α-Solanine, a glycoalkaloid (GA) extracted from the stems of the potato plant, exhibits bioactivity and medicinal potential that necessitate further investigation. The impact and underlying mechanisms of α-Solanine on osteoarthritis (OA) remain to be elucidated. To achieve enhanced therapeutic outcomes, we have designed and synthesized a UIO-66-NH 2 @α-Solanine@PEI charged particle (USP) that amplifies the therapeutic effects of α-Solanine, demonstrating superior efficacy. Our approach involved the synthesis of a novel drug delivery system, the USP, to augment the therapeutic potential of α-Solanine in the treatment of OA. An OA rat model was established, and USP treatment was administered. The therapeutic effects were verified through histochemical staining and micro-CT. In vitro, α-Solanine significantly suppressed the expression of proteins related to glycolysis and notably inhibited ferroptosis. RNA sequencing revealed hypoxia-inducible factor-1α (HIF-1α) as a potential pathway mediating the effects of α-Solanine, and it was found that the co-addition of cycloheximide (CHX) led to a shortened decay time of HIF-1α. In vivo, rats with OA demonstrated significant inhibition of glycolysis and ferroptosis following treatment with USP, along with improvements in OA characteristics. These findings suggest that α-Solanine can inhibit the intense glycolysis associated with OA via the HIF-1α pathway and alleviate ferroptosis in chondrocytes. Treatment with USP demonstrated superior efficacy in the management of OA, providing a new therapeutic strategy for the disease.
Pediatric bacterial pneumonia continues to pose a significant global health burden, often resulting in serious complications. Recent studies have emphasized the pivotal role of the gut-lung axis in the progression of respiratory diseases, wherein disruptions in gut microbiota can aggravate pulmonary inflammation. This research investigates the underlying mechanisms by which Ma-Xing-Shi-Gan Decoction (MXSG), a classical formula in traditional Chinese medicine, influences the gut-lung axis in the context of childhood bacterial pneumonia. Clinical data indicated pronounced alterations in intestinal microbial composition and a marked decline in short-chain fatty acid (SCFA) levels among affected pediatric patients—changes that coincided with dysfunctional gut-lung signaling. In a murine model of bacterial pneumonia, MXSG administration restored microbial diversity, elevated SCFA production, and attenuated inflammatory responses by suppressing the HDAC3/NF-κB signaling cascade. Key bioactive constituents of MXSG—namely, quercetin, osajin, nobiletin, and solasodine—were identified as critical regulators, modulating lipid metabolism and promoting SCFA biosynthesis. These results highlight the therapeutic promise of MXSG in reestablishing gut-lung homeostasis and shed light on its mechanistic potential in the treatment of pediatric bacterial pneumonia. Graphical This schematic illustrates how MXSG restores gut microbiota diversity and SCFA levels, suppresses HDAC3/NF-κB signaling, and alleviates lung inflammation in pediatric bacterial pneumonia. Integrated multi-omics and mouse model experiments reveal that MXSG modulates the gut-lung axis and provides a novel mechanism for its clinical efficacy.
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