Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we expl...Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks of Broussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1(Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase(JAK) 2, signal transducer and activator of transcription(STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.展开更多
With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nep...With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.展开更多
Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEF...Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats.EEFP(1.35,1.80,and 2.25 g·kg^–1)was administrated to Sprague Dawley(SD)rats for 30 d.We measured liver chemistries,histopathology,and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling.EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion,bile flow rate,and liver histopathology.iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats.Among these proteins,81 were upregulated and 32 were downregulated in the treatment group.KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450,glutathione metabolism,glycerolipid metabolism,and bile secretion were enriched with differentially expressed proteins.The expression of key proteins related to the farnesoid X receptor(FXR),i.e.,the peroxisome proliferators-activated receptor alpha(PPAR-α),were downregulated,and multidrug resistance-associated protein 3(MRP3)was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways.Furthermore,our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.展开更多
基金supported by the National Natural Science Foundation of China(Nos.81703530 and 81773995)the Natural Science Foundation of Jiangsu Province(Nos.BK20160032 and BK20170859)+2 种基金the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University(Traditional Chinese Pharmacology)Zhejiang Chinese Medical University(No.ZYAOX2018001)the Six Talent Peaks Project of Jiangsu Province(PANG Tao)
文摘Macrophages play an important role in inflammation, and excessive and chronic activation of macrophages leads to systemic inflammatory diseases, such as atherosclerosis and rheumatoid arthritis. In this paper, we explored the anti-inflammatory effect of broussonin E, a novel phenolic compound isolated from the barks of Broussonetia kanzinoki, and its underlying molecular mechanisms. We discovered that Broussonin E could suppress the LPS-induced pro-inflammatory production in RAW264.7 cells, involving TNF-α, IL-1β, IL-6, COX-2 and iNOS. And broussonin E enhanced the expressions of anti-inflammatory mediators such as IL-10, CD206 and arginase-1(Arg-1) in LPS-stimulated RAW264.7 cells. Further, we demonstrated that broussonin E inhibited the LPS-stimulated phosphorylation of ERK and p38 MAPK. Moreover, we found that broussonin E could activate janus kinase(JAK) 2, signal transducer and activator of transcription(STAT) 3. Downregulated pro-inflammatory cytokines and upregulated anti-inflammatory factors by broussonin E were abolished by using the inhibitor of JAK2-STAT3 pathway, WP1066. Taken together, our results showed that broussonin E could suppress inflammation by modulating macrophages activation state via inhibiting the ERK and p38 MAPK and enhancing JAK2-STAT3 signaling pathway, and can be further developed as a promising drug for the treatment of inflammation-related diseases such as atherosclerosis.
基金National Natural Science Foundation of China(Nos.81673684,81703626,81573690)Double First-Class University projects(No.CPU2018GY33)。
文摘With the internationally growing popularity of traditional Chinese medicine(TCM), TCM-induced nephropathy has attracted public attention. Minimizing this toxicity is an important issue for future research. Typical nephrotoxic TCM drugs such as Aristolochic acid, Tripterygium wilfordii Hook. f, Rheum officinale Baill, and cinnabar mainly damage renal proximal tubules or cause interstitial nephritis. Transporters in renal proximal tubule are believed to be critical in the disposition of xenobiotics. In this review, we provide information on the alteration of renal transporters by nephrotoxic TCMs, which may be helpful for understanding the nephrotoxic mechanism of TCMs and reducing adverse effects. Studies have proven that when administering nephrotoxic TCMs, the expression or function of renal transporters is altered, especially organic anion transporter 1 and 3. The alteration of these transporters may enhance the accumulation of toxic drugs or the dysfunction of endogenous toxins and subsequently sensitize the kidney to injury.Transporters-related drug combination and clinical biomarkers supervision to avoid the risk of future toxicity are proposed.
基金supported by the the National Key Research and Development Program, Specialized Research on Modernization of TCM (Nos. 2018YFC1708006 and 2018YFC1708003)National Major New Drug Creation Special Project “National Drug New Varieties Research and Development and Its Key Innovative Technology Topics” (No. 2017ZX09301060-005)+3 种基金the National Natural Science Foundation of China (No. 81320108029)Tianshan Cedar Plan (No. 2018XS21)National “Major Scientific and Technological Special Project for Significant New Drugs Creation” Project (No. 2015ZX09501004-002-004)Specific Fund for Pub-lic Interest Research of Traditional Chinese Medicine, Ministry of Finance of China (No. 201507004-002)。
文摘Fructus Psoraleae,which is commonly consumed for the treatment of osteoporosis,bone fracture,and leucoderma,induces liver injury.This study investigated the pathogenesis of the ethanol extract of Fructus Psoraleae(EEFP)-induced liver injury in rats.EEFP(1.35,1.80,and 2.25 g·kg^–1)was administrated to Sprague Dawley(SD)rats for 30 d.We measured liver chemistries,histopathology,and quantitative isobaric tags for relative and absolute quantitation(iTRAQ)-based protein profiling.EEFP demonstrated parameters suggestive of liver injury with changes in bile secretion,bile flow rate,and liver histopathology.iTRAQ analysis showed that a total of 4042 proteins were expressed in liver tissues of EEFP-treated and untreated rats.Among these proteins,81 were upregulated and 32 were downregulated in the treatment group.KEGG pathway analysis showed that the drug metabolic pathways of cytochrome P450,glutathione metabolism,glycerolipid metabolism,and bile secretion were enriched with differentially expressed proteins.The expression of key proteins related to the farnesoid X receptor(FXR),i.e.,the peroxisome proliferators-activated receptor alpha(PPAR-α),were downregulated,and multidrug resistance-associated protein 3(MRP3)was upregulated in the EEFP-treated rats.Our results provide evidence that EEFP may induce hepatotoxicity through various pathways.Furthermore,our study demonstrates changes in protein regulation using iTRAQ quantitative proteomics analysis.