Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis: How they modulate pain and inflammation

Matosinhos, Rafaela Cunha; Bezerra, Juliana Pantaleão; Barros, Camila Helena; Bernardes, Ana Catharina Fernandes Pereira Ferreira; Coelho, George Luiz Lins Machado; Araújo, Marcela Carolina de Paula Michel; Aguiar-Soares, Rodrigo Dian de Oliveira; Sachs, Daniela; Saúde-Guimarães, Dênia Antunes

doi:10.1016/j.jep.2021.114778

Cited by 7 publications

(5 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neochlorogenic acid has been studied for its potential effects on inflammation and is helpful in the treatment of rheumatoid arthritis ( Gao et al, 2020 ). Caffeic acid, another caffeoylquinic acid derivative, has been studied for its effects on pain and inflammation in a murine model of gouty arthritis ( Matosinhos et al, 2022 ). Recent studies have shown that berberine can inhibit the inflammatory response induced by monosodium urate (MSU) crystals and improve gouty arthritis symptoms ( Liu et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis

Wang,

Xu,

Tan

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Acute gouty arthritis (AGA) significantly impairs patients’ quality of life. Currently, existing therapeutic agents exhibit definite efficacy but also lead to serious adverse reactions. Therefore, it is essential to develop highly efficient therapeutic agents with minimal adverse reactions, especially within traditional Chinese medicine (TCM). Additionally, food polyphenols have shown potential in treating various inflammatory diseases. The Qingre-Huazhuo-Jiangsuan-Recipe (QHJR), a modification of Si-Miao-San (SMS), has emerged as a TCM remedy for AGA with no reported side effects. Recent research has also highlighted a strong genetic link to gout.Methods: The TCM System Pharmacology (TCMSP) database was used to collect the main chemical components of QHJR and AGA-related targets for predicting the metabolites in QHJR. HPLC-Q-Orbitrap-MS was employed to identify the ingredients of QHJR. The collected metabolites were then used to construct a Drugs-Targets Network in Cytoscape software, ranked based on their “Degree” of significance. Differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database using GEO2R online analysis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The DEGs were utilized to construct a Protein-Protein Interaction (PPI) Network via the STRING database. In vivo experimental validation was conducted using colchicine, QHJR, rapamycin (RAPA), and 3-methyladenine (3-MA) as controls to observe QHJR’s efficacy in AGA. Synovial tissues from rats were collected, and qRT-PCR and Western blot assays were employed to investigate Ampk-related factors (Ampk, mTOR, ULK1), autophagy-related factors (Atg5, Atg7, LC3, p62), and inflammatory-related factors (NLRP3). ELISA assays were performed to measure inflammatory-related factor levels (IL-6, IL-1β, TNF-α), and H&E staining was used to examine tissue histology.Results: Network analysis screened out a total of 94 metabolites in QHJR for AGA. HPLC-Q-Orbitrap-MS analysis identified 27 of these metabolites. Notably, five metabolites (Neochlorogenic acid, Caffeic acid, Berberine, Isoliquiritigenin, Formononetin) were not associated with any individual herbal component of QHJR in TCMSP database, while six metabolites (quercetin, luteolin, formononetin, naringenin, taxifolin, diosgenin) overlapped with the predicted results from the previous network analysis. Further network analysis highlighted key components, such as Caffeic acid, cis-resveratrol, Apigenin, and Isoliquiritigenin. Other studies have found that their treatment of AGA is achieved through reducing inflammation, consistent with this study, laying the foundation for the mechanism study of QHJR against AGA. PPI analysis identified TNF, IL-6, and IL-1β as hub genes. GO and KEGG analyses indicated that anti-inflammation was a key mechanism in AGA treatment. All methods demonstrated that inflammatory expression increased in the Model group but was reversed by QHJR. Additionally, autophagy-related expression increased following QHJR treatment. The study suggested that AMPKα and p-AMPKα1 proteins were insensitive to 3 MA and RAPA, implying that AMPK may not activate autophagy directly but through ULK1 and mTOR.Conclusion: In conclusion, this study confirms the effectiveness of QHJR, a modified formulation of SMS (a classic traditional Chinese medicine prescription for treating gout), against AGA. QHJR, as a TCM formula, offers advantages such as minimal safety concerns and potential long-term use. The study suggests that the mechanism by which QHJR treats AGA may involve the activation of the AMPK/mTOR/ULK1 pathway, thereby regulating autophagy levels, reducing inflammation, and alleviating AGA. These findings provide new therapeutic approaches and ideas for the clinical treatment of AGA.

show abstract

Section: Discussionmentioning

confidence: 99%

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis

Wang,

Xu,

Tan

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…1 Mass (Da) = calculated mass. 2 Charge: the total charge is the sum of positive (lysine, arginine, and histidine residues) and negative (glutamate and aspartate residues) charges present in each sequence. 3 Method: the primary sequence was obtained by transcriptomic (T) and/or proteomic (P) approach.…”

Section: Sequencing Database Search and Transcriptomic Analysis Of Co...mentioning

confidence: 99%

“…Coffee beans, frequently used to make beverages and food products, are the second-largest commodity worldwide and belong to the Rubiaceae family [ 1 ]. However, various parts of coffee plants have ethnomedicinal uses [ 2 , 3 ]. For example, seed decoction has been used to treat influenza and to increase milk production for nursing mothers, whereas leaf decoction has been used for treating anemia, edema, asthenia, and rage [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Ginsentide-like Coffeetides Isolated from Coffee Waste Are Cell-Penetrating and Metal-Binding Microproteins

Tam,

Huang,

Loo

et al. 2023

Molecules

View full text Add to dashboard Cite

Coffee processing generates a huge amount of waste that contains many natural products. Here, we report the discovery of a panel of novel cell-penetrating and metal ion-binding microproteins designated coffeetide cC1a–c and cL1–6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and a database search, we show that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif, but without a chitin-binding domain. NMR determination of cC1a reveals a compact structure that confers its resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis reveals that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement, like ginsentide precursors. Molecular modeling, together with experimental validation, revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have the potential to target intracellular proteins.

show abstract

“…Coffee beans, frequently used to make beverages and food products, are the secondlargest commodity worldwide and belong to the Rubiaceae family [1]. However, various parts of coffee plants have ethnomedicinal uses [2,3]. For example, seed decoction has been used to treat influenza and to increase milk production for nursing mothers, whereas leaf decoction has been used for treating anemia, edema, asthenia, and rage [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Ginsentide-Like Coffeetides Isolated from Coffee Waste Are Cell-Penetrating and Metal-Binding Microproteins

Tam,

Huang,

Loo

et al. 2023

Preprint

View full text Add to dashboard Cite

Coffee processing generates a huge amount of waste which contains many natural products. Here, we report the discovery of a panel novel cell-penetrating and metal-ion binding microproteins designated coffeetide cC1a-c and cL1-6 from the husk of two popular coffee plants, Coffea canephora and Coffea liberica, respectively. Combining sequence determination and database search, we showed that the prototypic coffeetide cC1a is a 37-residue, eight-cysteine microprotein with a hevein-like cysteine motif but without a chitin-binding domain. NMR determination of cC1a revealed a compact structure that confers it resistance to heat and proteolytic degradation. Disulfide mapping together with chemical synthesis revealed that cC1a has a ginsentide-like, and not a hevein-like, disulfide connectivity. In addition, transcriptomic analysis showed that the 98-residue micrcoproten-like coffeetide precursor contains a three-domain arrangement like ginsentide precursors. Molecular modeling together with experimental validation revealed a Mg2+ and Fe3+ binding pocket at the N-terminus formed by three glutamic acids. Importantly, cC1a is amphipathic with a continuous stretch of 19 apolar amino acids, and which enables its cell penetration to target intracellular proteins, despite being highly negatively charged. Our findings suggest that coffee by-products could provide a source of ginsentide-like bioactive peptides that have potential to target intracellular proteins.

show abstract

Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis: How they modulate pain and inflammation

Cited by 7 publications

References 30 publications

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis

Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis

Ginsentide-like Coffeetides Isolated from Coffee Waste Are Cell-Penetrating and Metal-Binding Microproteins

Ginsentide-Like Coffeetides Isolated from Coffee Waste Are Cell-Penetrating and Metal-Binding Microproteins

Contact Info

Product

Resources

About