Phytochemical, Chemopreventive and Antimalarial Activity Evaluation of Five Selected Medicinal Plants from the Cameroonian Flora

Screening of ethnomedicinal plants for antimalarial and chemopreventive activities among plants used in Cameroonian folklore medicine to treat fevers, malaria and tumour was conducted on Croton oligandrus (Euphorbiaceae), Justicia hypocrateriformis (Acanthanceae), Pseudospondias microcarpa (Anacardiaceae), Zanthoxylum lepreurii and Zanthoxylum zanthoxyloides (Rutaceae). The selection of plants was based on ethnomedicinal use and literature review. Bioassay-guided isolation of active components from the active plants was performed with the aim to scientifically validate their folklore usage. The plant materials were dried, ground, and Soxhlet-extracted, successively, with n-hexane, dichloromethane (DCM) and methanol (MeOH). The antimalarial and chemopreventive potential of the plants were evaluated using haem polymerisation and the luciferase assays, respectively. The n-hexane and the DCM extracts of C. oligandrus, and the DCM and MeOH extracts of Z. zanthoxyloides were the most active in the luciferase assay causing 18, 21, 34 and 36-fold induction of the level of luciferase in AREc32 cells, respectively. Pseudospondias microcarpa was the most active antimalarial plant with IC50 values of 73.9 ± 25.8, 2.5 ± 1.5 and 4.0 ± 1.7 µM for the stem bark n-hexane, DCM and MeOH extracts, respectively, and 13.0 ± 9.0 µM for the leaves MeOH extract. Fifty-one compounds including eleven novel ones were isolated from active fractions using column chromatography, thin layer chromatography and reversed-phase high-pressure liquid chromatography. Structural elucidation was carried out by spectroscopic means including 1D and 2D NMR and mass spectrometry. Crotonolins A-D, skimmianine, hesperidin and myrtopsine were identified as potent chemopreventive compounds with fold induction greater than 2. None of the isolated compounds demonstrated any inhibition of haem polymerisation. This study generated the first phytochemical report on P. microcarpa, the second of C. oligandrus and the third of J. hypocrateriformis. The biogenesis and chemotaxonomy of isolated compounds have also been discussed

Zanthoamides G-I: Three new alkamides from Zanthoxylum zanthoxyloides

Three new alkamides, zanthoamides G-I (1-3), together with ten known compounds, araliopsine, skimmianine, N-methylplatydesminium cation, isoplatydesmine, myrtopsine, atanine, N-methylatanine, sesamin, hesperetin and hesperidin, were isolated from the fruits of Zanthoxylum zanthoxyloides. Their structures were elucidated by spectroscopic means. All isolated compounds were assessed for their cytotoxicity against A549, MCF7, PC3 and PNT2 cell lines. Among the alkamides, only zanthoamide G (1) showed low level of cytotoxicity against MCF7 cells

Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-B transcription factor and NLRP3 inflammasome activation

Objectives: The effects of a root extract of Zanthoxylum zanthoxyloides on neuroinflammation in BV-2 microglia stimulated with LPS and hemozoin were investigated. Methods: ELISA, enzyme immunoassay and Griess assay were used to evaluate levels of cytokines, PGE2 and NO in culture supernatants, respectively. Microgliamediated neurotoxicity was evaluated using a BV-2 microglia-HT-22 neuron transwell co-culture. Key findings: Treatment with Z. zanthoxyloides caused reduced elevated levels of TNF, IL-6, IL-1, NO, and PGE2, while increasing the levels of IL-10. In addition, there were reduced levels of iNOS and COX-2 proteins. This was accompanied by a prevention of microglia-mediated damage to HT-22 mouse hippocampal neurons. Z. zanthoxyloides reduced elevated levels phospho-IB and of phospho-p65, while preventing degradation of IB protein and DNA binding of p65. Further mechanistic studies revealed that Z. zanthoxyloides reduced the levels of pro-IL-1 and IL-1 in hemozoin-activated BV-2 microglia. This was accompanied by a reduction in caspase-1 activity and NLRP3 protein expression. Bioassay-guided fractionation resulted in the isolation of skimmianine as an anti-inflammatory compound in Z. zanthoxyloides. Conclusion: This is the first report showing inhibition of neuroinflammation in LPSand hemozoin-activated BV-2 microglia by the root extract of Z. zanthoxyloides by targeting the activation of both NF-B and NLRP3 inflammasome

Flavonoids from two Turkish Centaurea species and their chemotaxonomic implications

Centaurea asutro-anatolica Hub.-Mor. and C. kizildaghensis Uzunh., E. Doğan & H. Duman, two indigenous perennial herbs from the Turkish flora, belong to the medicinally important genus Centaurea L. (fam: Asteraceae), which comprises ca. 600 species worldwide. While various Centaurea species are well-known for producing alkaloids, flavonoids, lignans and terpenoids, there is no report on any thorough phytochemical work on any of these two species available to date. In continuation of our phytochemical and bioactivity studies on the Turkish Centaurea species, four flavonoids apigenin (1), apigenin 7,4’-dimethyl ether (2), genkwanin (3) and quercetin (4) were isolated from the methanol extracts of the aerial parts of C. austro-anatolica and C. kizildaghensis, for the very first time. The structures of the flavonoids were elucidated conclusively by spectroscopic means, i.e., UV, MS and 1D and 2D NMR data analyses. The distribution of these flavonoids (1-4) within the genus Centaurea and their possible chemotaxonomic implications within the genus Centaurea or the family Asteraceae have been discussed