Carnosine and Beta-Alanine Supplementation in Human Medicine: Narrative Review and Critical Assessment.

The dipeptide carnosine is a physiologically important molecule in the human body, commonly found in skeletal muscle and brain tissue. Beta-alanine is a limiting precursor of carnosine and is among the most used sports supplements for improving athletic performance. However, carnosine, its metabolite N-acetylcarnosine, and the synthetic derivative zinc-L-carnosine have recently been gaining popularity as supplements in human medicine. These molecules have a wide range of effects-principally with anti-inflammatory, antioxidant, antiglycation, anticarbonylation, calcium-regulatory, immunomodulatory and chelating properties. This review discusses results from recent studies focusing on the impact of this supplementation in several areas of human medicine. We queried PubMed, Web of Science, the National Library of Medicine and the Cochrane Library, employing a search strategy using database-specific keywords. Evidence showed that the supplementation had a beneficial impact in the prevention of sarcopenia, the preservation of cognitive abilities and the improvement of neurodegenerative disorders. Furthermore, the improvement of diabetes mellitus parameters and symptoms of oral mucositis was seen, as well as the regression of esophagitis and taste disorders after chemotherapy, the protection of the gastrointestinal mucosa and the support of Helicobacter pylori eradication treatment. However, in the areas of senile cataracts, cardiovascular disease, schizophrenia and autistic disorders, the results are inconclusive.

Ultraviolet A protective potential of plant extracts and phytochemicals.

Chronic exposure to solar radiation is related to an increased incidence of various skin disorders, including premature skin aging and melanoma and non-melanoma skin cancers. Ultraviolet (UV) photons in particular are responsible for skin damage. Solar UV photons mainly belong to UVA wavebands, however UVA radiation has been mostly ignored for a long time. At the cellular level, UVA photons mainly provoke indirect oxidative damage to biomolecules via the massive generation of unstable and highly reactive compounds. Human skin has several effective mechanisms that forestall, repair and eliminate damage caused by solar radiation. Regardless, some damage persists and can accumulate with chronic exposure. Therefore, conscious protection against solar radiation (UVB+UVA) is necessary. Besides traditional types of photoprotection such as sunscreen use, new strategies are being searched for and developed. One very popular protective strategy is the application of phytochemicals as active ingredients of photoprotection preparations instead of synthetic chemicals. Phytochemicals usually possess additional biological activities besides absorbing the energy of photons, and those properties (e.g. antioxidant, anti-inflammatory) magnify the protective potential of phytochemicals and extracts. Therefore, compounds of natural origin are in the interest of researchers as well as developers. In this review, only studies on UVA protection with well-documented experimental conditions are summarized. This article includes 17 well standardized plant extracts (Camellia sinensis (L.) Kuntze, Silybum marianum L. Gaertn., Punica granatum L., Polypodium aureum L., Vaccinium myrtillus L., Lonicera caerulea L., Thymus vulgaris L., Opuntia ficus-indica (L.) Mill., Morinda citrifolia L., Aloe vera (L.) Burm.f., Oenothera paradoxa Hudziok, Galinsoga parviflora Cav., Galinsoga quadriradiata Ruiz et Pavón, Hippophae rhamnoides L., Cola acuminata Schott & Endl., Theobroma cacao L. and Amaranthus cruentus L.) and 26 phytochemicals.

Skin Protective Activity of Silymarin and its Flavonolignans.

Silybum marianum (L.) is a medicinal plant traditionally used in treatment of liver disorders. In last decades, silymarin (SM), a standardized extract from S. marianum seeds has been studied for its dermatological application, namely for UVB-protective properties. However, information on SM and its polyphenols effect on activity of enzymes participating in the (photo)aging process is limited. Therefore, evaluation of SM and its flavonolignans potential to inhibit collagenase, elastase, and hyaluronidase in tube tests was the goal of this study. The antioxidant and UV screening properties of SM and its flavonolignans silybin, isosilybin, silydianin, silychristin and 2,3-dehydrosilybin (DHSB) were also evaluated by a DPPH assay and spectrophotometrical measurement. DHSB showed the highest ability to scavenge DPPH radical and also revealed the highest UVA protection factor (PF-UVA) that corresponds with its absorption spectrum. SM and studied flavonolignans were found to exhibit anti-collagenase and anti-elastase activity. The most potent flavonolignan was DHSB. None of studied flavonolignans or SM showed anti-hyaluronidase activity. Our results suggest that SM and its flavonolignans may be useful agents for skin protection against the harmful effects of full-spectrum solar radiation including slowing down skin (photo)aging.

UVA-photoprotective potential of silymarin and silybin.

Exposure to solar radiation is a major cause of environmental human skin damage. The main constituent of solar UV light is UVA radiation (320-400 nm); however, the need for protection against UVA has been marginalized for a long time. As a result, there is still a lack of useful agents for UVA protection. In this study, the effect of silymarin (SM) and its main constituent silybin (SB) pre-treatment on UVA-stimulated damage to primary human dermal fibroblasts were carried out. The cells were pre-treated for 1 h with SB or SM and then were exposed to UVA light, using a solar simulator. The effect of SB and SM on reactive oxygen species (ROS) and glutathione (GSH) level, caspase-3 activity, single-strand breaks (SSB) formation and protein level of matrix metalloproteinase-1 (MMP-1), heme oxygenase-1 (HO-1), and heat shock protein (HSP70) was evaluated. Treatment with both SM and SB resulted in a reduction in UVA-stimulated ROS generation and SSB production, as well as in the prevention of GSH depletion, a decrease in the activation of caspase-3 and protein level of MMP-1. They also moderately increased HO-1 level and reduced HSP70 level. Our data showed that both SM and SB are non-phototoxic and have UVA-photoprotective potential and could be useful agents for UV-protective dermatological preparations.

The Phototoxic Potential of the Flavonoids, Taxifolin and Quercetin.

Quercetin, one of the most abundant polyphenols in the plant kingdom has been shown to be photodegraded on exposure to UV light. Despite the fact, it is a component of several dermatological preparations. Its phototoxic potential has not been evaluated to date. The aim of this study was to assess whether photo-induced degradation of quercetin is linked to phototoxic effects on living cells. Its dihydro derivative, taxifolin, was included in the study. For evaluation, the 3T3 Neutral Red Uptake Phototoxicity Test according to OECD TG 432 was used. To better approximate human skin, HaCaT keratinocytes, normal human epidermal keratinocytes and dermal fibroblasts were used, apart from the Balb/c 3T3 cell line. Quercetin showed a dose-dependent photodegradation in aqueous and organic environments and a phototoxic effect on all used cells. Quercetin pretreatment and following UVA exposure resulted in increased reactive oxygen species production and intracellular glutathione level depletion in human dermal fibroblasts. Taxifolin was found completely nonphototoxic and photostable. As only in vitro methodology was used, further studies using 3D skin models and/or human volunteers are needed to confirm whether exposure to sunlight, tanning sunbeds and/or phototherapy in people using cosmetics containing quercetin is a health risk.

Cranberry intervention in patients with prostate cancer prior to radical prostatectomy. Clinical, pathological and laboratory findings.

BACKGROUND AND OBJECTIVES: Recently, we described an inverse association between cranberry supplementation and serum prostate specific antigen (PSA) in patients with negative biopsy for prostate cancer (PCa) and chronic nonbacterial prostatitis. This double blind placebo controlled study evaluates the effects of cranberry consumption on PSA values and other markers in men with PCa before radical prostatectomy. METHODS: Prior to surgery, 64 patients with prostate cancer were randomized to a cranberry or placebo group. The cranberry group (n=32) received a mean 30 days of 1500 mg cranberry fruit powder. The control group (n=32) took a similar amount of placebo. Selected blood/urine markers as well as free and total phenolics in urine were measured at baseline and on the day of surgery in both groups. Prostate tissue markers were evaluated after surgery. RESULTS: The serum PSA significantly decreased by 22.5% in the cranberry arm (n=31, P<0.05). A trend to down-regulation of urinary beta-microseminoprotein (MSMB) and serum gamma-glutamyltranspeptidase, as well as upregulation of IGF-1 was found after cranberry supplementation. There were no changes in prostate tissue markers or, composition and concentration of phenolics in urine. CONCLUSIONS: Daily consumption of a powdered cranberry fruit lowered serum PSA in patients with prostate cancer. The whole fruit contains constituents that may regulate the expression of androgen-responsive genes.

Cranberry fruit powder (Flowens™) improves lower urinary tract symptoms in men: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia increase with age. To date, several medications are available to treat LUTS, including herbal remedies which offer less side effects but lack robust efficacy studies. METHODS: This 6-month, randomized, double-blind, placebo-controlled study aimed at evaluating the dose effect of 250 or 500 mg cranberry powder (Flowens™) on LUTS and uroflowmetry in men over the age of 45. A total of 124 volunteers with PSA levels <2.5 ng/mL and an international prostate symptoms score (IPSS) score ≥8 were recruited and randomized. The primary outcome measure was the IPSS, evaluated at 3 and 6 months. Secondary outcome measures included quality of life, bladder volume (Vol), maximum urinary flow rate (Q max), average urinary flow rate (Q ave), ultrasound-estimated post-void residual urine volume (PVR), serum prostate-specific antigen, selenium, interleukin 6, and C-reactive protein at 6 months. RESULTS: After 6 months, subjects in both Flowens™ groups had a lower IPSS (-3.1 and -4.1 in the 250- and 500-mg groups, p = 0.05 and p < 0.001, respectively) versus the placebo group (-1.5), and a dose-response effect was observed. There were significant differences in Q max, Q ave, PVR, and Vol in the Flowens™ 500-mg group versus baseline (p < 0.05). A dose-dependent effect on Vol was observed, as well as on PVR, for participants with a nonzero PVR. There was no effect on clinical chemistry or hematology markers. CONCLUSIONS: Flowens™ showed a clinically relevant, dose-dependent, and significant reduction in LUTS in men over 45.

Are High Proanthocyanidins Key to Cranberry Efficacy in the Prevention of Recurrent Urinary Tract Infection?

Most research on American cranberry in the prevention of urinary tract infection (UTI) has used juices. The spectrum of components in juice is limited. This study tested whether whole cranberry fruit powder (proanthocyanidin content 0.56%) could prevent recurrent UTI in 182 women with two or more UTI episodes in the last year. Participants were randomized to a cranberry (n = 89) or a placebo group (n = 93) and received daily 500 mg of cranberry for 6 months. The number of UTI diagnoses was counted. The intent-to-treat analyses showed that in the cranberry group, the UTIs were significantly fewer [10.8% vs. 25.8%, p = 0.04, with an age-standardized 12-month UTI history (p = 0.01)]. The Kaplan-Meier survival curves showed that the cranberry group experienced a longer time to first UTI than the placebo group (p = 0.04). Biochemical parameters were normal, and there was no significant difference in urinary phenolics between the groups at baseline or on day180. The results show that cranberry fruit powder (peel, seeds, pulp) may reduce the risk of symptomatic UTI in women with a history of recurrent UTIs.

Determination of nonpolar and polar lipid classes in human plasma, erythrocytes and plasma lipoprotein fractions using ultrahigh-performance liquid chromatography-mass spectrometry.

A novel normal-phase (NP) ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC/MS) method is developed for a separation and quantitation of nonpolar lipid classes occurring in human plasma, erythrocytes and plasma lipoprotein fractions. The baseline class separation of cholesteryl esters (CE), cholesterol, triacylglycerols (TG), regioisomers of 1,2- and 1,3-diacylglycerols (DG) and 1-monoacylglycerols (1-MG) is achieved using an optimized hexane - 2-propanol-acetonitrile mobile phase within 18min for all nonpolar lipid classes or only 9min excluding monoacylglycerols not detected in studied samples. The determination of individual nonpolar lipid classes is performed by the response factor approach and the use of dioleoyl ethylene glycol as a single internal standard. Polar lipid classes, such as phosphatidylglycerols (PG), phosphatidylethanolamines (PE), phosphatidylcholines (PC), sphingomyelins (SM) and lysophosphatidylcholines (LPC), are separated by hydrophilic interaction liquid chromatography (HILIC) using 5mmol/L aqueous ammonium acetate-methanol-acetonitrile gradient within 13minutes. The quantitation of polar lipid classes is done by a similar approach as for nonpolar lipid classes, but a different internal standard (sphingosyl PE d17:1/12:0) is used. The complementary information on fatty acyl profiles after the transesterification of the total lipid extract is obtained by gas chromatography with flame ionization detection (GC/FID). The applicability of developed methodology for fast and comprehensive characterization of blood lipidome is illustrated on samples of human plasma, erythrocytes, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) fractions.

Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate specific antigen in men.

The aim of this double-blind, placebo controlled clinical trial was to assess the effects of a combination of selenium and silymarin in men with lower urinary tract symptoms, benign prostatic hyperplasia and a prostate specific antigen (PSA) ≤2.5ng/ml. The volunteers were randomized to two groups: the first one (n=26) received 240µg selenium (in the form of yeast l-selenomethionine) plus 570mg silymarin daily for 6 months and the second (n=29) received placebo. Outcome measures were changes in the International Prostate Symptom Score (IPSS), bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical biochemistry, hematology and oxidative stress parameters at baseline and on day 180. The results showed statistically significant differences (p<0.05) between treatment and control groups for the following parameters: IPSS score, urodynamic parameters: maximal rate of urine flow (Qmax), average flow (Qave), V and RV, total PSA value and serum selenium levels. There was a significant reduction in PSA in the selenium-silymarin group but no effect on blood testosterone level. Overall the treatment was well-tolerated with no adverse effects.

The safety and efficacy of a silymarin and selenium combination in men after radical prostatectomy - a six month placebo-controlled double-blind clinical trial.

BACKGROUND: Silymarin, a milk thistle flavonolignan mixture, has anti-proliferative and anti-angiogenic activities in xenografts of human prostate cancer (PCa). Low dietary selenium on the other hand has been associated with increased incidence of PCa. The purpose of the current trial was to determine whether a daily administration of a silymarin and selenium (SM-Se) combination for 6 months would alter basic clinical chemistry and oxidative stress markers, and improve the quality of life score (QoL) in men after radical prostatectomy (RP). METHODS: Thirty seven participants, 2-3 months after RP, were randomly assigned to receive 570 mg of silymarin and 240 µg of selenium as selenomethionine (n = 19, SM-Se group) or placebo (n = 18, Placebo group) daily for six months. Both groups had similar clinical and demographic characteristics. Physical examination, QoL score, haematology, basic clinical chemistry and oxidative stress markers, selenium and testosterone levels, antioxidant status were evaluated at baseline, at 3 and 6 months. RESULTS: The six months administration of silymarin and selenium improved the QoL score, decreased low density lipoproteins (LDL) and total cholesterol and, increased serum selenium levels. The combination had no effect on blood antioxidant status and no influence on testosterone level. No adverse events were recorded. No improvement was found in the placebo group. CONCLUSIONS: The selected combination of silymarin and selenium significantly reduced two markers of lipid metabolism known to be associated with PCa progression, LDL and total cholesterol in the blood of men after RP. This suggests that this combination may be effective in reducing PCa progression.

Long-term effects of three commercial cranberry products on the antioxidative status in rats: a pilot study.

Cranberry (Vaccinium macrocarpon Ait. Ericaceae) fruits and juice are widely used for their antiadherence and antioxidative properties. Little is known however about their effects on clinical chemistry markers after long-term consumption. This study was conducted to evaluate the effect of three commercial cranberry products, NUTRICRAN90S, HI-PAC 4.0, and PACRAN on the antioxidative status of rodents, divided into three experimental groups. The products were given as dietary admixtures (1500 mg of product/kg of stock feed) for 14 weeks to male Wistar rats (Groups 2-4) and a control Group 1 which received only stock feed. There were no significant cranberry treatment-related effects on oxidative stress parameters, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, advanced oxidation protein products, total SH-groups, or any other measured clinical chemistry markers. Hematological parameters, body weight, and food consumption were also unaffected by intake of cranberries. Only liver glutathione reductase activity and glutathione levels were significantly lower in Group 4 than in Group 1. Plasma alkaline phosphatase alone was significantly decreased in Group 2. No gross pathology, effects on organ weights, or histopathology were observed. No genotoxicity was found, and total cytochrome P450 level in liver was unaffected in all groups. The levels of hippuric acid and several phenolic acids were significantly increased in plasma and urine in Groups 2-4. The concentration of anthocyanins was under the detection threshold. The dietary addition of cranberry powders for 14 weeks was well tolerated, but it did not improve the antioxidative status in rats.

Prunella vulgaris extract and rosmarinic acid prevent UVB-induced DNA damage and oxidative stress in HaCaT keratinocytes.

Solar radiation is a very important exogenous factor in skin pathogenesis and can lead to the development of a number of skin disorders. UVB irradiation is known to induce oxidative stress, inflammation and especially DNA lesions in exposed cells. It is important, therefore, to identify agents that can offer protection against UVB-caused skin damage. Natural compounds have been studied for their possible ability to control/modulate various lifestyle-related diseases. The application of plant compounds/extracts with screening, antioxidant and anti-inflammatory activities may also successfully protect the skin against UV-caused injury. We assessed the potency of Prunella vulgaris extract (PVE) and its main phenolic acid component, rosmarinic acid (RA), to suppress UVB-induced (295-315 nm) alterations to human keratinocytes HaCaT using a solar simulator. Pre- and post-treatment of HaCaT cells with PVE (5-50 mg/l) and RA (0.18-1.8 mg/l) reduced breakage together with the apoptotic process. PVE and RA also significantly eliminated ROS production and diminished IL-6 release. Taken together, both PVE and RA prevent UVB-caused injury to keratinocytes. However their efficacy needs to be demonstrated in vivo.

Lonicera caerulea and Vaccinium myrtillus fruit polyphenols protect HaCaT keratinocytes against UVB-induced phototoxic stress and DNA damage.

BACKGROUND: Sunlight is a very potent environmental factor in skin pathogenesis and can induce skin cancer. UVB irradiation is known to cause oxidative stress, inflammation and especially DNA damage. Topical application of agents with UV absorbing, antioxidant and anti-inflammatory activities is a successful strategy in the protection of the skin against UV-caused damage. OBJECTIVE: To examine the ability of the phenolic fraction of Lonicera caerulea and Vaccinum myrtillus fruits to moderate UVB-induced damage. METHODS: HaCaT keratinocytes, a well-established in vitro system for investigations on UV radiation induced cell damage, were used to assess the effects of pre- and post-treatment with L. caerulea (LCE) and V. myrtillus (VME) phenolic fractions (5-50 mg/l) on keratinocyte damage induced by a solar simulator (295-315 nm). RESULTS: In this study, a model of UVB-induced damage to HaCaT was established. LCE and VME efficiently reduced the extent of DNA breakage (especially at concentrations of 25 and 10 mg/l) together with caspase-3 and -9 activity and DNA laddering induced by UVB (100 or 200 mJ/cm(2)). LCE and VME significantly decreased RONS generation and partially diminished IL-6 expression. LCE pre-treatment also prevented keratinocytes proliferation. CONCLUSION: The results suggest that the phenolic fraction of L. caerulea and V. myrtillus fruits suppress UVB-caused injury to keratinocytes. These results now need to be demonstrated in vivo.

Natural feed additive of Macleaya cordata: safety assessment in rats a 90-day feeding experiment.

Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver.

Macleaya cordata extract and Sangrovit genotoxicity. Assessment in vivo.

BACKGROUND: Sanguinarine (SG) has been reported to form DNA adducts in vitro and increase the levels of DNA single strand breaks in the blood and bone marrow of mice treated intraperitoneally with SG. Recently, we showed no genotoxic effects of orally administrated 120 mg/kg feed Macleaya cordata extract (a mixture of sanguinarine and chelerythrine) in pigs or rats in 90-day studies. The goal of this paper was to assess the possible genotoxicity of M. cordata extract when included as a dietary admixture to rodents at concentrations providing 600 mg/kg feed and 100, 7000 or 14000 mg/kg feed Sangrovit (natural feed additive containing M. cordata extract and powdered M. cordata) in a 90-day pilot study. METHODS AND RESULTS: The rats consumed ad libitum either the standard diet or the diets containing 367 ppm of sanguinarine and chelerythrine in M. cordata extract, and 5, 330, or 660 ppm of total alkaloids in Sangrovit for 90 days. The DNA adducts formation in liver was analyzed by (32)P-postlabeling technique and DNA single strand breaks in lymphocytes were evaluated by Comet assay. The results showed that M. cordata extract and/or Sangrovit induced no DNA damage to rat lymphocytes or hepatocytes after 90-days oral administration. CONCLUSIONS: Data from the studies described in this paper and the fact that Sangrovit given to the rats in our experiments were higher than the recommended dose (50 to 100 mg/kg feed), argue strongly in favour of the use of Sangrovit in live stock.

Protective effects of phenolic fraction of blue honeysuckle fruits against UVA-induced damage to human keratinocytes.

In this study, the UVA (photo)protective activity of the phenolic fraction of L. caerulea fruits (PFLC) was assessed in human keratinocytes HaCaT. The keratinocytes were pre- or post-treated with PFLC (1-250 mg/l) and exposed to UVA irradiation (10-30 J/cm(2)). The results showed that both pre- and post-treatment with PFLC significantly suppressed UVA-induced ROS production, which was also revealed as a decrease in intracellular lipid peroxidation and elevation of reduced glutathione. Protection was concentration-dependent with a maximum at 50 mg/l. These results suggest that PFLC attenuates UVA-induced oxidative stress by reduction of ROS generation and ROS-mediated damage. For this reason, PFLC has potentially skin-protective functions against the deleterious effects of sunlight.

Bilberry extract reduces UVA-induced oxidative stress in HaCaT keratinocytes: a pilot study.

Exposure to UVA radiation is known to cause many adverse biological effects by inducing the stricken cells to produce reactive oxygen species (ROS). In recent years the use of botanicals has received considerable interest in the skin protection. Bilberry (Vaccinium myrtillus L.) fruit contains several polyphenols with strong antioxidant and anti-inflammatory properties. In this study we evaluated potential UVA preventive effect of V. myrtillus fruit extract (VME; anthocyanins, 25% w/w) in HaCaT keratinocytes. Pre-treatment (1 h) or post-treatment (4 h) of HaCaT with VME resulted in attenuation of UVA-caused damage. Application of the extract significantly reduced UVA-stimulated ROS formation in keratinocytes. VME also prevented/reduced UVA-caused peroxidation of membrane lipids and depletion of intracellular GSH. The observed cytoprotective effect may be linked to the antioxidant activity of the plant constituents, namely anthocyanins.

Flavonolignans from Silybum marianum moderate UVA-induced oxidative damage to HaCaT keratinocytes.

BACKGROUND: UV radiation from sunlight is a very potent environmental risk factor in the pathogenesis of skin cancer. Exposure to UV light, especially the UVA part, provokes the generation of reactive oxygen species (ROS), which induce oxidative stress in exposed cells. Topical application of antioxidants is a successful strategy for protecting the skin against UV-caused oxidative damage. OBJECTIVE: In this study, silybin (SB) and 2,3-dehydrosilybin (DS) (1-50 micromol/l), flavonolignan components of Silybum marianum, were tested for their ability to moderate UVA-induced damage. METHODS: Human keratinocytes HaCaT were used as an appropriate experimental in vitro model, to monitor the effects of SB and DS on cell viability, proliferation, intracellular ATP and GSH level, ROS generation, membrane lipid peroxidation, caspase-3 activation and DNA damage. RESULTS: Application of the flavonolignans (1-50 micromol/l) led to an increase in cell viability of irradiated (20 J/cm(2)) HaCaT keratinocytes. SB and DS also suppressed intracellular ATP and GSH depletion, ROS production and peroxidation of membrane lipids. UVA-induced caspases-3 activity/activation was suppressed by treatment with SB and DS. Lower concentrations of both compounds (10 micromol/l) significantly reduced cellular DNA single strand break formation. CONCLUSION: Taken together, the results suggest that these flavonolignans suppress UVA-caused oxidative stress and may be useful in the treatment of UVA-induced skin damage.