138
J. Pospíšil et al.
From the lignan compound class, (–)-arctigenin (56) (extracted from Arctium lappa)
shows interesting activity due its capability to decrease NO
• levels and those of a
pro-inflammatory cytokine. Other biological activities that have been determined for
(–)-arctigenin (56) include antiviral (against influenza A), antioxidant, and antiproliferative activities (inhibition of protein kinase B in PANC-1 pancreatic cancer cells).
It was also observed that compound 56 is, upon metabolism by intestinal bacteria,
transformed to a group of structurally related bioactive metabolites [206–210]. The
antiproliferative activity of lignan 56 is believed to be caused by inhibition of the transcription factor STAT3. In addition, several other cytotoxic activities were reported
for arctigenin (56), against breast cancer (MDA-MB-231, -435S, -453, and -468, with
IC 50 values ranging from 0.285 μM to 3.756 μM), gall bladder cancer (by modulation of epidermal growth factor pathway), and human glioma (by induction of
G0/G1 cell cycle arrest) cells [197, 211–213]. The biosynthetically related lignans,
5
-methoxy-yatein (57) and taiwanin C (58), were shown to interact via COX-2
(the cyclooxygenase-2 enzyme) to inhibit the transformation of arachidonic acid to
prostaglandin E2 (PGE2). Prostaglandins are required to trigger the inflammation
process [214]. Savinin (59) modulates the inflammatory process via the inhibition
of tumor necrosis factor-alpha (TNF-α) and as a result of the proliferation of T cells
[215]. Alashinol A (60) inhibits the production of TNF-α and interleukin-6 [216]. The
lignans asarinin B (61), neoasarinin A–C (62–64), and neoasarininoside A (65) and
B (66), isolated from Asarum heterotropoides, also possess anti-inflammatory activities, which are associated with the inhibition of PAF (platelet activation factor), based
on the cell-based assay used [217]. Secoisolariciresinol diglucoside (67) (a lignan
glycoside extracted from flax seeds) may be able to reduce inflammation in the brain
[218].
3.3.5 Antiallergenic Activity
“Allergy,” as a definition of a collection of diseases, was first introduced in 1906. Over
time, this definition has undergone minor modifications, to refer presently to an exaggerated immune sensitivity to certain environmental compounds or allergens. It is a
hypersensitive response mechanism of the immune system to these allergens, acting
as antigens, occurring in susceptible individuals. Most allergic reactions are mediated
by a type I (anaphylaxis) immune mechanism. The term “atopy” is used if a patient
has a hereditary predisposition toward the development of certain hypersensitivity
reactions. From a mechanistic viewpoint, atopy refers to the hereditary predisposition to produce immunoglobulin type E antibodies against common environmental
allergens causing atopic diseases (allergic rhinitis, asthma, and atopic eczema) [219].
Since this condition results from the overreaction of the immune system, it is perhaps
not surprising that many plant phenols (Fig. 11) possess activities potentially useful
for allergy treatment. Table 4 contains a simplified overview of several lignans and
neolignans that have shown allergy-related activities [220–226].
J. Pospíšil et al.
From the lignan compound class, (–)-arctigenin (56) (extracted from Arctium lappa)
shows interesting activity due its capability to decrease NO
• levels and those of a
pro-inflammatory cytokine. Other biological activities that have been determined for
(–)-arctigenin (56) include antiviral (against influenza A), antioxidant, and antiproliferative activities (inhibition of protein kinase B in PANC-1 pancreatic cancer cells).
It was also observed that compound 56 is, upon metabolism by intestinal bacteria,
transformed to a group of structurally related bioactive metabolites [206–210]. The
antiproliferative activity of lignan 56 is believed to be caused by inhibition of the transcription factor STAT3. In addition, several other cytotoxic activities were reported
for arctigenin (56), against breast cancer (MDA-MB-231, -435S, -453, and -468, with
IC 50 values ranging from 0.285 μM to 3.756 μM), gall bladder cancer (by modulation of epidermal growth factor pathway), and human glioma (by induction of
G0/G1 cell cycle arrest) cells [197, 211–213]. The biosynthetically related lignans,
5
-methoxy-yatein (57) and taiwanin C (58), were shown to interact via COX-2
(the cyclooxygenase-2 enzyme) to inhibit the transformation of arachidonic acid to
prostaglandin E2 (PGE2). Prostaglandins are required to trigger the inflammation
process [214]. Savinin (59) modulates the inflammatory process via the inhibition
of tumor necrosis factor-alpha (TNF-α) and as a result of the proliferation of T cells
[215]. Alashinol A (60) inhibits the production of TNF-α and interleukin-6 [216]. The
lignans asarinin B (61), neoasarinin A–C (62–64), and neoasarininoside A (65) and
B (66), isolated from Asarum heterotropoides, also possess anti-inflammatory activities, which are associated with the inhibition of PAF (platelet activation factor), based
on the cell-based assay used [217]. Secoisolariciresinol diglucoside (67) (a lignan
glycoside extracted from flax seeds) may be able to reduce inflammation in the brain
[218].
3.3.5 Antiallergenic Activity
“Allergy,” as a definition of a collection of diseases, was first introduced in 1906. Over
time, this definition has undergone minor modifications, to refer presently to an exaggerated immune sensitivity to certain environmental compounds or allergens. It is a
hypersensitive response mechanism of the immune system to these allergens, acting
as antigens, occurring in susceptible individuals. Most allergic reactions are mediated
by a type I (anaphylaxis) immune mechanism. The term “atopy” is used if a patient
has a hereditary predisposition toward the development of certain hypersensitivity
reactions. From a mechanistic viewpoint, atopy refers to the hereditary predisposition to produce immunoglobulin type E antibodies against common environmental
allergens causing atopic diseases (allergic rhinitis, asthma, and atopic eczema) [219].
Since this condition results from the overreaction of the immune system, it is perhaps
not surprising that many plant phenols (Fig. 11) possess activities potentially useful
for allergy treatment. Table 4 contains a simplified overview of several lignans and
neolignans that have shown allergy-related activities [220–226].