Kolonics 2017 MiP2017

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Attila Kolonics
Different molecular composition of Lysimachia species result in distinct metabolism.

Link: MiP2017

Toth A, Lener V, Riethmuller E, Kery A, Kolonics A (2017)

Event: MiP2017

COST Action MITOEAGLE
Mitochondria play a pivotal role in homeostasis, and their function is essential for the survival of cancer cells. Saponine enriched fractions of Lysimachia species have been reported to possess cytotoxic and antiproliferative activity [1]. The flavonoid aglycones in the hydrolysed Lysimachia extracts revealed the dominance of potent anti-oxidants in L. nummularia, L. punctate respectively [2]. Saponine and phenoloid fractions on mitochondrial function was evaluated.

The activity of complex I and II was evaluated in mitoplast from male Balb/c mice heart and liver using a specific electron acceptor, DCIP and NADH or succinate as electron donors. ROS production was measured by Amplex Red; ΔΨm by Rhod123. NADH-level was followed by its endogenous fluorescence. ATP-production was measured in H9C2 cells by bioluminescent luciferase assay.

Whole extract of L. nummularia elevates complex II, while L. punctate reduces spec. complex I and increases complex II activity. L. nummularia reduces succ. mediated elevation of ΔΨm and NADH. In contrast L. punctate inhibits basal and succ. induced elevation of ROS, NADH and ΔΨm Glu./mal. and succ. mediated ATP-production was also significantly inhibited after 1 day of L. nummularia treatment in H9C2 in state 3, but not in case of L. punctate. Phenoloid fraction of L. nummularia reduces both complex I and complex II activity. It reduces basal and succ. induced ROS production and moderates the elevation of ΔΨm and NADH. It inhibits mal./glu. and succ. mediated ATP production. Phenoloid compounds of L. punctate (kaempherol, myricetin, quercetin with glicons) strongly reduce complex I, basal and succ. induced ROS production. In contrast to L. nummularia the fraction increases succ. mediated ATP production. Saponine fraction of L. nummularia reduces complex I but it elevates complex II. It does not influence basal and succ. induced ROS production. It inhibits elevation of ΔΨm and NADH. In addition decrease mal./glu. and succ. mediated ATP production was observed. Saponine fraction of L. punctate reduces complex I but elevates complex II. It does not influence basal and succ. induced ROS production but it inhibits elevation of ΔΨm and NADH. It does not influence mal./glu. but elevates succ mediated ATP production.

L. punctate and L. nummularia both elevated mitochondrial complex II activity and decreased succinate mediated ΔΨm and NADH without influencing ROS production. These data may suggest potential ionophore effects of the extracts. In contrast to saponines, phenoloid fractions showed robust inhibition of ROS production. L. nummularia decreased mitochondrial function in vitro while L. punctate improved it. Composition and content of flavonoids (Table 1. & 2.) in the two species explains their observed different anticancer potential.


Bioblast editor: Kandolf G


Labels: MiParea: mt-Medicine, Pharmacology;toxicology 


Organism: Mouse, Plants  Tissue;cell: Heart, Liver 


Coupling state: OXPHOS  Pathway: N, NS 


Amplex Red 

Affiliations

Toth A(1), Lener V(2), Riethmuller E(1), Kery A(1), Kolonics A(2)
  1. Dept Pharmacognosy, Semmelweis Univ
  2. BioFirmware Ltd; Budapest, Hungary. - attila.kolonics@biofirmware.org

Tables

Toth table1 MiP2017.jpg

Table 1. Summary of mitochondrial effects of L. nummularia & L. punctate

Toth table2 MiP2017.jpg

Table 2. Contribution % of the main compounds detected in the Lysimachia extracts

References

  1. Tian JK, Xu LZ, Zou ZM, Yang SL (2006) Three novel triterpenoid saponins from Lysimachia capillipes and their cytotoxic activities. Chem Pharm Bull (Tokyo) 54(4):567-9.
  2. Toth A, Riethmuller E, Vegh K, Alberti A, Beni S, Kery A (2017) Contribution of individual flavonoids in Lysimachia species to the antioxidant capacity based on HPLC-DPPH assay. Nat Prod Res 27:1-4.