(M1330-07-38) Comparison of Hydrangea macrophylla Flower Extract on the Permeability and Skin Whitening of Ginsenoside Rh1 Based on Cream Formulation

Purpose: Among the components of ginseng, ginsenosides Rh1 and Rg2, two deglycosylated ginsenosides, have been reported to be effective for skin whitening. The skin-whitening efficacy of the mixture of ginsenosides Rh1 and Rg2 may be enhanced when used in combination with flower extracts with skin-whitening potential, such as that of Hydrangea macrophylla. In the present study, the ability of these substances in enhancing permeability of ginsenosides Rh1 and Rg2 and skin whitening efficacy by including flower extracts in cream formulations containing ginsenosides Rh1 and Rg2 was investigated.

Methods: To investigate the synergistic effect of these substances on skin whitening, the inhibitory effect on tyrosinase activity in melanocytes (SK-MEL-2 cells) and on pigmentation in a three dimensional (3D) artificial skin model were evaluated. In addition, we prepared a cream formulation containing ginsenoside Rh1, ginsenoside Rg2, and hydrangea extract and a solution without hydrangea extract and compared the skin permeability between the two formulations in a 3D artificial skin model.

Results: The combination of ginsenosides Rh1, Rg2, and Hydrangea extract had a synergistic effect on skin whitening, as it decreased the activity of tyrosinase and inhibited the synthesis of melanin more effectively than using each ingredient alone. In the skin permeability test using the artificial skin model, the addition of flower extract increased the permeability of ginsenoside Rh1 as demonstrated by the levels of ginsenoside Rh1 detected in the donor chamber, skin, and receptor chamber after the application of the cream formulation (60.2 ± 9.4%, 3.4 ± 0.4% and 36.4 ± 19.0%) and solution formulation (67.7 ± 7.6%, 4.4 ± 0.4% and 27.9 ± 8.3%), respectively.

Conclusion: The incorporation of the Rh1 and Rg2 mixture and Hydrangea extract increased the inhibitory efficacy on tyrosinase activity in the 2D and 3D models using SK-MEL-2 melanocytes and the KeraSkin-M^TM model, respectively. The addition of Hydrangea extract to the cream formulation conataining ginsenosides Rh1 and Rg2 also enhanced the permeability of the active compounds through the skin in a 3D artificial skin model. Thus, cream formulations including a combination of ginsenoside Rh1, ginsenoside Rg2, and Hydrangea extract show potential as natural products for skin whitening and treatment of hyperpigmentation.

References: Y. Jin, N. Baek, S. Back, C.-S. Myung, and K.-S. Heo, "Inhibitory effect of ginsenosides Rh1 and Rg2 on oxidative stress in LPS-stimulated RAW 264.7 cells," Journal of Bacteriology and Virology, vol. 48, no. 4, pp. 156-165, 2018.

Fig 1. Inhibitory effects on tyrosinase activity in SK-MEL-2 cells (n = 3).



Fig 2. Histological analysis of pigmentation in KeraSkin-Mᵀᴹ exposing with α-MSH with or without treated with different formulations: (A) control group, (B) vitamin C group, (C) Hydrangea extract group, and (D) Hydrangea extract + Rh1 + Rg2 group (n = 3).



Fig 3. In vitro permeation of ginsenoside Rh1 through artificial skin after 6h from cream formulation containing Rh1 + Rg2 and cream formulation containing Rh1 + Rg2 + Hydrangea extract (n = 3).