Spent hops extract (Humulus Lupulus L.) attenuates inflammation and angiogenesis of the retina via the nuclear factor-kappaB and protein kinase B/extracellular signal-regulated kinase pathways.

Spent hops extract (SHE) is a plant extract containing compounds with proven anti-inflammatory and anti-angiogenic activities. However, extract may exert synergic effects compared to its individual polyphenol components. Inflammatory diseases of the retina may lead to visual impairment, a reduction of the comfort of life, and even blindness due to the formation of new pathological blood vessels. More effective therapeutic options are being sought. The goal of the present study was to investigate the anti-inflammatory and anti-angiogenic potentials of SHE on human retinal pigment epithelial cells (ARPE-19) stimulated by lipopolysaccharide (LPS) or tumor necrosis factor alpha (TNF-α). The SHE (250 µg/mL) was found to downregulate the gene expression of interleukin 6 (IL-6) to 33% in LPS-triggered cells; it also reduced both matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) mRNA expression to 13% and 43% respectively, and their activity to 82% (MMP-2) and 57% (MMP-9), compared to TNF-α-stimulated cells. Also, SHE modulated the TNF-α-induced expression of vascular endothelial growth factor (VEGF) and endothelial growth factor receptor 2 (VEGFR2). It is possible that SHE inhibited retinal inflammation and angiogenesis by suppressing the nuclear factor kappa B (NF-κB), protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) pathways. Our results demonstrate that SHE has anti-inflammatory and anti-angiogenic potential against retinal diseases. This is the first such study to report on the efficacy of SHE on retinal inflammatory diseases.

Chemopreventive properties of spent hops (Humulus Lupulus L.) extract against angiogenesis, invasion and migration of colorectal cancer cells.

There is a great deal of interest in identifying new chemopreventive agents for colorectal cancer, one of the leading causes of cancer-related death. One promising group of candidates is the polyphenols; being natural compounds with high structural diversity, they have a very wide spectrum of anti-inflammatory, anti-oxidant and anti-cancer properties. The present study reports for the first time that spent hops extract (SHE) inhibits the angiogenesis, invasion and migration of SW-480 and HT-29 colorectal adenocarcinoma cells; after incubation with 200 µg/mL SHE, SW-480 and HT-29 cell invasion fell by 98.5% and 89% vs. controls, and migration was inhibited by 99% and 88% vs. controls. These changes were accompanied by a decline of matrix metalloproteinase 2 (MMP-2) and MMP-9 expression and activity. In addition, SHE reduced the expression of vascular endothelial growth factor and hypoxia-inducible factor 1α for both cell lines, indicating that the tested extract has anti-angiogenic potential. In conclusion, our data shows that SHE may be an effective chemopreventive agent acting via the inhibition of angiogenesis, invasion and migration of colorectal cancer cells.

Spent hops (Humulus Lupulus L.) extract as modulator of the inflammatory response in lipopolysaccharide stimulated RAW 264.7 macrophages.

Macrophages play important roles in acute and chronic inflammation. Upon their activation, they secrete a variety of mediators, including eicosanoids, nitric oxide and cytokines, which play different roles in the stimulation and resolution of inflammatory processes. There is a continuous search for selective modulators of these processes. Natural polyphenols and polyphenol-rich extracts have been found to possess preventive and therapeutic potential, including by their anti-inflammatory effects. In this study, the inhibition of the formation of inflammatory mediators by the spent hops extract (SHE), a polyphenol-rich extract from Humulus Lupulus L., was examined using lipopolysaccharide (LPS)- activated murine macrophages (RAW 264.7). The SHE suppressed inter alia the interleukin-6 (IL-6) mRNA expression to 32% in LPS-activated macrophages and to 61% at a protein level (at 25 µg/mL). SHE reduced both the cyclooxygenase-2 (COX-2) mRNA expression to 47% and their protein expression to 32%. Not only did SHE inhibit the IL-6 and COX-2 levels but also decreased both inducible nitric oxide synthase (iNOS) protein expression to 2% at 25 µg/mL and nitric oxide (NO) production for all tested concentrations. The inhibited expression of these inflammatory molecules was likely caused by the reduced activity of nuclear factor-κB (NF-κB). Both mRNA and protein expression of NF-κB was decreased to 38% and 42%, respectively. These results provide the first evidence that SHE decreases the expression of proinflammatory cytokines and inflammatory mediators, which merits further studies to investigate the potential of SHE as anti-inflammatory preparation.