Cadmium (Cd) is a type of high-risk heavy metal that can damage organs such as the liver, but its mechanism is not yet clear. Ferroptosis is a newly discovered mode of regulatory cell death. We explored whether ferroptosis is involved in Cd-induced liver damage and the underlying mechanism. Our research showed that Cd induced liver damage by inducing ferroptosis, and the use of ferroptosis inhibitors reduced the degree of liver damage. Moreover, the occurrence of ferroptosis was accompanied by the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway, and inhibiting endoplasmic reticulum (ER) stress reduced ferroptosis demonstrating that ferroptosis induced by Cd is dependent on ER stress. In addition, chloroquine, a common autophagy inhibitor, mitigated ferroptosis caused by Cd exposure. Then, the iron chelator deferoxamine reduced Cd-induced lipid peroxidation and cell death, demonstrating that the iron regulation disorder caused by ferritin phagocytosis contributes to the Cd-induced ferroptosis. In conclusion, our results show that Cd-induced liver toxicity is accompanied by ferroptosis, which contributes to Cd inducing oxidative stress to trigger autophagy and ER stress to promote the process of ferroptosis.

Endoplasmic reticulum (ER) stress is a basic cellular stress response that maintains cellular protein homeostasis under endogenous or exogenous stimuli, which depends on the stimulus, its intensity, and action time. The ER produces a corresponding cascade reaction for crosstalk of adaptive and/or pro-death regulation with other organelles. Hepatocellular carcinoma(HCC) is one of the most common malignant solid tumors with an extremely poor prognosis. Viral hepatitis infection, cirrhosis, and steatohepatitis are closely related to the occurrence and development of HCC, and ER stress has gradually been shown to be a major mechanism. Moreover, an increasing need for protein and lipid products and relative deficiencies of oxygen and nutrients for rapid proliferation and endoplasmic reticulum stress are undoubtedly involved. Therefore, to fully and comprehensively understand the regulatory role of endoplasmic reticulum stress in the occurrence and progression of HCC is of vital importance to explore its pathogenesis and develop novel anti-cancer strategies. We searched for relevant publications in the PubMed databases using the keywords "Endoplasmic reticulum stress", "hepatocellular carcinoma" in last five years,and present an overview of the current knowledge that links ER stress and HCC, which includes carcinogenesis, progression, and anti-cancer strategies, and propose directions of future research. ER stress were confirmed to be multiple regulators or effectors of cancer, which also be confirmed to drive tumorigenesis and progression of HCC. Targeting ER stress signaling pathway and related molecules could play a critical role for anti-HCC and has become a research hotspot for anti-cancer in recent years. ER stress are critical for the processes of the tumorigenesis and progression of tumors. For HCC, ER stress was associated with tumorigenesis, development, metastasis, angiogenesis and drug resistance, targeting ER stress has emerged as a potential anti-tumor strategy.

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Background: Exercise-induced fatigue involves a task-dependent reduction in the capacity to sustain physical performance, an increase in perceived fatigue during or after exercise, or both. Dietary plant saponins are amphiphilic glycosides widely distributed in edible plants and botanical preparations, but evidence regarding their effects on exercise-related fatigue remains heterogeneous across food chemistry, exercise physiology, and pharmacological research. Scope and approach: This narrative review critically evaluates dietary plant saponins using a composition–exposure–outcome framework. The framework links botanical source and processing history with structural and chemical definition, gastrointestinal transformation and systemic exposure, and clearly defined exercise-related outcomes. Human, animal, and mechanistic evidence are considered separately according to exercise-related outcome domain, and principal human trials are qualitatively appraised for randomization/blinding, sample size/attrition, outcome selection, and potential bias, with emphasis on distinguishing preparation-level effects from evidence attributable to individual saponins. Key findings and conclusions: Preclinical studies of saponin-rich preparations have reported improvements in exercise duration, glycogen-related indices, lactate-related measures, and changes in mitochondrial, inflammatory, or redox-associated markers. Human evidence remains limited and includes both preparation-level findings and emerging compound-specific evidence from purified ginsenoside Rg1; however, the available Rg1 trials are small, predominantly acute, and require independent replication. Preparation-level evidence is available for Panax ginseng, Gynostemma pentaphyllum, and Panax notoginseng, whereas controlled Tribulus terrestris trials have not demonstrated consistent ergogenic effects. Current evidence does not support a simple structure–activity relationship based solely on total-saponin content, sugar-chain number, aglycone class, or stereochemistry. Instead, processing-dependent composition, gastrointestinal deglycosylation, microbial transformation, and systemic exposure must be considered together when interpreting biological responses. The major unresolved question is therefore not whether saponins influence fatigue-related pathways, but whether chemically defined preparations achieve biologically relevant exposure levels that reproducibly improve prespecified exercise outcomes. Future studies should integrate compositional standardization, parent and metabolite exposure assessment, physiologically meaningful exercise endpoints, and food-format feasibility.