Chemical profiling and quantification of flavones in several Pseudognaphalium and Gnaphalium species of Mexican gordolobo using UHPLC/PDA/MS.

The inflorescences of the Mexican gordolobo are used as a folk medicine to treat various respiratory diseases. Currently, the botanical species that bear the name Mexican gordolobo belong to the genera Gnaphalium and Pseudognaphalium. Despite a long history of traditional use, most Mexican gordolobo species have never been fully chemically characterized, and the range of constituents in the species has not been comprehensively reported. To establish a quality control and chemical characterization method, a total of 49 samples belonging to 18 species of Pseudognaphalium and four species of Gnaphalium were studied. Nine flavones were quantified using a UPLC-PDA method. The method was validated in terms of linearity (R2 > 0.99), precision (intra- and inter-day: 0.1-3.9%), accuracy (96-103%), detection limit (10 ng/mL), limit of quantification (25 ng/mL) and robustness. 3-Methylquercetin, luteolin, quercetin, 3,5-dihydroxy-6,7,8-trimethoxyflavone, apigenin and gnaphaliin A were present at relatively high levels in most of the samples analyzed. The samples of P. oxyphyllum and P. liebmannii showed the highest content of the 9 compounds analyzed. Whereas the samples of the 5 species of Gnaphalium showed the lowest levels, including non-detectable, of the 9 compounds quantified. This marks an important difference with Pseudognaphalium species. Furthermore, using UHPLC-ESI-QToF data with targeted and non-targeted approaches, 57 compounds, were identified in Mexican gordolobo samples. Flavonoids were the main group of compounds found in Mexican gordolobo.

Flavones isolated from Pseudognaphalium liebmannii with tracheal smooth muscle relaxant properties.

The inflorescences of Pseudognaphalium liebmannii are used as folk medicine to treat various respiratory diseases. In this work, we report the isolation of seven known flavones: 5-hydroxy-3,7-dimethoxyflavone 1, 5,8-dihydroxy-3,7-dimethoxyflavone 2, 5,7-dihydroxy-3,8-dimethoxyflavone 3 (gnaphaliin A), 3,5-dihydroxy-7,8-dimethoxyflavone 4 (gnaphaliin B), 3,5-dihydroxy-6,7,8-trimethoxyflavone 5, 3,5,7-trimethoxyflavone 6 and 3-O-methylquercetin 7. All these flavones except 1 and 6 showed a relaxant effect on guinea pig tracheal preparation with EC50 between 69.91 ± 15.32 and 118.72 ± 7.06 µM. Aminophylline (EC50 = 122.03 ± 7.05 µM) was used as a relaxant reference drug. The active flavones shifted the concentration-response curves of forskolin and nitroprusside leftward, and significantly reduced the EC50 values of these drugs. Furthermore, these flavones dose-dependently inhibited phosphodiesterase (PDE) in an in vitro assay. This reveals that the inflorescences of P. liebmannii contain several flavones with relaxant effect on airway smooth muscle and with PDEs inhibition that contribute to supporting the anti-asthmatic traditional use.

Micro-Morphology characterization and HS-SPME-GC-MS Analysis of Floral parts of Quararibea funebris (La Llave) Vischer, traditionally known as Rosita de Cacao.

The flowers of Quararibea funebris are used to make a traditional drink called tejate, to which they add aroma, flavor and consistency. The study aims to profile the morphoanatomy of the floral parts of Q. funebris and analyze the changes in its volatile chemical composition during the drying process from 0 to 180 days by HS-SPME-GC-MS. The calyx, corolla, androecium, and gynoecium have distinct characteristics, such as non-glandular fused stellate trichomes, calcium oxalate crystals, and large secretory ducts. Histochemical localization reveals the presence of mucilage and total lipids in all parts of the flower. The chemical analysis of the essential oil, extracted from the flowers, showed that transfarnesol and geraniol were the most abundant compounds, with a yield of 0.04 %. HS-SPME analysis indicated that fresh flowers had a more complex composition than dried ones. In total, 31 components were identified. Nonanal and geranyl acetone were found to be distinctive components of dried flowers. Microscopic examination helps in identifying and authenticating raw materials and also reveals the presence of secretory ducts in all floral parts, which is a distinctive feature. The chemical profile of volatiles provides an important parameter for the evaluation of the quality of Rosita de Cacao raw materials.

UV Radiation Effect in New Materials Developed for the Construction of Beehives.

In recent decades, there has been an increasing focus on the alarming decline in global bee populations, given their critical ecological contributions to natural pollination and biodiversity. This decline, marked by a substantial reduction in bee colonies in forested areas, has serious implications for sustainable beekeeping practices and poses a broader risk to ecological well-being. Addressing these pressing issues requires innovative solutions, one of which involves the development and fabrication of beehives crafted from composite materials that are ecologically compatible with bee biology. Importantly, these materials should also exhibit a high resistance to environmental factors, such as ultraviolet (UV) radiation, in order to maintain their mechanical integrity and longevity. To investigate this, we conducted accelerated UV degradation tests on a variety of composite materials to rapidly assess their susceptibility to UV-induced changes. High-density polyethylene (HDPE) served as the matrix material and was reinforced with natural fibers, specifically fique fibers (Furcraea bedinghausii), banana fibers, and goose feathers. Our findings indicate that UV radiation exposure results in a noticeable reduction in the tensile strength of these materials. For example, wood composites experienced a 48% decline in tensile strength over a 60-day period, a rate of deterioration notably higher than that of other tested composite materials. Conversely, HDPE composites fortified with banana fibers initially demonstrated tensile strengths exceeding 9 MPa and 10 MPa. Although these values gradually decreased over the observation period, the composites still displayed favorable stress-strain characteristics. This research underscores the substantial influence of UV radiation on the longevity and efficacy of beehive materials, which in turn affects the durability of natural wood hives exposed to these environmental factors. The resultant increased maintenance and replacement costs for beekeepers further emphasize the need for judicious material selection in beehive construction and point to the viability of the composite materials examined in this study.

"Eritadenine as a regulator of anxiety Disorders: An experimental and docking Approach".

Uncertainty persists regarding the specific chemical causal factors and their corresponding behavioral effects in anxiety disorders. Commonly employed first-line treatments for anxiety target G protein-coupled receptors (GPCRs), including inhibitors of monoaminergic systems. Alternatively, emerging natural bioactive strategies offer potential for mitigating adverse effects. Recent investigations have implicated adenosine in anxiety-triggering mechanisms, while eritadenine, an adenosine analog derived from Shiitake mushroom, has displayed promising attributes. This study explores eritadenine's potential as a bioactive substance for anxiety disorders in mice, employing behavioral tests, pentobarbital-sleep induction, and molecular docking. Behavioral test results reveal a pronounced anxiolytic and sedative-hypnotic pharmacological effect of eritadenine. Our findings suggest that eritadenine may modulate locomotor functions mediated by adenosine receptors, with a stronger affinity for binding to A2AAR over A1AR, thus eliciting these effects.

Are neurologic symptoms associated with worse QoL in non-CNS cancer patients?

BACKGROUND: The burden of having neurologic symptoms (NS) in cancer patients has scantly been studied; therefore, we performed a study whose purpose was to measure the impact of having clinically active (NS) on the quality of life (QoL) of non-primary CNS cancer patients. METHODS: Patients with systemic cancer (non-primary CNS cancer) sent for neurological evaluation at a single cancer center (INCAN) were prospectively invited to respond the EORTC-QLQ-C30 and BN20 questionnaires. Associations of the questionnairés items were blindly measured for the following groups: NS+ or not (NS-) and having active cancer (AC+) or not (AC-). RESULTS: Of 205 patients aged 55.4 ± 15.4 years, 122 (60%) had NS+ and 107 (52%) AC +. The NS+ group (compared with the NS-) showed a significant worse perception in the following scales/items of the EORTC QLQ-C30: physical functioning (median 86 vs. 92, P = 0.012), role functioning (66 vs. 100, P < 0.001), emotional functioning (75 vs. 83, P = 0.005), cognitive functioning (66 vs. 83, P < 0.001), fatigue (33 vs. 22, P < 0.001), nausea and vomiting (P = 0.021), pain (33 vs. 16, P < 0.001), insomnia (33 vs. 0, P = 0.011), appetite loss (P = 0.021), and global health (66 vs. 75, P = 0.001). CONCLUSION: In patients with systemic (non-CNS) cancer, the QoL is significantly worse for patients with active neurologic symptoms.

Gastroprotective effect methanol extract of Caesalpinia coriaria pods against indomethacin- and ethanol-induced gastric lesions in Wistar rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Caesalpinia coriaria (Jacq.) Willd is widely used as a traditional medinal plant in Mexico for protective and healing purposes and the treatment of gastrointestinal diseases. AIM OF THE STUDY: To investigate the gastroprotective effect of extract of Caesalpinia coriaria pods against ethanol-induced and indomethacin-induced gastric lesion models, its anti-inflammatory and antioxidative activities, and its main compounds through LC-MS analysis. MATERIALS AND METHODS: Male Wistar rats were orally administered a methanol extract obtained from the pods of C. coriaria at doses of 10, 30, 100, and 300 mg/kg prior to inducing gastric lesions with ethanol or indomethacin. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations. Determination of prostaglandin E2 (PGE2), alpha tumor necrosis factor (TNF-α), leukotriene B4 (LTB4), nitrites/nitrates, superoxide dismutase (SOD), and H2S gastric levels were investigated. Its main compounds of the active extract through LC-MS analysis. RESULTS: Phenolic compounds were identified as major components of methanol extract. LC-MS analysis identified 15 constituents, and the significant compounds were gallic acid, 3-O-galloylquinic acid, digalloylglucose, tetragalloylglucose, valoneic acid dilactone, pentagalloylglucose, digalloylshikimic acid, and ellagic acid. Pretreatment with the extract at doses of 100 and 300 mg/kg significantly reduced gastric ulcer lesions in both models. Compared with the reference drugs (omeprazole or ranitidine, respectively), no significant difference was found (p < 0.05). The extract's gastroprotective effect was accompanied by significant decreases in leukocyte recruitment, and gastric levels of TNF-α and LTB4 by two to fourfold (p < 0.05). Also, gastric levels of PGE2 gastric levels were maintained and the antioxidant enzyme activities of SOD and nitrate/nitrite in the gastric tissue were improved (p < 0.05). The LC-MS analysis indicated the presence of hydrolyzable tannins (mainly gallic acid derivatives). CONCLUSION: The results suggest that the gastroprotective effect of the methanol extract of C. coriaria pods occurs through anti-inflammatory, antioxidant, and NO modulation properties, and gallic acid derivatives may be the main possible compounds responsible for its actions.

Wound healing activity of the hydroalcoholic extract and the main metabolites of Amphipterygium adstringens (cuachalalate) in a rat excision model.

ETHNOPHARMACOLOGICAL RELEVANCE: The bark of Amphipterygium adstringens Schiede ex Schltdl (Anacardiaceae), commonly known as 'cuachalalate' has been used in Mexican traditional medicine for the treatment of skin and oral lesions, gastric ulcers, and other conditions. The use as wound healing of the bark of this plant has been known since before the Spanish conquest of Mexico. Its uses are mentioned in the first writings of the Spanish in the 16th century. It is important to highlight that its use for wound healing treatment has no scientific previous reports. AIM OF THE STUDY: The objectives of this study were to determine the wound healing effect of the hydroalcoholic extract of the stem bark of Amphipterygium adstringens and its main metabolites, using a model of excision in the back of Wistar rats. To evaluate its antimicrobial effect against common bacteria that living on the skin of wounds and to evaluate its effect on angiogenesis. MATERIALS AND METHODS: The hydroalcoholic extract of cuachalalate (HAE, 10 mg/wound/day), the 3α-hydroxymasticadienoic acid (3 MA, 300 µg/wound/day), the masticadienoic acid (MA, 300 µg/wound/day), and a mixture of anacardic acids (ANA, 300 µg per wound) were tested in a murine excision model topically for 15 days, to evaluate their wound-healing effect. The results were reported in a wound closure percentage (n = 30 animals per treatment curve), using pirfenidone (PIR, 8% in vehicle) as a reference drug. In addition, histologic analysis was performed to evaluate the structure and quality of the scar. The effect on angiogenesis was assessed using the chick embryo chorioallantoic membrane (CAM) model (n = 6 eggs per treatment). The concentration evaluated for each treatment was 300 µg, using as proangiogenic reference drug the histamine (HIS, 5.6 µg) and as antiangiogenic drugs pirfenidone (9 µg) and acetylsalicylic acid (ASA, 9 µg). The antimicrobial test was performed against S. mutans, S. aureus, P. aeruginosa y E. coli using a minimum inhibitory concentration (MIC) assay. RESULTS: The 3α-hydroxymasticadienoic (3 MA) acid and the anacardic acids (ANA) improve the wound closure by approximates 30% (similar to pirfenidone) in comparison with the control-treated with the vehicle in the proliferative phase. On the other hand, the hydroalcoholic extract of cuachalalate (HAE) did not show an effect on the wound healing process. The histologic analysis demonstrated that the three main metabolites showed an improvement in the scar structure. According to the CAM results, it is probable that the main action mechanism of the 3α-hydroxymasticadienoic acid and the anacardic acids is related to their proangiogenic effect. In addition, ANA showed a modest antimicrobial effect. CONCLUSIONS: The 3α-hydroxymasticadienoic acid and anacardic acids showed a better tissue structure and reduced the time closure of the wound. In addition, the anacardic acids showed antimicrobial effects and both metabolites promote angiogenesis, suggesting that these effects may be related to their action mechanism. These metabolites of cuachalalate could be a good alternative for wound healing treatment.

Synergistic action between a synthetic cannabinoid compound and tramadol in neuropathic pain rats.

In the present study the interaction of cannabinoid, PhAR-DBH-Me [(R, Z)-18-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)-18-oxooctadec-9-en-7-ylphenyl-acetate] and tramadol in two neuropathy models, as well as their possible toxic effects, was analyzed. The anti-allodynic effect of PhAR-DBH-Me, tramadol, or their combination, were evaluated in neuropathic rats. Furthermore, the effective dose 35 (as the 35 % of the anti allodynic effect) was calculated from the maximum effect of each drug. Moreover, the isobolographic analysis was performed to determine the type of interaction between the drugs. A plasma acute toxicity study was carried out to assess the hepatic, renal, and heart functions after an individual or combined administration of the drugs, as well as histology using the hematoxylin-eosin or Masson-trichome method. PhAR-DBH-Me, tramadol, and their combination produced an antiallodynic effect on spinal nerve ligation (SNL) and cisplatin-induced neuropathic pain in rats. Moreover, PhAR-DBH-Me and tramadol combination showed a synergistic interaction in neuropathic pain rats induced by SNL but not for cisplatin-induced neuropathy. On the other hand, changes in renal and hepatic functions were not observed. Likewise, analysis of liver, kidney and heart histology showed no alterations compared with controls. Results show that the combination of PhAR-DBH-Me and tramadol attenuates the allodynia in SNL rats; the acute toxicology analysis suggests that this combination could be considered safe in administered doses.

Mexican Plants and Derivates Compounds as Alternative for Inflammatory and Neuropathic Pain Treatment-A Review.

Despite the availability of many anti-pain drugs, in the form of NSAIDs, steroids, gabapentinoids, opioids, and antidepressants, in this study we address the natural compounds belonging to the group of Mexican medicinal plants or "Mexican folk medicine", used for pain management in Mexico. Our interest in this subject is due to the growing idea that "natural is harmless" and to the large number of side effects exhibited in pharmacotherapy. The objective of this review was to document the scientific evidence about Mexican medicinal plants and their derivatives used for inflammatory and neuropathic pain treatment, as well as the mechanisms of action implicated in their antinociceptive effects, their possible adverse effects, and the main pharmacological aspects of each plant or compound. Our data review suggested that most studies on Mexican medicinal plants have used inflammatory experimental models for testing. The anti-pain properties exerted by medicinal plants lack adverse effects, and their toxicological assays report that they are safe to consume; therefore, more studies should be performed on preclinical neuropathic pain models. Moreover, there is no convincing evidence about the possible mechanisms of action involved in the anti-pain properties exerted by Mexican plants. Therefore, the isolation and pharmacological characterization of these plant derivatives' compounds will be important in the design of future preclinical studies.

Antinociceptive Effect of an Aqueous Extract and Essential Oil from Baccharis heterophylla.

Infusions and poultices prepared from the aerial parts of Baccharis heterophylla Kunth (Asteraceae) are widely used in Oaxaca (Mexico) for relieving painful and inflammatory complaints. Therefore, the antinociceptive potential of an aqueous extract (31.6-316 mg/kg, p.o.) and essential oil (30-177 µg/paw, i.pl.) of the plant was assessed using the formalin test. Both preparations inhibited the formalin-induced nociception response (100-316 mg/kg and 100-177 µg/paw, respectively) during the test's second phase. Chemical analysis of the aqueous extract revealed that the major active components were chlorogenic acid (1), 3,4-di-O-(E)-caffeoylquinic acid (2), 3,5-di-O-(E)-caffeoylquinic acid (3), 4,5-di-O-(E)-caffeoylquinic acid (4), 3,5-di-O-(E)-caffeoylquinic acid methyl ester (5), apigenin (6), genkwanin (7), acacetin (8). Compounds 1-5 and 8 are new for B. heterophylla. A high-pressure liquid chromatographic method for quantifying chlorogenic acid (1) and di-caffeoylquinic acids 2-4 in the plant was developed and validated. Analyses of the essential oil and the headspace solid-phase microextraction products, via gas-chromatography-mass spectrometry, revealed that the major volatiles were ß-pinene, myrcene, D-limonene, ß-caryophyllene, and α-caryophyllene, which have demonstrated antinociceptive properties.

Effect of the proportion of curcuminoids on the gastroprotective action of Curcuma longa L. in rats.

The gastroprotective effect of a turmeric acetone extract (TAE) (Curcuma longa L. [Zingiberaceae]) was evaluated and compared against its major curcuminoids; curcumin (CUR), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC). Additionally, to demonstrate the importance of the metabolites' ratio in the extract on the synergistic effect, different mixtures were evaluated. An ethanol-induced gastric injury model was used to evaluate the gastroprotection activity in Wistar rats. The pharmacologic interaction analysis was performed using the Combination Index (CI)-Isobologram Equation method. The CI calculated at 0.5 of affected fraction (fa) for the TAE indicated a synergistic interaction between its components. However, when the proportion of curcuminoids changed from 3.7:1:10 in TAE to a 1:1:1 ratio, the CI implied an antagonistic effect. The binary combinations of curcuminoids (1:1) also showed an antagonistic interaction. The results of this work suggest that the proportion of curcuminoids in the TAE is crucial for the gastroprotective effect against ethanol-induced damage.

Neoplasia quística mucinosa gigante del páncreas tratada con pancreatectomía corporocaudal y preservación esplénica / Giant mucinous cystic neoplasm of the pancreas undergoing pancreatectomy with splenic preservation

RESUMEN: La neoplasia quística mucinosa del páncreas (NQMP) es un tumor infrecuente, que afecta predominantemente a mujeres (90-95 %), afectando especialmente entre la quinta y séptima década de la vida; cuyo descubrimiento suele ser incidental. Por lo general, son lesiones solitarias, sin compromiso del conducto pancreático principal; poco sintomáticas y asociadas a malignidad (10 % a 40 %). El objetivo de este manuscrito fue reportar un caso de neoplasia quística mucinosa gigante del páncreas intervenida quirúrgicamente y revisar la evidencia existente respecto de sus características morfológicas, terapéuticas y pronósticas. Mujer de 29 años, con masa abdominal poco sintomática. El diagnóstico se verificó por medio de ultrasonografía, tomografía axial computarizada y resonancia nuclear magnética. Se intervino quirúrgicamente, realizándose pancreatectomía corporocaudal con preservación esplénica, sin incidentes. La paciente fue dada de alta al quinto día, sin complicaciones, y evolucionó de forma adecuada, sin complicaciones postoperatorias. La NMQP es una lesión compleja, que puede asociarse a malignidad, pero el diagnóstico preoperatorio de malignidad no puede establecerse con seguridad. El pronóstico depende de un diagnóstico precoz y un tratamiento oportuno.

SUMMARY: Mucinous cystic neoplasm of the pancreas (MCNP) are variable types of tumors, which predominantly affect women (90-95 %), and usually appear incidentally in the 5th to 7th decade of life. They are generally solitary lesions, with no involvement of the main pancreatic duct, rarely symptomatic and are associated with malignancy (10 % to 40 %). The aim of this manuscript was to report a case of giant mucinous cystic neoplasm of the pancreas surgically treated and review the existing evidence regarding its morphological, therapeutic and prognosis characteristics. Patient: A 29-year-old woman with a slightly symptomatic abdominal mass. The diagnosis was verified with ultrasound, computed axial tomography and magnetic nuclear resonance. The patient underwent surgery; an uneventful corporocaudal pancreatectomy with splenic preservation was performed. She was discharged on the fifth day, and has evolved adequately, without postoperative complications. MCNP is a complex lesion, which can be associated with malignancy, but the preoperative diagnosis of malignancy cannot be established with certainty. Its prognosis depends on early diagnosis and timely treatment.

Antiallodynic effect of PhAR-DBH-Me involves cannabinoid and TRPV1 receptors.

The antiallodynic effect of PhAR-DBH-Me was evaluated on two models of neuropathic pain, and the potential roles of CB1, CB2, and TRPV1 receptors as molecular targets of PhAR-DBH-Me were studied. Female Wistar rats were submitted to L5/L6 spinal nerve ligation (SNL) or repeated doses of cisplatin (0.1 mg/kg, i.p.) to induce experimental neuropathy. Then, tactile allodynia was determined, and animals were treated with logarithmic doses of PhAR-DBH-Me (3.2-100 mg/kg, i.p.). To evaluate the mechanism of action of PhAR-DBH-Me, in silico studies using crystallized structures of CB1, CB2, and TRPV1 receptors were performed. To corroborate the computational insights, animals were intraperitoneally administrated with antagonists for CB1 (AM-251, 3 mg/kg), CB2 (AM-630, 1 mg/kg), and TRPV1 receptors (capsazepine, 3 mg/kg), 15 min before to PhAR-DBH-Me (100 mg/kg) administration. Vagal stimulation evoked on striated muscle contraction in esophagus, was used to elicited pharmacological response of PhAR-DBH-ME on nervous tissue. Systemic administration of PhAR-DBH-Me reduced the SNL- and cisplatin-induced allodynia. Docking studies suggested that PhAR-DBH-Me acts as an agonist for CB1, CB2, and TRPV1 receptors, with similar affinity to the endogenous ligand anandamide. Moreover antiallodynic effect of PhAR-DBH-Me was partially prevented by administration of AM-251 and AM-630, and completely prevented by capsazepine. Finally, PhAR-DBH-Me decreased the vagally evoked electrical response in esophagus rat. Taken together, results indicate that PhAR-DBH-Me induces an antiallodynic effect through partial activation of CB1 and CB2 receptors, as well as desensitization of TRPV1 receptors. Data also shed light on the novel vanilloid nature of the synthetic compound PhAR-DBH-Me.

Anti-inflammatory, antioxidant, and gaso-protective mechanism of 3α-hydroxymasticadienoic acid and diligustilide combination on indomethacin gastric damage.

The co-administration of 3α-hydroxymasticadienoic acid (3α-OH MDA) and diligustilide (DLG) generates a synergist gastroprotective effect on indomethacin-induced gastric damage. However, the related protective activities of the compounds alone (or in combination) remain unclear. In the present study, we evaluated the anti-inflammatory and antioxidative activities, as well as the potential modulation of important gasotransmitters of each compound individually and in combination using the indomethacin-induced gastric damage model. Male Wistar rats were treated orally with the 3α-OH MDA, DLG, or their combination (at a fixed ratio of 1:1, 1:3, and 3:1) 30 min before the generation of gastric mucosal lesions with indomethacin (30 mg/kg, p.o.). Three hours later, the gastric injury (mm2) was determined. Results from these experiments indicate, in addition to maintaining basal levels of PGE2, the gastroprotective effect of the pre-treatment with 3α-OH MDA (70%), DLG (81%), and their combination (72%) which was accompanied by significant decreases in leukocyte recruitment, as well as decreases in TNF-α and LTB4 gastric levels (p < 0.05). We also found that the pre-treatment maintains the basal antioxidant enzyme activities (SOD) and gastric NO and H2S production even in the presence of indomethacin (p < 0.05). In conclusion, when 3α-OH MDA-DLG is given at a 1:1 combination ratio, the gastroprotective effect and the inflammatory, antioxidant, and gaso-modulation properties are not different from those of treatments using the maximum doses of each compound, revealing that this combination produces promising results for the treatment of gastric ulcers.

Hydroethanolic extract from Endopleura uchi (Huber) Cuatrecasas and its marker bergenin: Toxicological and pharmacokinetic studies in silico and in vivo on zebrafish.

Endopleura uchi, is used for the treatment of inflammatory disease and related to the female reproductive tract. The aim of this study was to evaluate the acute toxicity of the Endopleura uchi stem bark hydroethanolic extract (EEu) in zebrafish, emphasizing the histopathological and biochemical parameters, as well as evaluating the in silico pharmacokinetic and toxicological parameters of the phytochemical/pharmacological marker, bergenin, as their metabolites. The animals were orally treated with EEu at a single dose of 75 mg/kg, 500 mg/kg, 1000 mg/kg and 3000 mg/kg. the oral LD50 of the EEu higher to the dose of 3000 mg/kg. Behavioral, biochemical and histopathological changes were dose dependent. In silico pharmacokinetic predictions for bergenin and its metabolites showed moderate absorption in high human intestinal absorption (HIA) and Caco-2 models, reduced plasma protein binding, by low brain tissue binding and no P-glycoprotein (P-Gp) inhibition. Their metabolism is defined by the CYP450 enzyme, in addition to bergenin inhibition of CYP2C9, CYP3A4 and CYP2C19. In the bergenin and its metabolites in silico toxicity test it have been shown to cause carcinogenicity and a greater involvement of the bergenin with the CYP enzymes in the I and II hepatic and renal metabolism's phases was observed. It is possible to suggest that the histopathological damages are involved with the interaction of this major compound and its metabolites at the level of the cellular-biochemical mechanisms which involve the absorption, metabolization and excretion of these possible prodrug and drug.

Endopleura uchi (Huber) Cuatrec.: A medicinal plant for gynecological treatments - A reproductive toxicity assessment in zebrafish (Danio rerio).

ETHNOPHARMACOLOGICAL RELEVANCE: Endopleura uchi (Huber) Cuatrec is a plant species from the Brazilian Amazon. The barks of this tree are used in folk medicine - mainly as a decoction - for dyslipidemia, uterine infection, fibroids, polycystic ovary, menstrual disorders, as a contraceptive and abortive agent, among others. However, the data available about its developmental toxicity are still insufficient. AIM OF THE STUDY: This study aimed to evaluate the reproductive toxicity and teratogenic effects in embryos from zebrafish treated with the hydroethanolic extract from the barks of Endopleura uchi (EEu). MATERIALS AND METHODS: Both sexes of zebrafish (Danio rerio) were treated with EEu either through immersion (1.2, 2.5, and 5 mg/L) or orally (75, 200, and 500 mg/kg) over 21 consecutive days. Next, we assessed their fertility and gonads' histopathology; in their embryos were assessed teratogenesis, lethalities, and heart rate during daily observations (24, 48, 72, and 96 hpf). RESULTS: The phytochemical analysis of EEu through HPLC/MS shows bergenin as the major compounds. After 21 days of treatment were detected minor histopathological changes in parental fishes, such as atretic oocytes, interstitial fibrosis, and decreased the percentage of early vitellogenic oocytes, but without impairing the reproduction of treated animals. However, in the embryos was observed significantly increased frequency of malformation in all the groups treated through immersion, and in the group treated orally with the highest concentration (500 mg/kg). CONCLUSION: Based on the results, EEu caused no adverse effects in the progenitors on both treatments (immersion and oral). However, it was observed that the concentrations 1.2, 2.5, and 5 mg/L (immersion), and the dose 500 mg/kg (oral) caused malformations in the offspring (F1 generation). These results emphasize the need for attention when using preparations from E. uchi, mainly for pregnant women. Further studies are needed to compare its effects with the extract's primary compound (bergenin).

Mucoadhesive effect of Curcuma longa extract and curcumin decreases the ranitidine effect, but not bismuth subsalicylate on ethanol-induced ulcer model.

The study of pharmacological interactions between herbal remedies and conventional drugs is important because consuming traditional herbal remedies as supplements or alternative medicine is fairly common and their concomitant administration with prescribed drugs could either have a favorable or unfavorable effect. Therefore, this work aims to determine the pharmacological interactions of a turmeric acetone extract (TAE) and its main metabolite (curcumin) with common anti-ulcer drugs (ranitidine and bismuth subsalicylate), using an ethanol-induced ulcer model in Wistar rats. The analysis of the interactions was carried out via the Combination Index-Isobologram Equation method. The combination index (CI) calculated at 0.5 of the affected fraction (fa) indicated that the TAE or curcumin in combination with ranitidine had a subadditive interaction. The results suggest that this antagonistic mechanism is associated to the mucoadhesion of curcumin and the TAE, determined by rheological measurements. Contrastingly, both the TAE and curcumin combined with bismuth subsalicylate had an additive relationship, which means that there is no pharmacological interaction. This agrees with the normalized isobolograms obtained for each combination. The results of this study suggest that mucoadhesion of curcumin and the TAE could interfere in the effectiveness of ranitidine, and even other drugs.