Karacoline

Karacoline is an orally active PPARγ activator and ERK/JNK MAPK inhibitor. Karacoline restricts ROS production, maintains mitochondrial membrane potential, and inhibits pulmonary cell apoptosis. Karacoline inhibits NF-κB pathway activation, reduces acetylation levels of p65 and the expression of MMP14 and MMP9, enhances the expression of type II collagen (collagen II) and aggrecan (aggrecan), and suppresses extracellular matrix degradation. In a mouse model of sepsis-induced acute lung injury, Karacoline alleviates lung injury, inhibits the release of IL-1β, IL-6 and TNF-α, increases the Bcl-2/BAX ratio, and reduces caspase 3 expression. Karacoline can be used in research related to acute lung injury and intervertebral disc degeneration^[1][2]. In Vitro:Karacoline (1.6 μM; 24 h) inhibits LPS (HY-D1056)-induced apoptosis of MH-S cells by reducing ROS production and maintaining the stability of mitochondrial membrane potential^[1].
Karacoline (1.6 μM; 24 h) upregulates the expression of PPARγ in LPS-stimulated MH-S cells, inhibits the JNK/ERK MAPK signaling pathway (excluding p38), and simultaneously suppresses the expression of MMP9^[1].
Karacoline (0.001-1000.0 μM; 24 h) has an IC₅₀ of 6.444 μM in primary rat nucleus pulposus cells, and Karacoline (1.25 μM; 0-3 days) partially reverses TNF-α-induced cytotoxicity in these cells^[2].
Karacoline (1.25-12.88 μM; 24 h) reverses TNF-α-induced changes in gene expression in primary rat nucleus pulposus cells, downregulates MMP-14 expression and upregulates type II collagen expression, while the 1.25 μM concentration also upregulates aggrecan expression^[2].
Karacoline (1.25-12.88 μM; 48 h) reverses TNF-α-induced extracellular matrix degradation in primary rat nucleus pulposus cells and increases aggrecan secretion; at the concentration of 1.25 μM, it also increases type II collagen secretion and reduces MMP-14 secretion^[2].
Karacoline (1.25-12.88 μM; 4 days) increases the levels of type II collagen and proteoglycan, and decreases the level of MMP-14, in primary rat nucleus pulposus cells treated with TNF-α^[2].
Karacoline (1.25 μM-12.88 μM; 24-48 h) reduces TNF-α-induced MMP-14 protein expression and inhibits the activation of the NF-κB pathway in primary rat nucleus pulposus cells by decreasing the acetylation level of p65^[2].
Karacoline (1.25-12.88 μM; 48 h) reduces TNF-α-induced apoptosis in primary rat nucleus pulposus cells^[2]. In Vivo:Karacoline (10-40 mg/kg; i.g.) protects against sepsis-induced acute lung injury in male C57BL/6 mice by improving survival, reducing pulmonary edema, barrier dysfunction, inflammation, and apoptosis, via PPARγ-associated inhibition of JNK/ERK MAPK signaling^[1].