The mechanism of action of cordyceps in the anti-oxidative stress response involves multiple molecular pathways. Its core role lies in mitigating oxidative stress-induced cellular damage by regulating redox homeostasis, inhibiting excessive mitochondrial reactive oxygen species (ROS), and modulating related signal transduction pathways. This process is closely related to its rich content of active components, including polysaccharides, amino acids, nucleosides, sterols, and phenols. These components work synergistically to intervene in the development and progression of oxidative stress at various levels.
Mitochondria are the primary source of intracellular ROS. Leakage from the electron transport chain during oxidative phosphorylation generates large amounts of ROS, including superoxide anions. When mitochondrial function is impaired, the balance between ROS production and clearance is disrupted, leading to increased oxidative stress. Studies have shown that cordyceps can directly inhibit excessive mitochondrial ROS production by downregulating the activity and expression of mitochondrial oxidative phosphorylation-related proteins (such as mitochondrial complexes I and II), reducing electron leakage from the electron transport chain, and thereby inhibiting excessive mitochondrial ROS production. This action protects mitochondrial membrane integrity, maintains normal mitochondrial function, provides a stable energy supply to the cell, and reduces ROS-induced oxidative damage to intracellular macromolecules (such as DNA, proteins, and lipids).
Oxidative stress is closely related to inflammatory responses. ROS can act as a second messenger to activate inflammatory signaling pathways such as nuclear factor-κB (NF-κB). NF-κB is a key transcription factor regulating the expression of inflammatory factors. Its activation promotes the release of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), further exacerbating oxidative stress. Active ingredients in cordyceps (such as ergosterol and nucleosides) can inhibit the activation of the NF-κB signaling pathway. Specifically, these ingredients block the activity of IκB kinase (IKK), preventing the phosphorylation and degradation of IκB, thereby inhibiting the nuclear translocation of NF-κB (p65/p50) and reducing the transcription and expression of inflammatory factors. This effect not only alleviates the inflammatory response but also reduces the induction of oxidative stress by inflammatory factors, creating a virtuous cycle of antioxidant and anti-inflammatory effects.
Silent information regulator 1 (SIRT1) is an NAD+-dependent histone deacetylase that plays a key role in regulating oxidative stress and inflammatory responses. SIRT1 activates peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) through deacetylation, a key regulator of mitochondrial biogenesis and function. Nucleoside compounds in cordyceps activate SIRT1 and promote deacetylation of PGC-1α, thereby enhancing mitochondrial antioxidant capacity. Furthermore, SIRT1 inhibits NF-κB acetylation, reducing its transcriptional activity and further suppressing the expression of inflammatory factors. This pathway closely links antioxidant activity, mitochondrial function protection, and anti-inflammatory effects, demonstrating the multi-target regulatory nature of cordyceps.
Oxidative stress can lead to an imbalance in the intracellular redox state. Glutathione (GSH) is one of the most important intracellular antioxidants, and the ratio of its reduced form (GSH) to its oxidized form (GSSG) reflects the cellular redox state. By increasing intracellular GSH levels, cordyceps enhances the activity of antioxidant enzymes (such as superoxide dismutase (SOD) and catalase (CAT), thereby accelerating the clearance of reactive oxygen species (ROS). For example, the polysaccharides in cordyceps promote the expression of GSH synthase, increasing GSH synthesis. Furthermore, by inhibiting the consumption of GSH peroxidase, they maintain a high GSH/GSSG ratio, providing sustained antioxidant protection for cells.
Oxidative stress can induce the activation of apoptosis-related signaling pathways, such as the caspase family of proteins. Cordyceps reduces apoptosis by inhibiting ROS-mediated caspase-3 activation. Furthermore, its active ingredients can upregulate the expression of anti-apoptotic proteins (such as Bcl-2) and downregulate pro-apoptotic proteins (such as Bax), thereby maintaining mitochondrial membrane stability, preventing the release of cytochrome c, and further inhibiting apoptosis. This action protects cells from excessive oxidative stress damage and maintains tissue structural integrity.
The molecular pathways of cordyceps in the anti-oxidative stress response are characterized by multiple levels and targets. Cordyceps forms a comprehensive antioxidant network by inhibiting mitochondrial ROS production, regulating NF-κB and SIRT1 signaling pathways, enhancing GSH-mediated antioxidant defenses, and inhibiting apoptosis. These pathways synergize to mitigate cellular damage caused by oxidative stress, providing a scientific basis for the use of cordyceps in the prevention and treatment of oxidative stress-related diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, and liver fibrosis.
