Kaempferol inhibits renal fibrosis by suppression of the sonic hedgehog signaling pathway

Guan, Yiqing; Quan, Dongling; Chen, Kai; Kang, Liangqi; Yang, Danni; Wu, Haiwei; Yan, Mengqiu; Wu, Shaoyu; Lv, Lin; Zhang, Guohua

doi:10.1016/j.phymed.2022.154246

Cited by 11 publications

(8 citation statements)

References 30 publications

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“…Specifically, abnormal hedgehog signaling pathway activation activates hepatic stellate cells to activate mRNAs (like Shh, Ptch 1, Gli 1, and Smo) and inhibit apoptosis [27]. In addition, the hedgehog pathway is activated when renal fibrosis occurs in the body, significantly increasing the key component expression in the signaling pathway, thereby further promoting renal fibrosis [28]. In short, the hedgehog signaling pathway is notably correlated with fibrosis in the lung, kidney, liver, and other organs.…”

Section: Discussionmentioning

confidence: 99%

LncRNA Meg3 Aggravates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Rats by Activating the Hedgehog Pathway

Dong,

Zhang,

et al. 2024

Discovery Medicine

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Background: The hedgehog signaling pathway exerts vital functions in regulating epithelial-to-mesenchymal transition (EMT) in renal interstitial fibrosis (RIF). It was reported that lncRNA-maternally expressed gene 3 (lncRNA Meg3) can regulate hepatic fibrosis by regulating the expression of smoothened (Smo) in the hedgehog signaling pathway. However, the specific role of lncRNA Meg3 in renal fibrosis resulting from unilateral ureteral obstruction (UUO) by regulating the hedgehog signaling pathway has not been reported. Hence, this research aimed to expound the effects of lncRNA Meg3 on renal fibrosis induced by UUO in rats via the hedgehog pathway. Methods: Peripheral blood was collected from patients with chronic kidney disease (CKD, CKD group) and healthy volunteers (Normal group) at the same period. In addition, 6-week-old male Sprague-Dawley (SD) rats were divided to Sham, UUO, UUO+shRNA Negative control (shNC), and UUO+sh-Meg3 groups, and their kidney tissues and serum were gathered. Next, quantitative real-time polymerase chain reaction (qRT-PCR) was employed for detecting the lncRNA Meg3 expression level in the serum of patients and renal tissue of rats; kits for testing levels of blood urea nitrogen (BUN), creatinine (Cr), hydroxyproline (HYP), and 24-hour urine protein (24-up) in rats of each group; hematoxylin and eosin (HE) staining and Masson staining for observing kidney tissue and renal fibrosis level in rats; western blot for measuring levels of collagen type III (Col III), α-Smooth muscle actin (α-SMA), fibronectin, E-cadherin, sonic hedgehog (Shh), patched (Ptch) protein, smoothened (Smo) protein and glioma-associated oncogene homolog 1 (Gli1) protein expression. Results: LncRNA Meg3 was highly expressed in CKD patients and UUO rats (p < 0.01). In contrast to the UUO+shNC group, knocking down lncRNA Meg3 improved renal injury, relieved pathological renal lesions, and reduced kidney fibrosis and related protein levels. It inhibited the hedgehog pathway in kidney tissues of UUO rats (p < 0.05 and p < 0.01). Conclusions: LncRNA Meg3 can aggravate UUO-induced rat renal fibrosis by activating the hedgehog pathway.

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Section: Discussionmentioning

confidence: 99%

LncRNA Meg3 Aggravates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Rats by Activating the Hedgehog Pathway

Dong,

Zhang,

et al. 2024

Discovery Medicine

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“…Kaempferol and baicalein have been proven to play antifibrotic roles. [ 29 ] The common ingredient β-sitosterol (MOL000358) in PKSH also played a role in the treatment of liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of peach kernel and safflower herb-pair for the treatment of liver fibrosis based on network pharmacology and molecular docking technology: A review

Huang

Peng

et al. 2023

Medicine

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Peach kernel and safflower herb-pair (PKSH) are widely used in traditional Chinese medicine for the treatment of liver fibrosis. Therefore, network pharmacology was performed to explore potential therapeutic targets and pharmacological mechanisms of PKSH. The active components of PKSH from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database and potential targets of liver fibrosis from the Online Mendelian Inheritance in Man, Pharmacogenetics and Pharmacogenomics Knowledge Base, GeneCards, and DrugBank Database were identified. The protein-protein interaction network was constructed using Cytoscape (v3.8.0). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed for the treatment of liver fibrosis, and molecular docking was carried out to verify the results of network pharmacology analysis. After screening disease-related genes, 179 intersection genes overlapped between 196 target proteins of the active compound and 9189 potential disease targets. Furthermore, we obtained 15 hub nodes and 146 edges to establish a related network diagram using CytoNCA. 2559 Gene Ontology biological processes underlying PKSH have been explored for the treatment of liver fibrosis, in which the response to oxidative stress plays a vital role. Furthermore, Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that PKSH might play a role in inhibiting liver fibrosis, mainly through the PI3K-Akt signaling pathway. PKSH can regulate the response to oxidative stress through the PI3K-Akt signaling pathway for the treatment of liver fibrosis. The main bioactive components in PKSH, including quercetin and luteolin, can activate the PI3K-Akt signaling pathway by binding with the hub targets of the disease, which may provide insights into drug development for liver fibrosis.

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“…Recently, Han et al demonstrated that rutin prevents fibrosis progression in CKD [20]. Kaempferol (KAE) is a plant-derived flavonoid that controls renal fibrosis progression and the EMT in the renal tubular system [21]. Meanwhile, KAE attenuates renal injury and reverses phenotypic transformation and collagen accumulation in renal tubular epithelial cells [22].…”

Section: Qsg Chemical Constituent Analysis In Vitromentioning

confidence: 99%

Simultaneous determination of multiple constituents, serum composition, and tissue distribution of Qingshen granule using ultra‐high performance liquid chromatography‐quadrupole‐orbitrap high‐resolution mass spectrometry

Dai

Chen

et al. 2023

J of Separation Science

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Qingshen granule, composed of 14 herbal drugs, is primarily used as the assistant therapy for chronic kidney disease. Qingshen granule chemical composition was complex, but its chemical constituents and the pharmacodynamic material basis remain unreported. Ultra-high-performance liquid chromatography (UHPLC)-quadrupole-orbitrap high-resolution mass spectrometry was applied to recognize the chemical constituents of Qingshen granule. The analysis was performed using the ACQUITY UHPLC BEH C18 column (2.1 × 50 mm, 1.7 μm) with acetonitrile-0.1% formic acid as the mobile phase for gradient elution. The data were collected using heated electrospray ionization in positive and negative ion modes. This study successfully applied the UPHLC-quadrupole-orbitrap high-resolution mass spectrometry technique with the Compound Discoverer 3.3 platform to analyze Qingshen granule chemical composition. A total of 127 and 42 chemical components were identified in Qingshen granule in vitro and in vivo, respectively. In the tissue distribution of Qingshen granule, 9, 10, 11, 10, and 18 prototype components were detected in the heart, liver, spleen, lungs, and kidneys, respectively. Qingshen granule chemical constituents were characterized rapidly for the first time in this study, laying a foundation for further research on the substance basis and quality control of Qingshen granule in treating chronic kidney disease.

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Kaempferol inhibits renal fibrosis by suppression of the sonic hedgehog signaling pathway

Cited by 11 publications

References 30 publications

LncRNA Meg3 Aggravates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Rats by Activating the Hedgehog Pathway

LncRNA Meg3 Aggravates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Rats by Activating the Hedgehog Pathway

The mechanism of peach kernel and safflower herb-pair for the treatment of liver fibrosis based on network pharmacology and molecular docking technology: A review

Simultaneous determination of multiple constituents, serum composition, and tissue distribution of Qingshen granule using ultra‐high performance liquid chromatography‐quadrupole‐orbitrap high‐resolution mass spectrometry

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