154
J. Pospíšil et al.
Melanogenesis is a physiological process connected with melanin production that is carried out in melanosomes by melanocyte cells. Thus, specialized
dendritic cells (melanocytes) synthesize and transfer pigment to recipient cells.
However, if malignant melanocytes upregulate melanogenesis, the overall process
can become dangerous and, in some cases, even life threatening [354]. Several
phenolic compounds have demonstrated biological effects that may allow for the
regulation of this process. For example, when americanin A (150) was applied
at a concentration of 20 μM, it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) expression in melanocytes [355].
Gomisin N (107) at concentrations of 1–10 μM regulated the phosphatidylinositol 3kinase/serine/threonine protein kinase B (PI3K/Akt) and mitogen-activated protein
kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK) signaling pathway
[356]. (+)-Zuonin A ((+)-151), when applied at concentrations ranging from 1 to
20 μM, inhibited melanogenesis by decreasing levels of tyrosinase and tyrosinaserelated proteins (TRP-1 and 2). Interestingly, its enantiomer, (–)-zuonin A ((–)-151),
inhibited c-Jun N-terminal kinases that are associated with several diseases such as
cancer and neurological disorders, but did not interact with tyrosinase and tyrosinaserelated proteins [357, 358]. Galanganol D diacetate (152) inhibited melanogenesis
(IC 50 = 2.5 μM), presumably via a TYR, TRP-1, and 2 mRNA expression inhibition
mechanism [359].
The liver, the largest solid organ in the human body, is a vital metabolic and
immune “factory.” Its primary functions are to transform and “dismantle” substances,
mine energy, and detoxify the organism. The human liver has an enormous capacity
to regenerate, but even with such a regenerative capacity, can be harmed by many
diseases, toxins, and pathogens. It was shown that several plant phenols have potentially important hepatoprotective activity [360]. The lignan arctigenin (56) was found
to reduce via an immunosuppressive mechanism acute hepatitis [361]. Micrantherin A (153), gomisin M2 (154), and schizandrin (155), obtained from Schisandra
chinensis, showed an ability to protect liver tissue against paracetamol damage (tested
on HepG2 human liver carcinoma cells) [362]. Angeloylgomisin R (156) and schisantherin A (157), from Schisandra pubescens, on the other hand, increased the survival
of QSG7701 hepatocyte cells in the presence of d-galactosamine (d-GalN-induced
cell damage) [363]. As a final example, nectandrin B (158), a lignan isolated from
nutmeg, demonstrated an ability to prevent oxidative damage via Nrf2 activation
[317].
4 Concluding Remarks
It is the hope of the authors that the reader has been brought to the conclusion
that plant phenols inclusive of lignans and neolignans have great potential value in
the treatment of neglected tropical diseases such as leishmaniasis (Fig. 20) [364].
Indeed, their range of biological activities, which are extremely broad for this family
of natural compounds, is supportive of their possible future use. Only subtle changes
J. Pospíšil et al.
Melanogenesis is a physiological process connected with melanin production that is carried out in melanosomes by melanocyte cells. Thus, specialized
dendritic cells (melanocytes) synthesize and transfer pigment to recipient cells.
However, if malignant melanocytes upregulate melanogenesis, the overall process
can become dangerous and, in some cases, even life threatening [354]. Several
phenolic compounds have demonstrated biological effects that may allow for the
regulation of this process. For example, when americanin A (150) was applied
at a concentration of 20 μM, it downregulated microphthalmia-associated transcription factor (MITF) and tyrosinase (TYR) expression in melanocytes [355].
Gomisin N (107) at concentrations of 1–10 μM regulated the phosphatidylinositol 3kinase/serine/threonine protein kinase B (PI3K/Akt) and mitogen-activated protein
kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK) signaling pathway
[356]. (+)-Zuonin A ((+)-151), when applied at concentrations ranging from 1 to
20 μM, inhibited melanogenesis by decreasing levels of tyrosinase and tyrosinaserelated proteins (TRP-1 and 2). Interestingly, its enantiomer, (–)-zuonin A ((–)-151),
inhibited c-Jun N-terminal kinases that are associated with several diseases such as
cancer and neurological disorders, but did not interact with tyrosinase and tyrosinaserelated proteins [357, 358]. Galanganol D diacetate (152) inhibited melanogenesis
(IC 50 = 2.5 μM), presumably via a TYR, TRP-1, and 2 mRNA expression inhibition
mechanism [359].
The liver, the largest solid organ in the human body, is a vital metabolic and
immune “factory.” Its primary functions are to transform and “dismantle” substances,
mine energy, and detoxify the organism. The human liver has an enormous capacity
to regenerate, but even with such a regenerative capacity, can be harmed by many
diseases, toxins, and pathogens. It was shown that several plant phenols have potentially important hepatoprotective activity [360]. The lignan arctigenin (56) was found
to reduce via an immunosuppressive mechanism acute hepatitis [361]. Micrantherin A (153), gomisin M2 (154), and schizandrin (155), obtained from Schisandra
chinensis, showed an ability to protect liver tissue against paracetamol damage (tested
on HepG2 human liver carcinoma cells) [362]. Angeloylgomisin R (156) and schisantherin A (157), from Schisandra pubescens, on the other hand, increased the survival
of QSG7701 hepatocyte cells in the presence of d-galactosamine (d-GalN-induced
cell damage) [363]. As a final example, nectandrin B (158), a lignan isolated from
nutmeg, demonstrated an ability to prevent oxidative damage via Nrf2 activation
[317].
4 Concluding Remarks
It is the hope of the authors that the reader has been brought to the conclusion
that plant phenols inclusive of lignans and neolignans have great potential value in
the treatment of neglected tropical diseases such as leishmaniasis (Fig. 20) [364].
Indeed, their range of biological activities, which are extremely broad for this family
of natural compounds, is supportive of their possible future use. Only subtle changes