Stereoselective suppressive effects of protopanaxadiol epimers on UV-B-induced reactive oxygen species and matrix metalloproteinase-2 in human dermal keratinocytes

Abstract

This study aimed to assess the skin-related anti-photoaging activities of the 2 epimeric forms of protopanaxadiol (PPD), 20(S)-PPD and 20(R)-PPD, in cultured human keratinocytes (HaCaT cells). The anti-photoaging activity was evaluated by analyzing the levels of reactive oxygen species (ROS) and matrix metalloproteinases (MMPs), as well as cell viability for HaCaT cells under UV-B irradiation. The activities for MMP-2 and -1 in conditioned medium were determined using gelatin zymography, and MMP-2 protein in the conditioned medium was detected using Western blot analysis. 20(S)-PPD, but not 20(R)-PPD, suppressed UV-B-induced ROS elevation. Neither of the epimers, at the concentrations used, exhibited cytotoxicity, irrespective of UV-B irradiation. 20(S)-PPD, but not 20(R)-PPD, exhibited an inhibitory effect on UV-B-induced MMP-2 activity and expression in HaCaT cells. In brief, only 20(S)-PPD, a major metabolic product of PPD-type ginsenosides, inhibits UV-B-induced ROS and MMP-2 elevation, implying its stereospecific anti-photoaging activity on the skin.

Synthesis and Crystal Structure of Ocotillol-Type Metabolites Derived from (20R)-Protopanaxadiol

“…14 M3 and M4 were obtained from oxidation of M1 and M2 by pyridinium chlorochromate (PCC) in dichloromethane at room temperature for about 6 h, respectively. Their structures were confirmed by HRMS, 1 H NMR and 13 C NMR. M5 and M6 were prepared from M1 and M2 with acetic anhydride in pyridine at room temperature for about 12 h, respectively.…”

“…Melting points were determined on a digitising melting point apparatus (WRS-1B). 1 H NMR and 13 C NMR were recorded on Bruker VANCE-400, HRMS were determined on an Agilent 6210 TOF LC/MS. The X-ray data were collected on a Bruker Smart-1000 CCD area-detector diffractometer using graphite monochromator Cu Ka radiation (λ = 1.54178 Å) at 293(2) K.…”

“…Studies on its bioactivity and metabolism have found that (20R)-PPD and (20S)-PPD had stereoselectivity in pharmacological action. [11][12][13] Therefore, it is significant to carry out the pharmacological and stereoselectivity research on (20R)-PPD metabolites. However, the extraction and separation of (20R)-PPD metabolites are very difficult from the microsomal incubations of (20R)-PPD.…”

Hair-Growth Potential of Ginseng and Its Major Metabolites: A Review on Its Molecular Mechanisms

“…Finasteride has been shown to prevent male pattern hair loss through the inhibition of type II 5α-reductase, which affects androgen metabolism. Although the exact mechanism of minoxidil has still not been elucidated, available research findings suggest that the hair-growth promotional effects of minoxidil are mediated through enhanced nutrient supply to hair follicles through vasodilation, opening of the K + channel, and the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT/PKB) signaling, resulting in increased cell proliferation and inhibition of apoptosis in dermal papilla cells [ 4 , 5 ]. However, these drugs exhibit certain adverse effects, such as allergic contact dermatitis, erythema, and itching.…”

Synthesis and Crystal Structures of Two C24 Epimeric 3-Acetyled 20(R)-Ocotillol Type Sapogenins Obtained from 20(R)-Protopanaxadiol

“…15 20(S)-PPD, but not 20(R)-PPD, exhibited an inhibitory effect on UV-B-induced MMP-2 activity and expression in HaCaT cells. 16 However, investigations on the synthesis, pharmacodynamics and pharmacokinetics of 20(R)-ocotillol type sapogenins and their derivatives have rarely been reported. In this paper, epimeric 20R,24-epoxy-dammarane-3β,12β,25-triol (2) have been prepared from 20(R)-protopanaxadiol (1).…”