Isoliquiritigenin, an Orally Available Natural FLT3 Inhibitor from Licorice, Exhibits Selective Anti-Acute Myeloid Leukemia Efficacy In Vitro and In Vivo.

Licorice is a medicinal herb widely used to treat inflammation-related diseases in China. Isoliquiritigenin (ISL) is an important constituent of licorice and possesses multiple bioactivities. In this study, we examined the selective anti-AML (acute myeloid leukemia) property of ISL via targeting FMS-like tyrosine kinase-3 (FLT3), a certified valid target for treating AML. In vitro, ISL potently inhibited FLT3 kinase, with an IC50 value of 115.1 ± 4.2 nM, and selectively inhibited the proliferation of FLT3-internal tandem duplication (FLT3-ITD) or FLT3-ITD/F691L mutant AML cells. Moreover, it showed very weak activity toward other tested cell lines or kinases. Western blot immunoassay revealed that ISL significantly inhibited the activation of FLT3/Erk1/2/signal transducer and activator of transcription 5 (STAT5) signal in AML cells. Meanwhile, a molecular docking study indicated that ISL could stably form aromatic interactions and hydrogen bonds within the kinase domain of FLT3. In vivo, oral administration of ISL significantly inhibited the MV4-11 flank tumor growth and prolonged survival in the bone marrow transplant model via decreasing the expression of Ki67 and inducing apoptosis. Taken together, the present study identified a novel function of ISL as a selective FLT3 inhibitor. ISL could also be a potential natural bioactive compound for treating AML with FLT3-ITD or FLT3-ITD/F691L mutations. Thus, ISL and licorice might possess potential therapeutic effects for treating AML, providing a new strategy for anti-AML.

[Relationship between HBV-DNA in peripheral blood mononuclear cells and syndrome types of TCM in chronic hepatitis B patients].

OBJECTIVE: To study the relationship between TCM syndrome type and HBV-DNA in serum and peripheral blood mononuclear cells (PBMCs) in chronic hepatitis B (CHB) patients. METHODS: The serum HBV markers,HBV-DNA levels in serum and PBMCs, were quantitatively detected in 220 CHB patients by PCR method, and TCM syndrome type of 205 patients were differentiated. RESULTS: Arranged from low to high, the percentages of CHB patients with the serum HBV-DNA > or = 1.0 x l0(5) copy/mL (high viral loading) in the five syndrome types were as follows: damp-heat retention in middle-jiao syndrome (DHRS, 55.2%), blood stasis blocking collateral syndrome (BSBC), Gan-Shen yin deficiency syndrome (GSYS), Pi-Shen yang deficiency syndrome (PSDS) and Gan stagnation with Pi deficiency syndrome (GSPS, 82.5%), the difference was significant between DHRS and GSPS; those with HBV-DNA in PBMCs infection were: GSYS (27.3%), DHRS (34.3%), BSBC (53.1%) and GSPS (77.2%). The percentage in GSPS was the highest, which was significantly different to that in other syndromes. CONCLUSION: Amount of serum HBV-DNA and PBMCs HBV-DNA infection has certain correlation with the TCM syndrome type of CHB. The highest percentage of patients with HBV-DNA > or = 1.0 x l0(5) copy/mL and PBMCs HBV-DNA infection presented in CHB patients of GSPS type. We should pay more attention to strengthen genuine qi to eliminate pathogenic factors in treatment of CHB.