Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL‐1β, IL‐6 and TNF‐α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM‐induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM‐induced OA model. Induction of IκB degradation by IL‐1β was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor‐κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Although safflower seed extract exhibits pharmacological activity against various diseases, the effects of its individual compounds on osteoarthritis (OA) have not been elucidated. Here, we evaluated the effects of these extracts and their single compounds on OA. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, main components of safflower seed extract, were isolated by high-performance liquid chromatography. Under in vitro OA mimic conditions, the expression of the matrix metalloproteinases (MMPs) MMP3/13 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) ADAMTS5 were reduced in mouse chondrocytes treated with safflower seed extract. Furthermore, the oral administration of safflower seed extract attenuated cartilage destruction in a mouse OA model induced by destabilization of the medial meniscus. N-(p-Coumaroyl) serotonin and N-feruloyl serotonin, but not serotonin, reduced MMP3, MMP13, and ADAMTS5 expression in IL-1β-treated chondrocytes. Additionally, they significantly blocked the nuclear factor-κB (NF-κB) pathway by inhibiting IκB degradation and p65 phosphorylation. Our results suggest that safflower seed extract and its single compounds can attenuate cartilage destruction by suppressing MMP and ADMATS5 expression. The anti-arthritic effects are mediated by NF-κB signaling and involve the inhibition of IκB degradation and p65 phosphorylation. These results indicate that safflower seed extract may serve as a novel therapeutic agent against OA.

The natural polyphenolic compound known as Rosmarinic acid (RosA) can be found in various plants. Although its potential health benefits have been extensively studied, its effect on osteoarthritis (OA) progression and cartilage regeneration function still needs to be fully elucidated in OA animal models. This study elucidated the effect of RosA on OA progression and cartilage regeneration. In vitro assessments were conducted using RT-PCR, qRT-PCR, Western blotting, and ELISA to measure the effects of RosA. The molecular mechanisms of RosA were determined by analyzing the translocation of p65 into the nucleus using immunocytochemistry (ICC). Histological analysis of cartilage explant was performed using alcian blue staining and immunohistochemistry (IHC). For in vivo analysis, the destabilization of the medial meniscus (DMM)-induced OA mouse model was utilized to evaluate cartilage destruction through Safranin-O staining. The expression of catabolic and anabolic factors in mice knee joints was quantified by immunohistochemistry. The expression of catabolic factors in chondrocytes was significantly impeded by RosA. It also suppressed the NF-κB signaling pathway by decreasing phosphorylation of p65 and reducing degradation of IκB protein. In ex vivo experiments, RosA protected sulfated proteoglycan erosion triggered by IL-1β and suppressed the catabolic factors in cartilage explant. RosA treatment in animal models resulted in preventing cartilage destruction and reducing catabolic factors in the cartilage. RosA was also found to promote the expression of Sox9, Col2a1, and Acan in vitro, ex vivo, and in vivo analyses. RosA attenuated the OA progression by suppressing the catabolic factors expression. These effects were facilitated through the suppression of the NF-κB signaling pathway. Additionally, it promotes cartilage regeneration by inducing anabolic factors. Therefore, RosA shows potential as an effective therapeutic agent for treating OA.

Cholangiocarcinoma (CCA) is a devastating malignancy characterized by aggressive tumor growth and limited treatment options. Dysregulation of the Hippo signaling pathway and its downstream effector, Yes-associated protein (YAP), has been implicated in CCA development and progression. In this study, we investigated the effects of Isoalantolactone (IALT) on CCA cells to elucidate its effect on YAP activity and its potential clinical significance. Our findings demonstrate that IALT exerts cytotoxic effects, induces apoptosis, and modulates YAP signaling in SNU478 cells. We further confirmed the involvement of the canonical Hippo pathway by generating LATS1/LATS2 knockout cells, highlighting the dependence of IALT-mediated apoptosis and YAP phosphorylation on the Hippo-LATS signaling axis. In addition, IALT suppressed cell growth and migration, partially dependent on YAP-TEAD activity. These results provide insights into the therapeutic potential of targeting YAP in CCA and provide a rationale for developing of YAP-targeted therapies for this challenging malignancy.