Ginsenoside Rg3 is one of ginsenosides that are the well-known bioactive principles of Panax ginseng. Among the two stereoisomeric forms of Rg3, 20(S)-ginsenoside Rg3 [20(S)-Rg3] is predominant. 20(S)-Rg3 is capable of suppressing the nitric oxide (NO), reactive oxygen species (ROS) and prostaglandin E2 (PGE2) productions induced by lipopolysaccharide (LPS) in RAW264.7 macrophage cells in a concentration-dependent manner. In the same stimulated macrophages, 20(S)-Rg3 was able to suppress matrix metalloproteinase-9 (MMP-9) activity and suppress cyclooxygenase-2 (COX-2) expression. It suppressed the production of some proinflammatory cytokines, such as TNF-α, IL-1β and IL-6, and the cell mobility enhanced by LPS in the macrophage cells. 20(S)-Rg3 displayed suppressive effect on the ROS level but not on the NO level, and down-regulating effect on MMP-9 but not on MMP-2 in non-stimulated HaCat keratinocytes. 20(S)-Rg3 also exhibited suppressive effect on the MMP-9 gelatinolytic activity enhanced in the HaCat keratinocytes stimulated with tumor necrosis factor-α (TNF-α), one of the major proinflammatory cytokines. However, 20(S)-Rg3 was not able to modulate the NO level even in the presence of TNF-α. Taken together, anti-inflammatory and related antioxidative and MMP-9 inhibitory activities of 20(S)-Rg3, the major stereoisomeric form of ginsenoside Rg3, are confirmed in macrophage and keratinocyte cell lines.

Ginseng, one of the most widely used herbal medicines, has a wide range of therapeutic and pharmacological applications. Ginsenosides are the major bioactive ingredients of ginseng, which are responsible for various pharmacological activities of ginseng. Ginsenoside Rh2, known as an antitumour ginsenoside, exists as two different stereoisomeric forms, 20(S)-ginsenoside Rh2 [20(S)-Rh2] and 20(R)-ginsenoside Rh2 [20(R)-Rh2]. This work aimed to assess and compare skin anti-photoaging activities of 20(S)-Rh2 and 20(R)-Rh2 in UV-B-irradiated HaCat cells. 20(S)-Rh2, but not 20(R)-Rh2, was able to suppress UV-B-induced ROS production in HaCat cells. Both stereoisomeric forms could not modulate cellular survival and NO level in UV-B-irradiated HaCat cells. Both 20(S)-Rh2 and 20(R)-Rh2 exhibited suppressive effects on UV-B-induced MMP-2 activity and expression in HaCat cells. In brief, the two stereoisomers of ginsenoside Rh2, 20(S)-Rh2 and 20(R)-Rh2, possess skin anti-photoaging effects but possibly in different fashions.

Most UV-C radiation is absorbed by stratospheric ozone; very little reaches the Earth's surface. In contrast, UV-A and UV-B reach the Earth's surface and, subsequently, have the potential to harm humans. Although most biomolecules cannot absorb UV-A, UV-B is particularly harmful to living organisms. UV-A and UV-B contribute to detrimental effects via different molecular mechanisms, such as direct DNA damage, modulation of gene expression, and reactive oxygen species (ROS) generation.1) UV-B acts primarily on the epidermal basal cell layer of the skin. It initiates a photo-oxidation reaction that impairs the antioxidant status of the skin and increases the cellular ROS level, sequentially accelerating photoaging and the development of malignant diseases.2-5) UV-B is one of leading causes of skin changes, such as wrinkle formation, laxity, coarseness, mottled pigmentation, epidermal thickening, degradation of matrix macromolecules, vascularization, and immunosuppression. 6,7) Keratinocytes, the major cell population in the basal layer of the skin, are the primary targets of UV-B. In keratinocytes, UV-B induces the immediate generation of superoxide radical, which is sequentially converted to other ROS species, such as hydrogen peroxide and hydroxyl radical. Matrix metalloproteinases (MMPs) have been implicated in remodeling extracellular matrix (ECM) structures in wound healing, 9) dermal photoaging, 10) and severe pathologic states such as carcinogenesis.11) MMP-1 (interstitial collagenase) is produced by both dermal fibroblasts and epidermal keratinocytes. MMP-1 cleaves types I and III collagen into specific fragments that are further degraded by other MMPs, including MMP-2 (72 kDa gelatinase A/collagenase) and MMP-9 (92 kDa gelatinase B/type IV collagenase). UV radiation, including UV-B, induces the expression and secretion of MMP-1, -2, -3, -9, and/or -13 in the epidermis and dermis. 12,13) Destruction of collagen by UV irradiation, a cause of skin aging in both naturally aged and photoaged skin, is related to the enhanced induction of MMPs, which are secreted by epidermal keratinocytes and dermal fibroblasts. 14)Ginsenosides, also referred to as triterpenoid saponins, are the bioactive ingredients of ginseng, an herbal medication derived from the root of the Panax genus of plants that is widely used in traditional medicine. Ginsenosides are categorized into three groups on the basis of their aglycone (sapogenin) skeletons: the panaxadiol-type, including Rb1, Rb2, Rb3, Rc, Rd, Rg3, Rh2, and Rs1; the panaxatriol-type, including Re, Rf, Rg1, Rg2, and Rh1; and the oleanolic acid group, including Ro.Ginsenoside Rg3, one of the most effective ginsenosides, exerts a wide spectrum of pharmacological actions through anti-inflammatory, anti-tumor, anti-angiogenic, anti-metastatic, and anti-diabetic activities.15-21) Ginsenoside Rg3 exists in two stereoisomeric forms, 20(S)-Rg3 and 20(R)-Rg3 (Fig. 1), based on a chiral center at C-20 in its molecular structure. Of the two stereoisomers, 20(S)-Rg3 is the major constituen...

20(R)-Rh2, a minor stereoisomer of ginsenoside Rh2, possesses matrix metalloproteinase inhibitory, anti-inflammatory and antioxidative activity.