高影响因子
Food & Nutrition Research
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2022
·
IF 3.221
Tongxu Guan,Yingce Zheng,Shengzi Jin,Shuang Wang,Mengxin Hu,Xingyao Liu,Siqi Huang,Yun Liu
Background Troxerutin is a flavonoid compound and possesses potential anti-cancer, antioxidant, and anti-inflammatory activities. Besides, cisplatin is one of the most widely used therapeutic agents, but the clinical uses of cisplatin are often associated with multiple side effects, among which nephrotoxicity is more common. Objective and design This study explored the protective effects of troxerutin (150 mg kg −1 day −1 for 14 days) against cisplatin-induced kidney injury and the potential mechanism using Wistar rats as an experimental mammalian model. Results We discovered that troxerutin could significantly alleviate cisplatin-induced renal dysfunction, such as increased levels of blood urea nitrogen and creatinine ( P < 0.01), as well as improved abnormal renal tissue microstructure and ultrastructure. Additionally, troxerutin significantly decreased malondialdehyde (MDA), hydrogen peroxide (H 2 O 2 ), NO, inducible nitric oxide synthase (iNOS) levels ( P < 0.01), p-NF-κB p65/NF-κB p65, TNF-α, Pro-IL-1β, IL-6, B cell lymphoma-2 (Bcl-2)/Bcl-xl associated death promoter (Bad), Cytochrome C (Cyt C), Cleaved-caspase 9, Cleaved-caspase 3, and Cleaved-caspase 8 protein levels ( P < 0.01) in the kidney tissues of cisplatin-treated rats; and increased superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), total antioxidant capacity (T-AOC) activities ( P < 0.01), IL-10, Bcl-2 protein levels ( P < 0.01). Conclusion These results suggested that the underlying mechanism might be attributed to the regulation of Phosphoinositide 3 kinase/Protein kinase B (PI3K/AKT) pathway via enhancing MAP4 expression to attenuate cellular apoptosis, alleviating oxidative stress and inflammatory response.
研究领域:
药理学
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毒理学
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分子生物学
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细胞生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
Genes
·
2022
·Vol. 13
·期 7
·1113
·
IF 4.141
Biying Jiang,Baolong Cao,Zhichun Zhou,Zejiao Li,Can Lv,Jiannan Zhang,Heyuan Zhang,Yajun Wang,Juan Li
Adrenoceptors are suggested to mediate the functions of norepinephrine (NE) and epinephrine (EPI) in the central nervous system (CNS) and peripheral tissues in vertebrates. Compared to mammals, the functionality and expression of adrenoceptors have not been well characterized in birds. Here, we reported the structure, expression, and functionality of chicken functional α2A-adrenoceptor, namedADRA2A. The cloned chickenADRA2AcDNA is 1335 bp in length, encoding the receptor with 444 amino acids (a.a.), which shows high amino acid sequence identity (63.4%) with its corresponding ortholog in humans. Using cell-based luciferase reporter assays and Western blot, we demonstrated that the ADRA2A could be activated by both NE and EPI through multiple signaling pathways, including MAPK/ERK signaling cascade. In addition, the mRNA expression ofADRA2Ais found to be expressed abundantly in adult chicken tissues including thyroid, lung, ovary and adipose from the reported RNA-Seq data sets. Moreover, the mRNA expression ofADRA2Ais also found to be highly expressed in the granulosa cells of 6–8 mm and F5 chicken ovarian follicles, which thus supports that ADRA2A signaling may play a role in ovarian follicular growth and differentiation. Taken together, our data provide the first proof that the α2A-adrenoceptor is functional in birds involving avian ovarian follicular development.Keywords:chickens;α2-adrenoceptor;ADRA2A
研究领域:
分子生物学
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内分泌学
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生殖生物学
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DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Jiangpeng Pan,Juntao Wang,Wei Wang,Ziyang Liu,Shuai Huo,Lei Yan,Wei Jiang,Fengmin Shao,Yue Gu
Mitochondrial dysfunction-induced oxidative stress is a key pathogenic factor in acute kidney injury (AKI). Despite this, current mitochondrial-targeted antioxidant therapies have shown limited efficacy in clinical settings. In this study, we introduce a novel renal-clearable and mitochondria-targeted antioxidant nanozyme (TPP@RuCDzyme) designed to precisely modulate mitochondrial oxidative stress and mitigate AKI progression. TPP@RuCDzyme was synthesized by integrating ruthenium-doped carbon dots (CDs) with triphenylphosphine (TPP), a mitochondria-targeting moiety. This nanozyme system exhibits cascade enzyme-like activities, mimicking superoxide dismutase (SOD) and catalase (CAT), to efficiently convert cytotoxic superoxide (O 2 • - ) and hydrogen peroxide (H 2 O 2 ) into non-toxic water (H 2 O) and oxygen (O 2 ). This dual-enzyme mimicry effectively alleviates mitochondrial oxidative damage, restores mitochondrial function, and inhibits apoptosis. Compared to RuCDzyme alone, TPP@RuCDzyme demonstrated significantly enhanced efficacy in alleviating glycerol-induced AKI by inhibiting oxidative stress. By leveraging the catalytic activity derived from the integration of CDs and a metallic element, this study presents a promising therapeutic strategy for AKI and other renal diseases associated with mitochondrial dysfunction.
研究领域:
生物医学工程
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药理学
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纳米医学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2024
·
IF 4.8
Jianan Zhai,Zhengguo Chen,Qi zhu,Zhifang Guo,Xiance Sun,Liping Jiang,Jing Li,Ningning Wang,Xiaofeng Yao,Cong Zhang,Haoyuan Deng,Shaopeng Wang,Guang Yang
Patulin (PAT), the most common mycotoxin, is widespread in foods and beverages which poses a serious food safety issue to human health. Our previous research confirmed that exposure to PAT can lead to acute kidney injury (AKI). Curcumin is the most abundant active ingredient in turmeric rhizome with various biological activities. The aim of this study is to investigate whether curcumin can prevent the renal injury caused by PAT, and to explore potential mechanisms. In vivo , supplementation with curcumin attenuated PAT-induced ferroptosis. Mechanically, curcumin inhibited autophagy, led to the accumulation of p62 and its interaction with Keap1, promoted the nuclear translocation of nuclear factor E2 related factor 2 (Nrf2), and increased the expression of antioxidant stress factors in the process of ferroptosis. These results have also been confirmed in HKC cell experiments. Furthermore, knockdown of Nrf2 in HKC cells abrogated the protective effect of curcumin on ferroptosis. In conclusion, we confirmed that curcumin mitigated PAT-induced AKI by inhibiting ferroptosis via activation of the p62/Keap1/Nrf2 pathway. This study provides new potential targets and ideas for the prevention and treatment of PAT.
研究领域:
毒理学
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药理学
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分子生物学
·
食品安全
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产品关联
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
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生物化学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 5
·2458
·
IF 4.9
Lixing Cao,Kai Han,Lihong Fan,Chong Zhao,Shutao Yin,Hongbo Hu
Acute kidney injury (AKI) is a common clinical problem with high morbidity and mortality. The discovery of ferroptosis has provided novel insights into the mechanisms underlying AKI and paves the way for developing ferroptosis-based approaches to treat AKI. Glycyrol (GC) is a representative coumarin compound isolated from licorice that demonstrates various pharmacological activities. However, its potential for a protective effect against kidney injury remains unknown. We hypothesized that GC might be able to protect against AKI via suppression of ferroptosis. This hypothesis was tested in a cell-culture model of RSL3-induced nephrocyte ferroptosis and a mouse model of folic acid-induced AKI. The results showed that GC exerted a significant protective effect against nephrocyte ferroptosis in vitro and was effective against folic acid-induced AKI in vivo, where it was mechanistically associated with suppressing HO-1-mediated heme degradation. Collectively, the findings of the present study support the hypothesis that GC holds considerable potential to be developed as a novel agent for treating ferroptosis-related AKI.
研究领域:
药理学
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肾病学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2016
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IF 4.035
Lijiang Lei,Jin Zhu,Gangqiang Xia,Hui Feng,Hongman Zhang,Yuwang Han
NGAL is a promising novel biomarker for acute kidney injury (AKI) and chronic kidney disease (CKD). More rapid and user-friendly methods are needed for the timely monitoring of NGAL in human urine and serum. UCP technology-based lateral flow assay (UPT-LFA) was developed for rapid, user-friendly and quantitative detection of the NGAL in human serum specimens and urine specimens. Under optimal conditions, the UPT-LFA displayed a rapid response to NGAL with a LOD of 7.68 ng/mL and detection range from 7.68 to 1000 ng/mL. The UPT-LFA method was compared with commercial immunoturbidimetry (103 urine specimens), and by ELISA (26 serum specimens), respectively. The results demonstrated that the UPT-LFA was consistent with immunoturbidimetry assay, reporting a 97.92% of positive and 92.73% of negative coincidence rates, respectively. Meanwhile, the concordance rate between UPT-LFA and ELISA, as shown by correlative regression analysis, was also high (R 2 =0.95). The whole assay can be completed within 30 min compared to 4 h consuming with ELISA. The research implies that, the UPT-LFA provides a potential to be used in point of care testing (POCT) to define early acute kidney injury with advantages of user-friendly and rapid testing, promising this new assay a bright future.
研究领域:
医学诊断
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生物技术
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产品关联
DOI
PubMed
高影响因子
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