PMC

Demonstrates oxidative stress in aging and other age-related diseases. A healthy cell can balance the production of reactive oxidative species and antioxidant enzymes. However, in disease states, such as Alzheimer’s, Parkinson’s, a combination of increased levels of reactive oxidative species production and decreased antioxidant enzymes production have been observed. This imbalance is known as oxidative stress, observed in a large number of human diseases.

Mechanisms of the anti-diabetic effects of carotenoids. During oxidative stress, IκB is phosphorylated by IKK, resulting in the release of NF-κB. NF-κB is translocated to the nucleus, and the transcription of inflammatory cytokines can commence. Carotenoids inactivate the NF-κB pathway. Carotenoids inhibit the degradation of Nrf2 and interact with Keap1. Nrf2 migrates to the nucleus, and the transcription of antioxidant and detoxifying enzymes can start. Carotenoids inhibit MAPK signaling from reaching the nucleus [,,].

The use of saikosaponins and implications for age-related diseases. Several types of saikosaponins, such as saikosaponin a (SSa), saikosaponin b (SSb), saikosaponin c (SSc), and saikosaponin d (SSd), could be used to treat age-related diseases. SSa, SSb, and SSd may be used for the treatment of cancer as single anticancer or adjuvant agents. Inhibitory actions of saikosaponins against P-glycoprotein-mediated multidrug resistance are implicated in the ability of saikosaponins to sensitize cancer cells to chemotherapy or radiotherapy. SSc has dual effects on human Alzheimer's disease by targeting both tau and amyloid beta. SSa may slow or reverse the progression of atherosclerosis by inhibiting oxidized low-density lipoprotein-induced activation of p38 and the c-Jun N-terminal kinase mitogen-activated protein kinase pathway and assembly of the NLR family pyrin domain containing 3 inflammasome. SSa exerts antiobesity activity by acting as a 5-hydroxytryptamine 2C receptor agonist or by suppressing extracellular signal-regulated kinase/nuclear factor- (NF-) κB pathway-induced inflammation. SSd provides protection against diabetic nephropathy through the upregulation of Sirt3 followed by mitochondrial antioxidant enzymes like isocitrate dehydrogenase 2 and manganese-dependent superoxide dismutase. SSa, SSc, and SSd may be used for the treatment of inflammatory disorders, such as asthma, arthritis, and sepsis, by downregulating the NF-κB signaling pathway or inhibiting vascular injury/apoptosis. Lastly, SSa and SSd protect the liver against age-associated injury and fibrosis by suppressing cytokines, including platelet-derived growth factor and transforming growth factor-β1.

Consequences of tissue trauma on heme catabolism, reactive oxygen species, and polyunsaturated fatty acid metabolism.
Notes: Top panel: following tissue trauma, release of free heme can serve as a signal for proinflammatory events. The oxidative degradation of heme by heme oxygenase removes free heme, and generates catabolites with antioxidant and anti-inflammatory effects.– Iron released from heme by heme oxygenase catabolism can be stored by ferritin, preventing its participation in redox reactions. Middle panel: acute inflammation is associated with an increase in reactive oxygen species, which are regulated by cellular enzymes involved in redox reactions.,, Reactive oxygen species can have proinflammatory effects, and chronic inflammatory diseases are often associated with oxidative stress.,,, In some cases, reactive oxygen species can have anti-inflammatory effects., lower panel: in response to proinflammatory stimuli, phospholipase A2 mediates release of arachidonic acid from the cell membrane., an increase in inducible prostaglandin-endoperoxide synthase 2 also occurs.,– During the early inflammatory response, arachidonic acid is metabolized by prostaglandin synthases and lipoxygenases to generate eicosanoids and leukotrienes,,,– which is followed, at later times, by “lipid mediator class switching.” The latter is thought to serve as a switch from the production of proinflammatory lipid mediators to those involved in programmed resolution.,,–
Abbreviations: GSH, reduced glutathione; GSSG, glutathione disulfide; PGD₂, prostaglandin D₂; PGE₂, prostaglandin E₂; PGG₂, prostaglandin G₂; PGH₂, prostaglandin H₂; PGI₂, prostaglandin I₂; PUFA, polyunsaturated fatty acid.