Deoxycholic acid-chitosan coated liposomes combined with in situ colonic gel enhances renal fibrosis therapy of emodin

Xu, Zhishi; Hou, Yu; Sun, Jiang; Zhu, Lin; Zhang, Qibin; Yao, Wenjie; Fan, Xudong; Zhang, Ke; Piao, Ji-Gang; Wei, Yinghui

doi:10.1016/j.phymed.2022.154110

Cited by 13 publications

(5 citation statements)

References 74 publications

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“…The current study demonstrates that SKI and its three components chrysophanol, emodin, and rhein inhibit tubulointerstitial fibrosis by inhibiting the RAS/Wnt/β-catenin signalling axis in adenine-induced CKD rats. Recent studies show that emodin ameliorates tubulointerstitial fibrosis ( Wang et al, 2022b ; Xu et al, 2022 ). In addition, several publications revealed that rhein improves renal fibrosis and is associated with the nuclear factor kappa B and Twist1 pathways ( Chen et al, 2022 ; Song et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

et al. 2022

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Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensin system (RAS) has been used as a first-line standard therapy in patients with hypertension and CKD, patients still progress towards end-stage kidney disease, which might be closely associated with compensatory renin expression subsequent to RAS blockade through a homeostatic mechanism. The Wnt/β-catenin signalling pathway is the master upstream regulator that controls multiple intrarenal RAS genes. As Wnt/β-catenin regulates multiple RAS genes, we inferred that this pathway might also be implicated in blood pressure control. Therefore, discovering new medications to synchronously target multiple RAS genes is necessary and essential for the effective treatment of patients with CKD. We hypothesized that Shenkang injection (SKI), which is widely used to treat CKD patients, might ameliorate CKD by inhibiting the activation of multiple RAS genes via the Wnt/β-catenin signalling pathway. To test this hypothesis, we used adenine-induced CKD rats and angiotensin II (AngII)-induced HK-2 and NRK-49F cells. Treatment with SKI inhibited renal function decline, hypertension and renal fibrosis. Mechanistically, SKI abrogated the increased protein expression of multiple RAS elements, including angiotensin-converting enzyme and angiotensin II type 1 receptor, as well as Wnt1, β-catenin and downstream target genes, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in adenine-induced rats, which was verified in AngII-induced HK-2 and NRK-49F cells. Similarly, our results further indicated that treatment with rhein isolated from SKI attenuated renal function decline and epithelial-to-mesenchymal transition and repressed RAS activation and the hyperactive Wnt/β-catenin signalling pathway in both adenine-induced rats and AngII-induced HK-2 and NRK-49F cells. This study first revealed that SKI repressed epithelial-to-mesenchymal transition by synchronously targeting multiple RAS elements by blocking the hyperactive Wnt/β-catenin signalling pathway.

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Section: Discussionmentioning

confidence: 99%

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

et al. 2022

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“…[6][7][8] The pathological hallmark of CKD involves the accumulation of a substantial amount of extracellular matrix in the glomerulus and renal interstitium, which disrupts normal renal tissue architecture and interacts with renal tubular epithelial cells, myofibroblasts, and immune cells, further exacerbating the progression to renal fibrosis and nephron loss. [9,10] Dysbiosis of the gut microbiota has been implicated in the development of various diseases. [11,12] Notably, numerous studies [13][14][15][16] have indicated that changes in gut microbiota composition are related to CKD exacerbation.…”

Section: Bibliometric Analysis Of the Relationship Between Gut Microb...mentioning

confidence: 99%

“…[6–8] The pathological hallmark of CKD involves the accumulation of a substantial amount of extracellular matrix in the glomerulus and renal interstitium, which disrupts normal renal tissue architecture and interacts with renal tubular epithelial cells, myofibroblasts, and immune cells, further exacerbating the progression to renal fibrosis and nephron loss. [9,10]…”

Section: Introductionmentioning

confidence: 99%

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

Tao,

Huo,

Chen

2024

Integr Med Nephrol Androl

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Background: The gut microbiota is closely associated with chronic kidney disease (CKD) development and prognosis. However, a comprehensive understanding of publication trends and research focuses within this domain remains limited. This study aimed to elucidate the relationship between the gut microbiota and CKD through a bibliometric analysis. Methods: Literature published between 2001 and 2022 on gut microbiota and CKD was obtained from the Web of Science Core Collection database. Bibliometric analysis tools such as VOSviewer and CiteSpace were used to analyze research trends in this area. Results: We extracted 758 articles for further analysis. China ranked first with 240 published documents, followed by the USA with 211. However, the USA ranked first regarding citation frequency with 11,380 citations, while China ranked second. The University of California Irvine and Kidney International emerged as the leading institution and journal, respectively, with the former leading in document production and citations. Although Kidney International featured fewer documents than other journals, it exhibited the highest citation count. The keywords representing the research interests mainly included: (1) gut microbiota influences the development of CKD, (2) application of probiotics in the treatment of CKD, and (3) potential mechanism of gut microbiota in CKD. Conclusion: Our analysis indicates significant advancements in understanding the association between gut microbiota and CKD. It also provides a comprehensive overview of publication trends, research hotspots, and frontiers, which may provide guidelines for future research.

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“…To determine encapsulation efficiency (EE) and drug loading (DL), the lyophilized NYPs, meticulously weighed, were diluted with 10 mL of methanol and centrifuged at 3000 rpm for 10 min, and the filtrate Scheme 1 Schematic representation of microgels construction, Dectin-targeting, and microbiota recovering of Co-Loaded Microgels was injected into HPLC system. The concentration of EMO in the filtrate was measured by a previously validated high-performance liquid chromatography (HPLC) method at 250 nm [77]. To measure the concentration of AA, HPLC analysis was carried out on a Waters e2998 system consisting of a ZORBAX Extend-C18 (5 μm, 250 × 4.6 mm).…”

Section: Preparation and Characterization Of Npysmentioning

confidence: 99%

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation

Hou,

Zhu,

et al. 2024

J Nanobiotechnol

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Background Renal fibrosis is a progressive process associated with chronic kidney disease (CKD), contributing to impaired kidney function. Active constituents in traditional Chinese herbs, such as emodin (EMO) and asiatic acid (AA), exhibit potent anti-fibrotic properties. However, the oral administration of EMO and AA results in low bioavailability and limited kidney accumulation. Additionally, while oral probiotics have been accepted for CKD treatment through gut microbiota modulation, a significant challenge lies in ensuring their viability upon administration. Therefore, our study aims to address both renal fibrosis and gut microbiota imbalance through innovative co-delivery strategies. Results In this study, we developed yeast cell wall particles (YCWPs) encapsulating EMO and AA self-assembled nanoparticles (NPYs) and embedded them, along with Lactobacillus casei Zhang, in chitosan/sodium alginate (CS/SA) microgels. The developed microgels showed significant controlled release properties for the loaded NPYs and prolonged the retention time of Lactobacillus casei Zhang (L. casei Zhang) in the intestine. Furthermore, in vivo biodistribution showed that the microgel-carried NPYs significantly accumulated in the obstructed kidneys of rats, thereby substantially increasing the accumulation of EMO and AA in the impaired kidneys. More importantly, through hitchhiking delivery based on yeast cell wall and positive modulation of gut microbiota, our microgels with this synergistic strategy of therapeutic and modulatory interactions could regulate the TGF-β/Smad signaling pathway and thus effectively ameliorate renal fibrosis in unilateral ureteral obstruction (UUO) rats. Conclusion In conclusion, our work provides a new strategy for the treatment of renal fibrosis based on hitchhiking co-delivery of nanodrugs and probiotics to achieve synergistic effects of disease treatment and targeted gut flora modulation. Graphical Abstract

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Deoxycholic acid-chitosan coated liposomes combined with in situ colonic gel enhances renal fibrosis therapy of emodin

Cited by 13 publications

References 74 publications

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

Integrated oral microgel system ameliorates renal fibrosis by hitchhiking co-delivery and targeted gut flora modulation

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