Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages |
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Authors: | Huang Nan Rizshsky Ludmila Hauck Cathy Nikolau Basil J Murphy Patricia A Birt Diane F |
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Institution: | aThe Center for Research on Botanical Dietary Supplements, Iowa State University, Ames, IA 50011, United States;bInterdepartmental Graduate Program in Nutritional Sciences, Iowa State University, Ames, IA 50011, United States;cDepartment of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, United States;dDepartment of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, United States |
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Abstract: | Hypericum perforatum (St. John’s wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies established synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of a H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC–MS analysis established the 4 compounds were present in the H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract’s inhibitory activity on PGE2, NO, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study established that a different group of major anti-inflammatory constituents were present in H. gentianoides, while showing that the previously identified 4 compound combination was important for H. perforatum’s anti-inflammatory potential. |
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Keywords: | Hypericum perforatum Hypericum gentianoides Guttiferae RAW 264 7 macrophages Peritoneal macrophages Inflammation Lipopolysaccharide Acylphloroglucinols Pseudohypericin Prostaglandin E2 Nitric oxide |
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