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Highly Galloylated Tannin Fractions from Witch Hazel (Hamamelis virginiana) Bark: Electron Transfer Capacity, In Vitro Antioxidant Activity, and Effects on Skin-Related Cells
Abstract
Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were highly active as free radical scavengers against ABTS, DPPH (hydrogen donation and electron transfer), and HNTTM (electron transfer). They were also able to reduce the newly introduced TNPTM radical, meaning that they included some highly reactive components. Witch hazel phenolics protected red blood cells from free radical-induced hemolysis and were mildly cytotoxic to 3T3 fibroblasts and HaCat keratinocytes. They also inhibited the proliferation of tumoral SK-Mel 28 melanoma cells at lower concentrations than grape and pine procyanidins. The high content in pyrogallol moieties may be behind the effect of witch hazel phenolics on skin cells. Because the most cytotoxic and antiproliferative mixtures were also the most efficient as electron transfer agents, we hypothesize that the final putative antioxidant effect of polyphenols may be in part attributed to the stimulation of defense systems by mild prooxidant challenges provided by reactive oxygen species generated through redox cycling.
... Aktywność biologiczna ekstraktów z oczaru jest przede wszystkim związana z obecnością tanin, zarówno podlegających hydrolizie alkalicznej jak i niehydrolizujacych. Pomimo wielu prac poświęconych temu zagadnieniu [9][10][11][12][13] skład ekstraktów wciąż pozostaje niejasny. Przyczyną jest zarówno liczba występujących związków jak i ich reaktywność pod wpływem światła i ciepła [14]. ...
... I tak, w ekstrakcie wodnym z kory występuje 62,7% monomerycznych katechin (X-XII) i proantocyjanidyn (XIII), 7,0% hamamelitaniny (XIV) 21,9% kwasu galusowego (IX) i galusanu metylu oraz 7,4% pentagaloiloglukozy (XV). We frakcji flawonoidowej znaleziono 67,4% katechiny (X) i 5,8% epikatechiny (XI), prócz tego pochodne tych flawonoidów o różnych ciężarach cząsteczkowych estryfikowane kwasem galusowym (XII) [12]. Inna praca [9] opisuje wyodrębnienie i identyfikację proantocyjanidyn (XIII) zawierających 3-O-gallokatechinę i 3-O-galloepikatechinę. ...
... Przeprowadzone w warunkach klinicznych testy na ochotnikach potwierdziły działanie przeciwpodrażnieniowe proantocjonidyn oczaru. W innym badaniu [12] stwierdzono in vitro aktywność przeciwutleniającą i zdolność redukcyjną całej frakcji taninowej. Badano [16] również zdolność tej frakcji do hamowania 5-lipoksygenazy i acetylotransferazy AcCoA. ...
... [15] and Zhang et al. [16] ), compound 1, producing the anion at m/z169, which was a characteristic fragment of galloyl group formed by the loss of a mucic acid group (191 Da), was identified as mucic acid-1,4-lactone at m/z211, and the fragment ion at m/z169 showed a loss of a carboxyl group (44 Da) producing the fragment ion at m/z125. Thus, the peak was identified as 2ʹ,5ʹ-di-O-galloyl-ᴅ-hamamelose (hamamelitannin), which was previously reported by Touriño et al. [29] To our knowledge, this is the first time that this compound has been identified in P. emblica fruit. Quantification of the hamamelitannin content was calculated to 36 mg/100 ml in P. emblica fruit extracts by HPLC-DAD according to the methods described by Duckstein et al. [30] Compound 3 (T R = 41.720 ...
... min) showed precursor anions ([M−H] − ) at m/z 197and 183, and both showed two major fragment anions at m/z124 and 78. Through comparison of the MS 2 fragmentation data with other studies (Touriñoet al. [29] ; Zhang et al. [31] ) and the Mass Bank MS database, compounds 4 and 5 were identified as ethyl gallate and methyl gallate. Of these compounds, ethyl gallate has been identified in leaves of Juglansregia by Zhang et al. [31] , and methyl gallate has been identified in leaves of Hamamelis virginiana by Touriñoet al. [29] The mass spectra of compound 6 (T R = 71.966 ...
... Through comparison of the MS 2 fragmentation data with other studies (Touriñoet al. [29] ; Zhang et al. [31] ) and the Mass Bank MS database, compounds 4 and 5 were identified as ethyl gallate and methyl gallate. Of these compounds, ethyl gallate has been identified in leaves of Juglansregia by Zhang et al. [31] , and methyl gallate has been identified in leaves of Hamamelis virginiana by Touriñoet al. [29] The mass spectra of compound 6 (T R = 71.966 min) showed a precursor anion [M−H] − at m/z301 and fragment anions at m/z257(by the loss of one CO 2 , i.e.,−CO 2 ), and 229 (−CO), respectively. ...
A simple microwave-assisted method for extracting antioxidant phenolic compounds from emblic (Phyllanthus emblica L.) fruits was developed and optimized with response surface methodology (RSM). The influence of process conditions including microwave power, irradiation time, ethanol concentration, and solvent-to-solid ratio on the extraction of total phenolic content was analyzed by using a second-order regression equation. The optimum extraction parameters were as follows: microwave power, 480 W; irradiation time, 29 s; ethanol concentration, 66%; liquid-to-solid ratio, 25 mL/g. Under these conditions, the recovery of total phenolic content was 133.58 ± 15.61 mg gallic acid equivalent/g dry weight (DW). The extracts were also analyzed using HPLC-ESI-TOF-MS to identify eight compounds including hamamelitannin, mucic acid-1,4-lactone-3-O-gallate, ellagic acid, and isocorilagin. To our knowledge, this is the first report of hamamelitannin in emblic fruit. The extracts exhibited strong antioxidant capacities in DPPH and ABTS⁺ radical scavenging assays and showed an excellent inhibition of lipid peroxidation and reducing property. These findings illustrated that the optimized microwave-assisted extraction method was efficient in extracting phenolic compounds with high antioxidant activity from emblic fruits. It was suggested that emblic fruits may be a new potential source as natural antioxidant agents applied in food industry.
... 6 Recently, Torres et al. adapted this analytical method to synthesize new bio-based antioxidant compounds by depolymerization of plant-phenolic extracts in the presence of cysteamine and cysteine nucleophiles. 3,[7][8][9][10][11][12] The avan-3-ol-thiol conjugates resulting from this reaction showed higher antiradical capacity 7,8 and enhanced penetration through biological membranes 13 compared to their underivatized counterparts. ...
... Witch hazel phenolicsproanthocyanidins and hydrolysable tanninswere able to protect red blood cells from free radical-induced hemolysis and inhibited the proliferation of tumoral SK-Mel 28 melanoma cells and the HT29 and HCT116 human colon cancer cell lines. Moreover, this extract was shown to be an effective protector against DNA damage triggered by hydroxyl radicals, 11,25 and to exert an inhibitory effect over deleterious chronic wound enzymes. 26 The method for permanent functionalization of chitosan developed in this paper is expected to combine the chemistry of amino, thiol and phenolic groups for obtaining biopolymer material with enhanced antioxidant capacity, antimicrobial effect and capability to modulate deleterious wound enzyme activity. ...
... virginiana) as previously reported. 11 Briey, chopped witch hazel stems were incubated in an acetone-water mixture (7 : 3) for 24 h at room temperature with occasional shaking. The solid was ltered off and the acetone was evaporated at reduced pressure. ...
This work reports a straightforward approach for incorporation of plant-derived flavonoid-based antioxidants into an intrinsically antimicrobial chitosan platform in order to generate chitosan-based materials suitable for biomedical applications. The novelty of this approach consists in the use of thioacidolysis – a common analytical method for the characterization of proanthocyanidins – to covalently functionalize natural macromolecules such as chitosan with bioactive phenolic moieties. It is known that proanthocyanidins undergo depolymerization in acid medium, where in the presence of nucleophiles they form stable flavan-3-ol derivatives. Based on this reaction, flavan-3-ol moieties from the polyphenol extract of Hamamelis virginiana are incorporated covalently into a previously thiolated chitosan matrix. The phenolics-functionalized chitosan possesses improved antioxidant and antimicrobial properties, and inhibitory efficiency over deleterious wound enzymes in vitro.
... Previous investigations in fish muscle have revealed the effectiveness of grape proanthocyanidins to either delay the lipid oxidation progress or protect endogenous R-TOH against oxidative degradation (10,25,26). Moreover, polyphenols obtained from grape pomace, pine bark, and witch hazel bark have been suggested as active antioxidants in cell assays (27,28). The present investigation aimed to evaluate the potential impact of these polyphenolic compounds to protect R-TOH from oxidation and, also, to establish which of the structural factors of polyphenols are the most important for R-TOH regeneration via reduction of R-tocopheroxyl radicals. ...
... Witch Hazel Bark Fractions. Following a procedure modified from the previously described for grape pomace, a polyphenolic extract soluble in both ethyl acetate and water (OWH) was obtained from witch hazel bark (28 ). Briefly, a sugar free mixture was obtained by extraction with water/acetone (3, 7). ...
... The hydrolyzable tannins accounted for >80% of the polyphenolic content and had a much richer content of galloyl units than the proanthocyanidin fraction. The proanthocyanidins in the OWH and IVH fractions have mean degrees of polymerization (mDP) of 1.2 and 1.6 units, respectively, and galloylation ratios of 0.11 and 0.23 galloyl unit per proanthocyanidin unit (28 ). The degree of polymerization and percentage of galloylation were characterized as above-described for grape fractions. ...
The ability of several polyphenolic fractions from grape ( Vitis vinifera ) pomace, pine ( Pinus pinaster ) bark, and witch hazel ( Hammamelis virginiana ) bark to repair alpha-tocopherol (alpha-TOH) through reduction of the alpha-tocopheroxyl radical was investigated in a homogeneous hexane system and a phospholipid-like system based on SDS micelles. These natural polyphenols were compared with pure related phenolics (epicatechin, gallic acid, epigallocatechin gallate, quercetin, and rutin) and ascorbic acid, which is a substance with a well-recognized capacity for regenerating alpha-TOH. alpha-Tocopheroxyl radicals were monitored and quantified by electron spin resonance (ESR) spectroscopy in the absence and presence of phenolics. Polyphenols from grape and pine bark were essentially catechin monomers and proanthocyanidins differing in the content of galloyl residues; those from pine bark had a negligible degree of galloylation. Polyphenolic fractions from witch hazel bark were composed of approximately 80% hydrolyzable tannins rich in galloyl moieties, together with a smaller amount of catechin monomers and proanthocyanidins. In the homogeneous hexane system, polyphenols from grape and pine bark exhibited similar activities, reducing the alpha-tocopheroxyl radicals by over 27-40%, whereas phenols from witch hazel were more highly effective, reducing 80% of alpha-TOH. In contrast, pine bark polyphenols were found to be significantly less active than the grape fractions in SDS micelles, reducing 30 and 70% of alpha-tocopheroxyl radicals, respectively. Polyphenolic fractions from witch hazel were also able to reduce the highest amount of alpha-TOH in SDS-micelles. The reducing capacity on alpha-tocopheroxyl radical of polyphenolic fractions was found to be pH-dependent and more effective at higher pH in the range of pH studied (5.8-7.8). These results stress the potential role of polyphenols, in particular those rich in galloyl groups, to maintain intact endogenous alpha-TOH in biological membranes through reduction of alpha-tocopheroxyl radicals.
... Surprisingly, there is a lack of studies examining the antibacterial properties of this plant, despite studies reporting high levels of tannins in H. virginiana extracts. 7 Our study screened H. virginiana extracts of varying polarity and found appreciable inhibitory activities for the higher polarity methanolic and aqueous extracts against most Staphylococcus and Streptococcus spp. Only S. mutans remained relatively unaffected by these extracts. ...
... 60,61 Furthermore, studies on human dermal fibroblast cells have demonstrated a protective role of WH extracts against H 2 O 2 -induced damage, possibly due to their free radical scavenging capabilities. 7 Together, this highlights the potential for the safe use of WH extracts as a therapeutic option for the treatment of both systemic and superficial staphylococcal and streptococcal infections. ...
Staphylococcal and streptococcal species trigger a wide variety of infections involving epithelial tissues. Virginian witch hazel (WH; Hamamelis virginiana L.; family: Hamamelidaceae) is a plant that has been used traditionally by Native Americans to treat a variety of skin conditions. Extracts from the leaves were examined for their inhibitory effects on these bacterial species. Solvents of different polarity (water, methanol, ethyl acetate, hexane and chloroform) were used to prepare extracts from WH leaves, and the aqueous resuspensions were screened for antibacterial activities using disc diffusion and liquid dilution assays. Extract phytochemical profiles and toxicities were also examined, and combinations of extracts with conventional antibiotics were tested against each bacterial strain. The methanolic and aqueous extracts inhibited the growth of S. oralis, S. pyogenes, S. epidermidis and S. aureus, but not S. mutans. The extracts were especially active against staphylococcal species, with MIC values between 200-500 μg/ml. Combinations of active extracts with conventional antibiotics failed to yield beneficial interactions, except for two cases where additive interactions were observed (aqueous WH extract combined with chloramphenicol against S. oralis, and methanolic WH extract combined with ciprofloxacin against S. aureus). Phytochemical assays indicated an abundance of tannins, triterpenoids and phenolics in the water and methanol extracts, with trace amounts of these components in the ethyl acetate extract. Phytochemicals were not detected in hexane and chloroform extracts. Thus, phytochemical abundance in extracts was concordant with antibacterial activities. All extracts were found to be non-toxic in Artemia nauplii assays. These findings indicate the potential for WH leaf extracts for clinical use in treating staphylococcal and streptococcal infections, while substantiating their traditional Native American uses.
... The main constituents of the extract include: Tannin, gallic acid, catechins, proanthocyanins, flavonoids (kaempferol, quercetin), essential oils (carvacrol, eugenol, hexenol), choline, and saponins. It is a strong anti-oxidant and astringent, which makes it useful as a natural remedy also for acne, psoriasis, eczema, aftershave applications, ingrown nails, cracked or blistered skin, and for treating insect bites [16] . ...
... Hamamelitannin and catechins were also detected in the leaves at concentrations of < 0.04% (wt/wt) [20] . Polymeric proanthocyanidins were isolated from an acetonewater (7:3) extract from hamamelis bark in yields of about 5% by Dauer et al (2003) [22] , Touriño et al [16]. Terminal chain units were catechin and gallocatechin in a constant ratio of 95:5. ...
... HnAntiox + • R → HnAntiox +• + R -Relevant for electrophilic free radicals and antioxidants that are good electron donors.Viable in polar media. For antioxidants curcumin,[1255] and highly galloylated tannin fractions.[1256] Edaravone derivatives + • OH, • OCCl3 and CH3COO • .[1257] ...
Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. The data used in the analysis come from theoretical anc computational protocols, which have been proven to be very usefull in this context. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.
... Silybum marianum, a source of a very potent flavonoid, Silymarin, inhibits UV-induced apoptosis in Human malignant melanoma [36]. Experiments on UV -irradiated HaCaT and SK-Mel 28 melanoma cell lines have revealed that Galloylated Tannins, obtained from Witch Hazel (Hamamelis virginiana), have antioxidant, cytotoxic & anti-proliferative properties [37]. PCF, a polypeptide obtained from Chlamys farreri, has been reported to show an inhibitory effect on UV-B -induced apoptosis and DNA damage in normal human dermal fibroblasts [38]. ...
Skin areas exposed to ultraviolet radiation (UV) from sunlight are more prone to photoaging than unexposed areas evidenced by several signs which include skin dryness, irregular pigmentation, lentigines, hyperpigmentation, wrinkling, and decreased elasticity. Plant-based natural product ingredients with therapeutic potential against skin photoaging are gaining more attention. This article aims the reviewing the research work done in exploring the cellular and molecular mechanisms involved in UV-induced skin photoaging, followed by summarizing the mechanistic insights involved in its therapeutics by natural product-based ingredients. In the mechanistic section of the convoluted procedure of photoaging, we described the effect of UV radiation (UVR) on different cellular macromolecules (direct damage) and subsequently, the deleterious consequences of UVR-generated reactive oxygen species (indirect damage) and signaling pathways activated or inhibited by UV induced ROS generation in various cellular pathologies of skin photoaging like inflammation, extracellular matrix degradation, apoptosis, mitochondrial dysfunction, and immune suppression. We also discussed the effect of UV radiation on the adipose tissue, and transient receptor potential cation channel V of photoaging skin. In the past few decades, mechanistic studies performed in this area have deciphered various therapeutic targets, opening avenues for different available therapeutic options against this pathological condition. So the remaining portion of the review deals with various natural product-based therapeutic agents available against skin photodamage.
... Many studies discuss the antitumor potential of the actives studied here when exposed to tumor cells of mouse melanoma (B16F1), breast cancer (MCF-7), human melanoma (SK-Mel 28), colorectal cancer (RKO), neuroblastoma (SH-SY5Y), and among others. [14][15][16][17][18][19] However, it is important to emphasize that it was not possible to In the in vivo acute oral toxicity test to estimate the LD50, the maximum concentration used is generally 5000 mg·kg −1 because it is a known value that reduces the animal population by 50%. 6 There is a classification and labeling of chemical products that defines acute toxicity in five categories: category 1 (LD50 < 5 mg·kg −1 ), category 2 (LD50 > 5 mg·kg −1 < 50 mg·kg −1 ), category 3 (LD50 > 50 mg·kg −1 < 300 mg·kg −1 ), category 4 (LD50 > 300 mg·kg −1 < 2000 mg·kg −1 ), and category 5 (LD50 > 2000 mg·kg −1 < 5000 mg·kg −1 ). ...
Alternative in vitro methods are important, as there is a call to ban the use of animals in cosmetics research.
Aim:
To suggest the expansion of the use of in vitro safety techniques recommended by the OECD guidelines and to propose the use of the automation of the in vitro mammalian micronucleus test method by flow cytometry to assess the genotoxic potential of Centella asiatica, Horse Chestnut, Witch Hazel, Blend, Ecoblend and Caffeine extracts due to their widespread use in commercial products.
Methods:
Flow cytometer analysis were performed using the Accuri™ C6 equipment and analyzed using the FlowJo software. Cytotoxicity tests followed OECD 129 guidelines and Phototoxicity followed OECD/GD 432 guidelines.
Results:
The results showed that the cytotoxicity assay presented a decrease in cell viability when cells were exposed to Centella asiatica from a concentration of 5.0%, horse chestnut 2.5%, Witch hazel 2.5%, Blend 3.13%, Caffeine 3%, while Ecoblend at the tested concentrations did not show cytotoxicity. In the phototoxicity test the samples at the tested concentrations showed a PIF <2 being considered potentially non-phototoxic. Finally, in the genotoxicity automated assay, samples were considered potentially non-genotoxic.
Conclusion:
In vitro methods are of paramount importance for the development of pre-clinical tests and the use of test automation helps to reduce the time for analysis and dissemination of results, being a determining factor for the prospect of new compounds.
... Few of the previous studies attributed a cytoprotective effect to Hamamelis virginiana L. bark extract against skin oxidative stress [21]. As a first step for the characterization of the biological properties of HVE, we evaluated the radical scavenging activities of HVE and HT in two cell-free systems, ORAC (Table 2) and DPPH (Table 3) assays. ...
Cutibacterium acnes (C. acnes) is recognized as one of the main triggers of the cutaneous inflammatory response in acne vulgaris, a chronic skin disorder with a multifactorial origin. Witch hazel (Hamamelis virginiana L.) is a plant widely used for skin inflammatory conditions, with some preliminary anti-inflammatory evidence on the skin, but lacking data on acne conditions. This study aimed to evaluate the effect of a glycolic extract from Hamamelis virginiana bark (HVE) versus C. acnes-induced inflammation in human keratinocytes (HaCaT). Phytochemical investigations of HVE identified hamamelitannin (HT) and proanthocyanidins as the most abundant compounds (respectively, 0.29% and 0.30% w/wextract). HVE inhibited C. acnes-induced IL-6 release (IC50: 136.90 μg/mL), by partially impairing NF-κB activation; however, no antibacterial or antibiofilm activities were found. In addition, HVE showed greater anti-inflammatory activity when TNF-α was used as a proinflammatory stimulus (IC50 of 38.93 μg/mL for IL-8 release), partially acting by antioxidant mechanisms, as shown for VEGF inhibition. The effects of HVE are primarily based on the proanthocyanidin content, as HT was found inactive on all the parameters tested. These results suggest further investigations of HVE in other inflammatory-based skin diseases.
... It was previously detected in tea extract, albeit it is the first time that it has been detected in cinnamon. The pyrogallol moieties of (epi)gallocatechins (e.g., in tea) are more reactive than the catechol moieties of (epi)catechins regarding their antioxidant activity [62]. Whether peaks L27 and L63 could serve as markers for that species has yet to be confirmed. ...
The present study aimed to assess metabolites heterogeneity among four major Cin-namomum species, including true cinnamon (Cinnamomum verum) and less explored species (C. cas-sia, C. iners, and C. tamala). UPLC-MS led to the annotation of 74 secondary metabolites belonging to different classes, including phenolic acids, tannins, flavonoids, and lignans. A new proanthocy-anidin was identified for the first time in C. tamala, along with several glycosylated flavonoid and dicarboxylic fatty acids reported for the first time in cinnamon. Multivariate data analyses revealed, for cinnamates, an abundance in C. verum versus procyandins, dihydro-coumaroylglycosides, and coumarin in C. cassia. A total of 51 primary metabolites were detected using GC-MS analysis encompassing different classes, viz. sugars, fatty acids, and sugar alcohols, with true cinnamon from Malaysia suggested as a good sugar source for diabetic patients. Glycerol in C. tamala, erythritol in C. iners, and glucose and fructose in C. verum from Malaysia were major metabolites contributing to the discrimination among species.
... It has been used historically for treating diarrhea, skin burns, and rectal disorders [10]. In addition, tannins have been documented to exhibit antioxidant, antibacterial, antiviral, antiprotozoal, and anti-carcinogenic effects [11][12][13][14][15]. However, the effect of TA or tannins on the transdermal sensitization process of antigen proteins has not yet been investigated. ...
Transdermal sensitization to allergens is of great concern as a sensitization route for food allergies. This skin-mediated invasion and sensitization to allergens is involved in skin barrier breakdown and inflammation, followed by the production of several kinds of cytokines. Cytokines such as thymic stromal lymphopoietin and thymus and activation-regulated chemokine are also involved. In this study, we investigated the suppressive effect of tannic acid (TA) on transdermal sensitization using ovalbumin (OVA), a major egg-white allergen. We also analyzed the mechanisms associated with the inhibitory effects of TA. The results showed that the co-application with TA prevents transdermal sensitization to OVA. As possible mechanisms, its anti-inflammatory and astringent effect on the skin and binding ability with the protein were considered. These results indicate that TA could be applied to cosmetics and lotions, which could suppress the transdermal sensitization to allergens.
... Fractions rich in pyrogallol-containing polyphenols, such as proanthocyanidins, gallotannins and gallates, were shown to be active as free-radical scavengers in HAT (hydrogen atom transfer) and SET (single-electron transfer) assays. Additionally, it was found that they are able to protect red blood cells from free radical induced hemolysis [48]. ...
In this work, both direct and indirect cell-based antioxidant profiles were established for 27 plant extracts and 1 algal extract. To evaluate the direct antioxidant effects, fluorescent AOP1 cell assay was utilized, which measures the ability of different samples to neutralize intracellular free radicals produced by a cell-based photo-induction process. As the intestinal barrier is the first cell line crossed by the product, dose response curves obtained from Caco-2 cells were used to establish EC50 values for 26 out of the 28 natural extracts. Among them, 11 extracts from Vitis, Hamamelis, Syzygium, Helichrysum, Ilex and Ribes genera showed remarkable EC50s in the range of 10 µg/mL. In addition to this, a synergistic effect was found when combinations of the most potent extracts (S. aromaticum, H. italicum, H. virginiana, V. vinifera) were utilized compared to extracts alone. Indirect antioxidant activities (i.e., the ability of cells to trigger antioxidant defenses) were studied using the ARE/Nrf2 luminescence reporter-gene assay in HepG2 cells, as liver is the first organ crossed by an edible ingredient once it enters in the bloodstream. Twelve extracts were subjected to an intestinal epithelial barrier passage in order to partially mimic intestinal absorption and show whether basolateral compartments could maintain direct or indirect antioxidant properties. Using postepithelial barrier samples and HepG2 cells as a target model, we demonstrate that indirect antioxidant activities are maintained for three extracts, S. aromaticum, H. virginiana and H. italicum. Our experimental work also confirms the synergistic effects of combinations of post-intestinal barrier compartments issued from apical treatment with these three extracts. By combining cell-based assays together with an intestinal absorption process, this study demonstrates the power of cell systems to address the issue of antioxidant effects in humans.
... 17,and No. 19) [83]. Interestingly, the contradicted amount of total phenolic contents were also observed in the same plant extracts that were included in different cream samples; these extracts were Hamamelis virginiana (high amount of total phenolic content in sample No. 14, but low in sample No. 7) [100], Solanum lycopersicum (high amount in sample No. 23, but low in sample No. 7) [101], and Centella asiatica (high amount in sample No. 10, but low in sample No. 5) [55]. The reason might be due to a different quantity of the certain extract added to the cream formulation in each cream sample. ...
Recently, the global trend toward the use of natural extracts and antioxidant agents in the cosmetic cream industry to produce whitening effects has been increasing. This has also been a persistent trend in Thailand. In this study, samples of commercial cosmetic creams on the Thai market were assessed for a functional evaluation of their antioxidant activity, tyrosinase inhibitory effects, and phenolic contents. Samples were extracted using hot water and sonication extraction method to obtain the functional cream extracts. Total phenolic contents in all samples were within the range of 0.46–47.92 mg GAE/30 g cream. Antioxidant activities of the cream extracts were within the range of 3.61–43.98 mg Trolox equivalent/30 g cream, while tyrosinase inhibition activities were within the range of 2.58–97.94% of inhibition. With regard to the relationship between the total phenolic content and the antioxidant activity of the cosmetic creams, Pearson’s correlation coefficient revealed a moderately positive relationship with an r value of 0.6108. Furthermore, the relationship between the antioxidant activity and the tyrosinase inhibitory activity of the cosmetic creams was highly positive with an r value of 0.7238. Overall, this study demonstrated that the total phenolic contents in the functional cosmetic creams could play a role in antioxidant activity and anti-tyrosinase activities. The findings indicate how the whitening and antioxidant effects of cosmetic creams could be maintained after the products have been formulated, as this concern can affect the consumer’s decision when purchasing cosmetic products.
... It is also known to boost skin hydration, as well as treat razor burns and sunburns. [8] These plants are good sources of ascorbic acids, riboflavin, thiamin and niacin (Table 2). Natural ascorbic acid is playing a key role in the anti aging process for skin reducing wrinkles and an aged appearance, vitamin C also protects skin against toxins and free radicals. ...
Cosmeceuticals‟ is fastest growing segment of the beauty industry. Herbs which are used for their medicinal
values in the treatment of various systemic diseases are also used for alteration of appearance. In the present work,
phytochemical screening of leaves of Aloe Vera. Azadirachta Indica and Leucas Aspera were done for the
qualitative and quantitative analysis of various phytochemicals such as alkaloids, coumarins, saponins, flavonoids
and steroids for their cosmetic potential. There is a lack of scientific analysis of phytochemicals used in cosmetic
preparation so this work will provide a basis for the use of specific herbs and their efficacy as cosmetics.
... HV contains B-type PACs and the vast majority of the other polyphenols are hydrolysable tannins. The excessive presence of pyrogallol in HV [25] may contribute to the observed initially high, but relatively poorly sustained activity. ...
Objectives:
The interactivity of proanthocyanidins (PACs) with collagen modulates dentin matrix biomechanics and biostability. Herein, PAC extracts selected based on structural diversity were investigated to determine key PAC features driving sustained effects on dentin matrices over a period of 18months.
Methods:
The chemical profiles of PAC-rich plant sources, Pinus massoniana (PM), Cinnamomum verum (CV) and Hamamelis virginiana (HV) barks, as well as Vitis vinifera (VV) seeds, were obtained by diol HPLC analysis after partitioning of the extracts between methyl acetate and water. Dentin matrices (n=15) were prepared from human molars to determine the apparent modulus of elasticity over 18months of aging. Susceptibility of the dentin matrix to degradation by endogenous and exogenous proteases was determined by presence of solubilized collagen in supernatant, and resistance to degradation by bacterial collagenase, respectively. Data were analyzed using ANOVA and Games-Howell post hoc tests (α=0.05).
Results:
After 18months, dentin matrices modified by PM and CV extracts, containing only non-galloylated PACs, were highly stable mechanically (p<0.05). Dentin matrices treated with CV exhibited the lowest degradation by bacterial collagenase after 1h and 18months of aging (p<0.05), while dentin matrices treated with PM showed the least mass loss and collagen solubilization by endogenous enzymes over time (p<0.05).
Significance:
Resistance against long-term degradation was observed for all experimental groups; however, the most potent and long-lasting dentin biomodification resulted from non-galloylated PACs.
... Hamameli-daceae Witch hazel bark infusion used on sores bark [15] Bark: hamamelitannin cytotoxic to HT-29 colon tumor cells [223] Leaves: gallotannins (hydrolyzable tannins: monogalloyl, heptagalloyl, octagalloyl, and nonagalloyl hexoses), caffeoylquinic acids (3-, and 5-), kaempferol glycoside [224] Bark: polymeric proanthocyanidins (condensed tannins). [225] Bark: tannins, antioxidant, cytotoxic to SK-Mel-28 melanoma cells [226] Bark: condensed (proanthocyanidins) and hydrolyzable (galloylhamameloses) tannins [227] Helenium autumnale L. Asteraceae Sneezeweed root infusion used to prevent menstruation after childbirth; dried leaves used to induce sneezing roots, leaves Apparently the root extract has not been examined [15] Aerial parts: dihydromexicanin E [228] Aerial parts: flexuosin A [229] Aerial parts: helenalin [230] Aerial parts: tenulin [231] Helenalin is cytotoxic (human epithelial type 2, HEp-2, cells) [232] Whole plant: carolenin and carolenalin [233] Flowers: helenalin, autumnolide, mexicanin I; helenalin is cytotoxic [234] Plant: dihydroflorilenalin [235] Plant: 4-O-tigloyl-11,13-dihydroautumnolide [236] Hydrastis canadensis L. Ranuncu-laceae Goldenseal sedative, anti-inflammatory; sores, wounds, cancer root [15] Rhizomes: alkaloids (berberine, 8-oxotetrahydrothalifendine, canadine, and β-hydrastine); berberine shows antitubercular activity [237] Rhizomes: berberine alkaloids (berberine, β-hydrastine, canadine and canadaline); berberine is antibacterial. [238] Rhizomes: alkaloids (berberine, canadaline, canadine, β-hydrastine, and isocorypalmine) [239] Rhizomes: alkaloids (hydrastinine, hydrastine, canadaline, berberine, canadine) [240] Leaves: 3,4-dimethoxy-2-(methoxycarbonyl)benzoic acid, Leaves: flavonoids (sideroxylin, 8-desmethyl-sideroxylin, and 6-desmethyl-sideroxylin); inhibit N or A multidrug resistance pump; synergistic antibacterial activity with berberine [242] Hypericum gentianoides (L.) Britton, Sterns and Poggenb. ...
Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers in North America. Methods: The aim of this review was to examine the Cherokee ethnobotanical literature and the published phytochemical investigations on Cherokee medicinal plants and to correlate phytochemical constituents with traditional uses and biological activities. Results: Several Cherokee medicinal plants are still in use today as herbal medicines, including, for example, yarrow (Achillea millefolium), black cohosh (Cimicifuga racemosa), American ginseng (Panax quinquefolius), and blue skullcap (Scutellaria lateriflora). This review presents a summary of the traditional uses, phytochemical constituents, and biological activities of Cherokee aromatic and medicinal plants. Conclusions: The list is not complete, however, as there is still much work needed in phytochemical investigation and pharmacological evaluation of many traditional herbal medicines.
... However, SCW extraction has not been yet applied to pistachio hulls. Particularly, the extraction of gallotannins from pistachio hulls, e.g., galloyl glycosides, galloyl quinic/shikimic acids, and penta-O-galloyl-β-D-glucose might be feasible by SCW as previously exemplified by the hot water extraction of a gallotannin-rich plant, witch hazel (Hamamelis virginiana L.), at 100°C (Gonzales, Torres, & Medina 2010;Touriño et al., 2008). ...
Pistachio hulls, important by-products of pistachio processing, were extracted using an environmentally friendly process with subcritical water (SCW) at a pressure of 6.9 MPa in the range of 110 and 190 °C, and flow rate of 4 ml/min. Detailed HPLC-DAD-ESI/MSn analyses allowed the identification of 49 phenolic compounds in the SCW extracts. Total gallotannin yields up to 33 g/kg were reached at 150-170°C, where gallic acid (22.2 g/kg) and penta-O-galloyl-β-D-glucose (9.77 g/kg) levels were 13.2- and 10.6-fold higher than those in the aqueous methanol extracts. Flavonols were also effectively extracted at 110-150°C (4.37-5.65 g/kg), while anacardic acid recovery was poor (1.13-2.77 g/kg). Accordingly, high amounts of anacardic acids (up to 50.7 g/kg) were retained in the extraction residue, revealing that SCW extraction allowed selective extraction of gallotannins and flavonols. Antioxidant capacities ranged from 0.68 to 1.20 mmol Trolox equivalents (TE)/g for SCW extracts increasing with temperature up 190 °C.
... We hypothesized therefore, that the mechanisms by which HeT affects respiration may be related to the interaction with cell membrane and its intrinsic redox properties. The first piece of evidence supporting the It has been demonstrated that the redox properties of tannins may change from anti-to prooxidant as the oxygen partial pressure increases, being able to produce spontaneous free radicals [24,25] or be an effective electron scavenger [26][27][28]. This information led us to speculate initially that HeT may function as an electron scavenger of the respiratory chain, as reported previously [29,30]. ...
Plant secondary metabolism produces a variety of tannins that have a wide range of biological activities, including activation of plant defences and antimicrobial, anti-inflammatory and antitumoral effects. The ellagitannin HeT (1-0-galloyl-2,3;4,6-bis-hexahydroxydiphenoyl-β-D-glucopyranose) from strawberry leaves elicits a strong plant defence response, and exhibits antimicrobial activity associated to the inhibition of the oxygen consumption, but its mechanism of action is unknown. In this paper we investigate the influence of HeT on bacterial cell membrane integrity and its effect on respiration. A β-galactosidase unmasking experiment showed that HeT does not disrupt membrane integrity. Raman spectroscopy analysis revealed that HeT strongly interacts with the cell membrane. Spectrochemical analysis indicated that HeT is oxidized in contact with bacterial cell membranes, and functional studies showed that HeT inhibits oxygen consumption, NADH and MTT reduction. These results provide evidence that HeT inhibits the respiratory chain.
... hydrolysable tannins), flavone subunit (non-hydrolysable or condensed tannins) or phloroglucinol subunits (phloro-tannins). Tannins from different sources have been studied for their antiviral (Ueda et al., 2013), antibacterial (Akiyama et al., 2001), antioxidant (Gu et al., 2008;Tourino et al., 2008), pediatric dermatoses (Fölster-Holst and Latussek, 2007), anti-inflammatory (Mota et al., 1985;Liu et al., 2015) and radioprotective effects (Zhou et al., 2016). Tannins have been used medically for many years and their importance in dermatological application have gained significant importance because of their astringent effects, management of superficial skin condition, weeping, inflammation and itching with acceptable tolerability. ...
Diospyros kaki L.f. belonging to family Ebenaceae, commonly known as persimmon is used as a medicinal plant in Chinese traditional medicine since many years for different ailments including cosmetics and dermatologic applications. Traditionally this plant is used to treat different skin conditions including pimples, skin eruptions and eczema. Present interest has been focused toward use of natural bioactive compounds in various curative and beautifying applications in dermatological and cosmeceutical disciplines. The objective of this article is to present cumulative data on potential use of D. kaki for its possible role in dermatologic and cosmetic applications. Scientific data has revealed an excellent position of D. kaki in both dermatology and cosmetic discipline making it a valuable choice in respective field. Active principles from different plant parts have shown to possess anti-inflammatory, antiallergic, photo-protective, and anti-wrinkle effects with appreciable activities against tyrosinase, elastase, and collagenase enzymes. Promising antioxidant activity and skin whitening potential, augmented by reduction in sebum contents, and reduction in size and number of skin pores make it a suitable choice as cosmetic ingredient. Data has been summarized and presented on available molecular mechanism that can contribute toward phytoconstituents usage in cosmetics and dermatology mediated by different cellular pathways. Crude extracts and some of phytochemical obtained from this plant such as isoquercitrin and hyperin have better reported activities than well-known cosmetic ingredients viz., arbutin, kojic acid and hydroquinone with possibility of having no side effects. Photo protection against degenerative effects of UVA, UVB and gamma radiation can help skin to fight well against oxidative stress and reactive oxygen species. Further investigation need to be directed toward human subjects for evaluation of these reported activities for obtaining optimum commercial and industrial benefits from this valuable plant.
... [254] SET-I pathways have been proposed as key routes for the free radical scavenging activity of the enol isomer of curcumin, [303] and highly galloylated tannin fractions. [304] In addition it is believed to be particularly important for the reactions of edaravone derivatives with some radicals such as • OH, • OCCl 3 and CH 3 COO • , [305] planar catechin analogues with peroxyl radicals, [306] resveratrol with oxygen radical, [307] and carotenoids with CCl 3 OO • [308,309] and • NO 2 [291,310]. The SET-II pathway, on the other hand, has been proposed to be involved in the reactions of the superoxide radical anion (O 2 ...
Oxidative stress is frequently caused by an excess of free radicals and has been associated with a wide variety of health disorders. Therefore, finding strategies for scavenging free radicals has become an active area of research. This review summarizes, from a physicochemical perspective, relevant strategies to fight oxidative stress via antioxidants, including prevention, deactivation of oxidants, and repair of damaged targets. Different reaction mechanisms involved in the chemical protection exerted by antioxidants are discussed, as well as their relative importance depending on several aspects. Some of them are the polarity of the environment, the pH of aqueous phase, and the chemical nature of the reacting radicals. Data that can currently be obtained from computational, quantum, chemistry, protocols are detailed and their reliability is analyzed. Viable criteria to identify optimal antioxidants using such protocols are provided. Current challenges and future directions in this area of research are discussed. A large set of antioxidants are compared and their trends in activity, based on kinetic data, is provided.
... [254] SET-I pathways have been proposed as key routes for the free radical scavenging activity of the enol isomer of curcumin, [303] and highly galloylated tannin fractions. [304] In addition it is believed to be particularly important for the reactions of edaravone derivatives with some radicals such as • OH, • OCCl 3 and CH 3 COO • , [305] planar catechin analogues with peroxyl radicals, [306] resveratrol with oxygen radical, [307] and carotenoids with CCl 3 OO • [308,309] and • NO 2 [291,310]. The SET-II pathway, on the other hand, has been proposed to be involved in the reactions of the superoxide radical anion (O 2 ...
Oxidative stress is frequently caused by an excess of free radicals and has been associated with a wide variety of health disorders. Therefore, finding strategies for scavenging free radicals has become an active area of research. This review summarizes, from a physicochemical perspective, relevant strategies to fight oxidative stress via antioxidants, including prevention, deactivation of oxidants, and repair of damaged targets. Different reaction mechanisms involved in the chemical protection exerted by antioxidants are discussed, as well as their relative importance depending on several aspects. Some of them are the polarity of the environment, the pH of aqueous phase, and the chemical nature of the reacting radicals. Data that can currently be obtained from computational, quantum, chemistry, protocols are detailed and their reliability is analyzed. Viable criteria to identify optimal antioxidants using such protocols are provided. Current challenges and future directions in this area of research are discussed. A large set of antioxidants are compared and their trends in activity, based on kinetic data, is provided.
... 15 Due to its antiphlogistic and astringent properties, HV extracts have been used to treat small wounds and local inflammation. 16,17 Antimutagenic and antioxidant properties have also been described in HV. [18][19][20] At present, many mouthwashes with different compositions and active ingredients are available in the market. However, some formulations have still not been effectively tested for proving their clinical efficiency. ...
Aim:
To evaluate the effectiveness of five different mouthwashes through measurement of the plaque index.
Materials and methods:
Fifty subjects took part in this blind study, randomized into blocks of five groups according to the active ingredient of the mouthwash: CHX group (0.12% chlorhexidine gluconate), essential oils (EO) group, cetylpyridinium chloride (CPC) group, Tri group (triclosan) and Hamamelis virginiana (HV) group. All subjects were evaluated for a reduction in the bacterial plaque index at 7, 14 and 21 days.
Results:
There was a significant reduction in the mean plaque index during the period of evaluation (p < 0.01), and the reduction during the period of evaluation was different between mouthwashes (p < 0.01). The reduction in the plaque index at the end of 21 days was, in decreasing order, CHX > EO > CPC > Tri > HV.
Conclusion:
The reduction in the plaque index during the period of evaluation was different between the types of mouth-wash. The mouthwash containing the active ingredient chlor-hexidine was the most effective, followed by the essential oil, cetylpyridinium chloride, triclosan and H. virginiana.
... As células hepáticas convertem o etanol em um composto de maior toxicidade, o etanaldeído, que reduz os níveis de glutationa no fígado, ocasionando peroxidação lipídica e desencadeando a produção de radicais livres (Raphael & Kuttan, 2003), tornando-se importante a presença de compostos antioxidantes, como taninos e flavonóides, nas drogas vegetais. Vennat et al., (1992); Masaki et al., (1994); Haslam (1996); Sagareishvili et al., (1999); Silva et al., (2000); Choi et al., (2002); Tourino et al., (2008); relataram a existência de compostos responsáveis por essa atividade em H. virginiana. Já foi também demonstrado que os taninos estão associados com atividade antiulcerogênica em outras plantas (Esaki et al., 1985) e que auxiliam na cicatrização, devido à sua capacidade de complexação com proteínas, formando uma película sobre a região danificada (Lopes et al., 2005). ...
Úlcera é um tipo de inflamação que afeta um considerável número de pessoas no mundo, como muitas recorrem às plantas como um cuidado primário de saúde torna-se importante a realização de estudos sobre as mesmas. As plantas possuem componentes capazes de exercer ações farmacológicas. Já foram descritas para Hamamelis virginiana L. ação antiviral, antibacteriana, antiinflamatória, antioxidante. Enquanto para Sambucus australis Cham. & Schltdl. são conhecidas ações antiinflamatórias e antioxidantes, tendo grande popularidade no tratamento sintomático de moléstias eruptivas, gripes e resfriados. O objetivo desse trabalho foi avaliar a atividade antiulcerogênica dos extratos brutos de H. virginiana L. e S. australis Cham. & Schltdl., frente ao modelo de úlcera induzido por etanol, em ratos. O tratamento realizado foi de caráter preventivo, no qual se administrou cimetidina 100mg/Kg (controle positivo), água destilada (controle negativo), H. virginiana L. 100 e 200mg/Kg, S. australis Cham. & Schltdl. 150 e 200mg/Kg, posteriormente a úlcera foi induzida. . Dos extratos avaliados apenas H. virginiana L. apresentou atividade antiulcerogênica significativa (p<0,05), S. australis Cham. & Schltdl. não apresentou a mesma atividade, porém mostrou uma tendência à ação anti-edematogênico na dose de 150mg/Kg.
... Due to their antiphlogistic and astringent properties, these extracts are widely used in skin care, to treat small wounds, local inflammations [39][40][41], or hemorrhoids [42]. In addition, antimutagenic as well as antioxidant properties have been described [43][44][45]. ...
Antiviral activity has been demonstrated for different tannin-rich plant extracts. Since tannins of different classes and molecular weights are often found together in plant extracts and may differ in their antiviral activity, we have compared the effect against influenza A virus (IAV) of Hamamelis virginiana L. bark extract, fractions enriched in tannins of different molecular weights and individual tannins of defined structures, including pseudotannins. We demonstrate antiviral activity of the bark extract against different IAV strains, including the recently emerged H7N9, and show for the first time that a tannin-rich extract inhibits human papillomavirus (HPV) type 16 infection. As the best performing antiviral candidate, we identified a highly potent fraction against both IAV and HPV, enriched in high molecular weight condensed tannins by ultrafiltration, a simple, reproducible and easily upscalable method. This ultrafiltration concentrate and the bark extract inhibited early and, to a minor extent, later steps in the IAV life cycle and tannin-dependently inhibited HPV attachment. We observed interesting mechanistic differences between tannin structures: High molecular weight tannin containing extracts and tannic acid (1702 g/mol) inhibited both IAV receptor binding and neuraminidase activity. In contrast, low molecular weight compounds (
... One of the components of the patient's ink was H. virginiana, a kind of witch hazel that has been linked to anti-inflammatory properties, especially in cases of photodermatitis [37][38][39][40] and colonic cancer [41,42] , due to a molecule called hamamelitannin, with anti-TNF properties (in vitro inhibition of TNF-mediated cell death and DNA fragmentation) [43] and scavenging activity against reactive oxygen species [42,44,45] . Even if it were attractive to assume that H. virginiana could have had an inhibitory effect over the purpuric rash, we would have to presume that functional levels of the active principle still remained in the skin 5 years after its injection, which is to be proven. ...
Cutaneous complications associated with decorative tattooing are well known. However, the inhibition of a purpuric reaction by a tattoo is a fact that, as far as the authors know, has not been described before, fitting the definition of a 'sparing phenomenon', the absence of manifesting a particular skin disease in an area previously affected by another condition. From the clinical observation of purpuric lesions apparently inhibited by a tattoo in a 26-year-old patient, we performed an exact binomial test on the observed and expected proportion of purpuric lesions inside (0%, 95% confidence interval, CI, 0-2.6%) and outside (100%, 95% CI 97.4-100%) the tattooed skin, demonstrating a nonrandom distribution respecting the tattooed area (p < 0.001) and identifying the composition of the ink used in the tattoo (color pigment, glycerine, Hamamelis virginiana extract, water and alcohol). Moreover, we reviewed the cases of sparing phenomenon described in the literature. In conclusion this is the first report of a sparing phenomenon of purpuric lesions over tattooed skin. © 2013 S. Karger AG, Basel.
Coffee is not only a delicious beverage but also an important dietary source of natural antioxidants. We live in an oxidative world where it is impossible to avoid pollution, stress, food additives, radiation, and other sources of oxidants that eventually lead to severe health disorders. Fortunately, there are chemicals in our diet that counteract the hazards posed by the reactive species that trigger oxidative stress. They are usually referred to as antioxidants; some of them can be versatile compounds that exert such a role in various ways. This review summarizes, from a chemical point of view, the antioxidant effects of relevant molecules found in coffee. Their ways of action and trends in activity are analyzed, considering the data gathered so far from both theory and experiments. The influence of the media and pH in aqueous solution, and structure-activity relationships are discussed. The protective role of the explored compounds is examined. A particular section is devoted to derivatives of some coffee components, and another one to their bioactivity. Hopefully, the information provided here will promote further investigations into the amazing chemistry contained in our morning cup.
Several plant secondary metabolites are used in the production of different pharmaceuticals based on their biological activities. The conservation and sustainable use of medicinal plants is important for the industrial production of plant-based medicines. Different cryopreservation methods are used for long-term culture preservation, which allows fast regeneration of the preserved plant material with the maintenance of its primary original traits. These methods could ensure the sustainable indefinite supply of plant tissues for theoretically unlimited periods of time, and have gained considerable attention in recent years. It is important to assess the recovery rate and the genetic stability of the recovered plant tissues after cryopreservation because cryopreservation efficiency differs among plant tissues and species. This review lays particular emphasis on the pharmaceutical applications of plant secondary metabolites that are produced through tissue culture approaches, highlighting the methods used for their cryopreservation, as well as their recovery and genetic stability.
Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs.
The evolution of the regulatory framework for medical devices in the EU (Reg 2017/745) has opened the study of complex systems emerging properties. This makes necessary to identify new analytical approaches able of characterizing complex natural substrates as completely as possible. Therefore, omics approaches and advanced analytical methods for the determination of metabolite classes appear to be at the forefront to meet this need. In this perspective, a new approach based on the suspect screening was developed to detect gallotannins. Gallotannins are a class of phenols with a polymeric nature, thus, there are no pure analytical standards available for all possible structures and their quali‐quantitative determination in complex natural substrates can be a challenge. A new UHPLC‐qToF method was developed and used to create an “in‐house tannin database” with a dual purpose: 1) as a classic list of suspects 2) to identify core fragments common to gallotannins to have another list of putative suspects based on the common fragment. The method was validated. The application of the method to a "system of molecules" extracted from the leaves of Hamamelis virginiana L. (Witch‐hazel) allowed to the characterization of a total of 29 phenols by a suspect screening approach. Therefore, 15 gallotannins were putatively annotated while another 3 were confidently identified. All the gallotannins were semi‐quantified according to external regression curves of gallic acid and hamamelitannin based on core fragments at m/z 125.0244 and m/z 169.0142, the building blocks of the polymers. This new method provides a practical fit‐to‐purpose approach for the quali‐quantitative screening evaluation of gallotannins, useful for creating multivariate control charts applicable in process development of complex natural systems or in quality control. The approach is innovative and after specific checks it can in principle be suitable for metabolomic fingerprint analysis of gallotannins among WHE samples.
Skin carcinoma is the most common malignancy, including malignant melanoma and non-malignant melanoma throughout the world and in the last three decades, its incidences are increasing drastically. High cost, severe side-effects and development of resistance from conventional chemotherapy has decreased its acceptability and increased the urge for the search of alternate options. Therefore, plant derived phytochemicals have come up with cost effectiveness, ease of availability and promising potential for skin related cancers. In spite of the lack of the clinical data involving humans to support the positive effects of phytochemicals on different types of skin cancers, topical application of these plant derived anticancer phytochemicals is extremely promising. Many mechanisms and pathways underlie the antitumor activity of plant-derived phytochemicals such as loss of mitochondrial membrane potential, release of cytochrome-c, suppression of antiapoptotic proteins and induction of proapoptotic proteins, activation of caspases, Fas, FADD and p53 signaling pathway, inhibition of Akt signaling pathway, phosphorylation of ERK, P13K, Raf, survivin gene, STAT 3 and NF-kB. The use of cell line models in the in vitro study of skin cancer offers the opportunity to identify the mechanisms of action of plant derived phytochemicals against various types of skin cancer. As such, this article aims at providing a comprehensive review of plant extracts and phytochemicals which have been reported to exhibit promising anti-carcinogenic properties in animal models and against various skin cancer cell lines.
The Chemistry inside Spices and Herbs: Research and Development brings comprehensive information about the chemistry of spices and herbs with a focus on recent research in this field. The book is an extensive 2-part collection of 20 chapters contributed by experts in phytochemistry with the aim to give the reader deep knowledge about phytochemical constituents in herbal plants and their benefits. The contents include reviews on the biochemistry and biotechnology of spices and herbs, herbal medicines, biologically active compounds and their role in therapeutics among other topics. Chapters which highlight natural drugs and their role in different diseases and special plants of clinical significance are also included. Part II continues from the previous part with chapters on the treatment of skin diseases and oral problems. This part focuses on clinically important herbs such as turmeric, fenugreek, ashwagandha (Indian winter cherry), basil, Terminalia chebula (black myrobalan). In terms of phytochemicals, this part presents chapters that cover resveratrol, piperine and circumin.
Three undescribed diterpenes including two ent-abietanes, euphomauritanol A, and euphomauritanol B, and one jatrophane, euphomauritanophane A, in addition to eight previously described metabolites were isolated from the MeOH–CH2Cl2 (1:1) extract of the Euphorbia mauritanica. The chemical structures of isolates were established based on the spectroscopic means including FT-IR, HRMS, 1D and 2D NMR. The absolute stereochemistry of the undescribed diterpenes was deduced by experimental and calculated TDDFT-electronic circular dichroism (ECD). The anti-proliferative effects of the isolated diterpenes were evaluated against B16-BL6, Hep G2, and Caco-2. The euphomauritanol A, euphomauritanol B, and euphomauritanophane A significantly inhibited the growth of murine melanoma B16-BL6 cell lines with IC50 10.28, 20.22, and 38.81 μM, respectively with no responses against the other cells. These activities were rationalized by molecular docking of the active compounds in BRAFV600E and MEK1 active sites. Moreover, the in-silico pharmacokinetics predictions by Swiss ADME revealed that the active compounds possessed favorable oral bioavailability and drug-likeness properties.
Plant‐derived proanthocyanidins (PACs) mediate physicochemical modifications to the dentin extracellular matrix (ECM). The structure–activity relationships of PACs remain largely unknown, mostly due to the varied complex composition of crude extracts, as well as the challenges of purification and mechanistic assessment. To assess the role of galloylated PACs as significant contributors to high yet unstable biomodification activity to the dentin ECM, we removed the galloyl moieties (de‐galloylation) via enzymatic hydrolysis from three galloyl‐rich PAC‐containing extracts (Camellia sinensis, Vitis vinifera, and Hamamelis virginiana). The biomechanical and biological properties of dentin were assessed upon treatment with these extracts vs. their de‐galloylated counterparts. An increase in the complex modulus of the dentin matrix was found with all extracts, however, the crude extract was significantly higher when compared to the de‐galloylated version. Exhibiting the highest content of galloylated PACs among the investigated plants, Camellia sinensis crude extract also exhibited the biggest relapse in mechanical properties after one‐month incubation. De‐galloylation did not modify the damping capacity of dentin ECM. Moreover, PAC‐mediated protection against proteolytic degradation was unaffected by de‐galloylation. The de‐galloylation experiments confirmed that gallic acid in galloylated rich‐PAC extracts drive stronger yet significantly less sustained mechanical effects in dentin ECM.
Cancer is a heterogeneous disease and one of the major issues of health concern, especially for the public health system globally. Nature is a source of anticancer drugs with abundant pool of diverse chemicals and pharmacologically active compounds. In recent decade, some natural products and synthetic analogs have been investigated for the cancer treatment. This article presents the utilization of natural products as a source of antitumor drugs.
Many supplements and products containing botanical extracts are marketed to patients for the treatment of acne vulgaris. Additionally, increasing attention has been paid to the role of diet in acne vulgaris. Studies on this topic including pediatric patients are limited, with variable efficacy data. Despite these limitations, knowledge of alternative therapies in pediatric acne vulgaris is often expected from pediatric dermatologists. Here we review available data on the efficacy of complementary and alternative medicines for treatment of acne in pediatric patients, focusing on topical, oral, and dietary modifications.
Plants have been used as medicinal agents since the origin of mankind. High cost and severe side effects associated with conventional chemotherapy has limited their general acceptability and fuel up the search for alternate options. The alternative treatment options like phytochemicals have come up with ease of availability and cost effectiveness. Owing to their general acceptance, safety, low side effects and multistep targeting in signal transduction pathways, plant derived phyto-constituents have promising anti-carcinogenic potential for skin related cancers. This leads to the surge in research of new phytochemicals for the prevention and cure of a variety of skin cancers which are major cause of morbidity and mortality in present world. Although very limited clinical data involving humans is available in literature to demonstrate favorable eff ;ects of phyto-constituents on various types of skin carcinomas yet the topical treatment with these plant derived anticancer phytochemicals is very promising. There are various mechanisms and pathways responsible for antitumor activity of plant derived medicinal compounds such as loss of mitochondrial membrane potential, release of cytochrome-c, Down regulation of Anti-apoptotic proteins and Up regulation of pro-apoptotic proteins, Activation of Caspase, Fas, FADD, p53 and c-Jun signaling pathway, Inhibition of Akt signaling pathway, phosphorylation of ERK, P13K, Raf, survivin gene, STAT 3 and NF-kB. In-vitro testing of skin cancer cell lines models offers the opportunity for identifying mechanisms of action of compounds from plant origin against variety of skin related cancers. This review thus aims at providing an overview of plant derived anti-cancer compounds which have been reported to show promising anti-carcinogenic effects against various skin cancer cell lines and on animal models. Phytochemicals that are discussed in this review include steroids, coumarines, trepenes, essential oils, alkaloids, esters, ethers, resins, phenols and flavonoids. This review also provides information about marketed formulations developed so far from plant derived compounds for skin cancer prevention and treatment.
Cancer is nowadays one of the most devastating diseases, being a central public health problem as well as a leading cause of death worldwide. In an attempt to fight this illness, great efforts have been carried out to find more potent drugs with fewer side effects. Natural products have been a valuable source for such drugs, whether used as a natural resource or after chemical modifications. Natural phenolic compounds, in particular, have revealed interesting results concerning the inhibition of proliferation of several cancer cell lines, showing potential to be further studied as anticancer agents. In this chapter, we present a literature review on the phenolic compounds from medicinal herbs and plant extracts with anticancer activity published from 2008 until mid-2016. Particular emphasis is given to the principal phenolic compounds of the extracts as well as to the chemical modifications performed and the synthetic approaches followed to modulate the cytotoxic activity of those compounds. From this, the relevant structure–activity relationships are discussed. The mechanisms by which the extracts and the modified compounds exert their cytotoxic activity are also disclosed. Further, the relation on free radical-induced cancer and protection by phenolic derivatives is related. Finally, a critical analysis of the studies and guidelines for future research is reported in the conclusion.
SÍNTESIS
El Tamarindo (Tamarindus indica L) es una acidos grasos,elementos minerales,estabiliad poco estudiada en Cuba
y en el mundo. El uso etnobotánico de esta planta como hepatoprotector, se refiere
desde hace más de 50 años en Cuba. Las hojas han sido el órgano menos
investigado y la decocción de éstas es consumida por la población cubana para el
tratamiento de las hepatopatías. Sin embargo, en el Sistema de Salud se importan
los fármacos para el tratamiento de estas enfermedades, ya que en el Cuadro Básico
de Medicamentos de Cuba no se contempla ningún fármaco hepatoprotector. En el
presente trabajo se estandarizó el extracto blando de las hojas de Tamarindus indica
L. como un nuevo Ingrediente Farmacéutico Activo, rico en metabolitos entre los que
destacan: polifenoles, flavonoides, triterpenos, aceites esenciales, ácidos grasos,
compuestos volátiles y elementos minerales, como el cobre, cinc, manganeso, níquel
y selenio. Con este extracto se desarrolló una formulación de tabletas, a la cual se le
evaluó su capacidad antioxidante y hepatoprotectora. En este proceso se obtuvieron
modelos teóricos que permiten predecir las propiedades físicomecánicas de los
granulados y las propiedades tecnológicas de las tabletas. La estabilidad de las
propiedades tecnológicas de las tabletas se mantuvo hasta 18 meses, la estabilidad
microbiológica se mantuvo durante dos años y la estabilidad química se ha evaluado
hasta 9 meses. Por ello, la estabilidad integral de la formulación de tabletas,
envasadas en frasco de cloruro de polivinilo de alta densidad con tapa inviolable, y
almacenadas en lugar seco y fresco, se informa hasta nueve meses. Esta forma
farmacéutica no mostró toxicidad aguda oral en ratas Sprague Dawley a la dosis
límite de 2000 mg/kg de peso y produce una irritabilidad media de la mucosa oral.
Los dos niveles de dosis evaluados (100 y 200 mg/kg de peso) inhibieron la
peroxidación lipídica y mostraron actividad antioxidante y hepatoprotectora frente al
modelo de intoxicación hepática con tetracloruro de carbono. El efecto observado
resultó similar estadísticamente al producido por la silimarina; fármaco utilizado como
control en una dosis de 150 mg/kg de peso corporal. Los resultados de la tesis por
vez primera aportan elementos que evidencian las propiedades antioxidantes y
hepatoprotectoras de una forma farmacéutica sólida obtenida a partir de las hojas de
Tamarindus indica L.
Pteropyrum scoparium Jaub. & Spach (Polygonaceae) is a naturally growing shrub used as food crop in Oman. The chemical investigation of the ethyl acetate extracts of the leaf afforded phenylethanoid, benzofuranylethanoid and ethyl esters of caproic and lauric acids (1–3), proanthocyanidin trimer epicatechin-3-O-gallate-(4 → 8)-epicatechin-3-O-gallate-(4 → 8)-epicatechin-3-O-gallate (4) and epicatechin-3-O-gallate (5). Compounds 1 and 3 are new and isolated for the first time from P. scoparium. The structures of compounds were assigned based on 1D and 2D NMR spectroscopy and ESI–MS analysis. Compounds 1 and 3 were tested for free radical scavenging anti-oxidant properties and found to inhibit 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) by 1.7% and 41.0%, respectively compared to 71% and 78% for gallic acid and butylated hydroxyanisole used as control.
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.
Since oxidative stress is a causal factor in many chronic and degenerative pathologies, considerable effort has been made to find antioxidant compounds that prevent the onset of these diseases and counteract their progression. In fact, numerous polyphenols possess radical scavenging/antioxidant activity, especially when studied in cell-free systems as well as in cells in vitro, or even in vivo. Polyphenols-natural compounds with variable phenolic structures-are common in vegetables, fruit, grain, bark, roots, tea and wine. All polyphenols contain one or more aromatic rings with more than one hydroxyl group. They are generally classified into four different groups, depending on the number of phenol rings and chemical groups bound to the rings: flavonoids, phenolic acids, stilbenes, and lignans. This chapter reviews recent work on the capacity of polyphenols to protect cells against oxidative insult.
Maceration and Soxhlet methods were used to obtain methanol extracts from a Mexican grape (Ruby Cabernet) pomace and the biological activity and phenolic profiles were compared. The antioxidant capacity was used to evaluate the mechanism of action, using a physiological model (erythrocytes) of damage induced by AAPH-generated free radicals. The extract obtained by maceration presented a total phenolic content twice the one obtained using the Soxhlet method. It also contained the most potent antioxidants, reducing anisotropy in the presence of AAPH to the levels of untreated cells, restoring membrane fluidity, preventing the morphological changes, as demonstrated by scanning electron microscopy (SEM), and providing protection against protein oxidation at the higher concentration. Our work showed that both extracts presented significant antioxidant activity through positive interactions with the lipid bilayer.
There are many over-the-counter products used to treat dermatological conditions. Patients are inundated with information about these products. Dermatologists often encounter questions about the usefulness of over-the-counter products as anecdotal data about such products is often adapted as common practice in the medical field. Modern dermatology training does not include pharmacological education on many of the over-the-counter products commonly used by patients. In this current age when patients have increasing interest in using "natural" remedies, it is important that dermatologists can provide guidance to patients regarding some of the most common products that they may encounter. This article is designed to provide introductory information on the common uses for several over-the-counter products as well as to display any evidence in support of these products for dermatological diseases.
J Drugs Dermatol . 2014;13(8):960-966.
The performance of several direct and indirect computational strategies for the calculation of the first ionization energies (IEs) of free radicals and adiabatic detachment energies of their anions has been tested using experimental data as references. The outer valence Green's function and the partial third order approximations, which are based on electron propagator theory, have been identified as the most accurate. They were in turn used to estimate the IEs of a large set of free radicals for which these data have not been previously reported. The calculated data also have been used to assess the possible oxidation of nucleosides by these radicals, as well as the potential, antioxidant-protection effects of phenol, catechol, ascorbic acid and Trolox in their neutral and deprotonated forms, via electron transfer.
The tripotassium salt of tris(2,3,5,6-tetrachloro-4-hydroxysulfonylphenyl)methyl radical (3 K+ TSPTM3−) reacts in water with hydroxyl radical very fast with a rate constant (k = 2.4 × 1011 M−1 s−1) much higher than that of the reaction of hydroxyl radical with the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) (k = 3.4 × 109 M−1 s−1). The reaction affects the radical character of the molecule and is monitored by electron paramagnetic resonance (EPR). The hydroxyl radical scavenging is established by the characterization of the resulting water-soluble product as the dipotassium salt of 4-[bis(2,3,5,6-tetrachloro-4-hydroxysulfonylphenyl)methylene]-2,3,5,6-tetrachlorocyclohexa-2,5-dien-1-one (2).
A new stable organic free radical of the PTM (perchlorotriphenylmethyl) series very soluble in water is reported. This free radical is sensitive to electron transfer processes, and the selectivity of these reactions in the presence of ascorbic acid, pyrogallol, and catechol as reducing species is described. The electron paramagnetic resonance spectrum and the electrochemical behavior are also presented.
The chemistry of tea as a beverage is reviewed in depth, covering both historical and current chemical perspectives. Special attention is given to the polyphenols in tea, although the general composition and properties are also treated. Current trends in tea science, particularly in the area of polyphenol complexation and antioxidant properties, are also covered. The need for a chemically based understanding, rather than one hypothesized from generalized and indirect observation, is stressed.
Investigations on the mechanisms capable of influencing heart mitochondrial function constitute a central contribution to the understanding of cardiac bioenergetics. In contrast to the conventional idea that reactive oxygen species (ROS) mostly act as a trigger for oxidative damage of biological structures, in low physiological concentrations they can regulate a variety of important molecular mechanisms, including those related to mitochondrial respiratory function. Among others, moderate physical exercise seems to be an important agent to induce cellular and mitochondrial environmental redox modifications and it is possible that these alterations could mediate cardiac mitochondrial respiration patterns. This brief review summarizes some current knowledge on mitochondrial respiratory pathways and focuses on data provided by studies dealing with exercise and cardiac respiratory mechanisms. It is emphasized the need of further experimental studies that analyze the association between physical exercise, particularly endurance training, and several mechanisms hypothetically related to the improvement of mitochondrial function, such as the overexpression of some important chaperone machinery and the up-regulation of both cellular and mitochondrial antioxidants. The influence of chronic moderate exercise on the functionality of some inner membrane components and on mitochondrial calcium loading capacity remains to be established.
The flavonoids constitute a large group of polyphenolic phytochemicals with antioxidant properties in vitro. The interactions of four structurally related flavonoids (quercetin, kaempferol, rutin and luteolin) with Cu2+ ions were investigated in terms of the extent to which they undergo complex formation through chelation or modification through oxidation, as well as in their structural dependence. The ortho 3',4'-dihydroxy substitution in the B ring is shown to be important for Cu2+-chelate formation, thereby influencing the antioxidant activity. The presence of a 3-hydroxy group in the flavonoid structure enhances the oxidation of quercetin and kaempferol, whereas luteolin and rutin, each lacking the 3-hydroxy group, do not oxidize as readily in the presence of Cu2+ ions. The results also demonstrate that the reactivities of the flavonoids in protecting low-density lipoprotein (LDL) against Cu2+ ion-induced oxidation are dependent on their structural properties in terms of the response of the particular flavonoid to Cu2+ ions, whether chelation or oxidation, their partitioning abilities between the aqueous compartment and the lipophilic environment within the LDL particle, and their hydrogen-donating antioxidant properties.
Atmospheric pollutants represent an important source of oxidative and nitrosative stress to both terrestrial plants and to animals. The exposed biosurfaces of plants and animals are directly exposed to these pollutant stresses. Not surprisingly, living organisms have developed complex integrated extracellular and intracellular defense systems against stresses related to reactive oxygen and nitrogen species (ROS, RNS), including O3 and NO2. Plant and animal epithelial surfaces and respiratory tract surfaces contain antioxidants that would be expected to provide defense against environmental stress caused by ambient ROS and RNS, thus ameliorating their injurious effects on more delicate underlying cellular constituents. Parallelisms among these surfaces with regard to their antioxidant constituents and environmental oxidants are presented. The reactive substances at these biosurfaces not only represent an important protective system against oxidizing environments, but products of their reactions with ROS/RNS may also serve as biomarkers of environmental oxidative stress. Moreover, the reaction products may also induce injury to underlying cells or cause cell activation, resulting in production of proinflammatory substances including cytokines. In this review we discuss antioxidant defense systems against environmental toxins in plant cell wall/apoplastic fluids, dead keratinized cells/interstitial fluids of stratum corneum (the outermost skin layer), and mucus/respiratory tract lining fluids.
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Flavonoids are a family of antioxidants found in fruits and vegetables as well as in popular beverages such as red wine and tea. Although the physiological benefits of flavonoids have been largely attributed to their antioxidant properties in plasma, flavonoids may also protect cells from various insults. Nerve cell death from oxidative stress has been implicated in a variety of pathologies, including stroke, trauma, and diseases such as Alzheimer's and Parkinson's. To determine the potential protective mechanisms of flavonoids in cell death, the mouse hippocampal cell line HT-22, a model system for oxidative stress, was used. In this system, exogenous glutamate inhibits cystine uptake and depletes intracellular glutathione (GSH), leading to the accumulation of reactive oxygen species (ROS) and an increase in Ca(2+) influx, which ultimately causes neuronal death. Many, but not all, flavonoids protect HT-22 cells and rat primary neurons from glutamate toxicity as well as from five other oxidative injuries. Three structural requirements of flavonoids for protection from glutamate are the hydroxylated C3, an unsaturated C ring, and hydrophobicity. We also found three distinct mechanisms of protection. These include increasing intracellular GSH, directly lowering levels of ROS, and preventing the influx of Ca(2+) despite high levels of ROS. These data show that the mechanism of protection from oxidative insults by flavonoids is highly specific for each compound.
The 2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid)/H2O2/horseradish peroxidase (ABTS/H2O2/HRP) decoloration method permits the evaluation of the antioxidant activity of complex food samples. This method is capable of determining both hydrophilic (in buffered media) and lipophilic (in organic media) antioxidant properties in the same sample. Its application to the study of the antioxidant properties of grapes, one white and two black, has permitted us to establish important differences in the antioxidant activity. The black grapes showed higher antioxidant activity than the white variety. The determination of hydrophilic antioxidant activity (HAA) and lipophilic antioxidant activity (LAA) in the three grapes showed that a minor contribution (4-13%) of total antioxidant activity (TAA) was due to LAA in all cases. The experimentally determined HAA could be approximated using the relative contributions of the calculated values of reference compounds (total phenols as gallic acid and anthocyanins as malvidin).
Polymeric proanthocyanidins were isolated from the bark of Hamamelis virginiana L. in yields of about 5 %. Fractionation yielded fractions with similar structures but different molecular weights with DP between 17-29 (thiolysis) and 11-20 (GPC). Polymers were composed predominantly of epicatechin and epigallocatechin as chain extension units at ratio of about 1.3:1. Terminal chain units were catechin (approximately 95 %) and gallocatechin (approximately 5 %). All chain extension units were completely galloylated at position O-3, while chain terminating units were not galloylated. Predominant interflavan linkages were 4 --> 8-bonds.
We report the synthesis, electron paramagnetic resonance and electrochemical properties of a novel stable radical of the TTM series. Its strong electron acceptor ability has been tested with (-)-epicatechin, a natural polyphenolic antioxidant.
Fifty-one tannins and forty-one flavonoids isolated from Oriental medicinal herbs were evaluated for their antioxidant ability with a 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-generating system. The results showed that tannins and certain flavonoids are potential free-radical scavengers, and that their activity against the DPPH radical is closely associated with their chemical structure. A comparison of the two classes of compounds showed that tannins have more potential than flavonoids because almost all the tannins demonstrated significant scavenging action within a low concentration range, whereas the activity of flavonoids varied distinctively among the different compounds. An increase of galloyl groups, molecular weight, and ortho-hydroxyl structure enhanced the activity of tannins, whereas the number and position of hydroxyl groups were important features for the scavenging of free radicals by flavonoids. Moreover, it appeared that when the free hydroxyl group was methoxylated or glycosylated, the inhibitory activity was obviously decreased or even abolished.
We report an improved synthesis of bis(5,7,3',4'-tetra-O-benzyl)epicatechin 4beta,8-dimer (3) from 5,7,3',4'-tetra-O-benzylepicatechin (1) and 5,7,3',4'-tetra-O-benzyl-4-(2-hydroxyethoxy)epicatechin (2) by replacing the previously employed Lewis acid, titanium tetrachloride, with the clay mineral Bentonite K-10. Under the same conditions, the benzyl-protected all-4beta,8-trimer, -tetramer, and -pentamer were obtained regioselectively from their lower homologues, albeit in rapidly decreasing yields. Reaction of 2 with an organoaluminum thiolate generated from 2-mercaptobenzothiazole and trimethylaluminum followed by acetylation produced 3-O-acetyl-4-[(2-benzothiazolyl)thio]-5,7,3',4'-tetra-O-benzylepicatechin (12). Medium-sized protected oligomers with 4beta,8-interflavan linkages are obtained in improved yields by using this compound as the electrophile and silver tetrafluoroborate as activator and are isolated by reversed-phase HPLC. Their deprotection by ester saponification followed by hydrogenolysis yielded the free procyanidins, which were characterized as their peracetates. The synthetic procyanidins are identical by normal-phase HPLC with fractions isolated from cocoa. The principle of chain extension by two members was demonstrated using a dimeric electrophile obtained by self-condensation of compound 12. Both the synthetic and natural pentamer 32 inhibit the growth of several breast cancer cell lines. Using the MDA MB 231 line, it was established that this outcome is based on the induction of cell cycle arrest in the G0/G1 phase. Subsequent cell death is more likely necrotic rather than apoptotic. Control experiments demonstrate that the polyphenol itself, rather than hydrogen peroxide potentially formed by its autoxidation, is the causative agent.
Plant polyphenols act as antioxidants mainly by trapping reactive oxygen species and by regenerating endogenous membrane-bound alpha-tocopherol (vitamin E). In both processes polyphenols are oxidized. Hence, knowledge of the oxidation mechanisms of polyphenols is important for an understanding of their antioxidant activity at the molecular level. This work focuses on anthocyanins (pigments) and flavanols (tannins), two important classes of polyphenols which are both relatively abundant in human diet. The oxidation of the 3',4',7-trihydroxyflavylium ion (1) and catechin (2), respectively taken as models for anthocyanins and tannins, has been investigated. From kinetic data and partial product analysis, the mechanisms for the reactions of 1 and 2 with sodium periodate and DPPH, a H atom-abstracting radical, are proposed. Both polyphenols are shown to form o-quinone intermediates upon H atom abstraction and subsequent radical disproportionation. In the case of 2, the quinone and a second molecule of antioxidant quickly couple to form dimers. By contrast, 1 is extensively degraded into coumarins by repeating sequences of oxidation-solvent addition, which consume several equivalents of oxidants. In aqueous solutions, 1 is typically a mixture of coloured and colourless forms. The latter (chalcones) are also shown to take part in the antioxidant activity.
METHODS for measuring antioxidants and appraising antioxidant activity appear to be of two general types. If the chemical nature of the antioxidant is known, one may strive for a test specific for the compound or group of interest; for example, the nitroprusside test for sulphydryl groups. Alternatively one may observe the inhibition of some natural oxidative process such as the β-oxidation of fats, as a function of the added antioxidant.
Commonly used medicinal plant extracts with standardized content of polyphenols were investigated for their total antioxidant activity (TAA). Green tea, oligomeric procyanidins (from grape seed and pine bark), bilberry, and ginkgo exhibited TAA in the range of 5.12−2.57 mM Trolox, thereby indicating a valuable antioxidant capacity. Witch hazel, propolis EPID, artichoke, and hawthorn afforded lower TAA (1.54−0.44 mM Trolox), whereas echinacea, ginseng, passionflower, sweet clover, and eleuthero were rather uneffective (TAA < 0.32 mM Trolox). Excipients normally used to prepare the extracts did not interfere with the assay, and a good correlation between the content of polyphenols and the TAA was assessed. The measured TAA was higher than those calculated from the content and antioxidant potential of specific components, as exemplified for green tea and ginkgo extracts. This may be attributed to the presence in these extracts of other substances with antioxidant capacity. On the other hand, some components (such as ginkgolides in ginkgo extract) insensitive to the TAA assay played an important antioxidant role in vivo. These results suggest that TAA determination is of interest for a comparative evaluation of in vitro antioxidant potential, but it needs to be combined with in vivo data for adequate assessment of the antioxidant capacity of medicinal plant extracts. Keywords: Medicinal plants; polyphenols; total antioxidant activity; total radical-trapping antioxidant parameter
The effect of pure monomeric and dimeric procyanidins on superoxide anion radicals (O2°−) was studied with an enzymatic method and their IC50 was determined. A comparative study of the results suggested that the antiradical potential of these phenolic compounds closely depends on their stereochemical structure. Modification of the chiral carbon, C3 involved in the oxidation mechanism induces differences in the scavenging action of (+)-catechin (2R : 3S) or (−)-epicatechin (2R : 3R). The stereochemical conformation of the interflavan linkage (axial or pseudo) according to the chemical nature of dimeric procyanidin units also influences the radical oxidation mechanism. The nature of the interflavan linkage between the two units in dimeric procyanidins (C4–C8 or C4–C6 linkage) is an important factor responsible for effectiveness of the behaviour polyphenols towards O2°−. The extraction of oligomeric procyanidins in grape seeds enabled us to study the effect of polymerisation and galloylation on their scavenging activities. The results clearly showed that the molecular scavenging mechanism of these molecules is closely connected with their spatial conformation.© 1999 Society of Chemical Industry
An improved method used for the isolation and purification of low-molecular-mass procyanidins (i.e., dimeric B1, B2, B3, B4, B1-3-O-gallate, B2-3-O-gallate, B2-3′-O-gallate, trimer C1 and trimer T2) from grape seeds, is described. Pre-fractionation in oligomers and polymers was performed by chromatography on an open column (LiChroprep RP-18). The oligomer fraction, rich in dimeric and trimeric procyanidins, was then chromatographed on a Toyopearl TSK HW-40 (F) column. The major fractions obtained from Toyopearl TSK HW 40 (F) chromatography were further separated by semi-preparative HPLC, to obtain pure procyanidins. The main advantages of this method are that it is easy to use, less time-consuming and gives very high yield of dimeric and trimeric procyanidins by each manipulation.
The unique series of C-1 acylated galloylhamameloses is extended by the discovery of and its 1-O-β-anomer. They are accompanied by the parent 2′, 3, and the first pyranose analogue, shown to be 2′, . Assignment of 1H NMR data for the peracetates of hamamelitannin is revised on the basis of a NOESY experiment. Structural examination of the proanthocyanidins present in the bark of Hamamelis virginiana reveals the occurrence of the novel epicatechin-(4β→8)-catechin-3-O-(4-hydroxy)benzoate, the uncommon prodelphinidins, epigallocatechin-(4β→8)-catechin, 3-O-galloyl epigallocatechin-(4β→8)-catechin and 3-O-galloyl epigallocatechin-(4β→8)-gallocatechin, together with the procyanidins, 3-O-galloyl epicatechin-(4β→8)-catechin and catechin-(4α→8)-catechin, and a tentatively characterized oligomer. The structures of these compounds were established by chemical and spectroscopic methods.
Cysteamine hydrochloride is shown to be an alternative thiol reagent to toluene-α-thiol for the estimation of structural parameters
(mean size, galloylation) of plant polymeric procyanidins. Acid depolymerization in the presence of the thiol yields mixtures
which may be directly analysed by RPHPLC. Alternatively, the terminal units of the polymer may be separated from the extension
units by cation-exchange chromatography previous to RPHPLC. High reaction-recovery yields (ca. 90% thiolysis and RPHPLC, ca.
69% thiolysis, cation exchange and RPHPLC) are obtained and both procedures are precise.
The antiradical activities of various antioxidants were determined using the free radical, 2,2-Diphenyl-1-picrylhydrazyl (DPPH*). In its radical form. DPPH* has an absorption band at 515 nm which dissappears upon reduction by an antiradical compound. Twenty compounds were reacted with the DPPH* and shown to follow one of three possible reaction kinetic types. Ascorbic acid, isoascorbic acid and isoeugenol reacted quickly with the DPPH* reaching a steady state immediately. Rosmarinic acid and δ-tocopherol reacted a little slower and reached a steady state within 30 min. The remaining compounds reacted more progressively with the DPPH* reaching a steady state from 1 to 6 h. Caffeic acid, gentisic acid and gallic acid showed the highest antiradical activities with a stoichiometry of 4 to 6 reduced DPPH* molecules per molecule of antioxidant. Vanillin, phenol, γ-resorcylic acid and vanillic acid were found to be poor antiradical compounds. The stoichiometry for the other 13 phenolic compounds varied from one to three reduced DPPH* molecules per molecule of antioxidant. Possible mechanisms are proposed to explain the experimental results.
The total antioxidant activity (TAA) and antioxidant composition of orange juice, apple juice and blackcurrant drink have been studied. Phenolic antioxidants in these juices have been identified and values derived for their relative molar antioxidant activities or Trolox Equivalent Antioxidant Activity (TEAC). The bulk of the TAA of apple juice could be accounted for by chlorogenic acid and the phloretins, while that of orange juice was accounted for by hesperidin and narirutin. In contrast, the anthocyanins in blackcurrant drink contributed only a fraction of its non-vitamin C antioxidant activity and it is suggested that there is a significant unidentified antioxidant present in this beverage. After equalisation of the vitamin C content, juices were subjected to mild oxidation; the decline in ascorbate was of the order of apple > orange > blackcurrant drink. The results suggest that the phenolic antioxidants protect vitamin C against oxidative decomposition, with those in blackcurrant having the greatest vitamin Csparing activity. © 1997 Elsevier Science Ltd
(−)-Epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), (−)-epicatechin-3-gallate (ECG), and (−)-epicatechin (EC) were found to have different cytotoxicities to human colon carcinoma LoVo cells. EGCG and EGC suppressed the growth of LoVo cells in dose-dependent manner; ECG and EC, however, had no obvious effects. At lower concentrations, EC did seem to promote slight proliferation. Similarly, EGCG and EGC, rather than ECG and EC, were found to induce apoptosis in LoVo cells. Moreover, EGCG, EGC, and ECG arrested G1 phase in the cell cycle progression, whereas EC resulted in S phase arrest. We suggest that there are differences in the cytotoxicities of the four catechins to LoVo cells. They exert the effects by inducing apoptosis and regulating the cell cycle.
The oxidation of rat red blood cells (RBC) by molecular oxygen was performed in an aqueous suspension with an azo compound as a free-radical initiator. The RBC were oxidized at a constant rate by a free-radical chain mechanism, resulting in hemolysis. The extent of hemolysis was proportional to the concentration of free radical. α-Tocopherol in RBC membranes suppressed the oxidation and hemolysis to produce an induction period. Tocopherol was constantly consumed during the induction period, and hemolysis developed when tocopherol concentrations fell below a critically low level. Among the membrane lipids, phosphatidylethanolamine, phosphatidylserine, and arachidonic acids were predominantly oxidized in the absence of tocopherol. In the presence of tocopherol, however, such lipid changes were suppressed during a 120-min incubation even when hemolysis started. Membrane proteins as well as lipids were oxidized. The formation of proteins with high molecular weight and concomitant decrease of the lowmolecular-weight proteins were observed on gel electrophoresis with the onset of hemolysis. This study clearly showed the damage of RBC membranes caused by oxygen radical attack from outside of the membranes, and suggested that membrane tocopherol even below a critically low level could suppress lipid oxidation but that it could not prevent protein oxidation and hemolysis.
A number of methods for determining the general toxic effects of test chemicals on cells in culture are now at the validation stage. Three such methods based on measurement of total cell protein or neutral red uptake and on the detection of morphological effects have been compared. The cell line used was 3T3-L1 (a continuous fibroblast cell line derived from mouse embryos). The results obtained in a blind trial with 30 coded chemicals indicated a close correlation between the relative cytotoxicities of chemicals tested by all three methods.
A method is described which combines the use of a visual morphological cytotoxicity assay with a quantitative neutral red (NR) spectrophotometric test, for the assessment of the effect of toxic agents on 3T3 cells in culture. These sensitive and reproducible assays lend themselves to a screening procedure of potential toxicants which can help reduce the use of animals for toxicity testing.
A tetrazolium salt has been used to develop a quantitative colorimetric assay for mammalian cell survival and proliferation. The assay detects living, but not dead cells and the signal generated is dependent on the degree of activation of the cells. This method can therefore be used to measure cytotoxicity, proliferation or activation. The results can be read on a multiwell scanning spectrophotometer (ELISA reader) and show a high degree of precision. No washing steps are used in the assay. The main advantages of the colorimetric assay are its rapidity and precision, and the lack of any radioisotope. We have used the assay to measure proliferative lymphokines, mitogen stimulations and complement-mediated lysis.
The o-quinone forms of 2,3- and 3,4-catechol estrogens have been implicated in the carcinogenicity of these hormones. The concomitant production of reactive oxygen species during reduction of the o-quinone estrogens has been inferred to play a mechanistic role in their mutagenic potential. Conclusive evidence documenting the production of hydrogen peroxide, the hydroxyl radical, and the estrone 3,4-semiquinone in estrone 3,4-quinone (3,4-EQ)-treated human breast cancer subcellular fractions was demonstrated in the absence of exogenously added catalysts. Subcellular fractions of MCF-7 cells treated with 3,4-EQ and NADPH, including nuclei, mitochondria, and microsomes, were shown to support significant amounts of hydrogen peroxide production. Hydrogen peroxide production in 3,4-EQ-treated cellular fractions and the chromosomal DNA damage induced in 3,4-EQ-treated MCF-7 cells were abolished by the addition of catalase. A significant and potentially physiologically relevant spontaneous reduction of 3,4-EQ by NADPH resulting in hydrogen peroxide production was demonstrated. The results unequivocally demonstrate that free radicals are produced during the metabolism of estrone 3,4-quinone in human cells.
The recent explosion of interest in the bioactivity of the flavonoids of higher plants is due, at least in part, to the potential health benefits of these polyphenolic components of major dietary constituents. This review article discusses the biological properties of the flavonoids and focuses on the relationship between their antioxidant activity, as hydrogen donating free radical scavengers, and their chemical structures. This culminates in a proposed hierarchy of antioxidant activity in the aqueous phase. The cumulative findings concerning structure-antioxidant activity relationships in the lipophilic phase derive from studies on fatty acids, liposomes, and low-density lipoproteins; the factors underlying the influence of the different classes of polyphenols in enhancing their resistance to oxidation are discussed and support the contention that the partition coefficients of the flavonoids as well as their rates of reaction with the relevant radicals define the antioxidant activities in the lipophilic phase.
Tea polyphenols are known to inhibit a wide variety of enzymatic activities associated with cell proliferation and tumor progression. The molecular mechanisms of antiproliferation are remained to be elucidated. In this study, we investigated the effects of the major tea polyphenol (-)-epigallocatechin gallate (EGCG) on the proliferation of human epidermoid carcinoma cell line, A431. Using a [3H]thymidine incorporation assay, EGCG could significantly inhibit the DNA synthesis of A431 cells. In vitro assay, EGCG strongly inhibited the protein tyrosine kinase (PTK) activities of EGF-R, PDGF-R, and FGF-R, and exhibited an IC50 value of 0.5-1 microgram/ml. But EGCG scarcely inhibited the protein kinase activities of pp60v-src, PKC, and PKA (IC50 > 10 micrograms/ml). In an in vivo assay, EGCG could reduce the autophosphorylation level of EGF-R by EGF. Phosphoamino acid analysis of the EGF-R revealed that EGCG inhibited the EGF-stimulated increase in phosphotyrosine level in A431 cells. In addition, we showed that EGCG blocked EGF binding to its receptor. The results of further studies suggested that the inhibition of proliferation and suppression of the EGF signaling by EGCG might mainly mediate dose-dependent blocking of ligand binding to its receptor, and subsequently through inhibition of EGF-R kinase activity.
The antimutagenic activity of Hamamelis virginiana bark was examined in the Ames assay. A commercial tincture and a methanolic extract showed dose-dependent inhibitory effects on mutagenicity induced by 2-nitrofluorene. Tannin-free samples did not display any inhibition. Bioassay-guided fractionation resulted in the isolation of two active fractions which were shown to contain oligomeric, proanthocyanidins. They were capable of inhibiting the mutagenicity of selected nitroaromatic compounds. The mechanism of antimutagenic action was also studied. The proanthocyanidins did not act as bioantimutagens, but rather as direct-acting desmutagens. The antimutagenic effect increased with an increasing degree of polymerisation in the proanthocyanidins. The most active fraction consisted of catechin and gallocatechin oligomers with an average polymerisation degree of 9.2.
A range of catechins and oligomeric procyanidins was purified by high performance liquid chromatography (HPLC) from grape seed, apple skin, lentil and almond flesh. Catechins, galloylated epicatechin, glycosylated catechin, procyanidin dimers, galloylated dimers, trimer, and tetramer species were all identified, purified and quantified by HPLC, LC-MS and NMR. The antioxidant properties of these compounds were assessed using two methods: (a) inhibition of ascorbate/iron-induced peroxidation of phosphatidylcholine liposomes; (b) scavenging of the radical cation of 2,2'-azinobis(3-ethyl-benzothiazoline-6-sulphonate) (ABTS) relative to the water-soluble vitamin E analogue Trolox C (expressed as Trolox C equivalent antioxidant capacity, TEAC). Antioxidant activity in the lipid phase decreased with polymerisation in contrast with antioxidant action in the aqueous phase which increased from monomer to trimer and then decreased from trimer to tetramer. Galloylation of catechin and dimeric procyanidins decreased lipid phase and increased aqueous phase antioxidant activity. Glycosylation of catechin demonstrated decreased activity in both phases.