Chemical Composition, Antioxidant Activities, Antidepressant Effect, and Lipid Peroxidation of Peruvian Blueberry: Molecular Docking Studies on Targets Involved in Oxidative Stress and Depression.

Blueberries (Vaccinium corymbosum L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS•+), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than Vaccinium corymbosum fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly (p < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo (p < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT2. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian Vaccinium corymbosum L.

Antispasmodic Effect of Valeriana pilosa Root Essential Oil and Potential Mechanisms of Action: Ex Vivo and In Silico Studies.

Infusions of Valeriana pilosa are commonly used in Peruvian folk medicine for treating gastrointestinal disorders. This study aimed to investigate the spasmolytic and antispasmodic effects of Valeriana pilosa essential oil (VPEO) on rat ileum. The basal tone of ileal sections decreased in response to accumulative concentrations of VPEO. Moreover, ileal sections precontracted with acetylcholine (ACh), potassium chloride (KCl), or barium chloride (BaCl2) were relaxed in response to VPEO by a mechanism that depended on atropine, hyoscine butylbromide, solifenacin, and verapamil, but not glibenclamide. The results showed that VPEO produced a relaxant effect by inhibiting muscarinic receptors and blocking calcium channels, with no apparent effect on the opening of potassium channels. In addition, molecular docking was employed to evaluate VPEO constituents that could inhibit intestinal contractile activity. The study showed that α-cubebene, ß-patchoulene, ß-bourbonene, ß-caryophyllene, α-guaiene, γ-muurolene, valencene, eremophyllene, and δ-cadinene displayed the highest docking scores on muscarinic acetylcholine receptors and voltage-gated calcium channels, which may antagonize M2 and/or M3 muscarinic acetylcholine receptors and block voltage-gated calcium channels. In summary, VPEO has both spasmolytic and antispasmodic effects. It may block muscarinic receptors and calcium channels, thus providing a scientific basis for its traditional use for gastrointestinal disorders.

Valeriana pilosa Roots Essential Oil: Chemical Composition, Antioxidant Activities, and Molecular Docking Studies on Enzymes Involved in Redox Biological Processes.

Valeriana pilosa is usually employed in Peruvian folk medicine in the form of infusion to treat stomach pain, and has antispasmodic, relaxing, sleep-promoting, and sedative properties, as well as is an anti-inflammatory. In this study, Valeriana pilosa essential oil (VPEO) was obtained by hydrodistillation, analyzed by GC and GC/MS, and 47 compounds were identified. Major oil components were α-patchoulene (5.8%), α-humulene (6.1%), seychellene (7.6%), and patchoulol (20.8%). Furthermore, we assessed the in vitro antioxidant activities, molecular docking, and Ligand Efficiency studies on enzymes involved in cellular redox pathways such as CYP2C9, catalase, superoxide dismutase, and xanthine oxidase. Essential oil antioxidant activities were assessed by FRAP, ABTS•+, and DPPH• radical scavenging activity. VPEO displays high antioxidant activity as compared to essential oils of Valeriana jatamansi and Valeriana officinalis oil roots. In addition, molecular docking and ADMET prediction was employed to compare the absorption, metabolism, and toxicity properties of Valeriana pilosa compounds. In the molecular docking studies, limonene, p-cimene, carvone, α-cubebene, cyclosativene, α-guaiene, allo-aromadendrene, valencene, and eremophyllene were the compounds with the best docking score on CYP2C9 and xanthine oxidase. Thus, volatile components of Valeriana pilosa could be associated with the detected antioxidant activity, acting as putative inhibitors of CYP2C9 and xanthine oxidase.

Metabolomic Profiling of Mango (Mangifera indica Linn) Leaf Extract and Its Intestinal Protective Effect and Antioxidant Activity in Different Biological Models.

Mangifera indica Linn popularly known as mango is used in folk medicine to treat gastrointestinal disorders. The aim of this study was to identify the metabolomic composition of lyophilized extract of mango leaf (MIE), to evaluate the antioxidant activity on several oxidative stress systems (DPPH, FRAP, TBARS, and ABTS), the spasmolytic and antispasmodic activity, and intestinal protective effect on oxidative stress induced by H2O2 in rat ileum. Twenty-nine metabolites were identified and characterized based on their ultra-high-performance liquid chromatography (UHPLC) high-resolution orbitrap mass spectrometry, these include: benzophenone derivatives, xanthones, phenolic acids, fatty acids, flavonoids and procyanidins. Extract demonstrated a high antioxidant activity in in-vitro assays. MIE relaxed (p < 0.001) intestinal segments of rat pre-contracted with acetylcholine (ACh) (10-5 M). Pre-incubation of intestinal segments with 100 µg/mL MIE significantly reduced (p < 0.001) the contraction to H2O2. Similar effects were observed with mangiferin and quercetin (10-5 M; p < 0.05) but not for gallic acid. Chronic treatment of rats with MIE (50 mg/kg) for 28 days significantly reduced (p < 0.001) the H2O2-induced contractions. MIE exhibited a strong antioxidant activity, spasmolytic and antispasmodic activity, which could contribute to its use as an alternative for the management of several intestinal diseases related to oxidative stress.

Efecto oxitócico del decocto de la flor sagrada de los incas (Cantua buxifolia) sobre útero aislado de rata estrogenizada / Oxytocic effect of the deck of the sacred flower of the incas (Cantua buxifolia) on the isolated uterus of a strogenized rat

Objetivo. El objetivo de este estudio fue investigar el efecto del decocto de la flor sagrada de los incas (Cantua buxifolia) sobre útero aislado de rata estrogenizada. Materiales y métodos. La planta entera fue utilizada para preparar el decocto, obteniendo concentraciones finales 4 mg/mL. Se utilizaron seis ratas hembras procedentes del Instituto Nacional de Salud; posteriormente, se les estrogenizó con valerato de estradiol (solución 0,3%) durante tres días previos al experimento. Luego se sacrificaron mediante dislocamiento cervical y se aislaron los segmentos uterinos de las ratas; finalmente, se fijó en los baños de órgano aislado, determinándose la amplitud, frecuencia de contracción y actividad uterina en los grupos problema (Cantua buxifolia) y oxitocina. Resultados. El decocto de Cantua buxifolia 4 mg/mL evidenció incremento de la amplitud, frecuencia de la contracción y actividad uterina similar a oxitocina en concentración de 2X10-5 UI, (p=0,829; p=1,00 y p=0,762, respectivamente). Conclusión. El decocto de Cantua buxifolia tiene efecto oxitócico en útero aislado de rata estrogenizada.

Objective. The objective of this study was to investigate the effect of the decoct of the sacred flower of the Incas (Cantua buxifolia) on the isolated uterus of estrogenized rats. Materials and methods. The whole plant was used to prepare the decoct, obtaining final concentrations of 4 mg/mL. Six female rats from the National Institute of Health were used, subsequently they were estrogenized with estradiol valerate (0.3% solution) for three days prior to the experiment. Then, they were sacrificed by cervical dislocation and the uterine segments of the rats were isolated, finally it was fixed in the isolated organ baths, determining the amplitude, frequency of contraction and uterine activity in the problem groups (Cantua buxifolia) and oxytocin. Results. The decoct of Cantua buxifolia 4 mg/mL showed an increase in amplitude, frequency of contraction and uterine activity similar to oxytocin at a concentration of 2X10-5 IU, (p = 0.829; p = 1.00 and p = 0.762, respectively). Conclusion. Cantua buxifolia decoct has an oxytocic effect in the isolated uterus of estrogenized rats.

Efecto antiespasmódico de Rubus roseus y Mentha pulegium sobre íleon aislado de cobayo (Cavia porcellus) / Antispasmodic effect of Rubus roseus and Mentha pulegium on guinea pig (Cavia porcellus) isolated ileum

Objetivo. El objetivo de este estudio fue investigar el potencial efecto antiespasmódico de Rubus roseus y Mentha pulegium en íleon aislado de cobayo (Cavia porcellus) Materiales y Métodos. Los segmentos de íleon se precontrajeron con acetilcolina (ACh; 4 × 10−6 M) y cloruro de potasio (KCl; 4 × 10-4 M) luego se evaluó la respuesta de los decoctos de Rubus roseus (Rr) Mentha pulegium (Mp) en el baño de órganos aislado en concentraciones crecientes (no acumulativas), como controles positivos se utilizaron nifedipino 5 × 10-8 M (antagonista de canales de Ca2+ voltaje dependientes); atropina sulfato 5,5 × 10-9 M (antagonista muscarínico no selectivo), y N-butilbromuro de hioscina 3 x 10-3 M (antagonista muscarínico M3 selectivo). Se cuantificó la amplitud y la frecuencia de contracción (durante diez minutos) después de la administración de los decoctos. Resultados. Los decoctos de Rubus roseus y Mentha pulegium reducen las contracciones inducidas por acetilcolina (p < 0,001) y KCl (p < 0,01) similares a nifedipino (Mp: 4 y 8 mg/mL); atropina sulfato (Rr: 0,2-4 mg/mL; Mp: 0,8 y 1,6 mg/mL) y N-butilbromuro de hioscina (Mp: 2,4 y 8 mg/mL). Por otro lado, ambos decoctos reducen la frecuencia de contracción inducidas por Ach (p < 0,001) y KCl (p < 0,001). Conclusión. Los decoctos de Rubus roseus y Mentha pulegium tienen efecto antiespasmódico en íleon aislado de cobayo (Cavia porcellus).

Objective. This study aimed to investigate the potential antispasmodic effect of Rubus roseus and Mentha pulegium on isolated guinea pig (Cavia porcellus) ileum. Materials and Methods. The ileum segments were pre-contracted with acetylcholine (ACh, 4 × 10-6 M) and potassium chloride (KCl, 4 × 10-4 M) then the response of the Rubus roseus (Rr) and Mentha pulegium (Mp) decocts was evaluated in the organ bath isolated in increasing concentrations (non-cumulative), as positive controls were used nifedipine 5 × 10-8 M (antagonist of voltage dependent Ca2+ channels) atropine sulfate 5,5 × 10-9 M (non-selective muscarinic antagonist) and 3 x 10-3 M hyoscine N-butylbromide (selective M3 muscarinic antagonist). The amplitude and the frequency of contraction were quantified (during 10 minutes) after the administration of the decocts. Results. The decocts of Rubus roseus and Mentha pulegium decrease the contractions induced by acetylcholine (p < 0.001) and KCl (p <0.01) comparable to nifedipine (Mp: 4 and 8 mg/mL), atropine sulfate (Rr: 0.2 - 4 mg/mL, Mp: 0.8 and 1.6 mg/mL) and hyoscine N-butylbromide (Mp: 2.4 and 8 mg/mL). On the other hand, both decocts reduce the frequency of contraction induced by Ach (p <0.001) and KCl (p <0.001). Conclusions. The decocts of Rubus roseus and Mentha pulegium have an antispasmodic effect on isolated guinea pig ileum (Cavia porcellus).

Capacidad antioxidante in vitro del liofilizado de la pulpa y cáscara del rizoma de Zingiber officinale Roscoe (jengibre) / In vitro antioxidant capacity of freeze dried pulp and peel of the rhizome of Zingiber officinale Roscoe (ginger)

Objetivo. Evaluar la capacidad antioxidante in vitro del liofilizado de la pulpa y cáscara del rizoma de Zingiber officinale Roscoe (jengibre) mediante los ensayos DPPH, FRAP y TBARS. Materiales y métodos. Se separó la pulpa y la cáscara de los rizomas de Z. officinale, se preparó un macerado con solución hidroalcohólica (70:30 EtOH:H2O), y luego de rotaevaporar, se liofilizó. La capacidad antioxidante de los liofilizados se evaluó según porcentaje de inhibición del radical DPPH y el poder antioxidante de reducción férrica (FRAP), así como la capacidad de inhibir la peroxidación lipídica in vitro mediante el ensayo TBARS. Resultados. Los extractos liofilizados de la pulpa y cáscara evidenciaron moderada capacidad antioxidante, siendo similar según porcentaje de inhibición del radical DPPH (46,5 y 45,6% respectivamente). Sin embargo, mediante el ensayo FRAP la cáscara presentó una capacidad antioxidante de 31,09 µg/mL expresados como equivalentes de trolox (ET) en comparación a la pulpa (22,96 µg ET/mL). Además, solo el liofilizado de cáscara del rizoma de Z. officinale a bajas concentraciones (0,1, 0,2 y 0,3 mg/mL) es capaz de reducir significativamente (p < 0,01) la peroxidación lipídica in vitro. Conclusión. La cáscara del rizoma de Z. officinale posee mayor capacidad antioxidante en comparación con la pulpa según los ensayos FRAP y TBARS; sin embargo, la inhibición de radicales DPPH fue la misma tanto en la cáscara como en la pulpa.

Objective. To evaluate the in vitro antioxidant capacity of the freeze-dried pulp and peel of the rhizomes of Zingiber officinale Roscoe (ginger) using the DPPH, FRAP and TBARS assays. Materials and Methods. The pulp and peel were separated from the rhizomes of Z. officinale, then a macerate was prepared with a hydroalcoholic solution (70:30 EtOH: H2O), and after rotary evaporation, lyophilized. The antioxidant capacity of lyophilisates was evaluated according to the percentage of DPPH radical inhibition and the ferric reduction antioxidant power (FRAP), as well as the ability to inhibit lipid peroxidation in vitro using the TBARS assay. Results. Freeze-dried pulp and peel extracts showed moderate antioxidant capacity, being similar according to the percentage of DPPH radical inhibition (46.5% and 45.6% respectively). However, utilizing the FRAP assay, the peel presented an antioxidant capacity of 31.09 µg/mL expressed as Trolox Equivalents (ET) compared to the pulp (22.96 µg ET / mL). Also, only the freeze-dried peel of Z. officinale at low concentrations (0.1, 0.2 and 0.3 mg / mL) can significantly reduce p < 0.01 lipid peroxidation in vitro. Conclusion. The rhizome peel of Z. officinale has a higher antioxidant capacity compared to the pulp according to the FRAP and TBARS assays, however; DPPH radical inhibition was the same in both the peel and pulp.