The genus Phlomis (Lamiaceae) includes about 100 species distributed mainly in the Mediterranean region, central Asia and China. Ten species of Phlomis are found in the flora of Jordan. Among them, Phlomis kurdica Rech.f. is a hairy and woody perennial herb, 30-80 cm long and many stemmed, leaves petiolate ovate-cordate, flowers up to ten arranged in circles along the verticillate (1). Many species of Phlomis are used in the folk medicine for the treatment of various ailments including inflammation, diabetes, ulcer, allergy, infection and cancer (2). The Jordan flora is considered one of most attractive in the Middle East due to its biodiversity (1, 3) and potentiality to discover new bioactive natural molecules (4, 5). In the last decade our research group successfully detected a good number of compounds obtained from Jordanian plants with anticancer effect, elucidating different mechanisms of action including tyrosine ligase inhibition activity and binding affinity to heat shock protein 90 (4, 5). Since some species of Phlomis proved to possess anti-cancer properties (2), the crude extracts of P. kurdica aerial parts were assayed for their lactate dehydrogenase (LDH) inhibitory activity, an enzyme that is up-regulated in tumor tissues. In fact, cancer cells depend mainly on anaerobic respiration and their glycolytic rate is up to 200 times higher than that of the normal tissue. This fermentative glycolysis is catalyzed by an overexpression of the A form of LDH. Inhibition of LDH is so considered as a promising target in cancer treatment, since it is possible to cause a starving of cancerous cells by reducing glycolysis or by inhibiting the conversion of glucose to lactate (6). Active extracts were subjected to different fractionation procedures to isolate two new flavonoids (1 and 2) and one new phenylpropanoid (3) (Fig. 1), together with eleven known phenolic compounds, including flavonoids and phenylpropanoids. All pure compounds were assayed for their LDH inhibitory activity. Luteolin 7-O-β-D-glucopyranoside showed an IC50 value similar to that of reference compound galloflavin.
Flavonoids and phenylpropanoids from Phlomis kurdica rech. f. (Lamiaceae) as inhibitors of lactate dehydrogenase
BRACA, ALESSANDRA;MINUTOLO, FILIPPO
2014-01-01
Abstract
The genus Phlomis (Lamiaceae) includes about 100 species distributed mainly in the Mediterranean region, central Asia and China. Ten species of Phlomis are found in the flora of Jordan. Among them, Phlomis kurdica Rech.f. is a hairy and woody perennial herb, 30-80 cm long and many stemmed, leaves petiolate ovate-cordate, flowers up to ten arranged in circles along the verticillate (1). Many species of Phlomis are used in the folk medicine for the treatment of various ailments including inflammation, diabetes, ulcer, allergy, infection and cancer (2). The Jordan flora is considered one of most attractive in the Middle East due to its biodiversity (1, 3) and potentiality to discover new bioactive natural molecules (4, 5). In the last decade our research group successfully detected a good number of compounds obtained from Jordanian plants with anticancer effect, elucidating different mechanisms of action including tyrosine ligase inhibition activity and binding affinity to heat shock protein 90 (4, 5). Since some species of Phlomis proved to possess anti-cancer properties (2), the crude extracts of P. kurdica aerial parts were assayed for their lactate dehydrogenase (LDH) inhibitory activity, an enzyme that is up-regulated in tumor tissues. In fact, cancer cells depend mainly on anaerobic respiration and their glycolytic rate is up to 200 times higher than that of the normal tissue. This fermentative glycolysis is catalyzed by an overexpression of the A form of LDH. Inhibition of LDH is so considered as a promising target in cancer treatment, since it is possible to cause a starving of cancerous cells by reducing glycolysis or by inhibiting the conversion of glucose to lactate (6). Active extracts were subjected to different fractionation procedures to isolate two new flavonoids (1 and 2) and one new phenylpropanoid (3) (Fig. 1), together with eleven known phenolic compounds, including flavonoids and phenylpropanoids. All pure compounds were assayed for their LDH inhibitory activity. Luteolin 7-O-β-D-glucopyranoside showed an IC50 value similar to that of reference compound galloflavin.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
