Phytochemical Analysis of Selected Tephrosia Species for Anti-inflammatory Principles

Abstract

Inflammation is a vital immune process in the restoration of inflamed tissues and it is regulated by mediators such as cytokines. However, dysregulation of inflammation is associated with the onset and development of chronic respiratory diseases and cancer. The management of inflammation and associated diseases using currently available anti-inflammatory drugs such as ibuprofen has been linked with adverse side effects. Thus, there is a need to develop alternative anti-inflammatory drugs. Plants of the genus Tephrosia Pers. (Fabaceae) have been used widely in ethnomedicine in the management of various ailments and they elaborate diversity of flavonoids. Although flavonoids are reported to have anti-inflammatory effects, little has been reported on the anti-inflammatory properties of flavonoids from the genus Tephrosia. Therefore, in this study selected Tephrosia species (T. linearis, T. hildebrandtii, T. vogelii, T. elata, and T. rhodesica) were phytochemically analyzed with the aims of identifying flavonoids with anti-inflammatory effects. The methanol-dichloromethane (1:1) crude extracts of these plants were fractionated on silica gel and purified using Sephadex LH-20, chromatotron and preparative HPLC. HRESIMS, ECD and NMR data were used to characterize the compounds. The anti-inflammatory activities of the isolated compounds as well as the crude extracts were evaluated for inhibition of cytokine production [interleukins (IL-1β, IL-2, IL-6), interferon-gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-α)] from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs). Ibuprofen was used as a standard drug for anti-inflammation. Overall, fifty-six (56) compounds were identified from the selected Tephrosia species, eleven of which were new compounds and one derivative was prepared. From the aerial parts of T. linearis, seven new flavonoids [lineaflavone A-D (1-4), 6-methoxygeraldone (5), acetylobovatin (6) and 5-hydroxy-7-methoxysaniculamin A (7)] and seventeen known compounds (8-24) were isolated. From the aerial parts of T. hildebrandtii, a new flavone, hildeflavone (25) and ten known compounds (22, 26-34) were isolated. T. vogelii seedpods yielded two new isoflavones [vogelisoflavone A (35) and vogelisoflavone B (36)] and ten known compounds (34, 37-43). From the stem of T. elata one new isoflavone, elatisoflavone (44) and three known isoflavones (45-47) were isolated. Eleven known compounds (21, 23 and 48-56) were isolated from the extract of stem of T. rhodesica stem. Pyrazoisopongaflavone (57), a pyrazole derivative of isopongaflavone (38) was prepared. Lineaflavone B (2), luteolin (13), patuletin-3-O-rhamnoside (16), pisatin (30), vogelisoflavone B (36), isopongaflavone (38) and genistein (55) exhibited stronger anti-inflammatory activities compared to the standard drug, ibuprofen. In synergetic studies, combinations of flavonoids showed superior anti-inflammatory activities over the individual flavonoids. The findings of this study imply that flavonoids from the genus Tephrosia could be used as templates for anti-inflammatory drug discovery