9. Exp Dermatol. 2010 Aug;19(8):e182-90.  Dietary compound ellagic acid alleviates skin wrinkle and inflammation induced by UV-B irradiation.  Bae JY, Choi JS, Kang SW, Lee YJ, Park J, Kang YH.  Department of Food and Nutrition, Hallym University, Chuncheon, Korea. 

 Ellagic acid, a polyphenol compound present in berries and pomegranate, has received attention as an agent that may have potential bioactivities preventing chronic diseases. This study examined photoprotective effects of ellagic acid on  collagen breakdown and inflammatory responses in UV (ultraviolet)-B irradiated human skin cells and hairless mice. Ellagic acid attenuated the UV-B-induced toxicity of HaCaT keratinocytes and human dermal fibroblasts. Non-toxic ellagic acid markedly prevented collagen degradation by blocking matrix metalloproteinase production in UV-B-exposed fibroblasts. Anti-wrinkle activity of ellagic acid was further investigated in hairless mice exposed to UV-B, in which it attenuated UV-B-triggered skin wrinkle formation and epidermal thickening. Topical application of 10 micromol/l ellagic acid diminished production of pro-inflammatory cytokines IL-1beta and IL-6, and blocked infiltration of inflammatory macrophages in the integuments of SKH-1 hairless mice exposed to UV-B for 8 weeks. In addition, this compound mitigated inflammatory intracellular cell adhesion molecule-1 expression in UV-B-irradiated keratinocytes and photoaged mouse epidermis. These results demonstrate that ellagic acid prevented  collagen destruction and inflammatory responses caused by UV-B. Therefore, dietary and pharmacological interventions with berries rich in ellagic acid may be promising treatment strategies interrupting skin wrinkle and inflammation associated with chronic UV exposure leading to photoageing.  PMID: 20113347  [PubMed - indexed for MEDLINE] 

8. J Drugs Dermatol. 2010 Jun;9(6 Suppl):S72-81; quiz s82-3.  Innovations in natural ingredients and their use in skin care.  Fowler JF Jr, Woolery-Lloyd H, Waldorf H, Saini R.  University of Louisville, Division of Dermatology, Louisville, KY 40202, USA. fowlerjoe@msn.com 

 Natural ingredients have been used traditionally for millennia and their application in topical creams, lotions and preparations within the traditional medicines and healing traditions of many cultures has been observed. Over the last 20 years, clinical and laboratory studies have identified the benefits of an array of natural ingredients for skin care. Consequently, a number of these ingredients and compounds are today being developed, used or considered not only  for anti-aging effects, but also for use in dermatologic disorders. Certain ingredients, such as colloidal oatmeal and aloe vera, have been identified as beneficial in the treatment of psoriasis and atopic dermatitis, respectively, due to their anti-inflammatory properties. For combating acne and rosacea, green tea, niacinamide and feverfew are considered efficacious. As to hyperpigmentation and  antioxidative capabilities, licorice, green tea, arbutin, soy, acai berry, turmeric and pomegranate are among those plants and compounds found to be most beneficial. Additional research is needed to determine to confirm and elucidate the benefits of these ingredients in the prevention and management of skin disease.  PMID: 20626172  [PubMed - indexed for MEDLINE] 

7. J Drugs Dermatol. 2007 Nov;6(11):1141-8.  Evaluating the efficacy in improving facial photodamage with a mixture of topical antioxidants.  Hsu J, Skover G, Goldman MP.  University of California, San Diego, USA. 

 This study evaluates the efficacy and tolerability of an investigational study cream composed of 3 ingredients (green and white teas, mangosteen, and pomegranate extract), Vitaphenol Skin Cream (La Jolla Spa MD, La Jolla CA), as compared to a placebo cream in rejuvenating facial skin. Twenty healthy females between the ages of 35 and 65 with demonstrable facial wrinkling, achieving a Rao-Goldman wrinkle scale score of 2 or above, applied either Vitaphenol Skin Cream or placebo cream to a randomized half of their face twice daily for 60 days and returned for follow-up after 2 weeks. Twice as many subjects indicated an enhancement of skin texture (eg, reduction in pore size, roughness, and touch) with the usage of Vitaphenol versus placebo. In all, 41% of the study subjects preferred the half of their face that had been receiving Vitaphenol, while only 0.06% of the subjects favored the placebo side. PRIMOS images from periorbital skin treated with Vitaphenol demonstrated an average improvement in skin smoothness of 1 mm3, whereas skin treated with placebo showed an average decrease in smoothness or an increase in skin roughness of 0.9 mm3. The addition of 3 antioxidants, green and white teas, mangosteen, and pomegranate, have an additive effect to enhance the improvement of age-related changes in the skin.  PMID: 18038502  [PubMed - indexed for MEDLINE]  

6. J Ethnopharmacol. 2007 Jan 19;109(2):177-206. Epub 2006 Sep 10.  Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer.  Lansky EP, Newman RA.  Punisyn Pharmaceuticals Ltd, Haifa, Israel. info@punisyn.com 

 The last 7 years have seen over seven times as many publications indexed by Medline dealing with pomegranate and Punica granatum than in all the years preceding them. Because of this, and the virtual explosion of interest in pomegranate as a medicinal and nutritional product that has followed, this review is accordingly launched. The pomegranate tree, Punica granatum, especially its fruit, possesses a vast ethnomedical history and represents a phytochemical reservoir of heuristic medicinal value. The tree/fruit can be divided into several anatomical compartments: (1) seed, (2) juice, (3) peel, (4) leaf, (5) flower, (6) bark, and (7) roots, each of which has interesting pharmacologic activity. Juice and peels, for example, possess potent antioxidant properties, while juice, peel and oil are all weakly estrogenic and heuristically of interest for the treatment of menopausal symptoms and sequellae. The use of juice, peel and oil have also been shown to possess anticancer activities, including interference with tumor cell proliferation, cell cycle, invasion and angiogenesis. These may be associated with plant based anti-inflammatory effects, The phytochemistry and pharmacological actions of all Punica granatum components  suggest a wide range of clinical applications for the treatment and prevention of cancer, as well as other diseases where chronic inflammation is believed to play  an essential etiologic role.  PMID: 17157465  [PubMed - indexed for MEDLINE] 

5. J Ethnopharmacol. 2006 Feb 20;103(3):311-8. Epub 2005 Oct 10.  Pomegranate as a cosmeceutical source: pomegranate fractions promote proliferation and procollagen synthesis and inhibit matrix metalloproteinase-1 production in human skin cells.  Aslam MN, Lansky EP, Varani J.  Department of Pathology, The University of Michigan Medical School, 1301 Catherine Road/Box 0602, Ann Arbor, MI 48109, USA. 

 Pomegranate (Punica granatum) is an ancient fruit with exceptionally rich ethnomedical applications. The peel (pericarp) is well regarded for its astringent properties; the seeds for conferring invulnerability in combat and stimulating beauty and fertility. Here, aqueous fractions prepared from the fruit's peel and fermented juice and lipophilic fractions prepared from pomegranate seeds were examined for effects on human epidermal keratinocyte and human dermal fibroblast function. Pomegranate seed oil, but not aqueous extracts  of fermented juice, peel or seed cake, was shown to stimulate keratinocyte proliferation in monolayer culture. In parallel, a mild thickening of the epidermis (without the loss of ordered differentiation) was observed in skin organ culture. The same pomegranate seed oil that stimulated keratinocyte proliferation was without effect on fibroblast function. In contrast, pomegranate peel extract (and to a lesser extent, both the fermented juice and seed cake extracts) stimulated type I procollagen synthesis and inhibited matrix metalloproteinase-1 (MMP-1; interstitial collagenase) production by dermal fibroblasts, but had no growth-supporting effect on keratinocytes. These results  suggest heuristic potential of pomegranate fractions for facilitating skin repair in a polar manner, namely aqueous extracts (especially of pomegranate peel) promoting regeneration of dermis, and pomegranate seed oil promoting regeneration of epidermis.  PMID: 16221534  [PubMed - indexed for MEDLINE] 

4. Photochem Photobiol. 2005 Jan-Feb;81(1):38-45.  Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of nuclear factor kappa B in normal human epidermal keratinocytes paragraph sign.  Afaq F, Malik A, Syed D, Maes D, Matsui MS, Mukhtar H.  Department of Dermatology, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA. 

 Excessive exposure of solar ultraviolet (UV) radiation, particularly its UV-B component, to humans causes many adverse effects that include erythema, hyperplasia, hyperpigmentation, immunosuppression, photoaging and skin cancer. In recent years, there is increasing use of botanical agents in skin care products.  Pomegranate derived from the tree Punica granatum contains anthocyanins (such as  delphinidin, cyanidin and pelargonidin) and hydrolyzable tannins (such as punicalin, pedunculagin, punicalagin, gallagic and ellagic acid esters of glucose) and possesses strong antioxidant and anti-inflammatory properties. Recently, we have shown that pomegranate fruit extract (PFE) possesses antitumor  promoting effects in a mouse model of chemical carcinogenesis. To begin to establish the effect of PFE for humans in this study, we determined its effect on UV-B-induced adverse effects in normal human epidermal keratinocytes (NHEK). We first assessed the effect of PFE on UV-B-mediated phosphorylation of mitogen-activated protein kinases (MAPK) pathway in NHEK. Immunoblot analysis demonstrated that the treatment of NHEK with PFE (10-40 microg/mL) for 24 h before UV-B (40 mJ/cm(2)) exposure dose dependently inhibited UV-B-mediated phosphorylation of ERKl/2, JNK1/2 and p38 protein. We also observed that PFE (20  microg/mL) inhibited UV-B-mediated phosphorylation of MAPK in a time-dependent manner. Furthermore, in dose- and time-dependent studies, we evaluated the effect of PFE on UV-B-mediated activation of nuclear factor kappa B (NF-kappaB) pathway. Using Western blot analysis, we found that PFE treatment of NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha. Using immunoblot analysis, enzyme-linked immunosorbent assay and electrophoretic mobility shift assay, we found that PFE treatment to NHEK resulted in a dose- and time-dependent inhibition of UV-B-mediated nuclear translocation and phosphorylation of NF-kappaB/p65 at Ser(536). Taken together, our data shows that PFE protects against the adverse effects of UV-B radiation by inhibiting UV-B-induced modulations of NF-kappaB and MAPK pathways and provides a molecular basis for the photochemopreventive effects of PFE.  PMID: 15493960  [PubMed - indexed for MEDLINE]  

3. J Med Food. 2004 Summer;7(2):256-9.  Study on wound healing activity of Punica granatum peel.  Murthy KN, Reddy VK, Veigas JM, Murthy UD.  Department of Plant Cell Biotechnology, Central Food Technological Research Institute, Mysore-570 020, Karnataka, India. kncmurthy@rediffmail.com 

 The methanolic extract of dried pomegranate (Punica granatum) peels showed the presence of a high content of phenolic compounds (44.0%) along with other constituents. This extract was formulated as a 10% (wt/wt) water-soluble gel and  was studied for its wound healing property against an excision wound on the skin  of Wistar rats. The activity was compared with that of a commercial topical antibacterial applicant. The wound healing activity was assessed by measuring the percent contraction in skin and estimation of collagen content in terms of hydroxyproline content. Healed skin was also subjected to histopathological studies to examine the microscopic changes. The animals treated with 2.5% gel showed moderate healing (55.8% and 40.8% healing compared with negative and positive controls, respectively), whereas the group treated with 5.0% gel showed  good healing (59.5% and 44.5% healing compared with negative and positive controls, respectively). The amount of hydroxyproline increased by twofold in the group treated with 5.0% gel. Histopathological studies also supported the wound healing on application of the gels. The group of rats that received 5.0% gel showed complete healing after 10 days, whereas in rats treated with 2.5% gel, healing was observed on day 12, in contrast to the positive control animals receiving the blank gel, which took 16-18 days for complete healing. The results  of this study may be extended to different types of wounds so that the formulation could be exploited to develop it as a topical dermatological formulation. High-performance liquid chromatography analysis of the extract showed the presence of gallic acid and catechin as major components.  PMID: 15298776  [PubMed - indexed for MEDLINE] 

2. J Med Food. 2003 Fall;6(3):157-61.  Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1  mice.  Hora JJ, Maydew ER, Lansky EP, Dwivedi C.  Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007, U.S.A. 

 Pomegranate seed oil was investigated for possible skin cancer chemopreventive efficacy in mice. In the main experiment, two groups consisting each of 30, 4-5-week-old, female CD(1) mice were used. Both groups had skin cancer initiated  with an initial topical exposure of 7,12-dimethylbenzanthracene and with biweekly promotion using 12-O-tetradecanoylphorbol 13-acetate (TPA). The experimental group was pretreated with 5% pomegranate seed oil prior to each TPA application.  Tumor incidence, the number of mice containing at least one tumor, was 100% and 93%, and multiplicity, the average number of tumors per mouse, was 20.8 and 16.3  per mouse after 20 weeks of promotion in the control and pomegranate seed oil-treated groups, respectively (P <.05). In a second experiment, two groups each consisting of three CD(1) mice were used to assess the effect of pomegranate seed oil on TPA-stimulated ornithine decarboxylase (ODC) activity, an important event in skin cancer promotion. Each group received a single topical application  of TPA, with the experimental group receiving a topical treatment 1 h prior with  5% pomegranate seed oil. The mice were killed 5 h later, and ODC activity was assessed by radiometric method. The experimental group showed a 17% reduction in  ODC activity. Pomegranate seed oil (5%) significantly decreased (P <.05) tumor incidence, multiplicity, and TPA-induced ODC activity. Overall, the results highlight the potential of pomegranate seed oil as a safe and effective chemopreventive agent against skin cancer.  PMID: 14585180  [PubMed - indexed for MEDLINE] 

1. Oncogene. 2003 Feb 20;22(7):1035-44.  Inhibition of ultraviolet B-mediated activation of nuclear factor kappaB in normal human epidermal keratinocytes by green tea Constituent (-)-epigallocatechin-3-gallate.  Afaq F, Adhami VM, Ahmad N, Mukhtar H.  Department of Dermatology, University of Wisconsin, Madison, WI 53706, USA. 

Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, possesses  significant anti-inflammatory and cancer chemopreventive properties. Studies have shown the photochemopreventive effects of green tea and EGCG in cell culture, animal models, and human skin. The molecular mechanism(s) of photochemopreventive effects of EGCG are incompletely understood. We recently showed that EGCG treatment of the normal human epidermal keratinocytes (NHEK) inhibits ultraviolet (UV)B-mediated activation of the mitogen-activated protein kinase (MAPK) pathway. In this study, we evaluated the effect of EGCG on UVB-mediated modulation of the  nuclear factor kappa B (NF-kappaB) pathway, which is known to play a critical role in a variety of physiological functions and is involved in inflammation and  development of cancer. Immunoblot analysis demonstrated that the treatment of NHEK with EGCG (10-40 microM) for 24 h resulted in a significant inhibition of UVB (40 mJ/cm(2))-mediated degradation and phosphorylation of IkappaBalpha and activation of IKKalpha, in a dose-dependent manner. UVB-mediated degradation and  phosphorylation of IkappaBalpha and activation of IKKalpha was also observed in a time-dependent protocol (15 and 30 min, 1, 2, 3, 6, 12 h post-UVB exposure). Employing immunoblot analysis, enzyme-linked immunosorbent assay, and gel shift assay, we demonstrate that EGCG treatment of the cells resulted in a significant  dose- and time-dependent inhibition of UVB-mediated activation and nuclear translocation of a NF-kappaB/p65. Our data suggest that EGCG protects against the adverse effects of UV radiation via modulations in NF-kappaB pathway, and provide a molecular basis for the photochemopreventive effect of EGCG.  PMID: 12592390  [PubMed - indexed for MEDLINE] 

Pomegranate research has shown that it has many health benefits. In skin care pomegranate has been shown to protect against photoaging, support skin cell regeneration, promote healing, and prevents cancerous changes due to UV exposure.

Pomegranate Research