Hepatic encephalopathy (HE) is a neuropsychiatric syndrome derived from metabolic disorders due to various liver failures. Clinically, HE is characterized by hyperammonemia, EEG abnormalities, and different degrees of disturbance in sensory, motor, and cognitive functions. The molecular mechanism of HE has not been fully elucidated, although it is generally accepted that HE occurs under the influence of miscellaneous factors, especially the synergistic effect of toxin accumulation and severe metabolism disturbance. This review summarizes the recently discovered cellular mechanisms involved in the pathogenesis of HE. Among the existing hypotheses, ammonia poisoning and the subsequent oxidative/nitrosative stress remain the mainstream theories, and reducing blood ammonia is thus the main strategy for the treatment of HE. Other pathological mechanisms mainly include manganese toxicity, autophagy inhibition, mitochondrial damage, inflammation, and senescence, proposing new avenues for future therapeutic interventions.

Obesity is associated with a significantly increased risk of cardiovascular and metabolic diseases such as diabetes mellitus. Recently, a growing body of evidence shows that phytochemicals, especially many flavonoids, place an inhibitory regulatory effect on adipogenesis, obesity and diabetes. With computer-aided drug discovery, the action modes of more and more bioactive flavonoids are being identified and confirmed at the molecular level. Citrus fruit peels are particularly rich in bioactive flavonoids which have demonstrated strong therapeutic potentials in regulating lipid metabolisms. However, they are usually thrown away after consuming the flesh, sometimes even causing environmental problems. Thus, extraction of useful flavonoids from citrus fruit waste for pharmaceutical industry could be a profitable and environmentally friendly solution in the future, advocating the concepts of circular economy and sustainable society. The aim of this review is to summarize current evidence on the antiobesity and antidiabetic potentials of identified bioactive flavonoids extracted from the peels of citrus fruits. Our results suggest that various citrus fruit peels could be potential sources for novel drugs and nutraceuticals. Combining experimental data and artificial intelligence methods to study citrus flavonoids would facilitate the discovery of novel drugs against obesity and obesity-related metabolic diseases.

Cerebral vasospasm (CVS) following a subarachnoid hemorrhage (SAH) is a critical complication driven by imbalances between vasodilators and vasoconstrictors. This review explores the bidirectional interplay between nitric oxide (NO) and endothelin-1 (ET-1) in CVS pathogenesis. NO, a potent vasodilator mainly produced by endothelial and neuronal nitric oxide synthase (eNOS/nNOS) under normal physiological conditions, is scavenged early after SAH by hemoglobin derivatives, leading to microcirculatory dysfunction, pericyte constriction, and impaired neurovascular coupling. Conversely, ET-1 exacerbates vasoconstriction by suppressing NO synthesis via ROS-dependent eNOS uncoupling and Rho-kinase activation. The NO/ET-1 axis further influences delayed cerebral ischemia (DCI) through mechanisms like 20-HETE-mediated cGMP suppression and oxidative stress. Emerging therapies—including NO donors, NOS gene therapy, and ET-1 receptor antagonists—aim to restore this balance. Understanding these pathways offers translational potential for mitigating CVS and improving outcomes post-SAH.

Editorial on the Research Topic Pathophysiology and pharmacological treatments associated with liver failures This editorial summarizes the contributions to the Frontiers Research topic "pathophysiology and pharmacological treatments associated with liver failures" with peer-reviewed articles published in Frontiers in Pharmacology. Liver diseases (LD), which refers to chronic and acute hepatic failures, represent one of the main global health threats on the human life with associated high mortality. Several etiologies have been identified with relevance to the onset of liver diseases and disease progression, including excess alcohol consumption, inflammatory bowel disease, obesity and metabolic disorders; particularly diabetes and insulin-resistance, autoimmune and viral (HBV, HCV) hepatitis, drugs such as acetaminophen overdose and some mycotoxins (eg. aflatoxins) (Forrest et al.,