Pectolinarigenin

Pectolinarigenin is an orally active dual inhibitor of COX-2/5-LOX with anti-inflammatory, antioxidant, antitumor and neuroprotective activities. Pectolinarigenin exerts neuroprotective and anti-inflammatory effects on astrocyte inflammation via the NFκB and MAPK pathways. Pectolinarigenin inhibits LPS-induced phosphorylation of ERK1/2, N-FκB and p38MAPK, directly inhibits the enzymatic activity or binding of COX-2, 5-LOX and HIF-1α, and reduces the level of XIAP. Pectolinarigenin modifies Keap1 to promote nuclear accumulation of Nrf2, induces ARE-mediated antioxidant enzyme expression, and possesses direct free radical scavenging activity. Pectolinarigenin reduces the release of NO, proinflammatory mediators and leukotrienes, and increases the level of IL-10. Pectolinarigenin induces G₂/M cell cycle arrest, apoptosis (Apoptosis) and autophagy (Autophagy) via the PI3K/AKT/mTOR signaling pathway. Pectolinarigenin reduces renal crystal deposition and inhibits melanin synthesis. Pectolinarigenin inhibits inflammation and alleviates allergy in mouse models of inflammation. Pectolinarigenin alleviates renal injury, inflammation and oxidative stress in mice by inhibiting HIF-1α activity. Pectolinarigenin can be used for the research of neurodegenerative diseases, inflammatory/allergic diseases, calcium oxalate nephrocalcinosis, gastric cancer, melasma, post-inflammatory diseases and chloasma^{[1][2][3][4][5][6]}. In Vitro:Pectolinarigenin (5-160 μM; 24 h) reduces the viability of J774A.1 murine macrophages at the concentration of 160 μM, and inhibits LPS (HY-D1056)-induced NO release in J774A.1 murine macrophages^[1].
Pectolinarigenin (1-5 μM; 1 h pre-incubation plus 24 h incubation) inhibits LPS-induced activation of primary mouse cortical astrocytes, suppresses the release of IL-1β and IL-6 in cells, elevates basal IL-10 levels, and restores IL-10 levels reduced by lipopolysaccharide^[1].
Pectolinarigenin (5 μM; 1 h pre-incubation followed by 0.5-1 h incubation) inhibits the activation of NF-κB, ERK1/2 and p38MAPK in lipopolysaccharide-induced primary mouse cortical astrocytes^[1].
Pectolinarigenin (1-50 μM; 24 h, 15 min) inhibits COX-2-mediated PGE₂ production in LPS-stimulated RAW 264.7 cells in a concentration-dependent manner, with an inhibition rate of 99.0% at 50 μM for 24 h, and directly inhibits the enzymatic activity of COX-2 (with an inhibition rate of 44.8% at 50 μM for 15 min)^[2].
Pectolinarigenin (1-50 μM; 10 min pre-incubation + 15 min A23187 (HY-N6687) incubation) dose-dependently inhibits 5-LOX-mediated cysteinyl leukotriene production in A23187-stimulated RBL-1 cells, with an inhibition rate of 97.0% at the concentration of 50 μM (10 min pre-incubation + 15 min A23187 incubation)^[2].
Pectolinarigenin (0.1-10 μM; 24 h) significantly inhibits AAPH (HY-Y0525)-induced Nrf2 pathway-dependent ROS accumulation in HepG2 cells^[3].
Pectolinarigenin (0.1-10 μM; 24 h) induces the expression of antioxidant enzymes in HepG2 cells: it upregulates the expression of heme oxygenase-1, while the 10 μM concentration upregulates the expression of NAD (P) H:quinone oxidoreductase 1 and aldo-keto reductase family 1 member B10^[3].
Pectolinarigenin (0.1-10 μM; 3-24 h) significantly promotes the nuclear accumulation of Nrf2 and enhances ARE-mediated transcriptional activity in HepG2 cells^[3].
Pectolinarigenin (2-8 μM; 12 h pretreatment followed by COM stimulation) concentration-dependently inhibits the COM-induced upregulation of KIM-1 mRNA and protein expression in HK-2 cells, and suppresses cellular inflammatory responses^[4].
Pectolinarigenin (8 μM; 12 h pretreatment followed by COM stimulation) alleviates COM-induced oxidative stress injury in HK-2 cells by restoring the levels of antioxidant markers (GSH, HO-1, GPX4) and reducing the levels of pro-oxidant markers (MDA, iron, ROS)^[4].
Pectolinarigenin (8 μM; 12 h incubation) inhibits HIF-1α activity in HK-2 cells^[4].
Pectolinarigenin (8 μM; 12 h pretreatment followed by COM stimulation) alleviates COM-induced renal injury, inflammation and oxidative stress in HK-2 cells in vitro in a HIF-1α-dependent manner, as its protective effects are abolished when HIF-1α is knocked down^[4].
Pectolinarigenin (25-150 μM; 24 h) dose-dependently inhibits the viability of AGS and MKN28 human gastric cancer cells, with IC₅₀ values of 124.79 μM and 96.88 μM, respectively^[5].
Pectolinarigenin (50-100 μM; 24 h) induces G2/M cell cycle arrest in human gastric cancer cell lines AGS and MKN28, accompanied by sub-G1 phase cell accumulation (indicating apoptosis) in AGS cells. Its mechanism of action involves downregulating the protein expression levels of CDK1 and CDC25C, and upregulating the mRNA expression levels of p53 and p21^[5].
Pectolinarigenin (50-100 μM; 24 h) induces dose-dependent apoptosis in human gastric cancer cell lines AGS and MKN28 by downregulating XIAP and activating the caspase-PARP apoptotic pathway^[5].
Pectolinarigenin (50-100 μM; 24 h) induces Beclin-1-independent autophagy in human gastric cancer cell lines AGS and MKN28^[5].
Pectolinarigenin (50-100 μM; 24 h) dose-dependently inhibits the PI3K/AKT/mTOR signaling pathway in human gastric cancer cell lines AGS and MKN28, thereby reducing the phosphorylation levels of downstream pathway targets p70S6K, 4EBP1 and eIF4E^[5].
Pectolinarigenin (30 μM; 72 h) significantly reduces melanin content and tyrosinase activity in melan-a cells, decreases the protein expression levels of tyrosinase, TRP-1, TRP-2 and MITF, and lowers the mRNA expression levels of tyrosinase, TRP-1 and MITF in the cells^[6].
Pectolinarigenin (30 μM; 2 days) significantly reduces the melanin content in a recombinant human skin model to 20.8% of that in the control group, and decreases the L-DOPA content^[6]. In Vivo:Pectolinarigenin (4-100 mg/kg; p.o.; single dose) inhibits arachidonic acid (HY-109590)-induced ear edema in mice when administered orally at 100 mg/kg^[2].
Pectolinarigenin (4-100 mg/kg; p.o.; single dose) produces a 21.1% inhibitory effect on carrageenan-induced paw edema in mice when administered orally at 100 mg/kg^[2].
Pectolinarigenin (20 mg/kg; p.o.; two doses), administered orally at a dose of 20 mg/kg twice, exerts a 30.8% inhibitory effect on passive cutaneous anaphylaxis in rats^[2].
When pectolinarigenin (1.0-10 mg/kg; p.o.; daily; 7 days) is administered orally at a dose of 10 mg/kg once daily for 7 days, it activates the Nrf2/ARE pathway in the liver of male ICR mice, significantly induces the expression of antioxidant enzymes, and promotes Nrf2 nuclear translocation^[3].
Pectolinarigenin (7.25-25 mg/kg; i.g.; daily) alleviates calcium oxalate-induced renal injury, inflammation and oxidative stress in mice in a dose-dependent manner by inhibiting HIF-1α activity^[4].