Isopimaric acid

Isopimaric acid is a coniferous tree defense compound. Isopimaric acid binds to AKT and inhibits mTOR phosphorylation, thereby regulating the AKT/mTOR pathway. Isopimaric acid inhibits oxidative stress, inflammation, microglial migration, apoptosis, autophagic flux, ornithine decarboxylase activity, breast cancer proliferation and metastasis, and fungal spore germination. Isopimaric acid also induces M2 microglial polarization, mitochondrial damage, ROS accumulation, starvation-induced colon cancer cell apoptosis, and breast cancer cell cycle arrest. Isopimaric acid activates potassium channels, regulates sodium channels and calcium channels, reduces myocardial excitability, and improves arrhythmia. Isopimaric acid acts as an oxidative substrate for CYP6BW1/3, down-regulates PINK1/Parkin, and regulates calcium homeostasis, oxidative phosphorylation, EMT, and the Wnt pathway. Isopimaric acid exhibits activity against drug-resistant Staphylococcus aureus, repels feeding, and promotes the growth of rice seedlings. Isopimaric acid is suitable for research related to epilepsy, tumors, drug-resistant bacterial infections, atrial fibrillation, hypertension, hyperlipidemia, pulmonary tuberculosis, etc^{[1][2][3][4][5][6][7][8][9]}. In Vitro:Isopimaric acid (0.1-1000.0 µM; 24 h) at 0.1-100.0 µM is non-toxic to murine microglial BV2 cells after 24 h incubation, while 1000.0 µM increases cell survival^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) significantly inhibits lipopolysaccharide-induced migration of murine microglial BV2 cells after 24 h co-incubation, with 100.0 µM showing the strongest effect^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) significantly reduces lipopolysaccharide-induced lactate dehydrogenase release in murine microglial BV2 cells after 24 h co-incubation, with 100.0 µM showing the strongest effect^[1].
Isopimaric acid binds to the active pocket of AKT via interactions with residues Phe161 and Gly162, potentially inhibiting AKT phosphorylation^[1].
Isopimaric acid (1 mM; 1 h) is oxidized by heterologously expressed mountain pine beetle CYP6BW1 in vitro to form epoxidized and hydrolyzed epoxide (vicinal diol) products^[2].
Isopimaric acid (1 mM; 1 h) is oxidized by heterologously expressed mountain pine beetle CYP6BW3 in vitro to form a minor epoxidized product and a major hydrolyzed epoxide (vicinal diol) product^[2].
Isopimaric acid (25 µg/mL; 3 d) promotes shoot growth in multiple Oryza sativa L. rice seedling lines, with the WRs260 line showing the greatest increases of 36.48% in shoot length and 49.00% in shoot weight^[7].
Isopimaric acid (25 µg/mL) alters growth-related phytohormone concentrations in Oryza sativa L. rice seedling shoots and roots, including significant reductions in IAA in CJCx59 shoots and significant increases in IBA in JRC053 shoots^[7].
Isopimaric acid (25 µg/mL) reduces cytokinin-related phytohormone concentrations in Oryza sativa L. rice seedling shoots and roots, with the greatest reduction of 31.00% seen in tZ concentrations in CJCHC4 shoots^[7].
Isopimaric acid (25 µg/mL) reduces gibberellin-related phytohormone concentrations in Oryza sativa L. rice seedling shoots and roots, with a significant reduction of 32.53% seen in GA₇ concentrations in NG28 shoots^[7].
Isopimaric acid (25 µg/mL) reduces defense-related phytohormone concentrations in Oryza sativa L. rice seedling shoots and roots, with a significant reduction of 45.14% seen in ABA concentrations in NG28 shoots^[7].
Isopimaric acid (25 µg/mL) modulates the correlations between phytohormone concentrations and growth characteristics in Oryza sativa L. rice seedlings, including a significant negative correlation between shoot length and IBA concentrations, and a significant negative correlation between root weight and ABA concentrations^[7].
Isopimaric acid (0.1-100.0 µM; 12 h) significantly inhibits glutamate-induced reactive oxygen species production in murine microglial BV2 cells after 12 h co-incubation^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) significantly inhibits lipopolysaccharide-induced reactive oxygen species production in murine microglial BV2 cells after 24 h co-incubation^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) significantly suppresses lipopolysaccharide-induced late-phase apoptosis in murine microglial BV2 cells after 24 h co-incubation^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) preserves mitochondrial membrane potential in lipopolysaccharide-stimulated murine microglial BV2 cells after 24 h co-incubation^[1].
Isopimaric acid (1.0-100.0 µM; 24 h) upregulates antioxidant (SOD-1, SOD-2) and M2 polarization (Arg-1) gene expression, and at 100.0 µM downregulates inflammatory (IL-1β, TNF-α) gene expression in lipopolysaccharide-stimulated murine microglial BV2 cells after 24 h co-incubation^[1].
Isopimaric acid (0.1-100.0 µM; 24 h) suppresses inflammatory protein (IL-1β, TNF-α) expression and inhibits phosphorylation of AKT and mTOR, without affecting PI3Kα or PI3Kβ protein levels, in lipopolysaccharide-stimulated murine microglial BV2 cells after 24 h co-incubation^[1].
Isopimaric acid (512 µg/mL starting; 18 h) inhibits growth of XU212, SA-1199B, RN4220, EMRSA-15, EMRSA-16, and ATCC 25923 Staphylococcus aureus strains with MIC values ranging from 32 to 64 µg/mL^[3].
Isopimaric acid (10 µg/mL; 18 h) does not potentiate the activity of Tetracycline (HY-A0107), Norfloxacin (HY-B0132), Erythromycin (HY-B0220), or Oxacillin (HY-B0925A) against XU212, SA-1199B, RN4220, EMRSA-15, or EMRSA-16 Staphylococcus aureus strains^[3].
Isopimaric acid (512 µg/mL starting, combined with 20 µg/mL Reserpine (HY-N0480); 18 h) exhibits reduced antibacterial activity against XU212 and SA-1199B Staphylococcus aureus strains, with MIC values increasing to 128 µg/mL and 64 µg/mL, respectively^[3].
Isopimaric acid (combined with 10 µg/mL Epicatechin gallate ((-)-Epicatechin gallate) (HY-N0002) for EMRSA-15, 4 µg/mL Epicatechin gallate for EMRSA-16; 18 h) antibacterial activity against EMRSA-15 and EMRSA-16 Staphylococcus aureus strains is unaffected by combination with Epicatechin gallate, with MIC values remaining at 32 µg/mL and 64 µg/mL, respectively^[3].
Isopimaric acid (1-50 μM) reduces spontaneous action potential frequency in mouse atrial HL-1 cells by up to 50% at 1, 10, and 25 μM, with minimal effects on other action potential parameters except at 50 μM, where it prolongs action potential duration at 90% repolarization^[5].
Isopimaric acid (1-50 μM) promotes inactivation of sodium currents in mouse atrial HL-1 cells by shifting activation and steady-state inactivation curves to more negative voltages, dose-dependently slowing recovery from inactivation, and reducing late steady-state current, with peak current only reduced at 50 μM^[5].
Isopimaric acid (1-50 μM) increases peak transient outward potassium currents by 30% at 1 and 10 μM and shifts steady-state inactivation to more negative voltages in mouse atrial HL-1 cells, with no effect on activation gating^[5].
Isopimaric acid (1-50 μM) promotes opening of rapidly activating delayed-rectifier potassium currents in mouse atrial HL-1 cells by shifting activation to more negative voltages and speeding activation kinetics at 1, 10, and 50 μM, with no effect on steady-state inactivation^[5].
Isopimaric acid (1-50 μM) reduces L-type calcium currents in mouse atrial HL-1 cells by 53% at 1 μM, shifting activation and steady-state inactivation curves to more negative voltages, with greater effects on inactivation, and effects saturated at the lowest concentration tested^[5].
Isopimaric acid (1-50 μM) dose-dependently reduces T-type calcium currents in mouse atrial HL-1 cells, with a 40% reduction at 10 μM, and shifts activation and steady-state inactivation curves to more negative voltages, with greater effects on inactivation^[5].
Isopimaric acid (1-50 μM) has no significant effect on pace-maker hyperpolarization-activated non-selective cation currents in mouse atrial HL-1 cells at concentrations up to 50 μM^[5].
Isopimaric acid (1-10 μM) restores regular spontaneous action potential firing in isoproterenol-induced arrhythmic mouse atrial HL-1 cells, with near-complete restoration at 1 μM and full restoration at 10 μM^[5].
Isopimaric acid (24-72 h) potently inhibits the proliferation of 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a time- and concentration-dependent manner, with the strongest activity in 4T1 cells (IC₅₀ = 22.46 μg/mL at 72 h)^[8].
Isopimaric acid (5-30 μg/mL; 10 days) inhibits colony formation of 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner^[8].
Isopimaric acid (5-30 μg/mL; 24 h) reduces the rate of new cell proliferation in 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner^[8].
Isopimaric acid (10 μg/mL; 24 h) downregulates the calcium signaling and oxidative phosphorylation pathways in 4T1 breast cancer cells, as revealed by transcriptomic and GSEA analysis^[8].
Isopimaric acid (10-40 μg/mL; 48 h) induces apoptosis of 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner, with near-maximal apoptotic rates at 30-40 μg/mL in 4T1 cells^[8].
Isopimaric acid (10-40 μg/mL; 48 h) induces G1-phase cell cycle arrest in 4T1 breast cancer cells in vitro in a concentration-dependent manner^[8].
Isopimaric acid (5-20 μg/mL; 24 h) downregulates cell cycle-related proteins (CDK2, CDK4, CyclinD1) and anti-apoptotic proteins Bcl-XL and Bcl-2, while upregulating pro-apoptotic proteins BAD and BAX in 4T1 breast cancer cells in vitro in a concentration-dependent manner^[8].
Isopimaric acid (10-20 μg/mL; 24 h) inhibits the migration of 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner, with the strongest activity in 4T1 cells^[8].
Isopimaric acid (2.5-20 μg/mL; 24 h) inhibits the migration and invasion of 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner, with the strongest activity in 4T1 cells^[8].
Isopimaric acid (5-20 μg/mL; 24 h) upregulates E-cadherin and downregulates Vimentin, β-catenin, and ZEB1 in 4T1, MDA-MB-231, and MCF-7 breast cancer cells in a concentration-dependent manner, indicating inhibition of the EMT pathway^[8].
Isopimaric acid (20 μg/mL; 48 h) reduces the expression of Vimentin and β-catenin in 4T1 and MDA-MB-231 breast cancer cells, consistent with inhibition of the EMT pathway^[8]. In Vivo:Isopimaric acid (15-60 mg/kg; i.p.; once every other day; 15 days) dose-dependently inhibits in vivo proliferation and metastasis of 4T1 breast cancer xenografts, with the 60 mg/kg dose producing statistically significant tumor growth inhibition^[8].