>> Ellagic Acid
1. 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]"
2. J Dermatol. 2008 Sep;35(9):570-4. Efficiency of ellagic acid and arbutin in melasma: a randomized, prospective, open-label study.
Ertam I, Mutlu B, Unal I, Alper S, Kivšak B, Ozer O. Department of Dermatology and Pharmacy, Ege University School of Medicine, Izmir, Turkey. firstname.lastname@example.org.
"The aim of this study was to compare the effectiveness of gel formulations containing arbutin, synthetic ellagic acid and plant extracts that contain ellagic acid, on patients with melasma. Thirty patients who applied to Ege University Medical Faculty, Department of Dermatology, were included in the study. A signed consent was obtained from each patient prior to study. Patients whose type of melasma was determined via Wood's lamp were randomized to groups of arbutin, synthetic ellagic acid and plant extract containing natural ellagic acid. The pigment density of patients was evaluated via Mexameter before and after the treatment. The approval of the Institutional Ethics Committee of Ege University was obtained before the study. Wilcoxon and Kruskal-Wallis tests were used in the statistical analysis. Nine of 10 patients, for whom synthetic ellagic acid was started, completed the study. A decrease in the level of melanin was determined in eight of these nine patients (P = 0.038). A significant decrease in the level of melanin was also determined in all 10 patients who used plant extract containing ellagic acid (P = 0.05). A significant response was obtained from all of 10 patients who used arbutin. The difference between pre- and post-treatment levels of melanin was statistically significant (P = 0.05). Formulations prepared with plant extracts containing ellagic acid was found effective on melasma, similar to the formulations containing synthetic ellagic acid and arbutin. This material that is not yet being used widespread commercially on melasma could be an effective alternative for treatment of melasma. PMID: 18837701 [PubMed - indexed for MEDLINE]"
3. J Invest Dermatol. 2006 Jun;126(6):1272-80. Ellagic and tannic acids protect newly synthesized elastic fibers from premature enzymatic degradation in dermal fibroblast cultures.
Jimenez F, Mitts TF, Liu K, Wang Y, Hinek A. Research Department, Human Matrix Sciences, LLC, Visalia, California, USA.
"Progressive proteolytic degradation of cutaneous elastic fibers, that cannot be adequately replaced or repaired by adult dermal fibroblasts, constitutes a major feature of aging skin. Our present investigations, employing monolayer cultures of human dermal fibroblasts and organ cultures of skin biopsies, were aimed at testing whether the hydrophilic tannic acid (TA) and lipophilic ellagic acid (EA) would protect dermal elastin from exogenous and endogenous enzymatic degradation. Results from both culture systems indicated that dermal fibroblasts, maintained with TA or EA, deposit significantly more elastic fibers than untreated control cultures despite the fact that neither polyphenol enhanced transcription of elastin mRNA or cellular proliferation. Results of a pulse and chase experiment showed that pretreatment with both polyphenols enhanced biostability of tropoelastin and newly deposited elastin. Results of in vitro assays indicated that both polyphenols bound to purified elastin and significantly decreased its proteolytic degradation by elastolytic enzymes belonging to the serine proteinase, cysteine proteinase, and metallo-proteinase families. Importantly, both polyphenols also synergistically enhanced elastogenesis induced by selected elastogenic compounds in cultures of dermal fibroblasts. We propose that EA and TA may be useful for preventing proteolytic degradation of existing dermal elastic fibers and for enhancing more efficient elastogenesis in aged skin. PMID: 16601672 [PubMed - indexed for MEDLINE]"
4. Int J Cosmet Sci. 2000 Aug;22(4):291-303. In vitro and in vivo evaluation of ellagic acid on melanogenesis inhibition.
Shimogaki H, Tanaka Y, Tamai H, Masuda M. Life Science Research Center, Lion Corporation, Kanagawa, Japan.
"The efficacy of ellagic acid (EA), one of the naturally occurring polyphenols, in inhibiting melanogenesis was examined in vitro and in vivo. When mushroom-derived tyrosinase, a metaloprotein containing copper, was incubated with EA, enzymatic activity tended to decrease with decreasing copper concentration. Enzyme activity partially recovered when copper was added to the inactivated enzyme. Tyrosinase activity in the B16 melanoma cells was observed to recover in a dose-dependent manner when copper ions were added to the medium containing EA. Based on these results, EA is thought to react specifically with the copper located at the active centre of the tyrosinase molecule. Furthermore, when EA was applied for 6 weeks to brownish guinea-pigs, which have melanocytes in their skin, at the same time as irradiating for 2 weeks with ultra-violet light, skin pigmentation was clearly suppressed and the skin to which EA had been applied showed features similar to that of non-irradiated skin. These areas were irradiated again when the application of EA had been completed, and skin pigmentation occurred at the former site of EA application. In similar studies with hydroquinone, re-pigmentation did not occur on the sites at which hydroquinone (1%) had been applied. Based on the results reported here, EA is thought to suppress melanogenesis by reacting with activated melanocytes and without injuring cells. PMID: 18503416 [PubMed - in process]"
5. Plast Reconstr Surg. 1994 Dec;94(7):1027-37. Involvement of lipid peroxidation in necrosis of skin flaps and its suppression by ellagic acid.
Ashoori F, Suzuki S, Zhou JH, Isshiki N, Miyachi Y. Department of Plastic and Reconstructive Surgery, Kyoto University Hospital, Japan.
"To evaluate the pathogenesis of lipid peroxidation in skin-flap necrosis and to select a novel herbal antioxidant to suppress lipid peroxidation and salvage the flaps, in vitro and in vivo experiments were instituted. In vitro studies revealed (1) the potentiality of the cutaneous microsomal system (vesicular fragment of endoplasmic reticulum) to generate oxyradicals by FeCl3 (oxidative agent), since NADPH-dependent lipid peroxidation was elevated time-dependently, (2) suppression of microsomal lipid peroxidation by herbal antioxidants (dose- and time-dependently), further supporting the theory of oxyradical-induced lipid peroxidation in the skin, and (3) that ellagic acid showed the strongest response, with curcumin, chlorogenic acid, and alpha-tocopherol (tocopherol) being moderate, and ferulic acid and gallic acid remaining weakest. Thus ellagic acid, curcumin, chlorogenic acid, and tocopherol at doses of 10, 60, 80 and 100 microM (twice I50, the dose which could inhibit lipid peroxidation by 50 percent) were chosen for in vivo assessments, respectively. In vivo studies were performed using rat back skin random flaps (70 x 15 mm and based anteriorly) and circular island flaps (20 mm in diameter and raised on superficial epigastric vessels). Control flaps were painted with a Tris-ethanol solution, and test flaps were painted with either ellagic acid, curcumin, chlorogenic acid, or tocopherol (above-mentioned doses per 250 microliters of Tris-ethanol per 300 mm2 of flap surface 1 hour before the operation and once a day for 3 postoperative days). Doses, frequency, and period of drug application were based on in vitro and in vivo pilot experiments. The results were as follows: (1) a direct and time-dependent relation was noticed between lipid peroxide levels and the rate of necrosis in both types of flap; (2) time-dependent elevation of lipid peroxide levels of skin, subcutaneous fat, and exudate of island flaps during ischemia and those of skin and subdermal fat after reperfusion indicated pre- and post-reflow states of lipid peroxidation rather than the original conception of merely reperfusion state; and (3) in good agreement with the results of in vitro experiments, ellagic acid exerted the strongest effect to suppress lipid peroxide levels of skin and to augment the viability of random flaps more than that of island flaps.(ABSTRACT TRUNCATED AT 400 WORDS) PMID: 7972456 [PubMed - indexed for MEDLINE]"