12. Free Radic Res. 2011 Aug;45(8):918-24. Epub 2011 Jun 9.

 

Photochemical stability of lipoic acid and its impact on skin ageing.

 

Matsugo S, Bito T, Konishi T.

 

College of Science and Engineering, School of Natural System, Kanazawa

University, Kakuma, Kanazawa 920-1192, Japan. matsugoh@t.kanazawa-u.ac.jp

 

It is well known that α-lipoic acid (LA) functions as an essential co-factor of

the mitochondrial multi-enzyme complex and thus plays an important role in energy metabolism. Currently, it is attracting attention as a nutritional supplement because of its unique antioxidant properties and broad spectra of cellular functions. Skin protection from photodamage and ageing is one of the functional applications of LA. Medical and cosmetic application has been widely realized in the world. However, LA has a unique structure bearing a distorted five membered 1, 2-dithiolane ring, making it quite vulnerable to UV radiation. The present article briefly reviews skin ageing from the viewpoint of oxidative stress and sun exposure and analyses the photochemical properties of LA. It also discusses the effect of LA to cellular signalling and its adequate applications to treat skin ageing caused by oxidation. Data presented in this review suggest that LA is a powerful anti-ageing agent under the appropriate usage.

 

PMID: 21651453  [PubMed - in process]

 

 

11. Connect Tissue Res. 2010 Oct;51(5):378-87.

 

α-Lipoic acid induces collagen biosynthesis involving prolyl hydroxylase

expression via activation of TGF-β-Smad signaling in human dermal fibroblasts.

 

Tsuji-Naito K, Ishikura S, Akagawa M, Saeki H.

 

DHC Corporation, Laboratories Division 2, Mihama-ku, Chiba, Japan.

knaito@dhc.co.jp

 

The collapse of collagenous networks with aging results in comprehensive changes in the functional properties of skin. α-Lipoic acid (LA) is known to possess beneficial effects against skin aging, effects often presumed to be its

antioxidant potential. However, the effects of LA on fibrillogenesis in dermal

fibroblasts have not been adequately assessed. In this study, we demonstrated for the first time that LA enhances the biosynthesis of new collagen in normal human dermal fibroblasts (NHDFs). By using a quantitative dye-binding method and immunochemical approaches, we showed that LA effectively increased the expression and subsequently the deposition of type I collagen in NHDFs. LA also facilitated the expression of a collagen-processing enzyme, prolyl-4-hydroxylase, pointing to the existence of a posttranslational mechanism among the LA-mediated effects on collagen synthesis. In addition, we determined that both Smad 2/3 were rapidly phosphorylated by treatment with LA within 30 min, indicating that LA enhances type I collagen synthesis through the activation of Smad signaling. Pretreatment of SB431542, a specific transforming growth factor-β (TGF-β) receptor type I (TβRI) kinase inhibitor, blocked LA-mediated Smad 2/3 phosphorylations and both type I collagen and prolyl-4-hydroxylase expression, suggesting that LA-mediated cell responses are regulated by TβRI kinase-dependent pathway. Levels of TGF-β secretion after 4 hr of treatment with LA were not remarkably elevated, indicating that LA may be able to mimic TGF-β-mediated cell response. The study results produced new insights into the molecular pharmacology of LA in NHDFs, with potential applications in the treatment of aging skin.

 

PMID: 20604712  [PubMed - indexed for MEDLINE]

 

 

10. J Clin Biochem Nutr. 2009 May;44(3):218-22. Epub 2009 Apr 25.

 

The Degradation and Regeneration of alpha-Lipoic Acid under the Irradiation of UV Light in the Existence of Homocysteine.

 

Wada N, Wakami H, Konishi T, Matsugo S.

 

College of Science and Engineering, School of Natural System, Kanazawa

University, Kakuma, Kanazawa 920-1192, Japan.

 

Alpha-Lipoic acid (LA) is the one of the strongest antioxidants to be utilized in

supplement, skin ointment and so on. The distorted five membered dithiolane ring of LA, which is necessary structure to work as a cofactor of enzyme, is

considerably vulnerable to UV irradiation. LA is easily decomposed by photoirradiation resulting in the loss of its characteristic absorption band at

333 nm. The photodegradation of LA means loss of its physiological activity, so

that protection of LA from UV light is eagerly desired. Thiol compounds can be

regarded as a potential candidate. In order to pursue the possibility of the

thiol compounds in prevention of LA degradation, we examined the photoirradiation of LA in the presence and absence of homocysteine.

 

PMCID: PMC2675023

PMID: 19430609  [PubMed]

 

 

9. Cell Biol Toxicol. 2009 Aug;25(4):331-40. Epub 2008 Jun 13.

 

Radioprotective effect of DL-alpha-lipoic acid on mice skin fibroblasts.

 

Davis GD, Masilamoni JG, Arul V, Kumar MS, Baraneedharan U, Paul SF, Sakthivelu IV, Jesudason EP, Jayakumar R.

 

Department of Bioinformatics, Sri Ramachandra University, Chennai 600116, India.

 

During the course of cancer radiation treatment, normal skin invariably suffers

from the cytotoxic effects of gamma-radiation and reactive oxygen species (ROS), which are generated from the interaction between radiation and the water molecules in cells. The present study was designed to investigate the

radioprotective role of alpha-lipoic acid (LA), an antioxidant on murine skin

fibroblasts exposed to a single dose of 2, 4, 6, or 8Gy gamma-radiation.

Irradiation of fibroblasts significantly increased ROS, nitric oxide, and lipid

peroxidation (P < 0.001); all of these factors substantially decreased with 100

microM LA treatment. Hydroxyl radical (OH(.)) production from 8Gy irradiated

fibroblasts was measured directly by electron spin resonance using spin-trapping techniques. LA was found to inhibit OH(.) production at 100-microM

concentrations. Dose-dependent depletion of antioxidants, such as catalase and glutathione reductase, was observed in irradiated fibroblasts (P < 0.001), along with increased superoxide dismutase (P < 0.001). LA treatment restored

antioxidant levels. Concentration of the pro-inflammatory cytokine IL-1beta was significantly reduced in irradiated fibroblasts when treated with LA. MTT and lactate dehydrogenase assays demonstrated that LA treatment reduced cell injury and protected cells against irradiation-induced cytotoxicity. Thus, we conclude that results are encouraging and need further experiments to demonstrate a possible benefit in cancer patients and the reduction of harmful effects of radiation therapy.

 

PMID: 18553143  [PubMed - indexed for MEDLINE]

 

 

8. IUBMB Life. 2008 Jun;60(6):362-7.

 

Is alpha-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity.

 

Petersen Shay K, Moreau RF, Smith EJ, Hagen TM.

 

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.

 

The chemical reduction and oxidation (redox) properties of alpha-lipoic acid (LA) suggest that it may have potent antioxidant potential. A significant number of studies now show that LA and its reduced form, dihydrolipoic acid (DHLA), directly scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS) species and protect cells against a host of insults where oxidative stress is part of the underlying etiology. However, owing to its limited and transient accumulation in tissues following oral intake, the efficacy of nonprotein-bound LA to function as a physiological antioxidant has been questioned. Herein, we review the evidence that the micronutrient functions of LA may be more as an effector of important cellular stress response pathways that ultimately influence endogenous cellular antioxidant levels and reduce proinflammatory mechanisms.This would promote a sustained improvement in cellular resistance to pathologies where oxidative stress is involved, which would not be forthcoming if LA solely acted as a transient ROS scavenger.

 

PMID: 18409172  [PubMed - indexed for MEDLINE]

 

 

7. Biochem Pharmacol. 2007 Jun 1;73(11):1786-95. Epub 2006 Dec 10.

 

Dihydrolipoic acid inhibits skin tumor promotion through anti-inflammation and

anti-oxidation.

 

Ho YS, Lai CS, Liu HI, Ho SY, Tai C, Pan MH, Wang YJ.

 

Institute of Biomedical Technology, Taipei Medical University, Taipei, Taiwan,

ROC.

 

Alpha-Lipoic acid (LA) has been intensely investigated as a therapeutic agent for several diseases, including hepatic disorder and diabetic polyneuropathy.

However, the effects of LA or its reduced form, dihydrolipoic acid (DHLA), on

cancer chemoprevention has never been reported. In the present study, we examined the effects of DHLA/LA on the production of nitric oxide (NO) by inducible NO synthase (iNOS) and the formation of prostaglandin E2 (PGE(2)) by cyclooxygenase-2 (COX-2), two important mediators associated with inflammation. DHLA/LA significantly inhibited lipopolysaccharide (LPS)-induced NO and PGE(2) formation in RAW 264.7 cells. Meanwhile, treatment with DHLA/LA suppressed the expression of iNOS protein but, unexpectedly, did not affect or increase the expression of COX-2 protein. The in vivo anti-inflammatory and antitumor-promoting activities were evaluated by a topical

12-O-tetradecanoylphorbol 13-acetate (TPA) application to mouse skin with

measurement of edema formation, epidermal thickness and hydrogen peroxide

production. DHLA significantly inhibited the priming and activation stages of

skin inflammation induced by a double TPA application, by decreasing the

inflammatory parameters. Furthermore, DHLA inhibited DMBA (0.3 micromol)/TPA (2.0 nmol)-induced skin tumor formation by reducing the tumor incidence and tumor multiplicity. When applied topically onto the shaven backs of mice prior to TPA, DHLA markedly inhibited the expression of iNOS protein. DHLA also strongly and directly inhibited COX-2 activity. These results suggest that DHLA can be a possible chemopreventive agent in inflammation-associated tumorigenesis.

 

PMID: 17403519  [PubMed - indexed for MEDLINE]

 

 

6. J Invest Dermatol. 2004 Nov;123(5):996-8.

 

Alpha-lipoic acid is ineffective as a topical antioxidant for photoprotection of

skin.

 

Lin JY, Lin FH, Burch JA, Selim MA, Monteiro-Riviere NA, Grichnik JM, Pinnell SR.

 

PMID: 15482491  [PubMed - indexed for MEDLINE]

 

 

5. Br J Dermatol. 2003 Oct;149(4):841-9.

 

Randomized, placebo-controlled, double blind study on the clinical efficacy of a

cream containing 5% alpha-lipoic acid related to photoageing of facial skin.

 

Beitner H.

 

Department of Dermatology, Karolinska Hospital, 17176 Stockholm, Sweden.

harry.beitner@ks.se

 

BACKGROUND: alpha-lipoic acid (LA) or the reduced form dihydrolipoate (DHLA) is a potent scavenger with anti-inflammatory properties. Previous uncontrolled studies with topical treatment with 5% LA-containing creams indicate a beneficial effect on photoageing skin.

OBJECTIVE: The purpose of this study was to investigate whether a cream

containing 5% LA showed any advantages concerning a number of the criteria

associated with ageing of the facial skin, compared with an identical cream

lacking LA.

MATERIAL AND METHODS: Thirty-three women, mean age 54.4 years, were included in

this controlled study. After randomization half the face was treated twice daily

for 12 weeks with the LA cream and the other half with the control cream. The

following methods of assessment were used: self-evaluation by the test subjects, clinical evaluation, photographic evaluation and laser profilometry. Profilometry was performed before the start of treatment and at the end.

RESULTS: All four methods of assessment showed a statistically significant

improvement on the LA-treated half of the face. Laser profilometry, the most

objective method used, showed an average decrease in skin roughness of 50.8% (44.9-54.0) on the LA-treated side, compared with 40.7% (32.4-48.7) on the placebo-treated half of the face P < 0.001 (Wilcoxon matched pairs test).

CONCLUSIONS: It is indicated that 12 weeks of treatment with a cream containing 5% LA improves clinical characteristics related to photoageing of facial skin.

 

PMID: 14616378  [PubMed - indexed for MEDLINE]

 

 

4. Curr Probl Dermatol. 2001;29:43-51.

 

Activity of alpha-lipoic acid in the protection against oxidative stress in skin.

 

Podda M, Zollner TM, Grundmann-Kollmann M, Thiele JJ, Packer L, Kaufmann R.

 

Department of Dermatology, J.W. Goethe University, Frankfurt, Germany.

Podda@em.uni-frankfurt.de

 

PMID: 11225200  [PubMed - indexed for MEDLINE]

 

 

3. Gen Pharmacol. 1997 Sep;29(3):315-31.

 

The pharmacology of the antioxidant lipoic acid.

 

Biewenga GP, Haenen GR, Bast A.

 

Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, Department of

Pharmacochemistry, The Netherlands.

 

1. Lipoic acid is an example of an existing drug whose therapeutic effect has

been related to its antioxidant activity.

2. Antioxidant activity is a relative

concept: it depends on the kind of oxidative stress and the kind of oxidizable

substrate (e.g., DNA, lipid, protein).

3. In vitro, the final antioxidant

activity of lipoic acid is determined by its concentration and by its antioxidant

properties. Four antioxidant properties of lipoic acid have been studied: its

metal chelating capacity, its ability to scavenge reactive oxygen species (ROS),

its ability to regenerate endogenous antioxidants and its ability to repair

oxidative damage.

4. Dihydrolipoic acid (DHLA), formed by reduction of lipoic

acid, has more antioxidant properties than does lipoic acid. Both DHLA and lipoic acid have metal-chelating capacity and scavenge ROS, whereas only DHLA is able to regenerate endogenous antioxidants and to repair oxidative damage.

5. As a metal  chelator, lipoic acid was shown to provide antioxidant activity by chelating Fe2+ and Cu2+; DHLA can do so by chelating Cd2+.

6. As scavengers of ROS, lipoic acid and DHLA display antioxidant activity in most experiments, whereas, in particular cases, pro-oxidant activity has been observed. However, lipoic acid can act as an antioxidant against the pro-oxidant activity produced by DHLA.

7. DHLA has the capacity to regenerate the endogenous antioxidants vitamin E, vitamin C and glutathione.

8. DHLA can provide peptide methionine sulfoxide reductase with

reducing equivalents. This enhances the repair of oxidatively damaged proteins such as alpha-1 antiprotease.

9. Through the lipoamide dehydrogenase-dependent reduction of lipoic acid, the cell can draw on its NADH pool for antioxidant activity additionally to its NADPH pool, which is usually consumed during

oxidative stress.

10. Within drug-related antioxidant pharmacology, lipoic acid is a model compound that enhances understanding of the mode of action of antioxidants in drug therapy.

 

PMID: 9378235  [PubMed - indexed for MEDLINE]

 

 

2. Biochem Pharmacol. 1996 Aug 23;52(4):627-33.

 

Kinetic study of cutaneous and subcutaneous distribution following topical

application of [7,8-14C]rac-alpha-lipoic acid onto hairless mice.

 

Podda M, Rallis M, Traber MG, Packer L, Maibach HI.

 

University of California Berkeley, Department of Molecular and Cell Biology

94720-3200, USA.

 

To diminish oxidative injury, topically applied antioxidants must reach

susceptible cells. alpha-Lipoic acid is a potent thiol antioxidant that might be

useful for skin protection; therefore, its skin penetration kinetics were

assessed. The cutaneous and subcutaneous distributions of [7,8-14C]rac-alpha-lipoic acid were studied in anesthetized hairless mice after application of a 5% solution in propylene glycol for 0.5 to 4 hr. The mice were killed; then the skin was washed, and the stratum corneum was removed by 10 cellophane tape strippings. A punch biopsy of the frozen, stripped skin was

sectioned, and amounts of [14C]-alpha-lipoic acid were determined in strippings and slices of epidermis (4 x 5 microns), dermis, and subcutaneous fat (10 x 10 microns, 20 x 20 microns). The rate of [14C]-alpha-lipoic acid absorption into skin was constant by 30 min (0.10 +/- 0.01 nmol/cm2/min); maximum skin concentrations were reached by 2 hr. The [14C]-alpha-lipoic acid penetration kinetics into the first layer of the stratum corneum predicted its penetration through the stratum corneum and subsequent percutaneous absorption (r2 = 0.96, P < 0.02). Cutaneous absorption of unlabeled alpha-lipoic acid and its reduction to the more potent antioxidant form, dihydrolipoic acid, were also demonstrated, using HPLC analysis with electrochemical detection. In conclusion, alpha-lipoic acid topically applied to skin penetrated readily, and was reduced to dihydrolipoic acid. Thus, alpha-lipoic acid could potentiate skin antioxidant protection.

 

PMID: 8759036  [PubMed - indexed for MEDLINE]

 

 

1. Biochem Pharmacol. 1994 May 18;47(10):1725-30.

 

Alpha-lipoic acid reduction by mammalian cells to the dithiol form, and release

into the culture medium.

 

Handelman GJ, Han D, Tritschler H, Packer L.

 

University of California, Berkeley 94720.

 

Lipoic acid has been reported recently to be an effective antioxidant in

biological systems. It may act in vivo through reduction to its dithiol form,

dihydrolipoic acid. Using a dual Hg/Au electrode, and HPLC with electrochemical

detection, a method was developed which allowed simultaneous measurement of lipoic acid and dihydrolipoic acid, at nanomolar levels. (RS)-alpha-Lipoic acid was added to human cells in tissue culture (Jurkat T-lymphocytes and primary neonatal diploid fibroblasts). Lipoic acid was converted rapidly by the cells to dihydrolipoic acid, which accumulated in the cell pellet. Monitored over a 2-hr interval, dihydrolipoic acid was released, and several-fold more dihydrolipoic acid could be found in the medium than in the pellet.

 

PMID: 8204089  [PubMed - indexed for MEDLINE]

Advanced Skin Care Research on Alpha Lipoic acid: Studies have shown that Alpha Lipoic acid is an antioxidant used to treat and prevent the aging of skin, fine lines, and pigmentation abnormalities. Alpha Lipoic acid  may decrease the inflammation that leads to accelerated skin aging. Alpha Lipoic acid may prevent free radical damage to skin, reducing the effects of photoaging and carcinogenesis.

Alpha Lipoic Acid research