Many modalities of treatment for acquired skin hyperpigmentation are available including chemical agents or physical therapies, but none are completely satisfactory. Depigmenting compounds should act selectively on hyperactivated melanocytes, without short- or long-term side-effects, and induce a permanent removal of undesired pigment. Since 1961 hydroquinone, a tyrosinase inhibitor, has been introduced and its therapeutic efficacy demonstrated, and other whitening agents specifically acting on tyrosinase by different mechanisms have been proposed. Compounds with depigmenting activity are now numerous and the classification of molecules, based on their mechanism of action, has become difficult. Systematic studies to assess both the efficacy and the safety of such molecules are necessary. Moreover, the evidence that bleaching compounds are fairly ineffective on dermal accumulation of melanin has prompted investigations on the effectiveness of physical therapies, such as lasers. This review which describes the different approaches to obtain depigmentation, suggests a classification of whitening molecules on the basis of the mechanism by which they interfere with melanogenesis, and confirms the necessity to apply standardized protocols to evaluate depigmenting treatments.

https://onlinelibrary.wiley.com/doi/pdf/10.1034/j.1600-0749.2003.00029.x

Chemical and Instrumental Approaches to Treat Hyperpigmentation

An overview of agents causing hypopigmentation in human skin is presented. The review is organized to put forward groups of biological and chemical agents. Their mechanisms of action cover (i) tyrosinase inhibition, maturation and enhancement of its degradation; (ii) Mitf inhibition; (iii) downregulation of MC1R activity; (iv) interference with melanosome maturation and transfer; (v) melanocyte loss, desquamation and chemical peeling. Tyrosinase inhibition is the most common approach to achieve skin hypopigmentation as this enzyme catalyses the rate-limiting step of pigmentation. Despite the large number of tyrosinase inhibitors in vitro, only a few are able to induce effects in clinical trials. The gap between in-vitro and in-vivo studies suggests that innovative strategies are needed for validating their efficacy and safety. Successful treatments need the combination of two or more agents acting on different mechanisms to achieve a synergistic effect. In addition to tyrosinase inhibition, other parameters related to cytotoxicity, solubility, cutaneous absorption, penetration and stability of the agents should be considered. The screening test system is also very important as keratinocytes play an active role in modulating melanogenesis within melanocytes. Mammalian skin or at least keratinocytes/melanocytes co-cultures should be preferred rather than pure melanocyte cultures or soluble tyrosinase.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-0749.2006.00334.x

Hypopigmenting agents: an updated review on biological, chemical and clinical aspects

The genus Aloe in the family Liliaceae is a group of plants including Aloe vera (Aloe barbadensis MILLER) and Aloe arborescens (Aloe arborescens MILLER var. natalensis BERGER) that are empirically known to have various medical efficacies. In the present study, we evaluated the anti-hyperglycemic effect of Aloe vera gel and isolated a number of compounds from the gel. On the basis of spectroscopic data, these compounds were identified as lophenol, 24-methyl-lophenol, 24-ethyl-lophenol, cycloartanol, and 24-methylene-cycloartanol. These five phytosterols were evaluated for their anti-hyperglycemic effects in type 2 diabetic BKS.Cg-m+/+Leprdb/J (db/db) mice. In comparison with the hemoglobin A1c (HbA1c) levels of vehicle-treated mice, statistically significant decreases of 15 to 18% in HbA1c levels were observed in mice treated with 1 μg of the five phytosterols. Considering the ability to reduce blood glucose in vivo, there were no differences between the five phytosterols. Administration of β-sitosterol did not reduce the blood glucose levels in db/db mice. After administration of the five phytosterols for 28 d, fasting blood glucose levels decreased to approximately 64%, 28%, 47%, 51%, and 55% of control levels, respectively. Severe diabetic mice treated with phytosterols derived from Aloe vera gel did not suffer weight reduction due to glucose loss in the urine. These findings suggest that Aloe vera gel and phytosterols derived from Aloe vera gel have a long-term blood glucose level control effect and would be useful for the treatment of type 2 diabetes mellitus.

Identification of five phytosterols from aloe vera gel as anti-diabetic compounds

Synthesis, crystal structures, biological activities and fluorescence studies of transition metal complexes with 3-carbaldehyde chromone thiosemicarbazone.

Schiff bases of 3-formylchromone as thymidine phosphorylase inhibitors.

Currently, aloesin is used in the cosmetic industry as a whitening agent because it inhibits tyrosinase activity. Aloesin is a C-glycosylated chromone compound isolated from aloe, and it is difficult to synthesize because of C-glycosyl moiety in the molecule. The purpose of this study is to search for a new chromone compound which is easy to synthesize and which posesses stronger tyrosinase inhibitory activity than aloesin. Fourteen chromone derivatives were synthesized and screened for their mushroom-tyrosinase inhibitory activity. 5-Methyl-7-methoxy-2-(2'-benzyl-3'-oxobutyl)chromone (15) showed the strongest activity among tested compounds. Its activity was not only stronger than aloesin, but also stronger than arbutin and kojic acid. The kinetic analysis revealed a competitive inhibition of 15 with tyrosinase for the L-tyrosine binding site.

/pdf/mushroom-tyrosinase-inhibition-activity-of-some-chromones-342myh4qns.pdf

Mushroom tyrosinase inhibition activity of some chromones.

The present invention relates to novel ginseng saponin compounds having a potent anti-tumor activity, which are represented by formulae (I) and (II). The compounds (I) and (II) above are novel and can be produced by heating plants of ginseng genus for 0.5 to 20 hours at a high temperature of 110 to 180 °C, or can be synthesized by acetylating ginsenoside Rg3 and Δ20(22)-ginsenoside Rg?3? which are known ginseng saponin compounds, respectively. The present invention also relates to an anti-tumor composition comprising these compounds (I) and/or (II) as an active ingredient.

Novel ginseng saponin compounds, process for preparation thereof and anti-tumor agent comprising the same as an active component

The present invention relates to a cell growth stimulating composition containing aloesin as an active ingredient. More specifically, the present invention relates to a composition for stimulating cell growth, especially for stimulating epidermal cells and hepatic cells, which contains aloesin as an active ingredient. Aloesin is a component of Aloe vera, for which an effect for blocking ultraviolet ray from skin and an activity as mushroom tyrosinase inhibitor have been disclosed in the prior art. However, accordint to the present invention, it has now been identified that aloesin has the novel pharmacological use as a cell growth stimulating agent which has never been disclosed in the prior art.

Jeong Hill Park

Papers

Mushroom tyrosinase inhibition activity of some chromones.

Novel ginseng saponin compounds, process for preparation thereof and anti-tumor agent comprising the same as an active component

Cell growth stimulating compositions containing aloesin

Mushroom Tyrosinase Inhibition Activity of Some Chromones.