Anti-Metastatic Effect of Semi-Purified Nuphar Lutea Leaf Extracts

Abstract

Nuphar lutea L. SM., leaf and rhizome extracts (NUP), contain nupharidines as active components. Nupharidines belong to the sesquiterpene lactones class of a naturally occurring plant terpenoids. This family of compounds has gained considerable interest for treating infection, inflammation and cancer.NF-κB is a central, downstream regulator of inflammation, cell proliferation and apoptosis. In our previous work we demonstrated strong inhibition of NF-κB activity and induction of apoptosis by NUP. In addition, NUP exhibited anti-inflammatory properties and partial protection from LPS-induced septic shock by modulating ERK pathway and cytokine secretion in macrophages.In the present study, we examined the effect of NUP in a B16 melanoma experimental murine lung metastasis model and its ability to affect the ERK and NF-κB pathways in variety of cell lines.We showed that NUP and cisplatin combined treatment was synergistic and reduced the lung metastatic load. In addition NUP treatment inhibited TNFα-induced IκBα degradation and NF- κB nuclear translocation. We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-κB inactivation by NUP.Overall, our work implies that co-administration of NF-κB inhibitors such as NUP, with standard anti-cancer drugs, may act as “sensitizers” for more effective chemotherapy.

Nupharidine enhances Aggregatibacter actinomycetemcomitans clearance by priming neutrophils and augmenting their effector functions

“…Based on previous cytotoxic data on cell lines (El‐On et al., ; Ozer et al., , ) and validation on neutrophils (Figure a), two non‐toxic concentrations of Nupharidine (12.5 and 25 μg/ml), were tested on neutrophils. Viability analysis demonstrated approximately 6% non‐vital cells (negative for both apoptosis and necrosis markers) in the control, and 6.41% and 8.39% non‐vital cells in the 12.5 and 25 μg Nupharidine treated cells, respectively.…”

“…Several plant organs of Nuphar lutea (Yellow Water Lilly) are used in traditional medicine for the treatment of arthritis, fever, aches, pains and inflammation (Ozer et al., ). We showed that semi‐purified extracts of Nuphar lutea containing active thio‐sesquiterpene molecules, Nupharidine (6,6′‐Dihydroxythiobinupharidine), have anti‐cancer and pro‐apoptotic activity (Ozer, Fishman, Eilam, Golan‐Goldhirsh, & Gopas, ; Ozer et al., ), as well as anti‐inflammatory (Ozer, Levi, Golan‐Goldhirsh, & Gopas, ) and modulatory effects on NF‐κB (Ozer et al., ). In addition, it has anti‐leishmanial activity (El‐On, Ozer, Gopas, Sneir, & Golan‐Goldhirsh, ) and increased iNOS production by macrophages, against Leishmania major (Ozer, El‐On, Golan‐Goldhirsh, & Gopas, ).…”

Nuphar lutea Extracts Exhibit Anti-Viral Activity against the Measles Virus

“…The extract has anti-metastatic properties, synergistically with conventional chemotherapy drugs, both in vitro and in vivo. It also induces phospho-extracellular signal-regulated kinases (ERK) expression [14].…”

“…A systematic review of early studies revealed that the full therapeutic potential of Nuphar products is still largely unexplored by modern research [5]. Nevertheless, recent reports from various laboratories, including ours, on the medicinal properties of Nuphar extracts have indicated potential applications: as anti-inflammatory [6], anti-bacterial [7,8] against pathogenic fungi [9], against the leishmania and trypanosome parasites, [10][11][12], and against cancer [7,13,14].…”

6,6′-Dihydroxythiobinupharidine (DTBN) Purified from Nuphar lutea Leaves Is an Inhibitor of Protein Kinase C Catalytic Activity

“…We also observed that NUP induced ERK activation. Furthermore, ERK inhibition prevented NF-κB inactivation by NUP [ 5 , 11 , 12 ]. We have recently published that 6,6′-dihydroxythiobinupharidine (DTBN), purified from NUP, very efficiently and covalently inhibited human type II topoisomerase [ 13 ].…”