Novel inhibitors of the cellular renin‐angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β‐catenin pathway against renal fibrosis

Wang, Ming; Chen, Dan-Qian; Lin, Chen; Cao, Gang; Zhao, Hui; Liú, Dan; Vaziri, Nosratola D.; Guo, Yan; Yan, Zhao

doi:10.1111/bph.14333

Cited by 149 publications

(93 citation statements)

References 61 publications

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“…TCM gain increasingly more attention all over the world, based on their specific futures and long historical clinical practice . Metabolomics afforded a research idea that is similar to the overall concept of TCM .…”

Section: Discussionmentioning

confidence: 99%

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Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

et al. 2019

Chemistry & Biodiversity

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In this study, the metabolite profiling of three different parts of Crocus sativus L. was measured by using ultra‐performance liquid chromatography‐quadrupole time‐of‐flight mass spectrometry (UPLC‐QTof‐MS/MS). Multivariate statistical analysis was used to distinguish among the samples from different parts. A total of 54 compounds were identified in tepals, stigmas and stamens by UPLC‐QTof‐MS/MS. The results stated that chemical characteristics of saffron were obviously diverse in terms of the parts of flower. Through analysis, coniferin and crocin‐2 were special components in stigmas when compared to tepals and stamens. The content of flavonoids was high in tepals when compared with the stigmas. The tepal of saffron may processed as a source of flavonoids in the future. The research provided the basis for the theory that only the stigma can be used as medicine.

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Section: Discussionmentioning

confidence: 99%

“…TCM gain increasingly more attention all over the world, based on their specific futures and long historical clinical practice. [30][31][32][33][34][35] Metabolomics afforded a research idea that is similar to the overall concept of TCM. [36] Metabolomics technique has been extensively applied to the study of TCM and natural products.…”

Section: Discussionmentioning

confidence: 99%

Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

et al. 2019

Chemistry & Biodiversity

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“…We report for the first time that petA, a novel small molecule ex- The antifibrotic actions of petA may involve multiple mechanisms. Because TGF-β1/Smad3 signalling is the critical pathway of renal fibrosis, 3,4,[36][37][38] we first examined the effect of petA on the activation of TGF-β1/Smad3 signalling in the UUO model. Our results indicated that administering petA to prevent or treat UUO suppressed TGF-β1 expression and blocked the phosphorylation of Smad3, subsequently attenuating the expression of fibrotic genes (including α-SMA, collagen I and fibronectin).…”

Section: Discussionmentioning

confidence: 99%

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

You

Luo

Wang

et al. 2019

J Cellular Molecular Medi

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Obstructive nephropathy is the end result of a variety of diseases that block drainage from the kidney(s). Transforming growth factor‐β1 (TGF‐β1)/Smad3‐driven renal fibrosis is the common pathogenesis of obstructive nephropathy. In this study, we identified petchiether A (petA), a novel small‐molecule meroterpenoid from Ganoderma , as a potential inhibitor of TGF‐β1‐induced Smad3 phosphorylation. The obstructive nephropathy was induced by unilateral ureteral obstruction (UUO) in mice. Mice received an intraperitoneal injection of petA/vehicle before and after UUO or sham operation. An in vivo study revealed that petA protected against renal inflammation and fibrosis by reducing the infiltration of macrophages, inhibiting the expression of proinflammatory cytokines (interleukin‐1β and tumour necrosis factor‐α) and reducing extracellular matrix deposition (α‐smooth muscle actin, collagen I and fibronectin) in the obstructed kidney of UUO mice; these changes were associated with suppression of Smad3 and NF‐κB p65 phosphorylation. Petchiether A inhibited Smad3 phosphorylation in vitro and down‐regulated the expression of the fibrotic marker collagen I in TGF‐β1‐treated renal epithelial cells. Further, we found that petA dose‐dependently suppressed Smad3‐responsive promoter activity, indicating that petA inhibits gene expression downstream of the TGF‐β/Smad3 signalling pathway. In conclusion, our findings suggest that petA protects against renal inflammation and fibrosis by selectively inhibiting TGF‐β/Smad3 signalling.

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“…[151][152][153][154][155][156][157][158] Recently, our group isolated more than 90 triterpenoid compounds from the surface layer of Poria cocos, some of which exhibited significant antifibrotic properties. [159][160][161] New triterpenoids, including poricoic acid ZC, poricoic acid ZD, and poricoic acid ZE, significantly downregulated the expression of Wnt1, active β-catenin, Snail, Twist, MMP-7, PAI-1, and FSP1 in HK-2 cells induced by TGF-β1 and angiotensin II and mice with unilateral ureteral occlusion 29 (Figure 2 and Table 1). Moreover, new triterpenoids, including poricoic acid ZG and poricoic acid ZH, improved renal fibrosis by targeting the phosphorylation of Smad3 signaling and the Wnt/β-catenin signaling pathway 162 (Figure 2 and Table 1).…”

Section: Wnt Signaling Pathwaymentioning

confidence: 96%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

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109

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Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

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Novel inhibitors of the cellular renin‐angiotensin system components, poricoic acids, target Smad3 phosphorylation and Wnt/β‐catenin pathway against renal fibrosis

Abstract: The secolanostane tetracyclic triterpenoids effectively blocked RAS by simultaneously targeting multiple RAS components and lanostane tetracyclic triterpenoids inhibited renin and protected against tubulo-interstitial fibrosis.

Cited by 149 publications

References 61 publications

Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

Discrimination of Different Parts of Saffron by Metabolomic‐Based Ultra‐Performance Liquid Chromatography Coupled with High‐Definition Mass Spectrometry

Petchiether A attenuates obstructive nephropathy by suppressing TGF‐β/Smad3 and NF‐κB signalling

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

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