Gout Party is a Chinese medicine prescription composed of Aconiti Lateralis Radix Praeparaia, Aconiti Radix Cocta, Cremastrae Pseudobulbus Pleiones Pseudobulbus, Smilacis Glabrae Rhizoma, Rehmanniae Radix, and Glycyrrhizae Radix et Rhizoma, which can relieve joint pain caused by gouty arthritis (GA) and rheumatoid, and has a therapeutic effect on acute gouty arthritis (AGA). However, little information is available on the molecular biological basis and therapeutic mechanism of Gout Party for the treatment of AGA. AGA model was established by injecting sodium urate, and colchicine served as a positive control drug. We established a metabolomic method based on ultra-high-performance liquid chromatography–tandem quadrupole/time-of-flight mass spectrometry (UHPLC–Q–TOF/MS) to analyze the plasma samples of model group rats and blank group rats. Multiple statistical analyses, including principal component analysis (PCA) and partial least square discrimination analysis (PLS-DA), were used to examine metabolite profile changes in plasma samples. Finally, we identified 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, and so on; 22 endogenous metabolites associated with AGA. After successful molding, we found that 2–ketobutyric acid, 3–hexenedioic acid, but–2–enoic acid, argininic acid, galactonic acid, lactic acid, equol 4′–O–glucuronide, deoxycholic acid glycine conjugate, glycocholic acid, sphinganine 1–phosphate, LPE (0:0/20:3), LPE (0:0/16:0), LPC (15:0) decreased significantly (p < 0.05 or p < 0.01), alanine, erythrulose, 3–dehydrocarnitine, m–methylhippuric acid, 3–hydroxyoctanoic acid, p–cresol sulfate, estriol 3–sulfate 16–glucuronide, 10–hydroxy–9–(phosphonooxy)octadecenoate, docosahexaenoic acid increased significantly (p < 0.05 or p < 0.01). After Gout Party treatment, 14 biomarkers had a tendency to normal conditions. These above biomarkers were mainly involved in fatty acid metabolism, bile acid metabolism, amino acid metabolism, and energy metabolism pathways. These results suggested that Gout Party exerted therapeutic effects of treating AGA by improving energy metabolism disorder and amino acid metabolism dysfunction, and attenuating fatty acid metabolism abnormal and inflammation. The results of this experiment provided a reference for revealing the metabolic mechanism produced by Gout Party in the treatment of AGA, but the subsequent studies need to be further improved and supported by relevant cell experiments and clinical experiments.

Dynamin-related protein 1 (Drp1) is essential for mitochondrial dynamics in skeletal muscle, particularly in regulating fission, mitophagy, and maintaining mitochondrial function. Exercise is crucial for sustaining muscle function, promoting mitochondrial adaptations that enhance energy metabolism and oxidative capacity in skeletal muscle. In this Review, we discuss the role of Drp1 in exercise-induced mitochondrial adaptations and its potential implications for skeletal muscle health. We first address the evidence that Drp1 activity must be maintained within a narrow physiological range. Both Drp1 deficiency and overabundance provoke muscle atrophy and dysfunction, establishing a Goldilocks principle for mitochondrial fission. We then examine the multi-layered post-translational modification code that governs Drp1 activity, including canonical phosphorylation, redox-sensing modifications, and the receptor selectivity model that may specify distinct fission programs. A three-stage model of exercise-induced mitochondrial adaptation is presented, describing how Drp1 activity is temporally orchestrated from acute fragmentation through short-term remodeling to long-term network optimization, and how these morphological transitions govern substrate metabolism and determine exercise performance. The pathological consequences of Drp1 dysregulation are examined in metabolic disease, where Drp1 is chronically hyperactivated, and in aging, where Drp1 activity is deficient. Finally, we analyze the ROS-Drp1 signaling axis as the mechanistic basis for the bidirectional regulation of Drp1 by exercise. Moderate exercise-induced ROS production activates Nrf2 and AMPK signaling, which suppress excessive fission in metabolic disease while restoring insufficient fission in aging, thereby moving Drp1 activity toward the physiological Goldilocks zone in both contexts. This context-dependent, bidirectional regulation distinguishes exercise from pharmacological inhibitors and identifies the ROS-Drp1 axis as a therapeutic target for conditions at opposite ends of the Drp1 activity continuum, such as sarcopenia and type 2 diabetes.