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Non‐alcoholic fatty liver disease (NAFLD) is a major health problem. However, no effective treatments are currently available. Thus, there is a critical need to develop novel drugs that can prevent and treat NAFLD with few side effects. In this study, Tussilagone (TUS), a natural sesquiterpene isolated from Tussilago farfara L, was explored in vitro and in vivo for its potential to treat NAFLD. Our results showed that in vitro TUS reduced oleic acid palmitate acid‐induced triglyceride and cholesterol synthesis in HepG2cells, reduced intracellular lipid droplet accumulation, improved glucose metabolism disorders and increased energy metabolism and reduced oxidative stress levels. In vivo, TUS significantly reduced fat accumulation and improved liver injury in high‐fat diet (HFD)‐induced mice. TUS treatment significantly increased liver mitochondrial counts and antioxidant levels compared to the HFD group of mice. In addition, TUS was found to reduce the expression of genes involved in lipid synthesis sterol regulatory element binding protein‐1 (SREBP1), fatty acid synthase (FASN), and stearoy‐CoA desaturase 1 (SCD1) in vitro and in vivo. Our results suggest that TUS may be helpful in the treatment of NAFLD, suggesting that TUS is a promising compound for the treatment of NAFLD. Our findings provided novel insights into the application of TUS in regulating lipid metabolism. [ABSTRACT FROM AUTHOR]

Acute pancreatitis (AP) is a clinical emergency characterized by elevated levels of inflammation and oxidative stress, urging the need for the development of new and more efficacious treatments. Tussilagone (TSL), a compound from Tussilago farfara flower buds, is known to exhibit diverse properties, including anti-inflammatory activity, but its precise role in AP remains unclear. In this study, we investigated TSL’s impact on the progression of AP. To establish AP animal models, mice were intraperitoneally administered hyranolin. Our findings demonstrate that TSL effectively suppresses the progression of AP in these mice and decreases inflammation in their pancreatic tissues, as evidenced by reduced secretion of inflammatory cytokines such as interleukin (IL)- 1β, Tumor necrosis factor (TNF)-α and IL-6 (p < 0.05). Notably, TSL also mitigates neutrophil infiltration into the pancreatic tissues of AP-afflicted mice and alleviates oxidative stress in AP mice, as confirmed by the measurements of Superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) (p < 0.05). Remarkably, TSL exerts its inhibitory effects on inflammation and oxidative stress by blocking the nuclear factor (NF)-κB pathway and activating the NF-E2-related factor 2 (Nrf2) pathway. In conclusion, TSL can mitigate inflammation and oxidative stress, offering potential as a promising therapeutic agent for AP. [ABSTRACT FROM AUTHOR]

Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long‐term inhalation of particulate matter with a diameter < 2.5 μm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif‐1α by reducing its degradation mediated by PHD2 binding, which furtherly activated NF‐κB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif‐1α/PHD2 complex and restored the Hif‐1α protein level increased by PM2.5. When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved. Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif‐1α level and NF‐κB activation. Our findings provide a new therapeutic strategy for air pollution‐related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity. [ABSTRACT FROM AUTHOR]

A solid‐phase extraction cartridge was fabricated using diallyl isophthalate as the monomer with the addition of porous organic cage material via in situ free‐radical polymerization in a stainless‐steel column. The resulting monolithic adsorbent exhibited a relatively uniform porous structure, a high specific surface area of 113.98 m2/g, and multiple functional chemical groups according to the characterization results. An online solid‐phase extraction–high‐performance liquid chromatography procedure was fabricated to extract and determine tussilagone from Farfarae Flos. The results show that the complex sample matrices can be removed in the solid‐phase extraction procedure. Simultaneously, tussilagone can remain, which can be subsequently switched to an octadecylsilane bonded analytical column. The methodological validation showed that the correlation coefficient was 0.9999 with a linear range of 0.6–200.0 µg/mL, the limit of detection was 0.2 µg/mL, the limit of quantification was 0.6 µg/mL, accuracy was 100.3–100.6%, and relative standard deviation of precision was ≤1.9%. The present monolithic cartridge exhibits good reusability of not more than 100 times. The real sample of Farfarae Flos was determined with a tussilagone content of 0.74 mg/g. [ABSTRACT FROM AUTHOR]

[Display omitted] Reactive Oxygen Species (ROS) play an essential role in the pathogenesis of osteoporosis mainly characterized by excessive osteoclasts (OCs) activity. OCs are rich in mitochondria for energy support, which is a major source of total ROS. Tussilagone (TSG), a natural Sesquiterpenes from the flower of Tussilago farfara , has plentiful beneficial pharmacological characteristics with anti-inflammatory and anti-oxidative activity, but its effects and mechanism in osteopathology are still unclear. In our study, we investigated the regulation of ROS generated from the mitochondria in OCs. We found that TSG inhibited OCs differentiation and bone resorption without any cytotoxicity. Mechanistically, TSG reduced RANKL-mediated total ROS level by down-regulating intracellular ROS production and mitochondrial function, leading to the suppression of NFATc1 transcription. We also found that nuclear factor erythroid 2-related factor 2 (Nrf2) could enhance ROS scavenging enzymes in response to RANKL-induced oxidative stress. Furthermore, TSG up-regulated the expression of Nrf2 by inhibiting its proteosomal degradation. Interestingly, Nrf2 deficiency reversed the suppressive effect of TSG on mitochondrial activity and ROS signaling in OCs. Consistent with this finding, TSG attenuated post-ovariectomy (OVX)- and lipopolysaccharide (LPS) induced bone loss by ameliorating osteoclastogenesis. Taken together, TSG has an anti-bone resorptive effect by modulating mitochondrial function and ROS production involved Nrf2 activation. [ABSTRACT FROM AUTHOR]

TUS attenuates HFD-induced atherosclerosis via inhibiting MAPKs-mediated inflammatory response in macrophages. (By Figdraw, ID: YWWRAf33ce) [Display omitted] • Tussilagone significantly alleviates atherosclerosis via inhibiting MAPKs-mediated inflammation. • MAPK inhibition prevents the innately pharmacological effects of Tussilagone. • Tussilagone may be a potentially therapeutic candidate for atherosclerosis. Atherosclerosis is a common chronic inflammatory disease. Recent studies have highlighted the key role of macrophages and inflammation in process of atherosclerotic lesion formation. A natural product, tussilagone (TUS), has previously exhibited anti-inflammatory activities in other diseases. In this study, we explored the potential effects and mechanisms of TUS on the inflammatory atherosclerosis. Atherosclerosis was induced in ApoE-/- mice by feeding them with a high-fat diet (HFD) for 8 weeks, followed by administration of TUS (10, 20 mg ·kg−1·d−1, i.g.) for 8 weeks. We demonstrated that TUS alleviated inflammatory response and reduced atherosclerotic plaque areas in HFD-fed ApoE-/- mice. Pro-inflammatory factor and adhesion factors were inhibited by TUS treatment. In vitro , TUS suppressed foam cell formation and oxLDL-induced inflammatory response in MPMs. RNA-sequencing analysis indicated that MAPK pathway was related to the anti-inflammation and anti-atherosclerosis effects of TUS. We further confirmed that TUS inhibited MAPKs phosphorylation in plaque lesion of aortas and cultured macrophages. MAPK inhibition blocked oxLDL-induced inflammatory response and prevented the innately pharmacological effects of TUS. Our findings present a mechanistic explanation for the pharmacological effect of TUS against atherosclerosis and indicate TUS as a potentially therapeutic candidate for atherosclerosis. [ABSTRACT FROM AUTHOR]