Chronic pain is an atypical pain condition that imposes a significant personal and economic burden. Current medications for chronic pain offer only temporary relief to a subset of patients and may lead to considerable adverse effects. Naringenin, a dihydroflavonoid categorized as a flavone, exhibits a broad spectrum of pharmacological activities and holds significant promise for chronic pain management. Extensive research has demonstrated that naringenin possesses analgesic effects across various chronic pain models. This review explores the molecular mechanisms and functions of naringenin in the management of chronic pain. It achieves this by reducing neuroinflammation and oxidative stress, as well as modulating matrix metalloproteinases (MMPs), ion channels in nociceptive terminals, and various intracellular signaling pathways, including the calcitonin gene-related peptide (CGRP) signaling pathway and the NO-cGMP-PKG-ATP-sensitive potassium channel signaling pathway. The established safety based on current preclinical evidence and multimodal mechanisms of naringenin enable multimodal therapeutic strategies targeting chronic pain pathogenesis networks.

Brain injury remains a significant contributor to mortality and long-term neurological disability worldwide, despite ongoing research efforts to develop effective therapies that can mitigate secondary damage. One promising therapeutic target is peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a crucial regulator of mitochondrial homeostasis, antioxidant defense, and metabolic adaptation. This review explores the multifaceted roles of PGC-1α in various types of brain injuries, including traumatic, ischemic, and hemorrhagic injuries. In traumatic brain injury, PGC-1α has been found to play a pivotal role in reducing mitochondrial dysfunction and neuroinflammation. By promoting oxidative phosphorylation and inhibiting microglial activation, PGC-1α helps to preserve neuronal health and function. In ischemic brain injury, PGC-1α’s ability to restore energy metabolism through fatty acid oxidation and enhance antioxidant defenses against oxidative stress is particularly noteworthy. These actions contribute to improving neuronal survival and functional recovery. Similarly, in hemorrhagic brain injury, PGC-1α has demonstrated its protective effects by regulating lipid metabolism and inflammatory cascades. This helps to alleviate blood–brain barrier disruption and iron-induced oxidative damage, which are critical factors in the pathogenesis of this type of injury. Overall, these findings highlight the broad therapeutic potential of PGC-1α in brain injury. Furthermore, recent research has focused on developing pharmacological PGC-1α activators which have shown promise in pre-clinical models by restoring mitochondrial integrity and enhancing cellular resilience. In conclusion, the diverse roles of PGC-1α in traumatic, ischemic, and hemorrhagic brain injuries, as well as its spatiotemporal regulatory mechanisms, provide valuable insights into its therapeutic potential. As research continues to advance, PGC-1α-based strategies hold promise as innovative therapeutic approaches for brain injury, offering new hope for patients worldwide.

Brain injury is one of the leading causes of death and disability worldwide, attributable to diverse etiologies such as trauma, hypoxia, stroke, infection, or neurodegenerative diseases. Due to the complex pathophysiology, high prevalence, and limited therapeutic options, brain injury poses significant healthcare challenges. Current treatment for brain injury involves a combination of medical interventions, surgery, and rehabilitation therapies. Ligustilide, a bioactive component purified from traditional Chinese medicinal herb, has been studied as a promising candidate for neuroprotection. In this review, we summarize current research to understand the mechanisms underlying ligustilide neuroprotective activities and assess its therapeutic potential in treating brain injuries.