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The stimulation of melanogenesis by novel natural products is desirable for cosmetic applications such as skin tanning, anti-greying, and clinical use for treating vitiligo and leukoderma disorders. Microphthalmia transcription factor (MITF) is a central transcription factor that controls the expression of tyrosinase, which is a key enzyme responsible for catalyzing the rate-limiting processes of melanin production. Tetrahydrocurcuminoids (THCr), which mostly consist of tetrahydrocurcumin (THC), are a colorless bioactive mixture derived from curcuminoids that are extracted from the Curcuma longa plant. THCr has been reported to exhibit superior properties, including antioxidant and anti-inflammatory effects. Our previous study reported the greater melanogenesis-stimulating effects of purified THC, compared to hexahydrocurcumin (HHC) or octahydrocurcumin (OHC). Curowhite™ (CW) is a proprietary extract that consists of 25% hydrogenated curcuminoids (mixture of THCr, hexahydrocurcuminoids, and octahydrocurcuminoids) encapsulated in a β-cyclodextrin (βCyD) excipient. The encapsulation of THCr in a suitable excipient, such as the widely popular cyclodextrins, helps to enhance the stability, solubility, and bioavailability of the THCr. CW is marketed as a nutraceutical with GRAS status and is safe when administered orally, as shown in vivo studies. However, the impact of CW on melanogenesis remains unexplored. Herein, the impact of CW on melanogenesis were investigated using B16F10 and MNT-1 cells. Our findings show that CW is markedly cytotoxic to B16F10 cells without affecting the cellular melanin content. However, in MNT-1 cells, CW significantly stimulated intracellular melanin content over the concentration range (20–60 µg/mL) with increased dendrite formation while being nontoxic to MNT-1 cells or HaCaT cells after a 5-day treatment. Examination of the effects of the excipient βCyD on cytotoxicity and melanogenesis confirmed that the excipient had no contribution to the biological impacts that were found to be exclusively attributable to the encapsulated mixture (THCr). The mechanisms of CW’s promelanogenic effects in MNT-1 cells were found to be related, at least in part, to an increase in tyrosinase and MITF protein levels, as CW did not alter tyrosinase activity in MNT-1 cells. Moreover, CW exhibited antioxidant activity as obtained through DPPH radical scavenging assay. Together, the findings of this pilot study indicate that CW might hold an exciting avenue as a pro-pigmenting nutraceutical for treating hypopigmentation disorders, the detailed mechanisms of which warrant further exploration. Moreover, future investigations are necessary to examine CW’s effects on melanogenesis in normal human melanocytes and in vivo studies.

The stimulation of melanogenesis by novel natural products is desirable for cosmetic applications such as skin tanning, anti-greying, and clinical use for treating vitiligo and leukoderma disorders. Microphthalmia transcription factor (MITF) is a central transcription factor that controls the expression of tyrosinase, which is a key enzyme responsible for catalyzing the rate-limiting processes of melanin production. Tetrahydrocurcuminoids (THCr), which mostly consist of tetrahydrocurcumin (THC), are a colorless bioactive mixture derived from curcuminoids that are extracted from the Curcuma longa plant. THCr has been reported to exhibit superior properties, including antioxidant and anti-inflammatory effects. Our previous study reported the greater melanogenesis-stimulating effects of purified THC, compared to hexahydrocurcumin (HHC) or octahydrocurcumin (OHC). Curowhite™ (CW) is a proprietary extract that consists of 25% hydrogenated curcuminoids (mixture of THCr, hexahydrocurcuminoids, and octahydrocurcuminoids) encapsulated in a β-cyclodextrin (βCyD) excipient. The encapsulation of THCr in a suitable excipient, such as the widely popular cyclodextrins, helps to enhance the stability, solubility, and bioavailability of the THCr. CW is marketed as a nutraceutical with GRAS status and is safe when administered orally, as shown in vivo studies. However, the impact of CW on melanogenesis remains unexplored. Herein, the impact of CW on melanogenesis were investigated using B16F10 and MNT-1 cells. Our findings show that CW is markedly cytotoxic to B16F10 cells without affecting the cellular melanin content. However, in MNT-1 cells, CW significantly stimulated intracellular melanin content over the concentration range (20–60 µg/mL) with increased dendrite formation while being nontoxic to MNT-1 cells or HaCaT cells after a 5-day treatment. Examination of the effects of the excipient βCyD on cytotoxicity and melanogenesis confirmed that the excipient had no contribution to the biological impacts that were found to be exclusively attributable to the encapsulated mixture (THCr). The mechanisms of CW's promelanogenic effects in MNT-1 cells were found to be related, at least in part, to an increase in tyrosinase and MITF protein levels, as CW did not alter tyrosinase activity in MNT-1 cells. Moreover, CW exhibited antioxidant activity as obtained through DPPH radical scavenging assay. Together, the findings of this pilot study indicate that CW might hold an exciting avenue as a pro-pigmenting nutraceutical for treating hypopigmentation disorders, the detailed mechanisms of which warrant further exploration. Moreover, future investigations are necessary to examine CW's effects on melanogenesis in normal human melanocytes and in vivo studies. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tetrahydrocurcuminoids are derivatives of curcuminoids, produced chemically by hydrogenation of curcuminoids extracted from the rhizomes of C. longa L. The NF consists of more than 95% of tetrahydrocurcuminoids. The applicant proposed to use the NF in food supplements at a maximum dose of 300 mg/day for adults excluding pregnant and lactating women. Taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90‐day oral toxicity study and a reproduction/developmental toxicity screening test performed with the NF, the Panel derives a safe level of 2 mg/kg body weight per day. For the target population this level corresponds to 140 mg/day, which is lower than the use level as proposed by the applicant. The Panel concludes that the NF, tetrahydrocurcuminoids from turmeric (C. longa L.), is safe for the target population at 140 mg/day. [ABSTRACT FROM AUTHOR]

Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver an opinion on tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food (NF) pursuant to Regulation (EU) 2015/2283. Tetrahydrocurcuminoids are derivatives of curcuminoids, produced chemically by hydrogenation of curcuminoids extracted from the rhizomes of C. longa L. The NF consists of more than 95% of tetrahydrocurcuminoids. The applicant proposed to use the NF in food supplements at a maximum dose of 300 mg/day for adults excluding pregnant and lactating women. Taking into account the composition of the NF and the proposed conditions of use, consumption of the NF is not nutritionally disadvantageous. There are no concerns regarding genotoxicity of the NF. Based on a 90‐day oral toxicity study and a reproduction/developmental toxicity screening test performed with the NF, the Panel derives a safe level of 2 mg/kg body weight per day. For the target population this level corresponds to 140 mg/day, which is lower than the use level as proposed by the applicant. The Panel concludes that the NF, tetrahydrocurcuminoids from turmeric (C. longa L.), is safe for the target population at 140 mg/day.

Abstract: Several curcuminoids and tetrahydrocurcuminoids (THCs), bearing various hydroxyl and/or methoxy groups on their benzene rings, have been synthesized to study their antioxidant and hydrogen donating capacities using the DPPH method at 25°C in methanol. The results show that the tetrahydrocurcuminoids are in general much more efficient than their curcuminoid analogs if they include a phenol group in meta- or para-position of the linking chain and a neighboring phenol or methoxy group. This efficiency gain of THCs by comparison to curcuminoids was attributed to the presence of benzylic hydrogens involved in the oxidation process of these compounds and not to the beta-diketone moiety in the chain. [Copyright &y& Elsevier]

Abstract: The photochemical properties of 10 tetrahydrocurcuminoids (THCs) have been studied for the first time. They display very low fluorescence in ethanol solution at room temperature with quantum yields between 0.9 and 13×10−3 whereas their phosphorescence quantum yields in ethanol glass at 77K are between 0.025 and 0.5. Their disappearance quantum yield measured in ethanol solution, between 5×10−4 and 10−2, follows the same trend as their antiradical power efficiency (ARP) previously measured. The reactivity of THCs is enhanced if they include a phenol group in meta or para of the linking chain and a phenol or methoxy group as neighbor. UV absorption difference spectra of the irradiated solutions, HPLC and GC–MS analyses performed on 4-propylguaiacol (4PG), which displays similar behavior as tetrahydrocurcumin (THC2) indicates the formation of quinone methides and ortho-quinone. The formation of a phenoxy radical by photooxidation appears to be the first reaction step. This demonstrates that the general photodegradation mechanism of phenols found for guaiacyl lignins applies also to simplest molecules of natural origin such as THCs. The irradiation of the THCs in carboxymethylcellulose films follows the same trends as the solution studies, except that the quinone methides and ortho-quinones are not detected, probably because they react with the cellulosic matrix. The knowledge obtained in this study probably will help to promote the use of tetrahydrocurcuminoids in various applications where it is necessary to develop antioxidant properties in presence of solar light. [Copyright &y& Elsevier]

The α7 nicotinic acetylcholine receptor (α7 nAChR) is a ligand-gated ion channel that is involved in cognition disorders, schizophrenia, pain, and inflammation. Allosteric modulation of this receptor might be advantageous to reduce the toxicity in comparison with full agonists. Our previous results obtained with some hydroxy-chalcones, which were identified as positive allosteric modulators (PAMs) of α7 nAChR, prompted us to evaluate the potential of some structurally related naturally occurring flavonoids and curcuminoids and some synthetic curcumin analogues, with the aim of identifying new allosteric modulators of the α7 nAChR. Biological evaluation showed that phloretin, demethoxycurcumin, and bis-demethoxicurcuming behave as PAMs of α7 nAChR. In addition, some new curcumin derivatives were able to enhance the signal evoked by ACh; the activity values found for the tetrahydrocurcuminoid analog 23 were especially promising. [ABSTRACT FROM AUTHOR]