Aim or purpose Cistanche genus, belonging to Orobanchaceae family, comprises about 20 species, distributed in arid and semi-arid regions of Africa, Asia and Mediterranean area [1]. Several Cistanche species are used in the traditional Chinese medicine as tonic for treatment of different diseases [2]. The aim of this study is the phytochemical investigation of Cistanche phelypaea (L.) Coutinho, a perennial parasite plant, used in North Africa traditional medicine for diarrhoea, diabetes, intestinal troubles, infection, and as a diuretic [3]. The inhibitory activity of isolated compounds on human lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL), enzymes involved in the peculiar glycolytic or lipidic metabolism of cancer cells, was also investigated. Materials and methods C. phelypaea aerial parts were collected in March 2012 in the South-West of Algeria. The dried and powdered material was extracted at room temperature with solvent at increasing polarity. The n-butanol extract was subjected to column chromatography over Sephadex LH-20, followed by RP-HPLC. The structures of isolated compounds were elucidated on the basis of 1D and 2D NMR experiments and HRESI-MS technique. All the compounds were assayed against purified hLDH5 and hMAGL. The binding mode of the most active compound in the MAGL active site was investigated by modeling studies. Results The phytochemical study of the n-butanol extract of C. phelypaea aerial parts afforded the isolation of four new phenylethanoid glycosides (1-4), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-L-rhamnopyranosyl-β-D-glucopyranoside (1), 1-β-p-hydroxyphenyl-ethyl-3,6-O-di-α-L-rhamnopyranosyl-β-D-glucopyranoside (2), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-L-rhamnopyranosyl-4-p-coumaroyl-β-D-glucopyranoside (3), and 1-β-p-hydroxyphenyl-ethyl-3,6-di-α-L-rhamnopyranosyl-4-p-coumaroyl-β-D-glucopyranoside (4), together with three known compounds, named brandioside, pinoresinol 4-O-β-D-glucopyranoside, and apigenin 7-O-β-glucuronopyranoside. All the compounds were inactive on LDH, whereas some of them displayed a certain inhibition activity on MAGL. In particular, compound 1 was the most active on MAGL showing an IC50 = 88.0 µM and modeling studies rationalized the supposed binding mode of compound 1 in the MAGL active site. Conclusions In conclusion, four new phenylethanoids (1-4) were isolated from the C. phelypaea aerial parts, together with three known compounds. Moreover, several compounds showed a promising activity on hMAGL. This is the first report of naturally occurring phenyletanoid as a MAGL inhibitor.

Phenylethanoid glycosides from Cistanche phelypaea acting as monoacylglycerol lipase inhibitors

M. De Leo;C. Granchi;G. Bononi;A. Braca
2018-01-01

Abstract

Aim or purpose Cistanche genus, belonging to Orobanchaceae family, comprises about 20 species, distributed in arid and semi-arid regions of Africa, Asia and Mediterranean area [1]. Several Cistanche species are used in the traditional Chinese medicine as tonic for treatment of different diseases [2]. The aim of this study is the phytochemical investigation of Cistanche phelypaea (L.) Coutinho, a perennial parasite plant, used in North Africa traditional medicine for diarrhoea, diabetes, intestinal troubles, infection, and as a diuretic [3]. The inhibitory activity of isolated compounds on human lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL), enzymes involved in the peculiar glycolytic or lipidic metabolism of cancer cells, was also investigated. Materials and methods C. phelypaea aerial parts were collected in March 2012 in the South-West of Algeria. The dried and powdered material was extracted at room temperature with solvent at increasing polarity. The n-butanol extract was subjected to column chromatography over Sephadex LH-20, followed by RP-HPLC. The structures of isolated compounds were elucidated on the basis of 1D and 2D NMR experiments and HRESI-MS technique. All the compounds were assayed against purified hLDH5 and hMAGL. The binding mode of the most active compound in the MAGL active site was investigated by modeling studies. Results The phytochemical study of the n-butanol extract of C. phelypaea aerial parts afforded the isolation of four new phenylethanoid glycosides (1-4), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-L-rhamnopyranosyl-β-D-glucopyranoside (1), 1-β-p-hydroxyphenyl-ethyl-3,6-O-di-α-L-rhamnopyranosyl-β-D-glucopyranoside (2), 1-β-p-hydroxyphenyl-ethyl-2-O-acetyl-3,6-di-α-L-rhamnopyranosyl-4-p-coumaroyl-β-D-glucopyranoside (3), and 1-β-p-hydroxyphenyl-ethyl-3,6-di-α-L-rhamnopyranosyl-4-p-coumaroyl-β-D-glucopyranoside (4), together with three known compounds, named brandioside, pinoresinol 4-O-β-D-glucopyranoside, and apigenin 7-O-β-glucuronopyranoside. All the compounds were inactive on LDH, whereas some of them displayed a certain inhibition activity on MAGL. In particular, compound 1 was the most active on MAGL showing an IC50 = 88.0 µM and modeling studies rationalized the supposed binding mode of compound 1 in the MAGL active site. Conclusions In conclusion, four new phenylethanoids (1-4) were isolated from the C. phelypaea aerial parts, together with three known compounds. Moreover, several compounds showed a promising activity on hMAGL. This is the first report of naturally occurring phenyletanoid as a MAGL inhibitor.
File in questo prodotto:
File Dimensione Formato  
Abstract Book-ICMPR 2018.pdf

solo utenti autorizzati

Tipologia: Versione finale editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 877.42 kB
Formato Adobe PDF
877.42 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/926344
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact