Sappanone A is an orally active homoisoflavone found in sappan L. Sappanone A is a PDE4 and NF-κB inhibitor with anti-inflammatory and antioxidant effect. Sappanone A induces HO-1 expression through activation of Nrf2 pathway. Sappanone A also inhibits RANKL-induced osteoclastogenesis. Sappanone A has great potential in the research of inflammation-related and cardiovascular [1] [2] [3] [4] [5].
In Vivo, Sappanone A (20, 50 mg/kg, i.p., one dose) protects mice from death in the LPS-induced mortality in C57BL/6 mice model[1]. Sappanone A (50, 100 mg/kg, i.p., twice a day for seven consecutive days) significantly reduces LPS-induced mice acute lung injury (ALI) without obvious toxic side effects[2]. Sappanone A (50 mg/kg, i.p., injects every other day for a total of eight days) inhibits osteoclast formation in vivo in the LPS-induced mouse bone loss model[3]. Sappanone A (20 mg/kg, i.p., one dose) can reduce myocardial necrosis and apoptosis and promote the recovery of cardiac function in the myocardial ischemia reperfusion injury (MIRI) rat model[4]. Sappanone A (10-30 mg/kg, i.g., once a day for twelve weeks) reduces renal injury during hyperglycemia in a dose-dependent manner in a Streptozotocin -induced diabetic mouse model[5].
In Vitro, Sappanone A (5-30 μM, pretreatment for 1 h, then 24 h) inhibits LPS-induced NO, IL-6 and PGE 2 production in RAW264.7 cells in a concentration-dependent manner (IC50 6.8, 11.2 and 12.6 μM, respectively) without cytotoxicity[1]. Sappanone A (5-30 μM, 24 h) exerts anti-inflammatory effects in RAW264.7 cells by inducing HO-1 expression and inhibits LPS-induced NF-κB activation through activation of Nrf2[2]. Sappanone A (10-40 μM) remarkably inhibits PDE4 enzyme activity and reduces TNF-α production induced by LPS in RAW264.7 macrophages[2]. Sappanone A (0.007-1.0 mM, 40 min) has excellent ability to reduce Fe3+ and complex Fe2+, shows excellent antioxidant activity[2]. Sappanone A (3-30 μM, 7 days) inhibits RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophage (BMM)[3]. Sappanone A (0-30 μM, 7 days) inhibits RANKL-induced NFATc1 activation and AKT phosphorylation in BMMs[3]. Sappanone A (10-30 μM, pretreatment for 1 hour, then treatment for 24 hours) blocks the NF-κB pathway and inhibits the inflammatory response in the HG-induced mesangial cell model[5].
References:
[1]. Lee S, et, al. Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB. Int Immunopharmacol. 2015 Sep;28(1):328-36.
[2]. Wang YZ, et al. Sappanone A: A natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the heartwood of Caesalpinia sappan L. J Ethnopharmacol. 2023 Mar 25;304:116020.
[3]. Choo YY, et al. Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss. Int Immunopharmacol. 2017 Nov;52:230-237.
[4]. Shi X, et al. Sappanone A Protects Against Myocardial Ischemia Reperfusion Injury by Modulation of Nrf2. Drug Des Devel Ther. 2020 Jan 8;14:61-71.
[5]. Wang Z, et al. Sappanone a prevents diabetic kidney disease by inhibiting kidney inflammation and fibrosis via the NF-κB signaling pathway. Front Pharmacol. 2022 Aug 16;13:953004.
In Vivo, Sappanone A (20, 50 mg/kg, i.p., one dose) protects mice from death in the LPS-induced mortality in C57BL/6 mice model[1]. Sappanone A (50, 100 mg/kg, i.p., twice a day for seven consecutive days) significantly reduces LPS-induced mice acute lung injury (ALI) without obvious toxic side effects[2]. Sappanone A (50 mg/kg, i.p., injects every other day for a total of eight days) inhibits osteoclast formation in vivo in the LPS-induced mouse bone loss model[3]. Sappanone A (20 mg/kg, i.p., one dose) can reduce myocardial necrosis and apoptosis and promote the recovery of cardiac function in the myocardial ischemia reperfusion injury (MIRI) rat model[4]. Sappanone A (10-30 mg/kg, i.g., once a day for twelve weeks) reduces renal injury during hyperglycemia in a dose-dependent manner in a Streptozotocin -induced diabetic mouse model[5].
In Vitro, Sappanone A (5-30 μM, pretreatment for 1 h, then 24 h) inhibits LPS-induced NO, IL-6 and PGE 2 production in RAW264.7 cells in a concentration-dependent manner (IC50 6.8, 11.2 and 12.6 μM, respectively) without cytotoxicity[1]. Sappanone A (5-30 μM, 24 h) exerts anti-inflammatory effects in RAW264.7 cells by inducing HO-1 expression and inhibits LPS-induced NF-κB activation through activation of Nrf2[2]. Sappanone A (10-40 μM) remarkably inhibits PDE4 enzyme activity and reduces TNF-α production induced by LPS in RAW264.7 macrophages[2]. Sappanone A (0.007-1.0 mM, 40 min) has excellent ability to reduce Fe3+ and complex Fe2+, shows excellent antioxidant activity[2]. Sappanone A (3-30 μM, 7 days) inhibits RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophage (BMM)[3]. Sappanone A (0-30 μM, 7 days) inhibits RANKL-induced NFATc1 activation and AKT phosphorylation in BMMs[3]. Sappanone A (10-30 μM, pretreatment for 1 hour, then treatment for 24 hours) blocks the NF-κB pathway and inhibits the inflammatory response in the HG-induced mesangial cell model[5].
References:
[1]. Lee S, et, al. Sappanone A exhibits anti-inflammatory effects via modulation of Nrf2 and NF-κB. Int Immunopharmacol. 2015 Sep;28(1):328-36.
[2]. Wang YZ, et al. Sappanone A: A natural PDE4 inhibitor with dual anti-inflammatory and antioxidant activities from the heartwood of Caesalpinia sappan L. J Ethnopharmacol. 2023 Mar 25;304:116020.
[3]. Choo YY, et al. Sappanone A inhibits RANKL-induced osteoclastogenesis in BMMs and prevents inflammation-mediated bone loss. Int Immunopharmacol. 2017 Nov;52:230-237.
[4]. Shi X, et al. Sappanone A Protects Against Myocardial Ischemia Reperfusion Injury by Modulation of Nrf2. Drug Des Devel Ther. 2020 Jan 8;14:61-71.
[5]. Wang Z, et al. Sappanone a prevents diabetic kidney disease by inhibiting kidney inflammation and fibrosis via the NF-κB signaling pathway. Front Pharmacol. 2022 Aug 16;13:953004.