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13. Phytother Res. 2011 Dec;25(12):1854-60. doi: 10.1002/ptr.3507. Epub 2011 Apr 25. Photoprotective Effects of Topical Formulations Containing a Combination of Ginkgo biloba and Green Tea Extracts. Belo SE, Gaspar LR, Campos PM. Universidade de São Paulo, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Department of Pharmaceutical Sciences, Av. do Café s/n, Ribeirão Preto, Brazil.
The beneficial photoprotective effects of topical formulations containing combined extracts of Ginkgo biloba (GB) and green tea (GT) have not been investigated. The present study aims to assess the photoprotective effects of topical formulations containing GB and GT combined or not by applications on the dorsal skin of hairless mice prior to UVA/B irradiation. After 20?�h, skin barrier damage (TEWL), erythema, histological alterations and sunburn cell formation were evaluated. The results showed that only extract supplemented formulations protected the skin against the UV-induced damage. Formulations containing GB provided total protection of the skin barrier function avoiding UV radiation damage such as TEWL and erythema and were more effective than those containing GT. However, it is suggested that formulations containing combined GB and GT may provide substantial photoprotective effects since different aspects of skin damage were influenced by each extract. Copyright © 2011 John Wiley & Sons, Ltd. Copyright © 2011 John Wiley & Sons, Ltd. PMID: 21520309 [PubMed - in process]
12. Life Sci. 2007 Apr 3;80(17):1586-91. Epub 2007 Jan 27. Extract of Ginkgo biloba induces phase 2 genes through Keap1-Nrf2-ARE signaling pathway. Liu XP, Goldring CE, Copple IM, Wang HY, Wei W, Kitteringham NR, Park BK. Institute of Clinical Pharmacology, Key Laboratory of Anti-inflammatory and Immunopharmacology in Anhui, Anhui Medical University, Meishan Road 81, Hefei Anhui 230032, PR China.
The standard extract of Ginkgo biloba (EGb) has been demonstrated to possess remarkable antioxidant activity in both cell lines and animals. However, the molecular mechanism underlying this effect is not fully understood. Phase 2 enzymes play important roles in the antioxidant system by reducing electrophiles and reactive oxygen species (ROS). We demonstrated that EGb induced typical phase 2 genes: glutamate cysteine ligase catalytic subunit (GCLC) and glutathione-S-transferase subunit-P1 (GST-P1), by real-time PCR. To investigate the molecular mechanism of this induction, we used quinone oxidoreductase 1 (NQO1) -- Antioxidant response element (ARE) reporter assay and found that EGb activated the activity of the wild type but not the one with ARE mutated. It indicated that EGb induced these genes through ARE, a cis-acting motif located in the promoter region of nearly all phase 2 genes. Since nuclear factor erythroid 2-related factor 2 (Nrf2) binds ARE to enhance the expression of phase 2 genes, we detected the Nrf2 content in nucleus and found an accumulation of Nrf2 stimulated by EGb. In a further test of Kelch-like ECH-associated protein 1 (Keap1), the repression protein of Nrf2 in the cytosol under resting condition, we found that Keap1 content was inhibited by EGb and then more Nrf2 would be released to translocate into nucleus. Thus, EGb was testified for the first time to induce the phase 2 genes through the Keap1-Nrf2-ARE signaling pathway, which is (or part of) the antioxidant mechanism of EGb. PMID: 17316704 [PubMed - indexed for MEDLINE]
11. Arch Pharm Res. 2006 Jun;29(6):503-7. Inhibition of chronic skin inflammation by topical anti-inflammatory flavonoid preparation, Ato Formula. Lim H, Son KH, Chang HW, Kang SS, Kim HP. College of Pharmacy, Kangwon National University, Chunchon, Korea.
Flavonoids are known as natural anti-inflammatory agents. In this investigation, an anti-inflammatory potential of new topical preparation (SK Ato Formula) containing flavonoid mixtures from Scutellaria baicalensis Georgi roots and Ginkgo biloba L. leaves with an extract of Gentiana scabra Bunge roots was evaluated in an animal model of chronic skin inflammation. Multiple 12-O-tetradecanoylphorbol-13-acetate treatments for 7 consecutive days on ICR mouse ear provoked a chronic type of skin inflammation: dermal edema, epidermal hyperplasia and infiltration of inflammatory cells. When topically applied in this model, this new formulation (5-20 microL/ear/treatment) reduced these responses. Furthermore, it inhibited prostaglandin E2 generation (17.1-33.3%) and suppressed the expression of proinflammatory genes, cyclooxygenase-2 and interleulin-1beta in the skin lesion. Although the potency of inhibition was lower than that of prednisolone, all these results suggest that Ato Formula may be beneficial for treating chronic skin inflammatory disorders such as atopic dermatitis. PMID: 16833019 [PubMed - indexed for MEDLINE]
10. Biol Pharm Bull. 2006 May;29(5):1046-9. Effects of anti-inflammatory biflavonoid, ginkgetin, on chronic skin inflammation. Lim H, Son KH, Chang HW, Kang SS, Kim HP. College of Pharmacy, Kangwon National University, Chunchon, Korea.
Ginkgetin, a biflavonoid from Ginkgo biloba leaves (Ginkgoaceae), was previously demonstrated to inhibit phospholipase A2 and to suppress proinflammatory gene expression such as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase. In this study, the effects of ginkgetin were examined on an animal model of chronic skin inflammation and proinflammatory gene expression. When topically applied to ICR mouse ear, ginkgetin (20-80 microg/ear/treatment) inhibited ear edema (22.8-30.5%) and prostaglandin E2 production (30.2-31.1%) induced by multiple treatment of 12-O-tetradecanoylphorbol-13-acetate (TPA) for 7 consecutive days. By histological comparison, ginkgetin was also found to reduce epidermal hyperplasia. The expression of proinflammatory gene, interleukin-1beta, was suppressed by ginkgetin. From the results, it is suggested that ginkgetin may be beneficial against chronic skin inflammatory disorders like atopic dermatitis. PMID: 16651744 [PubMed - indexed for MEDLINE]
9. Med Hypotheses. 2006;66(6):1152-6. Epub 2006 Feb 17. An adjunctive preventive treatment for cancer: ultraviolet light and ginkgo biloba, together with other antioxidants, are a safe and powerful, but largely ignored, treatment option for the prevention of cancer. Eli R, Fasciano JA. firstname.lastname@example.org
Cancer has surpassed heart disease as the leading cause of death in the United States. The mortality rate for cancer is high (roughly 42%), and it increases dramatically with increasing age, especially in patients between the ages of 40 and 60 years old. Currently, the efforts at cancer prevention have been minimal. The drugs developed so far are expensive and have serious side effects. There are at least 18 vitamin D-sensitive cancers. Ultraviolet light, and specifically ultraviolet B (UVB), could reduce cancer by the limited exposure of suitable skin areas to UVB of an intensity and duration insufficient to produce skin cancer. An irrational fear of skin cancer is preventing this idea from being implemented. Though skin cancer incidence is significant, mortality from skin cancer is relatively rare. Roughly 1,000,000 Americans will be affected by skin cancer but only 10,000 deaths are expected in 2005 (a 1% mortality rate). Skin cancer is easily detected and often cured by excisional biopsy alone. Current practice among practicing clinicians is to use a prescription drug substitute for UV light, calcitriol (1-25 dihydroxycholcalciferol). However, high levels of (calcitriol) are dangerous, and there is no consensus on just what a high dose or a safe dose is. Apart from skin cancer, UV light exposure possesses few risks. Additionally, a number of botanical agents such as ginkgo biloba, vitamins E and C, carotenoids, selenium and proanthocyanidins can prevent the risk of skin cancer. Ginkgo biloba also possess the following additional cancer chemopreventive qualities: (1) promoting apoptosis of cancer cells; (2) an anti-clastogenic effect on chromosomes by repairing and reconstituting broken and damaged chromosomes; (3) a powerful therapeutic effect on the treatment of fibrosis-related cancer; (4) a therapeutic effect on free radical-induced cancer; (5) a therapeutic effect on the treatment of cancer incident to the result of numerous carcinogens; (6) a therapeutic effect on preventing free radical-induced cancer; (7) an enhancing effect on radiation therapy in the treatment of cancer; and (8) a therapeutic effect on reducing the size of cancer tumors. Ginkgo biloba is widely-used and has few adverse effects. The proposed preventive treatment for cancer consists of short intermittent exposure of the least sensitive areas of the body to sunlight and/or artificial ultraviolet light. The routine testing of plasma vitamin D levels help monitor the effectiveness of the treatment and periodic checkups with a dermatologist help monitor the safety. PMID: 16483725 [PubMed - indexed for MEDLINE]
8. J Pharm Biomed Anal. 2005 Feb 23;37(2):287-95. Assays of physical stability and antioxidant activity of a topical formulation added with different plant extracts. Di Mambro VM, Fonseca MJ. Department of Pharmaceutical Science, Faculty of Pharmaceutical Sciences of Ribeirão Preto, USP, Av. do Café s/n, 14040-903 Ribeirão Preto, SP, Brazil. email@example.com
In the present investigation the changes on physical stability (pH, viscosity, flow index and tixotropy) of topical formulations were evaluated following inclusion of different plant extracts containing flavonoids. Also, the antioxidant effect of these plant extracts alone and after addition in the formulation was evaluated using chemiluminescence and the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH(.-)) assays, as well as the inhibition of lipid peroxidation. Formulation added with dl-alpha-tocopherol was used to compare the physical stability and antioxidant activity. Formulations with plant extracts showed pseudoplastic behavior with decreasing on viscosity and tixotropy. The Glycyrrhiza glabra (GG) and Ginkgo biloba (GB) extracts alone and the formulations containing these extracts showed great antioxidant and free radical scavenging activities while the other extracts studied (mixture of Glycyrrhiza glabra, Symphytum officinale L and Arctium majus root, Nelumbium speciosum and soybean) showed lower activity. The results suggest that GG and GB extracts may be used in topical formulations in order to protect skin against damage caused by free radical and reactive oxygen species. PMID: 15708669 [PubMed - indexed for MEDLINE]
7. Planta Med. 2002 Apr;68(4):316-21. Effects of Ginkgetin from Ginkgo biloba Leaves on cyclooxygenases and in vivo skin inflammation. Kwak WJ, Han CK, Son KH, Chang HW, Kang SS, Park BK, Kim HP. SK Chemicals Ltd., Suwon, Korea.
Ginkgetin, a biflavone from Ginkgo biloba leaves, was previously reported to be a phospholipase A2 inhibitor and this compound showed the potent antiarthritic activity in rat adjuvant-induced arthritis as well as analgesic activity. This investigation was carried out to find effects on cyclooxygenase (COX)-1 and -2 including an in vivo effect. Ginkgetin (1 - 10 microM) and the biflavonoid mixture (10 - 50 microg/ml), mainly a 1 : 1 mixture of ginkgetin and isoginkgetin, from G. biloba leaves, inhibited production of prostaglandin E2 from lipopolysaccharide-induced RAW 264.7 cells. This inhibition was mediated, at least in part, by down-regulation of COX-2 expression, but not by direct inhibition of COX-1 or COX-2 activity. Down-regulation of COX-2 by ginkgetin was also proved in the dorsal skin of ICR mouse treated by 12-O-tetradecanoylphorbol 13-acetate (TPA). At total doses of 1,000 microg/site on the dorsal skin (15 mm x 15 mm), ginkgetin inhibited prostaglandin E2 production by 65.6 % along with a marked suppression of COX-2 induction. In addition, ginkgetin and the biflavonoid mixture (100 - 1,000 microg/ear) dose-dependently inhibited skin inflammation of croton oil induced ear edema in mice by topical application. The present study suggests that ginkgetin from G. biloba leaves down-regulates COX-2 induction in vivo and this down-regulating potential is associated with an anti-inflammatory activity against skin inflammatory responses. PMID: 11988854 [PubMed - indexed for MEDLINE]
6. Biol Trace Elem Res. 2001 May;80(2):175-9. Changes in zinc levels and superoxide dismutase activities in the skin of acute, ultraviolet-B-irradiated mice after treatment with ginkgo biloba extract. Aricioglu A, Bozkurt M, Balabanli B, Kilinç M, Nazaroglu NK, Türközkan N. Department of Biochemistry, Medical Faculty, Gazi University, Besevler, Ankara, Turkey.
Acute ultraviolet-B (UV-B) irradiation is known to act as an initiator in the formation of reactive oxygen species. These oxygen products are highly reactive and they are able to cause irreversible damage to cellular components. Oxygen free radicals are normally neutralized by very efficient systems in the body. These include antioxidant enzymes like superoxide dismutase (SOD). In a healthy subject, there is a balance between free radicals and the levels of antioxidants. In some pathological conditions such as oxidative stress, the level of antioxidants is significantly reduced. The skin contains relatively high levels of zinc (Zn), an essential element known to be a cofactor in some metabolic pathways. Zinc has also been reported to have antioxidant properties. In the present study, we investigated the effect of ginkgo biloba extract (Gbe), a potent free-radical scavenger, on UV-B-irradiated skin by measuring SOD activity and Zn levels in the skin, before and after treatment. The SOD activity was decreased after UV-B exposure, in comparison with the control group (p < 0.05). After Gbe treatment, the SOD activity increased (p < 0.05) as compared with the untreated UV-B irradiated group. The Zn levels changed in the same pattern as the SOD activity values. PMID: 11437182 [PubMed - indexed for MEDLINE]
5. J Pharm Pharmacol. 1999 Dec;51(12):1435-40. In-vivo and in-vitro assessment of the free-radical-scavenger activity of Ginkgo flavone glycosides at high concentration. Hibatallah J, Carduner C, Poelman MC. Département de Dermopharmacie et Biophysique Cutanée, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
Free radicals are involved in numerous skin diseases, especially inflammatory reactions and photosenescence. To identify possible free-radical scavenging by an original terpene-free Ginkgo biloba extract containing 33% Ginkgo flavone glycosides, mostly quercetin and kaempferol derivatives, we studied its activity by means of in-vitro and in-vivo experiments, using superoxide dismutase (SOD) as a positive control. By means of an in-vitro electron-spin resonance (ESR) assay we compared the activity of the Ginkgo extract with that of its two aglycones, quercetin and kaempferol. Quercetin and Ginkgo extract had significant antioxidant properties without pro-oxidant effect. In contrast, kaempferol, above an optimum antioxidant concentration, behaved as a pro-oxidant. The in-vivo experiments were conducted on an anti-inflammatory model. The cutaneous blood flux which reflects the skin inflammatory level was recorded by means of a laser Doppler perfusion imager. The data confirmed the free-radical-scavenging property of both Ginkgo extract and SOD. The Ginkgo extract significantly inhibited (37%) cutaneous blood flux to the same extent as SOD. These data confirmed the antioxidant property of Ginkgo extract. A complementary spin-trapping technique would enable identification of the free radicals involved. This Ginkgo extract should be useful for protection of the skin against free radicals. PMID: 10678500 [PubMed - indexed for MEDLINE]
4. Scand J Plast Reconstr Surg Hand Surg. 1998 Jun;32(2):135-9. The effect of Gingko biloba extract (Egb 761) as a free radical scavenger on the survival of skin flaps in rats. A comparative study. Bekerecio?lu M, Tercan M, Ozyazgan I. Department of Plastic and Reconstructive Surgery, Faculty of Medicine, Yüzüncü Yil University, Van, Turkey.
Free radicals may have a role in pedicle flap necrosis. We undertook this study to compare the effect of various antioxidants and scavengers of free radicals such as vitamin E, vitamin C, deferoxamine, and Gingko biloba extract (Egb 761) on McFarlane caudal-based dorsal rat flaps. Fifty rats were divided into five groups of 10 animals each. One group served as a control (saline) group. The remaining four groups were given vitamin C 340 mg/kg, deferoxamine 150 mg/kg, Egb 761 100 mg/kg, and vitamin E 20 mg/kg. The necrosed area of flap was significantly reduced in the deferoxamine (p < 0.001), Egb 761 (p < 0.001), and vitamin C (p < 0.05) groups compared with the control group. Vitamin E had no effect on distal flap necrosis (p = 0.20). PMID: 9646361 [PubMed - indexed for MEDLINE]
3. Methods Find Exp Clin Pharmacol. 1997 Jul-Aug;19(6):367-71. Induction of superoxide dismutase and catalase activity in different rat tissues and protection from UVB irradiation after topical application of Ginkgo biloba extracts. Lin SY, Chang HP. Department of Medical Research and Education, Veterans General Hospital, Taipei, Taiwan, Republic of China.
Ginkgo biloba extract (GBE) prepared from the leaves of Ginkgo biloba with 50% diluted alcohol was found to locally induce superoxide dismutase (SOD) and catalase (CAT) enzyme activity in epidermis after topical application, and also to systemically increase the activity of both enzymes in the liver, heart and kidney of Sprague Dawley rats. Skin pretreated with 50% diluted alcohol-extracted liquid formulation was protected from exacerbation of UVB damage. Changes in the lipid structure of the skin of rats determined by ATR/FT-IR spectroscopy demonstrated penetration of active components from GBE dosage formulations. PMID: 9385585 [PubMed - indexed for MEDLINE]
2. Skin Pharmacol. 1997;10(4):200-5. Effects of flavonoids of Ginkgo biloba on proliferation of human skin fibroblast. Kim SJ, Lim MH, Chun IK, Won YH. Department of Dermatology, Chonnam University Medical School, Kwangju, Korea.
Ginkgo biloba studies have focused on the anti-inflammatory effects of the major components, ginkgolide and bilobalide, whereas little is known about their effect on fibroblasts. This study demonstrated the enhancing effects of Ginkgo L. extracts, especially the flavonoid fractions: quercetin, kaempferol, sciadopitysin, ginkgetin, isoginkgetin, on the proliferation of normal human skin fibroblast in vitro measured by MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and direct hemocytometer cell count. Furthermore, increased production of collagen and extracellular fibronectin were documented by radioisotope (2,3-3H-proline) incorporated collagen assay, procollagen type I C-peptide assay and by immunoturbidimetric assay. These proliferative effects suggest another useful pharmacologic application of Ginkgo L. extracts in addition to their well-known anti-inflammatory effect. PMID: 9413894 [PubMed - indexed for MEDLINE]
1. Free Radic Biol Med. 1992 Sep;13(3):197-203. UV-C irradiation-induced peroxidative degradation of microsomal fatty acids and proteins: protection by an extract of Ginkgo biloba (EGb 761). Dumont E, Petit E, Tarrade T, Nouvelot A. Laboratoire de Biochimie, CNRS SDI 6129, Université de Caen, France.
After exposure of rat liver microsomes to UV-C irradiation, analysis of membrane fatty acids by gas chromatography confirmed that EGb 761, a drug containing a dosed and standardized extract of Ginkgo biloba, provides effective protection against free radical attack in vitro. This analysis, coupled with thiobarbituric acid (TBA) reaction, permitted qualitative and overall quantitative evaluation of radical-induced damage to polyunsaturated fatty acids (PUFA), as well as evidence of the antioxidant properties of the Ginkgo biloba extract. Assay of thiobarbituric acid reactive substances (TBARS) showed a correlation between TBARS concentration and the state of degradation of the polyunsaturated fatty acids. Mannitol (5.5 mM) did not prevent degradation of microsomal PUFA or malondialdehyde (MDA) production, nor did it prevent polymerization of membrane proteins. Low doses of EGb 761 were found to provide efficient protection of membrane PUFA regardless of individual susceptibility to peroxidation. This protection was accompanied by a decrease in the production of TBARS. EGb 761 also protected membrane proteins from the irreversible polymerization induced by these degradation products, but did not appear to prevent thiols oxidation into disulfide bonds. PMID: 1505777 [PubMed - indexed for MEDLINE]
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