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Introduction: The pathogenesis of Attention-Deficit Hyperactivity Disorder (ADHD) is thought to be multifactorial, with a potential role for the bidirectional communication between the gut microbiome and brain development and function. Since the "golden-standard" medication therapy with methylphenidate (MPH) is linked to multiple adverse effects, there is a need for alternative treatment options such as dietary polyphenols. These secondary plant metabolites exert antioxidant and anti-inflammatory effects, but much less is known about their impact on the gut microbiota. Since polyphenols are believed to modulate gut microbial composition, interventions might be advantageous in ADHD therapy. Therefore, intervention studies with polyphenols in ADHD therapy investigating the gut microbial composition are highly relevant. Methods: Besides the primary research questions addressed previously, this study explored a potential prebiotic effect of the polyphenol-rich French Maritime Pine Bark Extract (PBE) compared to MPH and a placebo in pediatric ADHD patients by studying their impact on the gut microbiota via amplicon sequencing of the full length 16S rRNA gene ribosomal subunit (V1-V9). Results: One interesting finding was the high relative abundance of Bifidobacteria among all patients in our study cohort. Moreover, our study has identified that treatment (placebo, MPH and PBE) explains 3.94% of the variation in distribution of microbial taxa (adjusted p-value of 0.011). Discussion: Our small sample size (placebo: n = 10; PBE: n = 13 and MPH: n = 14) did not allow to observe clear prebiotic effects in the patients treated with PBE. Notwithstanding this limitation, subtle changes were noticeable and some limited compositional changes could be observed. Clinical Trial Registration: doi: 10.1186/S13063-017-1879-6.

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The aim of the presented study was to qualitatively and quantitatively determine the chemical composition of oak bark extracts in order to gain insights into the effectiveness as alternative medication for various diseases. The primary emphasis was on developing a near-infrared spectroscopy (NIRS) method for precise quantification of two key polyphenolic compounds, specifically gallic acid and catechin, in form of a fast and non-destructive quality control. A comprehensive dataset consisting of 48 samples from various production batches was analyzed throughout this research. Qualitative analysis was conducted using High Performance Liquid Chromatography coupled with a mass detector (LC-MS) to separate and identify individual components of the oak bark extract. Individual components were identified, confirmed and quantified using existing literature combined with appropriate standard references. Whereas the predominant nature of identified substances was of polyphenolic nature. Furthermore, a semi-quantitative assessment was additionally performed for eight identified constituents to identify their chemical stability or possible occurring transformations during storage, utilizing quantification via internal standard met in order to identify fluctuations and chemical variability within oakbark, five key components were precisely quantified using LC-MS and corresponding standard substances. For this purpose, HPLC measurements coupled to an Ultraviolet/Visible (UV/Vis) detector were utilized as reference method. NIRS measurements were performed on a FT-NIR benchtop device in transmission mode. Partial least squares regression (PLSR) was then applied for model building, after identifying the optimal spectral pretreatment. Model evaluation was performed using leave-one-out-cross validation followed by evaluation of an independent test set. The model proved promising results for the quantification of gallic acid on the benchtop device with a standard error of cross validation (SECV) of 13.41 mg/L and a standard error of prediction (SEP) of 19.33 mg/L, while the absolute concentrations of the different batches analyzed ranged from 126.49 to 332.54 mg/L. For the quantification of catechin the SECV was reported at 23.61 mg/L, the SEP at 32.35 mg/L with sample concentrations falling between 13.50 and 383.72 mg/L. In this study, we introduce various analytical methodologies for both qualitative and quantitative assessment of a complex phytochemical sample, specifically oak bark extract, aimed at identifying and confirming the presence of active compounds within the extract.

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Active films based on chitosan incorporated with pine bark extract (PBE) were prepared and characterized. Subsequently, these films were utilized for packaging carp slices in refrigerated storage at 4 ± 1 °C. Analysis of the physicochemical properties and biological activity of the active films revealed that, except for water content, all assessed indices showed an increasing trend with an increase in the amount of supplemental PBE. As this trend progresses, scanning electron microscopy (SEM) analysis revealed deposition on the film surface accompanied by transverse lines and fractures, while the color of the film gradually changed from light yellow to reddish-brown. Fourier transform infrared spectroscopy (FTIR) indicated that the phenolic hydroxyl groups in PBE interacted with the hydrogen in the amino groups of chitosan molecules to form non-covalent bonds. X-ray diffraction analysis (XRD) showed that the reaction between PBE and chitosan altered the crystalline structure of chitosan molecules. Moreover, the analysis of the effects of active films on the pH, water-holding capacity, thiobarbituric acid values, and the total bacterial counts of carp slices revealed that in terms of preservation, films containing 30 % PBE were the most effective, using which the shelf life of carp slices could be extended by 50 %.

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Pycnogenol® French maritime pine bark extract is a well-known and thoroughly studied patented extract from the bark of Pinus pinaster Ait. ssp. Atlantica. In 39 randomized double-blind, placebo-controlled (RDP) human clinical trials including 2,009 subjects, Pycnogenol® French maritime pine bark extract supplementation for two weeks to six months has been shown to beneficially affect cardiovascular health, chronic venous insufficiency, cognition, joint health, skin health, eye health, women's health, respiratory health and allergies, oral health and sports performance. The mechanisms of action that can explain the respective effects on different conditions in the human body are discussed as well. As investigated in several in vitro, in vivo and in clinical studies, Pycnogenol® French maritime pine bark extract showed antioxidative effects, anti-inflammatory abilities, beneficial effects on endothelial function and reinforcing effects on the extracellular matrix. The present review aims to give a comprehensive overview of currently available "gold standard" RDP trials of Pycnogenol®'s benefits across various health domains compared to placebo. In addition, some of the processes on which the presented effects of Pycnogenol® French maritime pine bark extract are based will be elucidated and discussed. This broad overview of RDP studies on Pycnogenol® in different health domains can be used as a basis for further research on applications and mechanisms of this unique French maritime pine bark extract.

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Background: Anterior tooth discolorations can be treated conservatively and noninvasively through bleaching to achieve the desired esthetic outcomes. However, bleaching along with composite resin is advisable for certain clinical cases for optimum results. However, shear bond strength (SBS) of composite resin to the bleached tooth gets significantly lowered. Before placing the composite restoration, the bleached enamel needs to be treated with antioxidant agents to increase its SBS. The study aims to evaluate and compare the effect of herbal antioxidants on SBS of composite resin to bleached enamel at different time intervals. Materials and Methods: Sixty extracted single-rooted maxillary incisors postdecoronation, keeping their labial surfaces up were mounted in cold-cure acrylic resin. The samples were randomly divided into: Group I - unbleached; Group II - 10% pine bark extract for 10 min postbleaching; Group III - 10% pine bark extract for 20 min postbleaching; Group IV - application of 10% rosemary extract for 10 min postbleaching, Group V - application of 10% rosemary extract for 20 min postbleaching; Group VI - no application of antioxidant. 35% hydrogen peroxide was used for bleaching all the samples except those which served as negative control. Later composite cylinder 4 mm in diameter and length were built on prepared enamel. The maximum load at failure was recorded using the universal testing machine. Statistical Analysis: Data were analyzed using the analysis of variance and Tukey's t-test with significance level of P < 0.05. Results: Highest load was exhibited by Group I. Group V showed satisfactory shear strength followed by Groups IV, III, II, and VI. Conclusion: Both 10% rosemary and 10% pine bark extracts showed better results when applied for 20 min as compared to 10 min application. Increased duration of antioxidant application increases the SBS.

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Introduction: Inflammatory bowel disease (IBD) comprises a heterogeneous group of chronic diseases as ulcerative colitis (UC) and Crohn's disease (CD). IBD is the result of a dysregulation of intestinal homeostasis with a host's loss of tolerance toward normal enteric microflora. Plant-based extracts as phenolic compounds can play a role by modulating the intestinal inflammation response. Methods: The in vitro antimicrobial activity of French maritime pine bark extract (PBE) and its phenolic constituents has been investigated in this study. Furthermore, the ability of PBE and phenolic compounds (caffeic acid, chlorogenic acid, ferulic acid, gallic acid and taxifolin) to modulate the microbiota has been assessed. Results: Phenolic compounds and PBE showed a great inhibitory effect on the pathogens growth at the highest concentration assessed (1.25 mg/mL). The growth of E. sakazakii and E. faecalis were affected by the effect of caffeic acid and ferulic acid. Taxifolin showed a very strong activity against Listeria sp. (with a reduction ~98%). Gallic acid revealed antibacterial effect on S. aureus at different concentrations. The inhibitory effect of PBE was highly significant on the growth of E. coli O157:H7. PBE, caffeic acid and chlorogenic acid seem to provide the greatest beneficial effect on the probiotic bacteria. However, the highest concentrations of taxifolin may have impaired the growth of beneficial microbiota. Conclusion: Present findings could be of interest for considering PBE and/or its phenolic constituents as protectors against gastrointestinal disturbances which lead to ulcerative colitis and Crohn's disease.

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Diabetes remains an important disease worldwide with about 500 million patients globally. In tropical Africa, Morus mesozygia is traditionally used in the treatment of diabetes. Biological and phytochemical investigation of the root bark extracts of the plant led to the isolation of a new prenylated arylbenzofuran named 7-(3-hydroxy-3-methylbutyl)moracin M (1) and two congeners, moracins P (2) and M (3). When compared to acarbose (IC50 = 486 µM), all the isolated compounds are better inhibitors of α-glucosidase with in vitro IC50 values of 16.9, 16.6, and 40.9 µM, respectively. However, they were not active against α-amylase. The compounds also demonstrated moderate inhibition of dipeptidyl peptidase-4 (DPP4). Based on in silico docking studies, all isolates (1, 2, and 3) exhibit binding affinities of -8.7, -9.5, and -8.5 kcal/mol, respectively against α-glucosidase enzyme (PDB: 3AJ7). They are stabilized within the α-glucosidase active site through hydrogen bonds, pi interactions, and hydrophobic interactions. This study provides scientific support for the traditional use of Morus mesozygia in the treatment of diabetes as well as adding to the repository of α-glucosidase inhibitory agents.

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Epidermolysis bullosa (EB) is a group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Impaired wound healing is central and can lead to serious clinical complications, deformities, and symptoms with a devastating impact on quality of life (QoL). Dressing changes and wound care are central to the management of EB. Recently Oleogel-S10 (also known as birch bark extract or birch triterpenes) was approved in Europe and the UK for treating EB wounds. This approval was based on data from the EASE phase 3 study, which demonstrated Oleogel-S10 accelerated wound healing, reduced total wound burden, and decreased the frequency of dressing changes in patients with EB. A retrospective analysis of medical records was conducted for up to 24 months in 13 patients with EB treated with Oleogel-S10 through an early access programme in Colombia. Effectiveness was assessed by measuring body surface area percentage (BSAP) and total body wound burden (EBDASI). Tolerability and safety were monitored throughout. This is the first report to evaluate the effectiveness of Oleogel-S10 in clinical practice. The results showed a reduction in percentage of BSA affected, from a mean of 27.3% at baseline to 10.4% at 24-month follow-up, despite treatment interruptions. A reduction in EBDASI skin activity score of - 16.2 (24 months) together with a reduced skin damage index score of - 15.4 (18 months) was also observed. Physicians, patients, and caregivers perceived faster wound closure. Adherence with therapy by patients was good, and patients expressed satisfaction with treatment and reported improvements in self-esteem, productivity, and social interaction. Oleogel-S10 was well tolerated; however, two patients reported worsening wounds related to gauze adherence. Two deaths during treatment interruption were reported and was not considered related to Oleogel-S10. This study supports the effectiveness of Oleogel-S10 in a real-world scenario in a country with scarce resources for the treatment of EB.

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Due to seasonally appearing viruses and several outbreaks and present pandemic, we are surrounded by viruses in our everyday life. In order to reduce viral transmission, functionalized surfaces that inactivate viruses are in large demand. Here the endeavor was to functionalize cellulose-based materials with tannic acid (TA) and tannin-rich extracts by using different binding polymers to prevent viral infectivity of both non-enveloped coxsackievirus B3 (CVB3) and enveloped human coronavirus OC43 (HCoV-OC43). Direct antiviral efficacy of TA and spruce bark extract in solution was measured: EC50 for CVB3 was 0.12 and 8.41 µg/ml and for HCoV-OC43, 78.16 and 95.49 µg/ml, respectively. TA also led to an excellent 5.8- to 7-log reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus infectivity. TA functionalized materials reduced infectivity already after 5-min treatment at room temperature. All the tested methods to bind TA showed efficacy on paperboard with 0.1 to 1% (w/v) TA concentrations against CVB3 whereas material hydrophobicity decreased activities. Specific signatures for TA and HCoV-OC43 were discovered by Raman spectroscopy and showed clear co-localization on the material. qPCR study suggested efficient binding of CVB3 to the TA functionalized cellulose whereas HCoV-OC43 was flushed out from the surfaces more readily. In conclusion, the produced TA-materials showed efficient and broadly acting antiviral efficacy. Additionally, the co-localization of TA and HCoV-OC43 and strong binding of CVB3 to the functionalized cellulose demonstrates an interaction with the surfaces. The produced antiviral surfaces thus show promise for future use to increase biosafety and biosecurity by reducing pathogen persistence.

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Structuring liquid oils into oleogels using natural and abundant biomass components as gelling agents is of great significance in fields such as foods, pharmaceuticals, and cosmetics. In this work, a more energy-efficient and technologically simpler approach for directly preparing birch outer bark extract particles containing oleogel was used. This method involves introducing birch outer bark extract particles into the oil phase directly from the extract solution, combining both the evaporation of solution and gel formation. As a result, stable oleogels of various vegetable oils (sunflower, almond, olive, and hemp seed) were obtained with birch outer bark extract particle contents of 4-10%. Infrared spectroscopy and particle size analysis confirmed that when increasing the content of extract particles in the oil, increasing self-assembly of extract particles via hydrogen bonding occurs, leading to the formation of a more structured network. This is consistent with gel strength values from rheological tests of oleogels, which also increased with particle concentration. The obtained oleogels showed important properties such as good tolerance to time-dependent deformation, shear thinning, and thermoreversibility.

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Calotropis gigantea stem bark extract, particularly the dichloromethane fraction (CGDCM), demonstrated the most potent antiproliferative effects on hepatocellular carcinoma HepG2 and colorectal HCT116 cells. The current study focused on enhancing the effectiveness of cancer treatment with CGDCM at concentrations close to the IC50 in HCT116 cells by reducing their nutrient supply. CGDCM (2, 4, and 8 µg/mL) treatment for 24 h under glucose conditions of 4.5 g/L without fetal bovine serum (FBS) supplementation or serum starvation (G+/F-), glucose 0 g/L with 10% FBS or glucose starvation (G-/F+), and glucose 0 g/L with 0% FBS or complete starvation (G-/F-) induced a greater antiproliferative effect in HCT116 cells than therapy in complete medium with glucose 4.5 g/L and 10% FBS (G+/F+). Nonetheless, the anticancer effect of CGDCM at 4 µg/mL under (G-/F-) showed the highest activity compared to other starvation conditions. The three starvation conditions showed a significant reduction in cell viability compared to the control (G+/F+) medium group, while the inhibitory effect on cell viability did not differ significantly among the three starvation conditions. CGDCM at 4 µg/mL in (G-/F-) medium triggered apoptosis by dissipating the mitochondrial membrane potential and arresting cells in the G2/M phase. This investigation demonstrated that a decrease in intracellular ATP and fatty acid levels was associated with enhanced apoptosis by treatment with CGDCM at 4 µg/mL under (G-/F-) conditions. In addition, under (G-/F-), CGDCM at 4 µg/mL increased levels of reactive oxygen species (ROS) and was suggested to primarily trigger apoptosis in HCT116 cells. Thus, C. gigantea extracts may be useful for the future development of alternative, effective cancer treatment regimens.

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Cellulose nanofibrils (CNFs) are increasingly used as precursors for foams, films and composites, where water interactions are of great importance. In this study, we used willow bark extract (WBE), an underrated natural source of bioactive phenolic compounds, as a plant-based modifier for CNF hydrogels, without compromising their mechanical properties. We found that the introduction of WBE into both native, mechanically fibrillated CNFs and TEMPO-oxidized CNFs increased considerably the storage modulus of the hydrogels and reduced their swelling ratio in water up to 5-7 times. A detailed chemical analysis revealed that WBE is composed of several phenolic compounds in addition to potassium salts. Whereas the salt ions reduced the repulsion between fibrils and created denser CNF networks, the phenolic compounds - which adsorbed readily on the cellulose surfaces - played an important role in assisting the flowability of the hydrogels at high shear strains by reducing the flocculation tendency, often observed in pure and salt-containing CNFs, and contributed to the structural integrity of the CNF network in aqueous environment. Surprisingly, the willow bark extract exhibited hemolysis activity, which highlights the importance of more thorough investigations of biocompatibility of natural materials. WBE shows great potential for managing the water interactions of CNF-based products.

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In recent years, phytofunctionalized AgNPs have attracted great interest due to their remarkable biological activities. In the present study, AgNPs were synthesized using Abies alba and Pinus sylvestris bark extracts. The chemical profile of these bark extracts was analyzed by LC-HRMS/MS. As a first step, the synthesis parameters (pH, AgNO3 concentration, ratio of bark extract and AgNO3, temperature, and reaction time) were optimized. The synthesized AgNPs were characterized by ATR-FTIR spectroscopy, DLS, SEM, EDX, and TEM. Their antioxidant, cytotoxic, and antibacterial properties were evaluated by the DPPH, ABTS, MTT, and broth microdilution assays, respectively. Abies alba and Pinus sylvestris bark extract-derived AgNPs were well-dispersed, spherical, small (average particle size of 9.92 and 24.49 nm, respectively), stable (zeta potential values of -10.9 and -10.8 mV, respectively), and cytotoxic to A-375 human malignant melanoma cells (IC50 = 2.40 ± 0.21 and 6.02 ± 0.61 µg/mL, respectively). The phytosynthesized AgNPs also showed antioxidant and antibacterial effects.

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Aim: To evaluate the effect of antioxidants on the shear bond strength of composite resin to bleached enamel. Materials and methods: A total of 120 extracted permanent anterior teeth were split into four major groups, one among them being a control group. Group I (bleaching + without antioxidant), group II (bleaching + 10% sodium ascorbate), group III (bleaching + 5% grape seed extract), and group IV (bleaching + 5% pine bark extract). All of the groups were bleached using a gel containing 35% carbamide peroxide, and then they were divided into two subgroups depending on when the bonding operation was to be completed-subgroup A was done in 24 hours, while subgroup B took 3 weeks. The universal testing machine was used to measure the shear bond strength. Results: Subgroup IA showed poor shear bond strength than other groups, there was no statistically significant difference between subgroup IB, IIA, and IVA. Subgroup IIIA showed the highest shear bond strength than the remaining groups. Between subgroups IIA and IIB, IIIA and IIIB, and IVA and IVB there was no statistically significant difference. This shows that delaying the bonding procedure for 3 weeks shows similar shear bond strength when compared to groups that were immediately bonded after antioxidant applying groups. Conclusion: All the antioxidants' immediate application could reverse compromised bond strength. Among them, 5% grape seed extract shows the highest increase in shear bond strength. How to cite this article: Maddula DC, Vasepalli M, Martha S, et al. Comparative Evaluation of Effect of Different Antioxidants on Shear Bond Strength of Composites on Bleached Enamel: An In Vitro Study. Int J Clin Pediatr Dent 2023;16(1):87-92.

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OBJECTIVE: Present study was designed to evaluate the efficacy of Acacia nilotica bark extract as an alternative to antibiotic growth promoters in broilers. METHODS: Six hundred, day-old broiler chicks were randomly divided into six groups (NC, without any supplementation; AB, NC+Zinc Bacitracin; PB, NC+Safmannan; ANBE1, NC+A. nilotica bark extract 0.1%; ANBE3, NC+A. nilotica bark extract 0.3%; ANBE5, NC+A. nilotica bark extract 0.5%), with ten replicates per group (10 chicks/replicate) and feeding trial was lasted for 35 days. RESULTS: Results showed that weight gain (1,296.63 g) and feed conversion ratio (FCR, 1.59) of AB was better than NC, during the finisher phase. Overall FCR of AB (1.53), PB (1.54), and ANBE5 (1.54) was significantly (p<0.05) better than NC. From carcass parameters relative weight of wing and heart were highest in ANBE3 (2.5% and 1.51%, respectively). Significantly (p<0.05) highest blood glucose level was observed in NC (264.5 mg/dL) and highest albumin concentration was found in AB (1.46 mg/dL). In addition, antibody titer levels against ND and IBD were higher in ANBE5 than NC, while higher relative weight of bursa was observed in ANBE3 than NC. The villus height to crypt depth ratio in all experimental groups was better than NC. CONCLUSION: Acacia nilotica bark extract could be a suitable alternative to antibiotic growth promoters to support the growth in broilers.

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Raw data obtained by ultra-high pressure liquid chromatography-mass spectrometry, and processed lipid compositional data are presented alongside detailed methodology. Data were obtained as bovine liver lipid extract oxidizes, initiated by 2,2'-Azobis(2-amidinopropane) dihydrochloride, at 0, 6 and 24 h post initiation. Lipid oxidation data in the presence and absence of some supplements with antioxidant properties was obtained. The supplements used were grape seed extract, pine bark extract, milk thistle extract, hawthorn extract and turmeric extract.

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OBJECTIVES: Periodontal disease is triggered by oral microbiome dysbiosis. Thus, to prevent its onset, it is important to maintain relative abundance of periodontal pathogenic bacteria in the oral microbiome at a low level. While Phellodendron bark extract (PBE) and its active ingredient, berberine, exert antibacterial effects on periodontal pathogenic bacteria, such as Porphyromonas gingivalis, their effects on the oral microbiome as a whole remain unknown. Therefore, we aimed to clarify the potential of PBE and berberine chloride (BC) in regulating the relative abundance of periodontal pathogenic bacteria in the oral microbiome. METHODS: Saliva was collected from 20 participants. Each participant's saliva was combined separately with P. gingivalis suspension and either PBE or BC in a modified basal medium. The samples were then incubated under anaerobic conditions for 24 h. After cultivation, we determined the total bacterial concentration using quantitative polymerase chain reaction analysis and the bacterial composition using 16 S ribosomal RNA gene sequencing. RESULTS: The total bacterial concentration was reduced because of treatment with PBE and BC. Bacterial 16 S ribosomal RNA gene sequencing confirmed that treatment with PBE and BC significantly reduced the relative abundance of periodontal pathogenic bacteria, including red and orange complex bacteria. CONCLUSIONS: Our findings suggest that PBE and BC reduce the relative abundance of periodontal pathogenic bacteria in the oral microbiome. Thus, PBE and BC can aid in preventing periodontal disease, given their ability to regulate the oral microbiome composition and their anti-inflammatory effects.

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Abstract Malaria, a disease of public health concern is a known cause of kidney failure, and dependence on herbal medicines for its treatment is increasing due to the high cost of drugs. So this study is designed to evaluate the ameliorating effect of ethanol extract from Salacia nitida root bark on electrolyte and renal perturbations in Plasmodium berghei-infected mice. Thirty malariainfected mice divided into five groups of six mice each and another group of six uninfected mice were used for the study. 280, 430, and 580 mg/kg of extract were given to infected mice in groups B, C, and D, 4 mg/kg of artesunate given to group E mice, and 4 ml/kg of physiological saline given to group A and uninfected group F mice for five days. Serum Na+, K+, HCO3, Cl-, TB, urea, creatinine, BUN concentrations, and BUN/creatinine ratio were determined using standard methods. Results showed significant increases (p < 0.05) in Na+, K+, and HCO3 and decreases in Cl-, TB, urea, creatinine, BUN, and BUN/creatinine ratio in the infected treated mice in groups B - E. This study showed that ethanol extract of S. nitida root bark is efficient in the treatment of renal disorders and blood electrolyte perturbations

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Ziziphus abyssinica root bark is widely used in folk medicine to manage liver diseases, particularly, jaundice but its effect on paracetamol-induced liver toxicity (PILT) has not yet been validated. This study explored the ameliorative effect of ethanolic root bark extract of Ziziphus abyssinica (ZAE) against PILT in rats. The flavonoid and phenolic content of ZAE was evaluated using Folin-Ciocalteau and aluminium trichloride colorimetric methods, respectively. Antioxidant activity of ZAE was determined in vitro by evaluating its ferrous reducing antioxidant capacity (FRAC) as well as DPPH and nitic oxide (NO) radicals scavenging activities. Sprague-Dawley rats were assigned to six groups (n = 6) and administered with normal saline (10 mL/kg, p.o.), N-acetylcysteine (50 mg/kg, i.p.) and ZAE (30, 100, and 300 mg/kg, p.o.) respectively for seven days after which they received paracetamol (PCM, 3000 mg/kg, p.o.). Animals were sacrificed 48 h after paracetamol administration under light anaesthesia and assessed for liver toxicity and oxidative stress. Total flavonoid and phenolic contents of ZAE were 1313.425 µg/mL quercetin equivalence and 268.31 µg/mL gallic acid equivalence respectively. ZAE exhibited marked FRAC as well as DPPH and NO radical scavenging activities with IC50s of 80.41 ± 1.56, 67.56 ± 1.11 and 7.11 ± 1.48 µg/mL respectively. ZAE and N-acetylcysteine significantly (p < 0.05) reduced the paracetamol-mediated elevation of serum total bilirubin, proteins and activity of liver enzymes (AST, ALP, and ALT). Similarly, ZAE increased hepatic glutathione, total thiols and catalase activity of the paracetamol intoxicated rats. Morphological changes associated with the paracetamol hepatotoxicity were also ameliorated by ZAE. Overall, the hepatoprotective effect of ZAE may be related to its antioxidant property.

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Alnus glutinosa (namely black alder or European alder) is a tree of the Betulaceae family widely spread through Europe, Southeastern Asia, the Caucasus mountains, and Western Siberia. Its bark is traditionally used for medicinal purposes as an astringent, cathartic, febrifuge, emetic, hemostatic, and tonic, suggesting that it may contain bioactive compounds useful to counteract inflammation. The aim of this study was to investigate the phytochemical profile of A. glutinosa stem bark extract (AGE) by LC-DAD-ESI-MS/MS analysis and to validate some biological activities such as antioxidant, anti-inflammatory and anti-angiogenic properties by in vitro and in vivo models (chick chorioallantoic membranes and zebrafish embryos), that can justify its use against inflammatory-based diseases. The AGE showed a high total phenols content expressed as gallic acid equivalents (0.71 g GAE/g of AGE). Diarylheptanoids have been identified as the predominant compounds (0.65 g/g of AGE) with oregonin, which alone constitutes 74.67% of the AGE. The AGE showed a strong and concentration-dependent antioxidant (IC50 0.15-12.21 µg/mL) and anti-inflammatory (IC50 5.47-12.97 µg/mL) activity. Furthermore, it showed promising anti-angiogenic activity, inhibiting both the vessel growth (IC50 23.39 µg/egg) and the release of an endogenous phosphatase alkaline enzyme (IC50 44.24 µg/embryo). In conclusion, AGE is a promising source of antioxidant, anti-inflammatory and angio-modulator compounds.