Canadian goldenrod (Solidago canadensis) and Arthritis / joint pain: evidence and sources

Inflammation is a major risk factor for a variety of human diseases, such as sepsis, Inflammatory Bowel Disease (IBD) and also major cardiovascular disease including atherosclerosis. Solidago canadensis is used as a traditional medicine to treat inflammation-related diseases. However, the component with anti-inflammatory activity of Solidago canadensis is not clear. In this study, we aimed to search for new bioactive steroids from Solidago canadensis and investigate their anti-inflammatory activity both in vitro and in vivo. Lipopolysaccharides (LPS)-stimulated RAW264.7 cells, mouse bone marrow-derived macrophages (BMDMs) and peripheral blood mononuclear cells (PBMCs) were used to induce an inflammation response. Compound 10 outperformed other compounds for superior anti-inflammatory activity and significant inhibition of NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation. Mechanistically, compound 10 induced mitophagy by activating AMP-activated protein kinas (AMPK) to suppress NLRP3 inflammasome activation. Inhibiting AMPK by inhibitor BML-275 significantly attenuated compound 10 induced mitophagy and subsequent the NLRP3 inflammasome. Besides, the NF-κB activation, key step in NLRP3 inflammasome priming, was also suppressed by compound 10 via activation of AMPK. In addition, the in vivo experiments showed that compound 10 could alleviate LPS-induced inflammatory and dextran sulfate sodium salt -induced colitis in C57BL/6 mice. Collectively, the present study, for the first time, shows that the steroids compound 10 exhibited anti-inflammatory effect via AMPK/mitophagy/NLRP3 as well as AMPK/NF-κB/NLRP3 signaling pathway, which strongly suggests the therapeutic potential of compound 10 in various inflammatory diseases.

: The Canadian goldenrod (L.) is one of the most widespread species of the genusfrom the Asteraceae family. It has a rich composition of biologically active compounds and is traditionally used to address kidney, urinary tract, and liver diseases. Previously, it was proven that theextract obtained with a 40% ethanol solution had the most promising anti-inflammatory and hepatoprotective activity. Therefore, this extract was selected for the further formulation of amino acid preparations and 3D-printed dosage forms. The aims of the present study were to investigate the chemical composition, toxicity, and antimicrobial, anti-inflammatory, and hepatoprotective activity ofdry extract, its amino acid preparations, and 3D-printed dosage forms.: A total of 18 phenolic compounds and 14 amino acids were determined in the extracts. Theherb extracts were verified to be practically non-toxic preparations (toxicity class V, LD₅₀ > 5000 mg/kg). They also showed moderate antimicrobial activity against,and β-hemolytic. The most pronounced hepatoprotective activity was observed withherb extract and its amino acid preparations with phenylalanine, alanine, and lysine at a dose of 25 mg/kg body weight. The most pronounced anti-inflammatory activity was found withherb extract and its preparation with arginine. According to the calculated docking score array and the analysis of binding modes in the active sites of COX-1 and COX-2, the flavonoid fraction and caffeic acid in theextracts presented moderate inhibitory activity.: The development of innovative 3D-printed oral dosage forms represents a promising strategy to formulate dietary supplements or pharmaceutical preparations for these herbal extracts.