Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice

BACKGROUND/OBJECTIVES The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. MATERIALS/METHODS The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. RESULTS ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. CONCLUSIONS Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

[1]  V. Insolia,et al.  Photoprotective and Antiaging Effects of a Standardized Red Orange (Citrus sinensis (L.) Osbeck) Extract in Asian and Caucasian Subjects: A Randomized, Double-Blind, Controlled Study , 2022, Nutrients.

[2]  R. Acquaviva,et al.  Phytocomplex of a Standardized Extract from Red Orange (Citrus sinensis L. Osbeck) against Photoaging , 2022, Cells.

[3]  Lucas Pinheiro de Lima,et al.  A review of the lipolytic effects and the reduction of abdominal fat from bioactive compounds and moro orange extracts , 2021, Heliyon.

[4]  N. M. Hassimotto,et al.  Pera orange (Citrus sinensis) and Moro orange (Citrus sinensis (L.) Osbeck) juices attenuate left ventricular dysfunction and oxidative stress and improve myocardial energy metabolism in acute doxorubicin-induced cardiotoxicity in rats. , 2021, Nutrition.

[5]  E. Cho,et al.  Effects of Aloe vera Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies , 2021, Molecules.

[6]  K. Socha,et al.  The impact of ultraviolet radiation on skin photoaging — review of in vitro studies , 2021, Journal of cosmetic dermatology.

[7]  D. Nelson,et al.  Effects of moro orange juice (Citrus sinensis (L.) Osbeck) on some metabolic and morphological parameters in obese and diabetic rats. , 2020, Journal of the science of food and agriculture.

[8]  Tae Young Kim,et al.  Gynostemma Pentaphyllum Extract Ameliorates High-Fat Diet-Induced Obesity in C57BL/6N Mice by Upregulating SIRT1 , 2019, Nutrients.

[9]  Changhee Kim,et al.  Agastache rugosa Kuntze Attenuates UVB-induced Photoaging in Hairless Mice through the Regulation of MAPK/AP-1 and TGF-β/Smad Pathways. , 2019, Journal of microbiology and biotechnology.

[10]  K. Geoffrey,et al.  Sunscreen products: Rationale for use, formulation development and regulatory considerations , 2019, Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society.

[11]  Á. Juarranz,et al.  Environmental Stressors on Skin Aging. Mechanistic Insights , 2019, Front. Pharmacol..

[12]  O. Lee,et al.  Anti-photoaging effect of fermented agricultural by-products on ultraviolet B-irradiated hairless mouse skin , 2019, International journal of molecular medicine.

[13]  Hong-Guang Jin,et al.  Dianthus superbus Improves Glomerular Fibrosis and Renal Dysfunction in Diabetic Nephropathy Model , 2019, Nutrients.

[14]  S. Lee,et al.  Hydrangea serrata (Thunb.) Ser. Extract Attenuate UVB-Induced Photoaging through MAPK/AP-1 Inactivation in Human Skin Fibroblasts and Hairless Mice , 2019, Nutrients.

[15]  Á. Juarranz,et al.  Oral Photoprotection: Effective Agents and Potential Candidates , 2018, Front. Med..

[16]  Hyung-Sik Kang,et al.  The flavonoid hesperidin exerts anti-photoaging effect by downregulating matrix metalloproteinase (MMP)-9 expression via mitogen activated protein kinase (MAPK)-dependent signaling pathways , 2018, BMC Complementary and Alternative Medicine.

[17]  D. Topgaard,et al.  Skin hydration: interplay between molecular dynamics, structure and water uptake in the stratum corneum , 2017, Scientific Reports.

[18]  M. Cavinato,et al.  Plant extracts and natural compounds used against UVB-induced photoaging , 2017, Biogerontology.

[19]  Costantino Balestra,et al.  A red orange extract modulates the vascular response to a recreational dive: a pilot study on the effect of anthocyanins on the physiological consequences of scuba diving , 2016, Natural product research.

[20]  J. Meephansan,et al.  Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis , 2016, International journal of molecular sciences.

[21]  A. Jimtaisong,et al.  Natural products as photoprotection , 2015, Journal of cosmetic dermatology.

[22]  Sang-yong Park,et al.  Gallic Acid Regulates Skin Photoaging in UVB‐exposed Fibroblast and Hairless Mice , 2014, Phytotherapy research : PTR.

[23]  Jieun Park,et al.  The protective effect of Kaempferia parviflora extract on UVB‐induced skin photoaging in hairless mice , 2014, Photodermatology, photoimmunology & photomedicine.

[24]  Ying-Hui Shan,et al.  Inhibitory effects of salidroside and paeonol on tyrosinase activity and melanin synthesis in mouse B16F10 melanoma cells and ultraviolet B-induced pigmentation in guinea pig skin. , 2013, Phytomedicine : international journal of phytotherapy and phytopharmacology.

[25]  G. Grosso,et al.  Red Orange: Experimental Models and Epidemiological Evidence of Its Benefits on Human Health , 2013, Oxidative medicine and cellular longevity.

[26]  Hsiu-Mei Chiang,et al.  Michelia alba extract attenuates UVB-induced expression of matrix metalloproteinases via MAP kinase pathway in human dermal fibroblasts. , 2012, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[27]  S. Buscemi,et al.  Effects of red orange juice intake on endothelial function and inflammatory markers in adult subjects with increased cardiovascular risk. , 2012, The American journal of clinical nutrition.

[28]  G. Frasca,et al.  Protective effects of a standardised red orange extract on air pollution-induced oxidative damage in traffic police officers , 2008, Natural product research.

[29]  Masahiko Kato,et al.  Release of cytokines/chemokines and cell death in UVB‐irradiated human keratinocytes, HaCaT , 2008, Cell biology international.

[30]  Xiao-jun Zhou,et al.  Ultraviolet B‐induced alterations of the skin barrier and epidermal calcium gradient , 2007, Experimental dermatology.

[31]  J. Fischer,et al.  Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. , 2007, The American journal of pathology.

[32]  A. Young,et al.  Acute effects of UVR on human eyes and skin. , 2006, Progress in biophysics and molecular biology.

[33]  F. Bonina,et al.  Effect of a standardized extract of red orange juice on proliferation of human prostate cells in vitro. , 2006, Fitoterapia.

[34]  Yasuhiro Matsumura,et al.  Toxic effects of ultraviolet radiation on the skin. , 2004, Toxicology and applied pharmacology.

[35]  A. Tyner,et al.  Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[36]  M. Karin,et al.  AP-1 as a regulator of cell life and death , 2002, Nature Cell Biology.

[37]  A. Saija,et al.  In vitro antioxidant activity and in vivo photoprotective effect of a red orange extract , 1998, International journal of cosmetic science.

[38]  R. Yasuda,et al.  UVB-induced alterations in permeability barrier function: roles for epidermal hyperproliferation and thymocyte-mediated response. , 1997, The Journal of investigative dermatology.

[39]  M. Yaar,et al.  Ageing and photoageing of the skin: observations at the cellular and molecular level , 1992, The British journal of dermatology.

[40]  Tao Wu,et al.  Vicenin-2 ameliorates oxidative damage and photoaging via modulation of MAPKs and MMPs signaling in UVB radiation exposed human skin cells. , 2019, Journal of photochemistry and photobiology. B, Biology.

[41]  S. Aggarwal,et al.  Anticedants and natural prevention of environmental toxicants induced accelerated aging of skin. , 2015, Environmental toxicology and pharmacology.

[42]  M. Cristani,et al.  Protective effects of a red orange extract on UVB‐induced damage in human keratinocytes , 2007, BioFactors.

[43]  Oprs Alert.  Guidance for Industry Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers , 2005 .