Boerhaavia diffusa active treats hyperpigmentation

Until now, most cosmetics treatments for hyperpigmentation have this enzyme as the primary target, but Provital has developed a novel active that acts by means of a very unique mechanism: the prolonged stimulation of PPAR; which leads to the inhibition of a transcription factor that control the genes encoding tyrosinase and other enzymes. Both in vitro and in vivo studies have demonstrated the efficacy and safety of this active.

There are several parameters that contribute to the appearance of skin in an important way, such as moisturisation, firmness or wrinkles. However, one of the signs that has most influence on the different standards for beauty throughout history is skin pigmentation, or tone, since it seems to reveal aspects related to age and health. Furthermore, it has been considered that lighter skin increases women’s sexual attractiveness for men.1 Currently, hyperpigmentation affects millions of people all over the world with all skin types, and it is the third greatest cosmetic concern, as it is one of the evident signs of the decline of youth. For this reason, the cosmetic goal is to reduce spots and to balance skin tone. The difference in skin colour is mainly due to the presence of melanin, a pigment that protects against external aggressions, such as UV rays. Melanin production occurs in the melanocytes, in specific lysosome-like structures called melanosomes.2 When the body generates too much melanin to protect itself against these aggressions, or simply because of ageing, this may cause spots or changes in skin tone. This disorder is called hyperpigmentation.3 Two main types exist: eumelanin and pheomelanin; leading to the multiple nuances in skin colour. Nevertheless, not only is the type of melanin produced important, but also its distribution throughout the tissue.4 Tyrosinase is the key enzyme involved in the synthesis of all melanin types (melanogenesis). It is a rate-limiting enzyme which catalyses a succession of oxidations of tyrosine (its initial precursor), leading to the synthesis of 3,4-dihydroxyphenylalanine (DOPA), to further produce a common intermediary compound: dopaquinone (DQ). As of this point, two different pathways lead to the formation of eumelanin and pheomelanin.3,4 Until now, most whitening products are targeted to inhibit tyrosinase activity; however, recent studies indicate that there are also other pathways for the melanogenesis regulation.5,6 Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three isoforms have been identified, PPAR, PPAR/and PPAR, which are found in different tissues. They participate in several physiological processes, by controlling gene expression in different cells.7 PPARis expressed in the epidermis and it is able to influence gene expression through interactions with transcription factors or signalling proteins. It has been verified that prolonged PPARstimulation brings about an important reduction in MITF (a transcription factor that controls the genes that encode tyrosinase and other enzymes).8 This fact is of vital importance for tyrosinase expression, due to the inhibition of mRNA.9 The first studies on PPARinfluence on melanogenesis performed on melanoma cells demonstrated that PPARagonists inhibited their proliferation in a dosedependent fashion, and reduced tyrosinase production and/or the average lifespan of this enzyme.10,11 The presence of PPARin normal melanocytes was also confirmed, so the action of receptor agonists on these cells could also be expected.12 In summary, it is observed that the main consequence of PPAR-agonist binding on melanocytes is the reduction of tyrosinase production, which translates to a reduction in melanogenesis.7 Finally, it has also been described that PPARmodulation on certain keratinocyte activities might likewise be important in a lightening effect. It has been verified that PPARactivators (ciglitazone or troglitazone) increase keratinocyte differentiation.13 This would aid in avoiding a local accumulation of pigment in the epidermis, and would improve hyperpigmentation or spots on the skin. It is believed that in nature there are certain plants containing PPARagonists in their compositions. We set out to identify possible candidates by a computational approach with the ultimate goal of achieving a whitening effect by means of natural actives. From this study, the plant Boerhaavia diffusa emerged as an excellent candidate to meet this goal. Boerhaavia diffusa, commonly known as punarnava in Sanskrit, is a plant that belongs to the Nyctaginaceae family. This plant is found both in the tropics and in the subtropics, but it is native to India and it has been traditionally used to relieve several kinds of illness, as well as to rejuvenate the body. Punarnava contains diverse components, such as flavonoids, alkaloids, steroids, triterpenoids, lipids, lignins, carbohydrates, proteins, and glycoproteins.14,15 Melavoid is obtained from the root of B. diffusa and standardised in boeravinones, which have been considered one of the most interesting metabolites of punarnava. Boeravinones are the main rotenoids contained in its root, and several different ones have been identified to date: Boeravinone A to F.16 Taking into account all this information and within the different types of melanogenesis modulation mechanisms of current cosmetic ingredients, this active introduces a new concept based on its action on PPAR.

Materials and methods