Herbs And Phytochemicals: Antioxidant 3,4,5-Tri-O-Caffeoylquinic Acid From Nymphoides Peltata Has Photoaging Prevention And Anti-Wrinkle Properties!

Herbs And Phytochemicals: The quest for effective and natural anti-aging agents has driven researchers to explore the rich world of phytochemicals derived from plants. In recent years, the focus has shifted towards understanding the therapeutic potential of herbal compounds, especially in the context of skincare and anti-wrinkling effects. One such promising discovery is the compound 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) isolated from Nymphoides peltata, a perennial aquatic plant widely used in traditional Chinese medicine. This Herbs And Phytochemicals study, conducted by researchers from Pusan National University, Korea Institute of Science and Technology, University of Science and Technology, and Sungkyunkwan University in the Republic of Korea, aims to shed light on the anti-wrinkling properties of TCQA through its impact on various cellular signaling pathways.


 
The skin, being the largest organ in the human body, plays a pivotal role in protecting internal organs from physical damage and chemical irritants. However, a multitude of intrinsic and extrinsic factors contribute to skin aging, with continuous exposure to ultraviolet (UV) radiation being a significant external factor. In fact, photoaging, resulting from prolonged UV exposure, accounts for more than 80% of facial aging, making it a key contributor to the development of wrinkles and skin aging. UVB irradiation, in particular, can penetrate the skin's epidermis and dermis, causing oxidative stress by generating reactive oxygen species (ROS). This oxidative stress can lead to skin inflammation, aging, and even skin cancer.
 
Nuclear factor erythroid-2-related factor 2 (Nrf2) is a crucial player in the skin's defense mechanism against oxidative stress. It is activated in response to oxidative stress and regulates antioxidant activity and cellular redox levels by neutralizing ROS and reactive electrophiles. When exposed to oxidative stress, Nrf2 separates from its inhibitory protein Keap1 and binds to the antioxidant response element (ARE), promoting the expression of antioxidant-related enzymes like heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1). This, in turn, helps inhibit ROS-induced oxidative damage, thereby slowing down the aging process.
 
The Role of Signaling Pathways in Photoaging
Photoaging is characterized by the activation of key transcription factors, including mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and activator protein-1 (AP-1). These factors promote collagen degradation in skin tissue by inducing matrix metalloproteinase-1 (MMP-1) expression, which leads to abnormal skin structure. MMPs, including MMP-1, MMP-3, and MMP-9, degrade extracellular matrix (ECM) and basement membrane components, and MMP-1, in particular, is a collagen-degrading protease. It targets procollagen type-I, an essential component of ECM, contributing significantly to skin aging and wrinkle formation. NF-κB is another transcription factor that increases MMP-1 levels in the dermis and is activated by UVB-generated ROS. Activation of the NF-κB pathway results in the synthesis of proinflammatory enzymes and cytokines, leading to inflammation, tissue damage, and enhanced MM P-1 production, all of which accelerate skin aging. Therefore, compounds with antioxidant properties that promote Nrf2 activation and inhibit the MAPK/NF-κB/AP-1 signaling pathway hold the promise of being potential anti-photoaging and anti-wrinkle agents.
 
Nymphoides Peltata and Its Medicinal Significance
The genus Nymphoides is known for its various species and is endemic in Korea. Among these species, Nymphoides peltata stands out for its traditional medicinal uses in treating conditions such as heat strangury and polyuria. Extracts derived from N. peltata have shown to have anti-inflammatory and anti-tumor activities.
 
Recent studies have indicated the potential of N. peltata extracts in alleviating atopic dermatitis and activating the Nrf2/HO-1 signaling pathway, demonstrating its therapeutic properties in the context of skin health.
 
In this study, the researchers delved into the phytochemical composition of the methanolic extract of N. peltata roots, leading to the isolation and identification of 15 compounds, including a novel oleanane saponin. This saponin, 3-O-β-D-glucopyranosyl-oleanolic acid 28-O-β-D-glucuronopyranoside, was characterized using advanced analytical techniques, such as nuclear magnetic resonance (NMR) spectroscopy and high-resolution electrospray ionization mass spectrometry (HRESIMS). It was within this treasure trove of compounds that the spotlight fell on 3,4,5-tri-O-caffeoylquinic acid (TCQA).
 
3,4,5-Tri-O-Caffeoylquinic Acid (TCQA): A Skin Savior
The researchers found that among the 15 compounds isolated, TCQA exhibited a unique ability to significantly enhance Nrf2 levels in Nrf2-ARE reporter HaCaT cells. This, in essence, suggested that TCQA could effectively mitigate oxidative stress and oxidative damage, making it a promising candidate for an anti-wrinkle agent.
 
UVB exposure, as a significant driver of oxidative stress, elevates ROS levels in skin cells. This leads to the phosphorylation and activation of MAPK signaling pathways, which, in turn, induce the expression of transcription factors like AP-1 and NF-κB. These factors, among their various roles, promote the production of MMPs, specifically MMP-1. TCQA demonstrated its anti-aging potential by significantly reducing the protein expressions of p-ERK, p-JNK, and p38 in UVB-irradiated HaCaT cells. In doing so, it inhibited the activation of the MAPK signaling pathway, which plays a central role in skin aging. Furthermore, TCQA reduced the expressions of phosphorylated c-Fos and c-Jun, two key components of the AP-1 transcription factor. By suppressing AP-1 activation, TCQA effectively curtailed the production of MMPs, particularly MMP-1, thus protecting against collagen breakdown in the dermis and contributing to the reduction of wrinkles and the preservation of skin elasticity.
 
TCQA also proved its anti-inflammatory capabilities by inhibiting the transcription of inflammatory cytokines through the suppression of NF-κB, p65, and IκBα in UVB-irradiated HaCaT cells. This not only addressed skin inflammation but also contributed to the overall anti-aging and anti-wrinkling effects of TCQA.
 
Understanding Caffeoylquinic Acids (CQA)
Caffeoylquinic acid (CQA) derivatives, including TCQA, have long been recognized for their potent antioxidant and anti-inflammatory properties. These attributes are often attributed to the presence of an ortho-hydroxy group and esterification groups on both caffeic acid and quinic acid moieties. Among different isomers of dicaffeoylquinic acids (DCQA), 4,5-DCQA and 3,4-DCQA have been found to exhibit stronger physiological activities than 3,5-DCQA. This observation underscores the significance of the cis-caffeoyl group in DCQA's bioactivity. Interestingly, TCQA has shown to possess even more potent pharmacological activities compared to DCQA. This heightened bioactivity can be attributed to the steric hindrance introduced by TCQA's three caffeoyl groups. This unique molecular structure contributes to TCQA's stronger antiradical ability, its ability to induce ATP synthesis, and its effectiveness in inhibiting proinflammatory substances such as TNF-α.
 
Conclusion: TCQA - A Promising Anti-Wrinkle Agent
In conclusion, this study unravels the potential of 3,4,5-Tri-O-Caffeoylquinic Acid (TCQA) isolated from Nymphoides peltata as a potent anti-wrinkle agent. Its impact on Nrf2, MAPK/NF-κB/AP-1 signaling pathways, and MMP-1 activity in UVB-damaged skin cells highlights its multifaceted mechanism of action against photoaging and skin wrinkling. TCQA's antioxidant and anti-inflammatory properties, as well as its unique molecular structure, make it a promising candidate for the development of effective, natural anti-aging skincare products. This research underscores the rich potential of herbal compounds in the realm of skincare and presents exciting opportunities for the future development of anti-wrinkling agents that harness the power of nature. As the pursuit of healthier, more youthful skin continues, TCQA stands as a promising beacon of hope.
 
The study findings were published in the peer reviewed journal: Antioxidants.
https://www.mdpi.com/2076-3921/12/10/1899
 
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