Sophoraflavanone G

Anaerobe. 2013 Feb;19:17-21.

Antimicrobial effect of sophoraflavanone G isolated from Sophora flavescens against mutans streptococci.[Pubmed: 23178373]

METHODS AND RESULTS:
In this study, the antibacterial properties of Sophoraflavanone G isolated from the methanol extract of Sophora flavescens were tested against 16 strains of mutans streptococci to screen and determine the optimal concentration of anti-caries natural extract. The antimicrobial activity was evaluated by measuring minimum bactericidal concentration (MBC). The cell viability of normal human gingival fibroblast (NHGF) cells was tested using the methyl thiazolyl tetrazolium assay after exposure to Sophoraflavanone G. The data showed that Sophoraflavanone G had a remarkable antimicrobial effect on the bacteria tested with an MBC ranging from 0.5 μg/ml to 4 μg/ml. Sophoraflavanone G had no cytotoxic effect on NHGF cells at concentrations where it produced an antimicrobial effect.
CONCLUSIONS:
These findings demonstrate that Sophoraflavanone G has strong antimicrobial activity against mutans streptococci and could be useful in the development of novel oral hygiene products, such as a gargle solution or dentifrice.

Phytother Res. 2009 Sep;23(9):1326-31.

Antibacterial activity of sophoraflavanone G isolated from the roots of Sophora flavescens against methicillin-resistant Staphylococcus aureus.[Pubmed: 19288534]

METHODS AND RESULTS:
In this study, Sophoraflavanone G obtained from Sophora flavescens was evaluated against 10 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), either alone or in combination with ampicillin or oxacillin, via checkerboard assay. At the end point of an optically clear well, the minimum inhibitory concentrations (MICs) ranged from 0.5 to 8 microg/ml for Sophoraflavanone G, from 64 to 1024 microg/ml for ampicillin, and from 256 to 1024 microg/ml for oxacillin. The combination of Sophoraflavanone G and ampicillin or oxacillin yielded a fractional inhibitory concentration index ranging from 0.188 to 0.375, thereby indicating a principally synergistic effect. The synergistic interaction was verified by time-kill studies using Sophoraflavanone G and/or antibiotics. Thirty minutes of treatment with Sophoraflavanone G with ampicillin or oxacillin resulted in an increase in the rate of killing in units of CFU/ml to a greater degree than was observed with Sophoraflavanone G alone.
CONCLUSIONS:
These findings indicated that the application of the tested Sophoraflavanone G alone or in combination with antibiotics might prove useful in the control and treatment of MRSA infections.

Am J Chin Med . 2016;44(1):165-76.

Sophoraflavanone G Induces Apoptosis in Human Leukemia Cells and Blocks MAPK Activation[Pubmed: 26916921]

Abstract Sophoraflavanone G (SG) was isolated from Sophora flavescens. Previously, we have found that SG is able to suppress the inflammatory response in lipopolysaccharide-stimulated RAW 264.7 macrophages. This study aimed to evaluate the effects of SG on apoptosis, and explore its molecular mechanism in human leukemia HL-60 cells. HL-60 cells were treated with various concentrations of SG (3-30 [Formula: see text]M). The viability of the HL-60 cells was assessed using the MTT method, and the nuclear condensation indicative of apoptosis was observed by DAPI fluorescence staining. In addition, apoptotic signal proteins were examined using Western blotting. The results showed that apoptosis, including DNA fragmentation and nuclear condensation, increased significantly in SG-treated HL-60 cells. SG activated caspase-3 and caspase-9, and downregulated Bcl-2 and Bcl-xL. SG also upregulated Bax and released cytochrome c from the mitochondria into the cytoplasm, enabling apoptosis via the mitochondrially-mediated "intrinsic" pathway. Additionally, SG was able to cleave poly (ADP-ribose) polymerase 1 and activate mitogen-activated protein kinase (MAPK) pathways. These results suggest that SG might increase the effect of apoptosis on HL-60 cells through caspase-3 activation, mitochondrial-mediated pathways, and the MAPK pathway.

Phytomedicine . 2019 Aug;61:152852.

Sophoraflavanone G from Sophora flavescens induces apoptosis in triple-negative breast cancer cells[Pubmed: 31035052]

Abstract Background: A compound isolated from Sophora flavescens-Sophoraflavanone G (SG)-showed anti-tumor and anti-inflammatory properties. We previously demonstrated that SG promoted apoptosis in human leukemia HL-60 cells. In the present study, we investigated the effects of SG on apoptosis in human breast cancer MDA-MB-231 cells, and explored the underlying molecular mechanisms. Methods: MDA-MB-231 cells were treated with various SG concentrations, and cell viability was evaluated by MTT assay. Apoptotic signal proteins were detected by western blotting, and cell apoptosis was assessed using flow cytometry. Results: Our results demonstrated that SG induced nuclear condensation, DNA fragmentation, reactive oxygen species production, and increased cell apoptosis in MDA-MB-231 cells. SG also suppressed migration and invasion, likely via blockage of the MAPK pathway. In the apoptotic signaling pathway, SG increased cleaved caspase-8, caspase-3, and caspase-9. SG treatment also decreased Bcl-2 and Bcl-xL expression, increased Bax expression, and prompted release of more cytochrome c from mitochondria to the cytoplasm in MDA-MB-231 cells. Conclusion: Overall, our findings suggest that SG might increase apoptosis, and decrease migration and invasion, in MDA-MB-231 cells through suppression of a MAPK-related pathway. Keywords: Apoptosis; Caspase-3; MDA-MB-231 cells; Sophoraflavanone G.

Biochem Pharmacol. 2013 Oct 1;86(7):950-9.

Sophoraflavanone G induces apoptosis of human cancer cells by targeting upstream signals of STATs.[Pubmed: 23962443]

Aberrantly activated signal transducer and activator of transcription (STAT) proteins are implicated with human cancers and represent essential roles for cancer cell survival and proliferation. Therefore, the development of small-molecule inhibitors of STAT signaling bearing pharmacological activity has therapeutic potential for the treatment of human cancers.
METHODS AND RESULTS:
In this study, we identified Sophoraflavanone G as a novel small-molecule inhibitor of STAT signaling in human cancer cells. Sophoraflavanone G inhibited tyrosine phosphorylation of STAT proteins in Hodgkin's lymphoma and tyrosine phosphorylation of STAT3 in solid cancer cells by inhibiting phosphorylation of the Janus kinase (JAK) proteins, Src family tyrosine kinases, such as Lyn and Src, Akt, and ERK1/2. In addition, Sophoraflavanone G inhibited STAT5 phosphorylation in murine-bone-marrow-derived pro-B cells transfected with translocated Ets Leukemia (TEL)-JAKs and cytokine-induced rat pre-T lymphoma cells, as well as STAT5b reporter activity in TEL-JAKs and STAT5b reporter systems. Sophoraflavanone G also inhibited nuclear factor-κB (NF-κB) signaling in multiple myeloma cells. Furthermore, Sophoraflavanone G inhibited cancer cell proliferation and induced apoptosis by regulating the expression of apoptotic and anti-apoptotic proteins.
CONCLUSIONS:
Our data suggest that Sophoraflavanone G is a novel small-molecule inhibitor of STAT signaling by targeting upstream signals of STATs that may have therapeutic potential for cancers caused by persistently activated STAT proteins.

Food Chem Toxicol. 2013 Dec;62:255-61.

Anti-inflammatory effect of sophoraflavanone G isolated from Sophora flavescens in lipopolysaccharide-stimulated mouse macrophages.[Pubmed: 24007739]

Sophoraflavanone G (SG; 5,7,D, 2',4'-tetrahydroxy-8-lavandulylflavanone) has been isolated from Sophora flavescens and found to be effective against bacteria and to decrease cyclooxygenase (COX)-2 expression in RAW 264.7 macrophage. However, the anti-inflammatory mechanisms of SG are not well understood.
METHODS AND RESULTS:
RAW 264.7 cells were pretreated with various concentrations of SG (2.5-20 μM) and inflammatory responses were induced with lipopolysaccharide. Using enzyme-linked immunosorbent assay, the levels of pro-inflammatory cytokines and prostaglandin E2 (PGE2) were determined. Western blot was used to examine the protein expression of inducible nitric oxide synthase (iNOS), COX-2, and heme oxygenase-1 (HO-1). To investigate the molecular mechanism, we analyzed inflammatory-associated signaling pathways, including nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK). SG inhibited the levels of nitric oxide and PGE2 and decreased the production of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor α. The expression of iNOS and COX-2 was also suppressed. However, SG increased HO-1 production in a concentration-dependent manner and significantly decreased MAPK activation and inhibited NF-κB subunit p65 proteins to translocate into the nucleus.
CONCLUSIONS:
These results suggest that SG has an anti-inflammatory effect, inhibiting pro-inflammatory cytokines and mediators production via interruption of the NF-κB and MAPK signaling pathways.

J Food Sci. 2014 Jul;79(7):T1462-8.

Metabolism of the hepatotoxic compound sophoraflavanone G in rat liver microsomes.[Pubmed: 24894298]

Our study aimed at investigating the metabolic characteristics of Sophoraflavanone G (SFG), one of the hepatotoxic constituents of Sophora flavescens, in rat liver microsomes (RLMs).
METHODS AND RESULTS:
SFG was metabolized to 3 phase I metabolites, di-hydroxylated SFG (M1), mono-hydroxylated SFG (M2), dehydrogenated product of mono-hydroxylated SFG (M3) and 3 SFG glucuronides (M4, M5, and M6) by RLMs. The formation kinetics of M2 conformed to biphasic kinetics in RLMs. The formation kinetics of M4 and M5 best-fitted the Hill equation kinetics.
CONCLUSIONS:
Chemical inhibition studies found that CYP1A2 and CYP2E1 were the major enzymes responsible for the formation of M2, and the formation of M4 and M5 may be catalyzed by multiple UGT1A isoforms.