Canadian goldenrod (Solidago canadensis) and Inflammation (general): evidence and sources

Neuroinflammation is a key pathogenic factor in neurodegenerative diseases, while the anti-neuroinflammatory effects of Solidago canadensis L. have not been reported to date. This study aimed to identify the anti-neuroinflammatory active components of S. canadensis and elucidate their regulatory effects on neuroinflammation-related protein expression. A total of 20 compounds, including 17 clerodane diterpenoids (1-7 and 10-19) and 3 acetophenone derivatives (8, 9, and 20) were isolated from S. canadensis. Seven clerodane diterpenoids (1-7) and two acetophenone compounds (8 and 9) are previously unreported, and their structures were were elucidated via a comprehensive approach integrating spectroscopic data analysis, empirical stereochemical rules, DP4+ probability analysis using GFN2NMR, and ECD calculations. Compounds 1-5 are novel 1,2-seco-(3 → 1)-abeo-clerodane diterpenoids, which expand the chemical diversities of the genus Solidago. The anti-neuroinflammatory activity of all isolated compounds was evaluated in LPS-stimulated BV2 microglial cells. The results revealed that compounds 3, 10, 11, 12, 17, and 18 exhibited potent activity, yielding ICvalues of 14.54, 12.35, 14.32, 16.42, 13.86, and 15.64 μM, respectively. Western Blot analysis demonstrated that these compounds decreased NLRP3 and IL-1β protein expressions to display anti-neuroprotective effects. These results support the potential of clerodane diterpenoids from S. canadensis as anti-neuroinflammatory agents for treating neurodegenerative diseases.

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.

Representatives of Solidago species have been used in European phytotheraphy for centuries as a component of urological and antiphlogistical remedies. Solidago canadensis L. (Asteraceae) contains a wide range of active ingredients, such as flavonoids, saponins, hydroxycinnamates and mineral elements, which are responsible for its characteristic anti-inflammatory, spasmolytic and diuretic properties. Quality control of collected Solidaginis herba were performed according to the instructions of the X. German Pharmacopoea, while different LC-MS technologies were applied to evaluate the exact phenoloid composition. Three flavonol aglycons (quercetin, kaempferol and isorhamnetin) connected to several sugar components (glucose, rhamnose, galactose and rutinose), caffeoylquinic acid and a caffeoyl-shikimic acid glycoside were identified in the samples. Quercetin-3-O-beta-glucoside (isoquercitrin), quercetin-3-O-beta-galactoside (hyperoside), quercetin-3-O-beta-rhamnoside (quercitrin), quercetin-3-O-beta-rutinoside (rutin), kaempferol-3-O-beta-rhamnoside (afzelin), kaempferol-3-O-beta-rutinoside (nicotiflorin), caffeoil-quinic acid (chlorogenic acid) were identified in sample "A", while the presence of quercetin, quercetin-3-O-beta-glucoside (isoquercitrin), quercetin-3-/6"-O-acetyl-/-beta-glucopiranoside, quercetin-3-O-beta-rutinoside (rutin), kaempferol, kaempferol-3-O-beta-glucoside (astragalin), kaempferol-3-/6"-O-acetyl-/-beta-glucopiranoside, isorhamnetin, isorhamnetin-3-/6"-O-acetyl-/-beta-glucopiranoside, isorhamnetin-3-O-beta-rutinoside (narcissin), caffeoil-quinic acid (chlorogenic acid), caffeoil-shikimic acid-glucoside (dattelic acid-glucoside) were confirmed in sample "B". According to the occurrence of acetyl-glycosides and the diversity of sugar component of flavonoid glycosides Solidaginis herba samples chemotaxonomically were classified into different varieties. Incidence of acetyl-glycosidic flavonoids and absence of flavonoid galactosides and rhamnosides in the sample "B" together give support for the taxonomic recognition of varietases Solidago canadensis L. var. canadensis and var. scabra. Sample "A" was identified as Solidago canadensis L. var. canadensis, while sample "B" has proved to be belong to variety Solidago canadensis L. var. scabra. Due to the same flavonoid aglycons and the large amounts of flavonol glycosides occurring in each drug, phytochemical characteristics of investigated samples proved to be very similar.