How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS

Ye, Xietao; Wu, Jinlin; Zhang, Dayong; Lan, Zelun; Yang, Songhong; Zhu, Jing; Yang, Ming; Gong, Qingjie; Zhong, Lei

doi:10.3389/fphar.2021.618844

Cited by 14 publications

(9 citation statements)

References 63 publications

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“…The polyphenols of cultivated P. igniarius (CPP) were prepared in the same way as above. Furthermore, to elucidate the main active components in WPP and CPP better, UPLC-ESI-qTOF-MS, which is characterized by fast separation, high sensitivity, and accurate relative molecular mass calculation ( Ye et al, 2021 ), was used for identification. Surprisingly, similar active ingredients, such as protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A, were identified in both WPP and CPP by UPLC-ESI-qTOF-MS. As members of the polyphenol family, the antioxidant and anti-inflammatory activities of protocatechuic aldehyde ( Chang et al, 2011 ), hispidin ( Jin et al, 2021 ), davallialactone ( Lee et al, 2008 ; Lee et al, 2011 ), phelligridimer A ( Wang et al, 2005b ), hypholomine B ( Shou et al, 2016 ) and inoscavin A ( Lee et al, 2006 ; Shou et al, 2016 ) have been widely reported.…”

Section: Discussionmentioning

confidence: 99%

Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Zhang

et al. 2022

Front. Pharmacol.

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Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.

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Section: Discussionmentioning

confidence: 99%

Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Zhang

et al. 2022

Front. Pharmacol.

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“…Bioinformatics tools that are constantly updated provide new insights for drug development through high-throughput screening, targets prediction, and pathways enrichment. Traditional Chinese herbs have shown to be effective in treating joint disorders such as OA, RA [ 24 ], and gouty arthritis [ 25 ]; however, the key ingredients responsible for their therapeutic effects and underlying mechanisms by which their effects are manifested are still unknown. According to our bioinformatics results, Ginkgo biloba may exert anti-arthritic effects by inhibiting inflammatory cytokines such as IL-6 and modulating oxidative stress proteins such as hypoxia-inducible factor 1 subunit alpha (HIF-1α) and nuclear factor erythroid 2-related factor 2 (NFE2L2, NRF2).…”

Section: Discussionmentioning

confidence: 99%

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Zhao

Liu

et al. 2022

Arthritis Res Ther

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Background Uncoupled extracellular matrix (ECM) causes cartilage degeneration and osteoarthritis (OA) by suppressing the synthesis and activating the degradation of ECM components. Gingko biloba is a natural Chinese herb with a variety of biological functions; however, the extent to which it can protect against OA and the mechanisms involved are unknown. Methods In our study, using bioinformatics tools, we were able to identify an important lactone, bilobalide (BB), from Gingko biloba. In vitro experiments were performed to evaluate the potential therapeutic effects of BB on ECM homeostasis. In vivo experiments were conducted to assess the protection of systemic administration of BB on cartilage degeneration. Molecular mechanisms underlying BB-regulated anti-arthritic role were further explored. Results In interleukin-1β-incubated human chondrocytes, in vitro treatment with BB increased the expression of cartilage anabolic proteins, while inhibiting the activities of ECM degrading enzymes. In a mice model, systemic administration of BB, in vivo, prevented post-traumatic cartilage erosion and attenuated the formation of abnormal osteophytes in the subchondral bone. Mechanistically, the activation of the adenosine 5′-monophosphate-activated protein kinase (AMPK)-sirtuin 1 (SIRT1) signaling pathway was involved in the anti-arthritic effects of BB. In vitro, blocking BB’s chondroprotection with the AMPK-specific inhibitor Compound C abrogated it. Conclusions These results demonstrated that BB extracted from Gingko biloba regulates ECM balance to prevent OA by activating the AMPK-SIRT1 signaling pathway. This study proposed the monomer BB, a traditional Chinese medicine, as a de novo therapeutic insight for OA. Graphical Abstract Schematic representation of the experimental design. Based on the bioinformatic analysis, bilobalide (BB), a natural herb Gingko biloba-derived ingredient, was identified as a candidate for treating osteoarthritis. In vitro, BB treatment not only facilitates cartilage extracellular matrix synthesis but also inhibits proteolytic enzyme activities. In vivo intraperitoneal injection of BB improves cartilage degeneration and subchondral bone sclerosis. BB, in particular, had anti-arthritic effects by activating the AMPK-SIRT1 signaling pathway.

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“…Moreover, the remaining 6 active compounds were also relatively easy to bind to the IL-1β receptor, and all had good affinities. Many studies showed that inhibition of PTGS2 (i.e., COX-2), NOS2, MAPK14, MMP9, MMP2, and activation of PPARG could improve inflammation in GA models, suggesting that these targets had potential importance in the pathogenesis of GA [45][46][47][48][49][50][51].…”

Section: Discussionmentioning

confidence: 99%

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments

Zeng

Lin

Kang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Background. This study aimed to investigate the molecular mechanism of Tongfengding capsule (TFDC) in treating immune-inflammatory diseases of gouty arthritis (GA) and interleukin-1-beta (IL-1β) inhibitors by using network pharmacology, molecular docking, and cell experiments. Methods. In this study, the compounds of TFDC and the potential inflammatory targets of GA were obtained from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Online Mendelian Inheritance in Man (OMIM), and GeneCards databases. The TFDC-GA-potential targets interaction network was accomplished by the STRING database. The TFDC-active compound-potential target-GA network was constructed using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to further explore the GA mechanism and therapeutic effects of TFDC. Quantitative real-time PCR (qPCR) was used to verify whether the TFDC inhibited IL-1β in GA. Molecular docking technology was used to analyze the optimal effective compounds from the TFDC for docking with IL-1β. Result. 133 active compounds and 242 targets were screened from the TFDC, and 25 of the targets intersected with GA inflammatory targets, which were considered as potential therapeutic targets. Network pharmacological analysis showed that the TFDC active compounds such as quercetin, stigmasterol, betavulgarin, rutaecarpine, naringenin, dihydrochelerythrine, and dihydrosanguinarine had better correlation with GA inflammatory targets such as PTGS2, PTGS1, NOS2, SLC6A3, HTR3A, PPARG, MAPK14, RELA, MMP9, and MMP2. The immune-inflammatory signaling pathways of the active compounds for treating GA are IL-17 signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, HIF-1 signaling pathway, etc. The TFDC reduced IL-1β mRNA expression in GA by qPCR. Molecular docking results suggested that rutaecarpine was the most appropriate natural IL-1β inhibitor. Conclusion. Our findings provide an essential role and bases for further immune-inflammatory studies on the molecular mechanisms of TFDC and IL-1β inhibitors development in GA.

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How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS

Cited by 14 publications

References 63 publications

Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

Gingko biloba-inspired lactone prevents osteoarthritis by activating the AMPK-SIRT1 signaling pathway

Identification of Interleukin-1-Beta Inhibitors in Gouty Arthritis Using an Integrated Approach Based on Network Pharmacology, Molecular Docking, and Cell Experiments

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