Objective To investigate the ameliorative effects of the traditional Chinese medicine formula Fuling Yin on heart failure and its potential mechanisms at the mitochondrial level. Methods Ninety SD rats were randomly divided into a blank control group (n=15) and a modeling group (n=75) using a random number table method. A chronic heart failure model was established in the modeling group by intraperitoneal injection of doxorubicin hydrochloride. One rat from the blank control group and five rats from the modeling group were randomly selected to verify the success of modeling. After confirming that the model was successfully established, the rest successfully modeled rats were randomly divided into the model group, positive drug (trimetazidine) group, and Fuling Yin low-, medium-, and high-dose groups (n=14 per group). Treatment groups were administered the respective drugs via gavage daily, while the blank control group and model group received an equal volume of pure water for 4 consecutive weeks. Cardiac function was assessed by echocardiography. Heart weight index (HWI) was calculated. Serum brain natriuretic peptide (BNP) levels and myocardial adenosine triphosphate (ATP) content were detected by enzyme-linked immunosorbent assay. Histopathological changes were observed via hematoxylin-eosin staining. Mitochondrial ultrastructure was examined using transmission electron microscopy. Mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening were detected by JC-1 fluorescence probe and colorimetric assay, respectively. The expression of apoptosis-related proteins, peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and key proteins of the mitogen-activated protein kinase (MAPK) signaling pathway were determined by Western Blot. Results Compared with the blank control group, the HWI and serum BNP levels in the model group were increased (P<0.01). Compared with the model group, the HWI and serum BNP levels in Fuling Yin groups were decreased (P<0.01). Pathological and ultrastructural observations showed disordered myocardial fiber arrangement, mitochondrial swelling, and cristae rupture in the model group; whereas in the Fuling Yin groups, myocardial pathological injury was alleviated, mitochondrial swelling was reduced, and membrane structure tended to be intact. Regarding mechanism indicators, compared with the model group, the myocardial ATP content increased, the red fluorescence intensity of MMP enhanced, and the mPTP opening degree decreased in the Fuling Yin groups (P<0.01). Additionally, the Bax/Bcl-2 ratio decreased, and caspase-3 protein expression was downregulated (P<0.01). Furthermore, PGC-1α protein expression was upregulated, while the expression of MAPK proteins was downregulated (P<0.01). Conclusions Fuling Yin can alleviate myocardial injury and delay ventricular remodeling in doxorubicin-induced heart failure rats. Its mechanism may be related to regulating the PGC-1α/MAPK signaling pathway to maintain mitochondrial homeostasis, thereby inhibiting mitochondria-mediated cardiomyocyte apoptosis.
ObjectiveTo summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects. Methods The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA. Results Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA. Conclusion The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.