3,5‐Dicaffeoyl‐Epi‐Quinic Acid Isolated from Edible Halophyte <i>Atriplex gmelinii</i> Inhibits Adipogenesis via AMPK/MAPK Pathway in 3T3‐L1 Adipocytes

Evidence-Based Complementary and Alternative Medicine

Lee

et al. 2020

Self Cite

Luteolin is a common phytochemical from the flavonoid family with a flavone structure. Studies reported several bioactivities for luteolin and similar flavones. Attenuating the increased adipogenesis of bone marrow cells (hBM-MSCs) has been regarded as a therapeutic target against osteoporotic bone disorders. In the present study, the potential roles of luteolin and its sulfonic acid derivative luteolin-OSO3Na in regulating adipogenic differentiation of hBM-MSCs were investigated. Adipo-induced cells were treated with or without compounds, and their effect on adipogenesis was evaluated by adipogenic marker levels such as lipid accumulation and PPARγ pathway activation. Luteolin hindered the adipogenic lipid accumulation in adipo-induced hBM-MSCs. Immunoblotting and reverse transcription-polymerase chain reaction analysis results indicated that luteolin downregulated PPARγ and downstream factors of C/EBPα and SREBP1c expression which resulted in inhibition of adipogenesis. Luteolin-OSO3Na showed similar effects; however, it was significantly less effective compared to luteolin. Investigating p38, JNK, and ERK MAPKs and AMPK activation indicated that luteolin suppressed the MAPK phosphorylation while stimulating AMPK phosphorylation. On the other hand, luteolin-OSO3Na was not able to notably affect the MAPK and AMPK activation. In conclusion, this study suggested that luteolin inhibited adipogenic differentiation of hBM-MSCs via upregulating AMPK activation. Replacing its 4′-hydroxyl group with sulfonic acid sodium salt diminished its antiadipogenic effect indicating its role in regulating AMPK activation. The general significance is that luteolin is a common phytochemical with various health-beneficial effects. The current study suggested that luteolin may serve as a lead compound for developing antiosteoporotic substances with antiadipogenic properties.

Section: Resultssupporting

confidence: 74%

Effect and Comparison of Luteolin and Its Derivative Sodium Luteolin‐4′‐sulfonate on Adipogenic Differentiation of Human Bone Marrow‐Derived Mesenchymal Stem Cells through AMPK‐Mediated PPARγ Signaling

Evidence-Based Complementary and Alternative Medicine

Lee

et al. 2020

Self Cite

“…3,5-Dicaffeoyl-epi-quinic acid (DCEQA) was isolated from Atriplex gmelinii as a white powder. Isolation, characterization, and identification of the compound were carried out as reported earlier [21].…”

Section: Isolation Of 35-dicaffeoyl-epi-quinic Acidmentioning

confidence: 99%

“…e remaining cycles consisted of 42°C for 60 min and 72°C for 5 min. e target cDNA was amplified using the sense and antisense primers as previously noted [21]. e amplification was carried out with 30 cycles; each cycle consisted of 95°C for 45 sec, 60°C for 1 min, and 72°C for 45 sec.…”

Section: Reverse Transcription Semiquantitative Polymerase Chainmentioning

confidence: 99%

“…Up to date, CQA and CQA-based compounds have been exhibited to show important health benefits such as antioxidant [16], antihistaminic [17], antibacterial [18], antiviral [19], and anticancer [20] activities. As a part of our continuous effort to develop natural products with bioactivities, 3,5-dicaffeoyl-epi-quinic acid (DCEQA), a bioactive derivative of CQA, has been shown to possess antiobesity [21] and photoprotective antioxidant abilities [22]. e current study is aimed at evaluating the photoprotective effect of DCEQA against UVB-induced changes in skin cells and analyzing its possible mechanism of action for antiphotoaging potential.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antiphotoaging Effects of 3,5‐Dicaffeoyl‐epi‐quinic Acid via Inhibition of Matrix Metalloproteinases in UVB‐Irradiated Human Keratinocytes

Lee

Evidence-Based Complementary and Alternative Medicine

et al. 2020

Self Cite

UVB exposure is one of the causes of several skin complications including but not limited to premature aging, wrinkle formation, and hyperpigmentation. UV-induced skin aging is called photoaging, and oxidative stress-induced overexpression of matrix metalloproteinases (MMPs) is the main reason behind the photoaging-mediated collagen degradation. Natural origin inhibitors of MMPs are regarded as a promising approach to prevent or treat photoaging. Therefore, the present study investigated the protective effects of 3,5-dicaffeoyl-epi-quinic acid (DCEQA) in human HaCaT keratinocytes against UVB irradiation-related dysregulation of MMPs. Changes in the mRNA and protein expression and release of MMP-1, -2, and -9 were observed after UVB irradiation with or without DCEQA treatment. In addition, the effect of DCEQA on the activation of p38, JNK, and ERK MAPKs was analyzed. Treatment of UVB-irradiated HaCaT cells with 10 μM DCEQA significantly suppressed the overexpression of both mRNA and protein of MMP-1, -2, and -9 while slightly increasing the diminished type I procollagen production. UVB-induced activation of MAPKs was also ameliorated by DCEQA treatment in a dose-dependent manner. Results indicated that DCEQA treatment was able to protect keratinocytes from UVB-induced photoaging by inhibiting the stimulated production of MMPs and the related decrease in collagen production. It was suggested that DCEQA downregulated the collagen degradation via inhibition of MAPK activation, which resulted in decreased MMP activity.

“…Caffeoylquinic acid and its derivatives have been reported to show antioxidant [ 17 ], antibacterial [ 18 ], antiviral [ 19 ] and antiobesic effects [ 20 ]. Previous studies have demonstrated the protective effect of 3,5-dicafeoyl-epi-qinic acid (DEQA) in UVB-irradiated keratinocytes [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Antiphotoaging Effect of 3,5-Dicaffeoyl-epi-quinic Acid against UVA-Induced Skin Damage by Protecting Human Dermal Fibroblasts In Vitro

Kong

et al. 2020

IJMS

Self Cite

Cutaneous aging is divided into intrinsic and exogenous aging correspondingly contributing to the complex biological phenomenon in skin. Intrinsic aging is also termed chronological aging, which is the accumulation of inevitable changes over time and is largely genetically determined. Superimposed on this intrinsic process, exogenous aging is associated with environmental exposure, mainly to ultraviolet (UV) radiation and more commonly termed as photoaging. UV-induced skin aging induces increased expression of matrix metalloproteinases (MMPs) which in turn causes the collagen degradation. Therefore, MMP inhibitors of natural origin are regarded as a primary approach to prevent or treat photoaging. This study investigated the effects of 3,5-dicaffeoyl-epi-quinic acid (DEQA) on photoaging and elucidated its molecular mechanisms in UVA-irradiated human dermal fibroblasts (HDFs). The results show that treatment with DEQA decreases MMP-1 production and increases type I collagen production in UVA-damaged HDFs. In addition, treatment of UVA-irradiated HDFs with DEQA downregulates MMP-1, MMP-3 and MMP-9 expression via blocking MAPK-cascade-regulated AP-1 transcriptional activity in UVA-irradiated HDFs. Furthermore, DEQA relieves the UVA-mediated suppression of type I procollagen and collagen expression through stimulating TGF-β/Smad signaling, leading to activation of the Smad 2/3 and Smad 4 nuclear translocation. These results suggest that DEQA could be a potential cosmetic agent for prevention and treatment of skin photoaging.