Variation in Population and Solvents as Factors Determining the Chemical Composition and Antioxidant Potential of Arctostaphylos uva-ursi (L.) Spreng. Leaf Extracts.

The bearberry Arctostaphylos uva-ursi (L.) Spreng. has a long history of ethnopharmacological use. This species has been used in folk medicine for centuries as a rich source of raw material abundant in secondary metabolites and is important for medicinal and pharmacological purposes. The plant is a source of herbal material-Uvae ursi folium, which is highly valued and sought by pharmaceutical and cosmetic industries. The studied bearberry leaves can be classified as a suitable herbal material for use in pharmacy; therefore, the investigated populations can be a potentially valuable source of plant material for cultivation and can be used in in vitro cultures and in biotechnological processes. The objective of this study was to characterize the variability of the phytochemical composition and antioxidant activity of water and ethanol bearberry extracts from raw material collected from different natural populations. In each of the twelve A. uva-ursi sites, three leaf samples were collected and analyzed. The water extracts from bearberry leaves were characterized by similar concentration of arbutin (77.64-105.56 mg g-1) and a significantly higher concentration of hydroquinone (6.96-13.08 mg g-1) and corilagin (0.83-2.12 mg g-1) in comparison with the ethanol extracts -77.21-103.38 mg g-1, 10.55-16.72 mg g-1, 0.20-1.54 mg g-1, respectively. The concentration of other metabolites in the water extracts was significantly lower in comparison with the ethanol extracts. In the case of the water extracts, a significant effect of not only total phenolic compounds, but also hydroquinone on the antioxidant parameters, was observed, which indicates the solvent-related activity of these metabolites. Therefore, it is suggested that special attention should be paid to the concentration of not only arbutin, but also hydroquinone in Uvae ursi folium. The latter metabolite serving a very important function as an active bearberry ingredient should be controlled not only in alcoholic extracts but also in water extracts, since bearberry leaves are applied as infusions and decoctions. The results presented in this paper can contribute to appropriate selection of plant material for pharmaceutical, cosmetic, and food industries, with special emphasis on the antioxidant activity of different types of extracts.

Proteome changes in human bladder T24 cells induced by hydroquinone derived from Arctostaphylos uva-ursi herbal preparation.

ETHNOPHARMACOLOGICAL RELEVANCE: Arctostaphylos uva-ursi (L.) Spreng. (bearberry) is a well-known traditional herbal plant used as a urinary tract disinfectant. Its antiseptic and diuretic properties can be attributed to hydroquinone, obtained by hydrolysis of arbutin. AIM OF THE STUDY: This study aimed to determine the toxic profile of free hydroquinone on urinary bladder cells (T24) as a target of therapeutic action. MATERIALS AND METHODS: Quantitative and qualitative analysis of the extract and the digestive stability and bioavailability of arbutin and hydroquinone were performed by HPLC assay and simulated in vitro digestion, respectively. Cytotoxic effect, reactive oxygen species induction and proteome changes in T24 cells after hydroquinone treatment were determined using Neutral red assay, 2',7'-dichlorofluorescein-diacetate (DCFH-DA) assay and mass spectrometry, respectively. RESULTS: Through in vitro digestion, arbutin was stable, but hydroquinone increased after pepsin treatment (109.6%) and then decreased after the small intestine phase (65.38%). The recommended doses of Uva-ursi had a cytotoxic effect on T24 cells only when all hydroquinone conjugates were converted to free hydroquinone (320 and 900 µg/mL) and the toxic effect was enhanced by recovery. One cup of the therapeutic dose had a prooxidative effect after 4 h of incubation. Shorter time of cell exposure (2 h) to hydroquinone did not have any impact on reactive oxygen species induction. Proteomic analysis found 17 significantly up-regulated proteins compared to control. Hydroquinone activated proteins related to oxidative stress response, stress-adaptive signalling, heat shock response and initiation of translation. CONCLUSIONS: Despite the therapeutic properties of bearberry, up-regulated T24 cell proteins are evidence that plant compounds, although from a natural source, may exhibit negative properties.

Investigation of phenolic compounds at the leaves and shoots Arctostaphylos spp. and their antioxidant and antityrosinase activities.

Comparative phytochemical and pharmacological analysis of leaves and shoots of Arctostaphylos uva-ursi (L.) Spreng. and endemic of Transcaucasia and North Caucasia Arctostaphylos caucasica Lipsch. was carried out. Phenolic compounds in methanol extracts were investigated by HPLC-PDA-ESI-MS. Pharmacological investigation was carried out at the models of generation of superoxide, DPPH, hydroxyl and nitrosyl radicals. The antityrosinase properties were evaluated in the reaction of tyrosinase inhibition using L -tyrosine as a substrate. Five new compounds were identified in the shoots and leaves of A. uva-ursi: 4,6-di-О-galloylglucose; 2,3-di-О-galloylglucose; 1,4,6-tri-О-galloylglucose; 1,2,4,6-tetra-О-galloylglucose; tetra-О-galloylhexose. Thirty-five phenolic compounds and two saponins were identified for the first time in A. caucasica. Water-alcohol extract (70% ethanol) from A. caucasica had the highest antiradical activity. Water extracts from both species had antityrosinase activity and possessed comparable efficiency (IC50 = 36.4 ± 1.2 µg/ml and IC50 = 35,5 ± 2 µg/ml, respectively).

Medicinal Plants Extracts Impact on Oxidative Stress in Mice Brain Under the Physiological Conditions: the Effects of Corn Silk, Parsley, and Bearberry.

This study was performed to examine the effects of medicinal plant extracts of corn silk (Stigma maydis), parsley leaf (Petroselini folium), and bearberry leaf (Uvae ursi folium) on antioxidant status of the brain of experimental animals (mice) under the physiological conditions. Biological properties of these plants are insufficiently investigated and the aim was to explore their possible antioxidant effects that can alleviate oxidative damage of the brain tissue. Corn silk extract showed positive effect on activities of antioxidant enzymes in mice brain tissue. Parsley extract induced the increase in glutathione content and decrease of lipid peroxidation. Bearberry leaf extract induced catalase activity and decrease of hydroxyl radical content, while malonyldialdehide accumulation was maintained at the control level. Results obtained in this study support the use of corn silk, parsley and bearberry leaves as natural antioxidant sources in the prevention and treatment of brain tissue damages and different diseases caused by oxidative stress.

Chemical Characteristics and Antioxidant Activity of Arctostaphylos uva-ursi L. Spreng. at the Southern Border of the Geographical Range of the Species in Europe.

The bearberry (Arctostaphylos uva-ursi L. Spreng.) is a source of herbal material-bearberry leaf (Uvae ursi folium), which is highly valued and sought by pharmaceutical and cosmetic industries. For many years, leaves of this plant have been used in traditional medicine as a diuretic, antimicrobial, and anti-inflammatory agent for various diseases of the urogenital tract. The bearberry has also been proposed as a natural antioxidant additive due to the high contents of phenolic compounds in its leaves. The study was focused on characterization of the basic phytochemical composition and antioxidant activity of extracts derived from bearberry leaves collected from plants located at the southern border of the geographical range of the species in Europe. The investigated herbal material is characterized by a different chemical profile compared to the chemical profiles of bearberry found in other parts of the continent. Bearberry extracts from plants growing in two different habitat types-heathlands and pine forests showed a wide range of variation, especially in the concentration of hyperoside, corilagin, and methylartutin and the total flavonoid contents. In addition to arbutin, bearberry can be a valuable source of phenolic compounds, which are mainly responsible for the antioxidant properties of extracts. The high content of phenols and high values of antioxidant parameters indicate a high potential of bearberry leaves to be used as a powerful natural source of antioxidants in herbal preparations. Therefore, the A. uva-ursi populations can be a source of plant material for pharmaceutical, cosmetic, and food industries.

Herbal treatment with uva ursi extract versus fosfomycin in women with uncomplicated urinary tract infection in primary care: a randomized controlled trial.

OBJECTIVE: We explored whether initial treatment with the herbal drug uva ursi (UU) reduces antibiotic use in women with uncomplicated urinary tract infection (UTI) without increasing symptom burden and complication frequency compared with antibiotic treatment. METHODS: A double-blind randomized controlled trial was conducted in 42 family practices in Germany. The participants were adult women with suspected uncomplicated UTIs receiving either UU 105 mg 3 × 2 tablets for 5 days (intervention) or fosfomycin a 3-g single dose (control), and their respective placebos. Participants and investigators were blinded. The primary outcome included (1) antibiotic courses day 0-28 as superiority, and (2) symptom burden (sum of daily symptom scores) day 0-7, as non-inferiority outcome (margin 125%). Clinicaltrials.gov: NCT03151603. RESULTS: Overall, 398 patients were randomly allocated to groups receiving UU (n = 207) and fosfomycin (n = 191). The number of antibiotic courses was 63.6% lower (95% CI 53.6%-71.4%; p < 0.0001) in the UU group than in the fosfomycin group. The ratio of total symptom burden in the UU group compared with control was 136.5% (95% CI 122.7-151.9; p 0.95), failing non-inferiority. Eight women developed pyelonephritis in the UU group compared with two in the fosfomycin group (mean difference 2.8; 95% CI 0.2-5.9; p 0.067). Adverse events were similar between the groups. DISCUSSION: In women with uncomplicated UTIs, initial treatment with UU reduced antibiotic use but led to a higher symptom burden and more safety concerns than fosfomycin.

Effects of hot­water extracts from 26 herbs on α­glucosidase activity.

α­glucosidase is a key enzyme that plays a role in glucose absorption in the gastrointestinal tract, and the inhibition of its activity induces the prevention of postprandial hyperglycemia. Several α­glucosidase inhibitors have been used as medicines for type 2 diabetes, but a similar effect is observed in natural resources, including traditional herbs and their phytochemicals. To identify the presence of the α­glucosidase inhibitory activity in herbs, in which various functional effects have been known to occur, the present study investigated the effects of hot­water extracts of 26 types of herbs on α­glucosidase activity in an in vitro assay. The results indicated significant increases in the inhibition of α­glucosidase activity in 1,000 µg/ml olive (P<0.01), white willow (P<0.01) and red rooibos hot­water extracts. Furthermore, ≥50% inhibition of α­glucosidase activity was determined to be significant in 1,000 µg/ml coltsfoot, green tea and bearberry hot­water extracts. In addition, the effects of bearberry, green tea and coltsfoot hot­water extracts on α­glucosidase activity in vivo were evaluated according to the blood glucose levels (BGLs) in maltose and glucose load model rats. It was indicated that the administration of these three herb extracts significantly reduced the increasing BGLs after maltose loading until 0.5 h compared with the control group. However, only coltsfoot extract significantly reduced the increasing BGLs after glucose loading until 0.5 h compared with the control group. Thus, the present results may facilitate the understanding of a novel functionality in traditional herbs, which could be useful for the prevention of disease onset and progression, such as in hyperglycemia and type 2 diabetes.

Predicting the antioxidant capacity and total phenolic content of bearberry leaves by data fusion of UV-Vis spectroscopy and UHPLC/Q-TOF-MS.

The total phenolic content (TPC) and antioxidant capacity have been considered as important quality parameters for plant extracts. In this study, bearberry leaves were regarded as studied subject and a reliable method was established to predict the TPC and antioxidant capacity of bearberry leaves. Ultraviolet-visible spectrometry (UV-Vis) and ultra high pressure liquid chromatography coupled to time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) were used to provide spectral fingerprinting and metabolomic profiling. The data obtained (separately and merged) were used to build partial least squares (PLS) regression model. The PLS model built by using ultraviolet-visible spectra provided a satisfactory prediction result. Mid-level data fusion using the scores significantly improved the performance of PLS regression model, the residual predictive deviations (RPDs) for TPC and α, α-diphenyl-ß-picrylhydrazyl (DPPH) were 6.258 and 6.699, respectively, showing an excellent predictive ability. This study proved the potential of combination of UV-Vis spectrometry and UHPLC/Q-TOF-MS in the prediction of TPC and antioxidant capacity of plant extracts.

Antihypertensive efficacy and safety of Vaccinium arctostaphylos berry extract in overweight/obese hypertensive patients: A randomized, double-blind and placebo-controlled clinical trial.

OBJECTIVES: To evaluate the antihypertensive efficacy and safety of a standardized Vaccinium arctostaphylos (V. arctostaphylos) berry hydro-alcoholic extract in the overweight/obese hypertensive patients. DESIGN: Randomized placebo-controlled trial. SETTING: Baqiyatallah hospital (Tehran, Iran). INTERVENTIONS: The antihypertensive efficacy and safety of 3-month intake of 400 mg extract capsule three times daily alongside standardized anti-hypertensive regimen in the treatment of 50 patients was compared with the placebo (n = 50). MAIN OUTCOME MEASURES: SBP (systolic blood pressure), DBP (diastolic blood pressure), body mass index, waist circumference, CBC (complete blood count), blood levels of AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase), BUN (blood urea nitrogen) and creatinine. RESULTS: SBP decreased from 152.1 ± 7.7 to 140.5 ± 10.7 in the V. arctostaphylos group and from 152.9 ± 8.1 to 150.8 ± 9.3 in the placebo group (P < 0.001). DBP decreased from 90.3±8 to 82.1±8.8 in the V. arctostaphylos group and from 89.6 ± 7.8 to 87.6 ± 7.9 in the placebo group (P < 0.001). The extract capsule had no significant effect on the other parameters (P > 0.05). Moreover, no drug side effect and adverse interaction with other antihypertensive drugs was observed in the patients. CONCLUSIONS: V. arctostaphylosberry extract improves blood pressure control and has safety and tolerability in the overweight/obese hypertensive patients taking standard antihypertensive drugs.

Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Identification of botanicals with potential therapeutic use against methicillin-resistant Staphylococcus aureus (MRSA) infections.

Staphylococcus aureus is an opportunistic pathogen. Over- and improper-use of pharmaceuticals against S. aureus has led to the development of antibiotic resistance, including methicillin-resistant S. aureus (MRSA). This study examined the efficacy of botanical extracts as an alternative form of treatment to S. aureus and MRSA, including penicillin/methicillin-resistant S. aureus (PenR ), and multidrug resistant S. aureus (MDR). Initial screening of botanicals was done via a minimum inhibitory concentration procedure. In addition, a temporal growth curve was performed in order to quantify the growth of the bacteria in the presence of the extracts. Results demonstrated 13 botanicals that had varying activities against S. aureus, PenR , and MDR. These botanicals were separated into mild, moderate, and highly efficacious based on the concentration needed to inhibit bacterial growth. These results propose a comparison of botanical-derived antimicrobial extracts that may be utilized against S. aureus and different antibiotic resistant strains of MRSA.

Identification and characterization of in vitro inhibitors against UDP-glucuronosyltransferase 1A1 in uva-ursi extracts and evaluation of in vivo uva-ursi-drug interactions.

Uva-ursi leaf is widely used to treat symptoms of lower urinary tract infections. Here, we evaluated the in vitro inhibitory effects of uva-ursi extracts on 10 major human UDP-glucuronosyltransferases (UGT) isoforms. Of the 10 tested UGT isoforms, uva-ursi extracts exerted the strongest inhibitory effect on UGT1A1-mediated ß-estradiol 3-glucuronidation with the lowest IC50 value of 8.45 ±â€¯1.56 µg/mL. To identify the components of uva-ursi extracts showing strong inhibitory effects against UGT1A1, the inhibitory effects of nine major constituents of the extracts were assessed. Among the tested compounds, gallotannin exerted the most potent inhibition on UGT1A1, followed by 1,2,3,6-tetragalloylglucose; both demonstrated competitive inhibition, with Ki values of 1.68 ±â€¯0.150 µM and 3.55 ±â€¯0.418 µM. We found that gallotannin and 1,2,3,6-tetragalloylglucose also inhibited another UGT1A1-specific biotransformation, SN-38-glucuronidation, showing the same order of inhibition. Thus, in vitro UGT1A1 inhibitory potentials of uva-ursi extracts might primarily result from the inhibitory activities of gallotannin and 1,2,3,6-tetragalloylglucose present in the extracts. However, in rats, co-administration with uva-ursi extracts did not alter the in vivo marker for UGT1A1 activity, expressed as the molar ratio of AUCSN-38 glucuronide/AUCSN-38, because plasma concentrations of gallotannin and 1,2,3,6-tetragalloylglucose may be too low to inhibit the UGT1A1-mediated metabolism of SN-38 in vivo. The poor oral absorption of gallotannin and 1,2,3,6-tetragalloylglucose in uva-ursi extracts might cause the poor in vitro-in vivo correlation. These findings will be helpful for the safe and effective use of uva-ursi extracts in clinical practice.

Enzymatic Acylation of Anthocyanins Isolated from Alpine Bearberry ( Arctostaphylos alpina) and Lipophilic Properties, Thermostability, and Antioxidant Capacity of the Derivatives.

Cyanidin-3- O-galactoside (cy-gal) isolated from alpine bearberry ( Arctostaphylos alpine L.) was enzymatically acylated with saturated fatty acids of different chain lengths with Candida antarctica lipase immobilized on acrylic resin (Novozyme 435). The acylation reaction was optimized by considering the reaction medium, acyl donor, substrate molar ratio, reaction temperature, and reaction time. The highest conversion yield of 73% was obtained by reacting cy-gal with lauric acid (molar ratio of 1:10) in tert-butanol at 60 °C for 72 h. A novel compound was synthesized, which was identified as cyanidin-3- O-(6″-dodecanoyl)galactoside by mass spectrometry and nuclear magnetic resonance. Introducing lauric acid into cy-gal significantly improved both the lipophilicity and thermostability and substantially preserved the ultraviolet-visible absorbance and antioxidant properties. The research provides important insight in expanding the application of natural anthocyanins in the cosmetic and food industries.

Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial.

BACKGROUND: Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. METHODS/DESIGN: Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 - Uva-ursi + advice to take ibuprofen Group 2 - Placebo + advice to take ibuprofen Group 3 - Uva-ursi + no advice to take ibuprofen Group 4 - Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2-4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. DISCUSSION: The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015.

Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats.

BACKGROUND: This study was carried out to evaluate the antioxidant and hepatoprotective effects of Vaccinium arctostaphylos (V.a) methanolic extract on carbon tetrachloride (CCl4)-induced acute liver injury in Wistar rats. METHODS: Total phenolic and total flavonoid contents as well as antioxidant activity of V.a were determined. Extracts of V.a at doses of 200 and 400 mg/kg were administered by oral gavage to rats once per day for 7 days and then were given an intraperitoneal injection of 1 mL/kg CCl4 (1:1 in olive oil) for 3 consecutive days. Serum biochemical markers of liver injury, oxidative markers, as well as hydroxyproline (HP) content and histopathology of liver were evaluated. RESULTS: The obtained results showed that V.a had strong antioxidant activity. Treatment of rats with V.a blocked the CCl4-induced elevation of serum markers of liver function and enhanced albumin and total protein levels. The level of hepatic HP content was also reduced by the administration of V.a treatment. Histological examination of the liver section revealed that V.a prevented the occurrence of pathological changes in CCl4-treated rats. CONCLUSIONS: These findings suggested that V.a may be useful in the treatment and prevention of hepatic injury induced by CCl4.

Botanicals With Dermatologic Properties Derived From First Nations Healing: Part 2-Plants and Algae.

INTRODUCTION: Plants and algae have played a central role in the treatment of skin conditions in both traditional First Nations healing and in modern dermatology. The objective of this study was to examine the evidence supporting the dermatological use of seaweed, witch hazel, bearberry, and mayapple. METHODS: Four plants and algae used in traditional First Nations treatments of skin disease were selected based on expert recommendations. Several databases were searched to identify relevant citations without language restrictions. RESULTS: Seaweed has potential clinical use in the treatment of acne and wrinkles and may be incorporated into biofunctional textiles. Witch hazel is an effective and well-tolerated treatment of inflammation and diaper dermatitis. Bearberry leaves contain arbutin, a skin-lightening agent that is an alternative for the treatment of hyperpigmentation. Mayapple contains podophyllotoxin, a treatment for condyloma accuminata, molluscum contagiosum, and recalcitrant palmoplantar warts. DISCUSSION: Common plants and algae are replete with bioactive agents that may have beneficial effects on the skin. Further research will open the door to new and innovative products in the future. Limitations of this study include that the scope of our study is limited to 4 plants and algae, a small sample of the breadth of plants used by First Nations for dermatological treatments.

UHPLC-PDA-ESI-TOF/MS metabolic profiling of Arctostaphylos pungens and Arctostaphylos uva-ursi. A comparative study of phenolic compounds from leaf methanolic extracts.

The aim of this study was to get a rapid metabolic fingerprinting and to gain insight into the metabolic profiling of Arctostaphylos pungens H. B. K., a plant morphologically similar to Arctostaphylos uva-ursi (L.) Spreng. (bearberry) but with a lower arbutin (Arb) content. According to the European Pharmacopoeia the Arb content in the dried leaf of A. uva-ursi (L.) Spreng. must be at least 7% (wt/wt) but other species, like A. pungens, are unintentionally or fraudulently marketed instead of it. Therefore, methanolic leaf extracts of nine A. uva-ursi and six A. pungens samples labeled and marketed as "bearberry leaf" have been analyzed. A five-minute gradient with a UHPLC-PDA-ESI-TOF/MS on an Acquity BEH C18 (50×2.1 mm i.d.) 1.7 µm analytical column has been used for the purpose. A comprehensive assignment of secondary metabolites has been carried out in a comparative study of the two species. Among twenty-nine standards of natural compounds analyzed, fourteen have been identified, while other fifty-five metabolites have been tentatively assigned. Moreover, differences in both metabolic fingerprinting and profiling have been evidenced by statistical multivariate analysis. Specifically, main variations have been observed in the relative content for Arb, as expected, and for some galloyl derivative like tetra- and pentagalloylglucose more abundant in A. uva-ursi than in A. pungens. Furthermore, differences in flavonols profile, especially in myricetin and quercetin glycosilated derivatives, were observed. Based on principal component analysis myricetrin, together with a galloyl arbutin isomer and a disaccharide are herein proposed as distinctive metabolites for A. pungens.

Medicinal plant extracts variously modulate susceptibility of Escherichia coli to different antibiotics.

Antioxidant activity of green and black tea and extracts of medicinal plants and their ability to modulate antibiotic susceptibility in Escherichia coli were studied. Among a number of extracts tested the maximal capacity to scavenge DPPH radicals and chelate iron in chemical tests was found in green and black tea, Arctostaphylos uva-ursi and Vaccinium vitis-idaea. These extracts contained high level of polyphenols and in aerobic conditions exhibited prooxidant features, producing H2O2 and inducing expression of the katG gene encoding catalase HPI in E. coli cells. A good correlation between the polyphenol content and the ability of extracts to protect bacteria against peroxide stress was observed (r = 0.88). Polyphenol-rich extracts and iron chelators demonstrated the highest modulating effect on the antibiotic susceptibility by changing the time period before lysis started and by influencing the colony-forming ability of bacteria. The direction of the modulating effect was dependent on nature of antibiotic applied: under treatment with ciprofloxacin and ampicillin the extracts predominantly provided protective effects, while under treatment with kanamycin a bactericidal action was enhanced. Mechanism of modulating action of extracts on bacterial antibiotic susceptibility probably involves antioxidant, preferentially iron-chelating, or prooxidant properties of polyphenols.

Bearberry identification by a multidisciplinary study on commercial raw materials.

Herbal species different from the official bearberry, Arctostaphylos uva-ursi, are sold through conventional markets and also through non-controlled Internet websites, putting consumer safety at risk owing to the lack of quality control. Recently, Arctostaphylos pungens has become one of the most used species as a raw material for herbal medicines and dietary supplements in the place of official bearberry, a plant used for the treatment of various urinary disorders. A fingerprint identification based on an integrated application of different analytical techniques (HPTLC, NMR, HPLC-DAD and LC-ESI-MS) is here described to distinguish A. uva-ursi from A. pungens. The HPTLC and HPLC-DAD fingerprints resulted the simplest methods to differentiate the two species, whereas LC-ESI-MS was more useful to quantify arbutin, the main component of bearberry, and to evaluate its different content in the two species. This multidisciplinary study showed for the first time a specific phytochemical fingerprint of the new species A. pungens.