ISHS Acta Horticulturae 668: I International Humulus Symposium
HOP AND MODIFIED HOP EXTRACTS HAVE POTENT IN VITRO ANTI-INFLAMMATORY PROPERTIES |
| Authors: | M. Tripp, G. Darland, R. Lerman, D. Lukaczer, J. Bland, J. Babish |
| Keywords: | Humulus lupulus, hops, hop extracts, alpha acids, isoalpha acids, cyclooxygenase, anti-inflammatory activity, prostaglandin E2 inhibition |
| Abstract:
A key component of inflammation is the increase in prostaglandin biosynthesis resulting from induction of the cyclooxygenase 2 (COX2) gene. The COX2 enzyme is the prime target of non-steroidal anti-inflammatory drug (NSAID) therapy. COX2 is constitutively expressed in some tissues such as the gastrointestinal tract and its inhibition may result in GI toxicity. Our goal was to identify inhibitors of prostaglandin production that were not direct COX enzyme inhibitors. We screened natural products for inhibition of prostaglandin E2 production in lipopolysaccharide (LPS)-induced mouse macrophage RAW 264.7 cells. Altering the test, methodology allowed circumstantial assessment of in vitro inhibition of COX1 and COX2 enzymes, or COX2 gene induction. Various hop (hydrophobic and hydrophilic) and modified (IAA, RIAA, THIAA, HHIAA) hop extracts were found to be among the most potent PGE2 inhibitors in LPS induced (PGE2 from COX2) but not non-induced (PGE2 from COX1) RAW 264.7 cells, indicating COX2 selectivity (ranging from 1.5- to 363-fold). In a human gastric mucosal cell (AGS) model where COX2 is constitutively expressed, a CO2 hop extract showed strong inhibition of PGE2; in contrast, no significant PGE2 inhibition was observed by the other hop extracts, indicating a lack of direct COX enzyme inhibition. Correlating the in vitro models [log10 (IC50AGS/IC50 RAW264.7)] allowed us to calculate a therapeutic index for each hop extract compared to various NSAIDs. We conclude that RIAA, IAA, THIAA, HHIAA, BA, and AA have strong potential as anti-inflammatory agents and predict, from our models, that they may have a low GI toxicity. An RIAA based anti-inflammatory preparation, Meta050, was tested clinically in a human pilot trial and showed efficacy against osteoarthritis pain. | |
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