Anti-austeric Activity of Phenolic Constituents of Seeds of Arctium lappa

Abstract

From seeds of Arctium lappa L. (Asteraceae) we obtained arctigenin (1), arctiin (2), chlorogenic acid (3), 4,5-dicaffeoylquinic acid (4), 3,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), matairesinol (11), isolappaol A (12), lappaol F (14), and lappaol B (15), together with 1:1 mixtures of isolappaol C (7) and lappaol C (8), arctignan E (9) and arctignan D (10), and 12 and lappaol A (13), while 3,3',4'-triO -demethylarctigenin (16), 3,3'-di-O-demethyl-4'dehydroxyarctigenin (17), and 3-O-demethylarctigenin (18) were obtained by anaerobic microbiological metabolism of 1. Then, we evaluated the in vitro preferential cytotoxic activity of these pure compounds and 1:1 mixtures, together with enterodiol (19) and enterolactone (20), against human pancreatic cancer PANC-1 cells in nutrient-deprived medium (NDM). Among them, 1 and 18 showed potent activity, with PC 50 values of 1.75 and 4.38 M, respectively, while 11, 15, and 17 showed mild activity with PC 50 values of 31.1, 30.9, and 38.7 M, respectively. By comparing their structures and PC 50 values, the following structural moieties could be concluded to be important for the preferential cytotoxicity of 1: 1) the 3-hydroxy-4-methoxyphenyl group at the 2-position on the -butyrolactone ring, 2) the less polar substituent at the 3-position on the -butyrolactone ring, and 3) the -butyrolactone ring.

Therapeutic Value of Arctium Lappa Linn. – A Review

“…ATG specifically inhibited the proliferation of cancer cells, which might consequently lead to the induction of apoptosis [21]. ATG and many other chemicals from Arctium were found to have cytotoxic activity against human pancreatic cancer PANC-1 cells in nutrient-deprived medium [22]. Lappaol F from plant AL L. Lappaol F suppressed cancer cell growth in a time-and dose-dependent manner in human cancer cell lines of various tissue types [23].…”

Antiausterity Activity of Arctigenin Enantiomers: Importance of (2R,3R)-Absolute Configuration

“…Among the seven arctigenin derivatives, on the other hand, (-)-enantiomers of arctigenin (1*) [9], matairesinol (2*) [9], and trachelogenin (3*) [18] were isolated from a CHCl 3 extract of the powdered stems of Trachelospermum asiaticum Nakai (Apocynaceae). Then, we evaluated the in vitro preferential cytotoxic activity of all of the isolated compounds against human pancreatic cancer PANC-1 cells in nutrient-deprived medium (NDM) ( Figure 2).…”

“…In a continuing study, we examined the preferential cytotoxicity of arctigenin-related compounds and the following structural moieties could be concluded to be important for the preferential cytotoxicity of arctigenin: 1) the 3-hydroxy-4-methoxyphenyl group at the 2-position on the -butyrolactone ring, 2) the less polar substituent at the 3-position on the -butyrolactone ring, and 3) the -butyrolactone ring [9]. On the other hand, it is well known that the chirality is important for pharmacological activity and/or toxicity [10,11].…”

“…In the separation procedure, we also obtained a new guaian-type sesquiterpene (4,10,11-guaiatrien-3one-14-oic acid) and eight known compounds: oleodaphnal, 1,7,10H-guaia-4,11-dien-3-one, 7-methoxycoumarin, 7hydroxycoumarin (umbelliferone), daphnogitin, daphnoretin, salicifoliol, and (−)-pinoresinol [17]. Among the seven arctigenin derivatives, on the other hand, (-)-enantiomers of arctigenin (1*) [9], matairesinol (2*) [9], and trachelogenin (3*) [18] were isolated from a CHCl 3 extract of the powdered stems of Trachelospermum asiaticum Nakai (Apocynaceae). Then, we evaluated the in vitro preferential cytotoxic activity of all of the isolated compounds against human pancreatic cancer PANC-1 cells in nutrient-deprived medium (NDM) (Figure 2).…”

“…The PANC-1 cell line is highly resistant to nutrient starvation, and can survive in NDM even after 48 h of starvation [6][7][8]. This tolerance to nutrient starvation was reported to be eliminated by (-)-arctigenin and (-)-matairesinol [8,9]. As reported, (-)-enantiomers [(-)arctigenin (1*), (-)-matairesinol (2*), and (-)-trachelogenin (3*)], which have the (2R,3R)-absolute configuration, exhibited preferential cytotoxicity in a concentration-dependent manner with PC 50 values of 0.54, 6.82, and 5.85 M, respectively.…”