Skin assessment in congenital untreated isolated GH deficiency.

PURPOSE: The separation between the inside and outside through the skin was fundamental for the evolution of prevertebrates, which grow through extrapituitary circuits, to vertebrates, which grow through the somatotrophic axis, namely pituitary growth hormone (GH). and circulating IGF1.Individuals with untreated isolated growth hormone (GH) deficiency (IGHD) due to a mutation in the GH-releasing hormone receptor (GHRH) gene, residing in Itabaianinha, Brazil, are vulnerable to skin cancer and have reduced sweating. However other aspects of their skin physiology are still unknown. Our objectives were to evaluate the number of skin cancers, skin aging, and functional aspects of the skin in this IGHD cohort. METHODS: Twenty-six IGHD individuals and 26 controls matched by age, sex, ethnicity, and occupation were submitted to a biochemical, dermatological and a functional skin assessment by the Multi Probe Adapter Cutometer® MPA 580. RESULTS: There was no difference in the number of skin cancers and in the degrees of photodamage between the groups. The melanin content in the forearm was similar between the groups but was lower in the buttocks (p = 0.005), as well as skin resistance (p < 0.0001) and elasticity (p = 0.003), lower in the IGHD. There was no difference in hydration and sebum content between the two groups. CONCLUSION: IGHD is apparently associated with a neutral profile in terms of skin cancer and photodamage, with similar melanin on the forearm and lower buttocks, lower skin resistance and elasticity, with hydration and sebum similar to controls.

The protective effects of naringenin, a citrus flavonoid, non-complexed or complexed with hydroxypropyl-ß-cyclodextrin against multiorgan damage caused by neonatal endotoxemia.

BACKGROUND: Endotoxemia is a severe and dangerous clinical syndrome that results in elevated morbidity, especially in intensive care units. Neonates are particularly susceptible to endotoxemia due to their immature immune systems. There are few effective treatments for neonatal endotoxemia. One group of compounds with potential in the treatment of neonatal inflammatory diseases such as endotoxemia is the flavonoids, mainly due to their antioxidant and anti-inflammatory properties. Among these, naringenin (NGN) is a citrus flavonoid which has already been reported to have anti-inflammatory, antioxidant, anti-nociceptive and anti-cancer effects. Unfortunately, its clinical application is limited by its low solubility and bioavailability. However, cyclodextrins (CDs) have been widely used to improve the solubility of nonpolar drugs and enhance the bioavailability of these natural products. OBJECTIVE: We, therefore, aimed to investigate the effects of NGN non-complexed and complexed with hydroxypropyl-ß-cyclodextrin (HPßCD) on neonatal endotoxemia injuries in a rodent model and describe the probable molecular mechanisms involved in NGN activities. METHOD: We used exposure to a bacterial lipopolysaccharide (LPS) to induce neonatal endotoxemia in the mice. RESULTS: It was found that NGN (100 mg/kg i.p.) exposure during the neonatal period reduced leukocyte migration and decreased pro-inflammatory cytokine (TNF-α, IL-1ß and IL-6) levels in the lungs, heart, kidneys or cerebral cortex. In addition, NGN upregulated IL-10 production in the lungs and kidneys of neonate mice. The administration of NGN also enhanced antioxidant enzyme catalase and SOD activity, reduced lipid peroxidation and protein carbonylation and increased the reduced sulfhydryl groups in an organ-dependent manner, attenuating the oxidative damage caused by LPS exposure. NGN decreased ERK1/2, p38MAPK and COX-2 activation in the lungs of neonate mice. Moreover, NGN complexed with HPßCD was able to increase the animal survival rate. CONCLUSION: NGN attenuated inflammatory and oxidative damage in the lungs, heart and kidneys caused by neonatal endotoxemia through the MAPK signaling pathways regulation. Our results show that NGN has beneficial effects against neonatal endotoxemia and could be useful in the treatment of neonatal inflammatory injuries.

d-Limonene complexed with cyclodextrin attenuates cardiac arrhythmias in an experimental model of doxorubicin-induced cardiotoxicity: Possible involvement of calcium/calmodulin-dependent protein kinase type II.

BACKGROUND: Arrhythmias are one manifestation of the cardiotoxicity that results from doxorubicin (Doxo) administration. Although cardiotoxicity is an anticipated outcome in anticancer therapies, there is still a lack of treatment options available for its effective management. This study sought to evaluate the possible cardioprotective effect of complex d-limonene (DL) plus hydroxypropyl-ß-cyclodextrin (HßDL) during treatment with Doxo, focusing on the arrhythmic feature. METHODS: Cardiotoxicity was induced in Swiss mice with Doxo 20 mg/kg, with 10 mg/kg of HßDL being administered 30 min before the Doxo. Plasma CK-MB and LDH levels were analyzed. Cellular excitability and susceptibility to cardiac and cardiomyocyte arrhythmias were evaluated using in vivo (pharmacological cardiac stress) and in vitro (burst pacing) ECG protocols. Ca2+ dynamics were also investigated. The expression of CaMKII and its activation by phosphorylation and oxidation were evaluated by western blot, and molecular docking was used to analyze the possible interaction between DL and CaMKII. RESULTS: Electrocardiograms showed that administration of 10 mg/kg of HßDL prevented Doxo-induced widening of the QRS complex and QT interval. HßDL also prevented cardiomyocyte electrophysiological changes that trigger cellular arrhythmias, such as increases in action potential duration and variability; decreased the occurrence of delayed afterdepolarizations (DADs) and triggered activities (TAs), and reduced the incidence of arrhythmia in vivo. Ca2+ waves and CaMKII overactivation caused by phosphorylation and oxidation were also decreased. In the in silico study, DL showed potential inhibitory interaction with CaMKII. CONCLUSION: Our results show that 10 mg/kg of ßDL protects the heart against Doxo-induced cardiotoxicity arrhythmias, and that this is probably due to its inhibitory effect on CaMKII hyperactivation.

Lippia grata essential oil complexed with ß-cyclodextrin ameliorates biochemical and behavioral deficits in an animal model of progressive parkinsonism.

Parkinson's disease (PD) is identified by the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), and is correlated to aggregates of proteins such as α-synuclein, Lewy's bodies. Although the PD etiology remains poorly understood, evidence suggests a main role of oxidative stress on this process. Lippia grata Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro", "alecrim-da-chapada", is a native bush from tropical areas mainly distributed throughout the Central and South America. This plant species is commonly used in traditional medicine for relief of pain and inflammation conditions, and that has proven antioxidant effects. We evaluated the effects of essential oil of the L. grata after its complexed with ß-cyclodextrin (LIP) on PD animal model induced by reserpine (RES). Behavioral assessments were performed across the treatment. Upon completion the treatment, the animals were euthanized, afterwards their brains were isolated and processed for immunohistochemical and oxidative stress analysis. The LIP treatment delayed the onset of the behavior of catalepsy, decreased the number of oral movements and prevented the memory impairment on the novel object recognition task. In addition, the treatment with LIP protected against dopaminergic depletion in the SNpc and dorsal striatum (STRd), and decreased the α-syn immunoreactivity in the SNpc and hippocampus (HIP). Moreover, there was reduction of the oxidative stability index. These findings demonstrated that the LIP treatment has neuroprotective effect in a progressive parkinsonism model, suggesting that LIP could be an important source for novel treatment approaches in PD.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Pharmacological effects of a complex α-bisabolol/ß-cyclodextrin in a mice arthritis model with involvement of IL-1ß, IL-6 and MAPK.

Inflammatory arthritis is the most prevalent chronic inflammatory disease worldwide. The pathology of the disease is characterized by increased inflammation and oxidative stress, which leads to chronic pain and functional loss in the joints. Conventional anti-arthritic drugs used to relieve pain and other arthritic symptoms often cause severe side effects. α-bisabolol (BIS) is a sesquiterpene that exhibits high anti-inflammatory potential and a significant antinociceptive effect. This study evaluates the anti-arthritic, anti-inflammatory and antihyperalgesic effects of BIS alone and in a ß-cyclodextrin (ßCD/BIS) inclusion complex in a CFA-induced arthritis model. Following the intra-articular administration of CFA, male mice were treated with vehicle, BIS and ßCD/BIS (50 mg/kg, p.o.) or a positive control and pain-related behaviors, knee edema and inflammatory and oxidative parameters were evaluated on days 4, 11, 18 and/or 25. Ours findings shows that the oral administration of BIS and ßCD/BIS significantly attenuated spontaneous pain-like behaviors, mechanical hyperalgesia, grip strength deficit and knee edema induced by repeated injections of CFA, reducing the joint pain and functional disability associated with arthritis. BIS and ßCD/BIS also inhibited the generation of inflammatory and oxidative markers in the knee and blocked MAPK in the spinal cord. In addition, ours results also showed that the incorporation of BIS in cyclodextrin as a drug delivery system improved the pharmacological profile of this substance. Therefore, these results contribute to the pharmacological knowledge of BIS and demonstrated that this terpene appears to be able to mitigate deleterious symptoms of arthritis.

Seroprevalence of SARS-CoV-2 antibodies in radio and television workers.

We investigated the seroprevalence of SARS-CoV-2 antibodies in individuals working in radio and television stations (TV) in Sergipe state, Northeast Brazil. This cross-sectional study was conducted from December 1 to December 20, 2020, a period which was considered as the beginning of the second wave of COVID-19 in the state. One hundred and thirteen professionals from the three largest media companies in the state were included in this study. Venous blood was collected using venipuncture and a fluorescence immunoassay for qualitative detection and differentiation of IgM and IgG antibodies against SARS-CoV-2 was performed. Twenty-eight media workers had detectable levels of SARS-CoV-2 antibodies (11 IgM+, 6 IgM+/ IgG+, and 11 IgG+) and the estimated seroprevalence was 24.8 % (95 % CI 17.7 - 33.5). Our findings showed a high seroprevalence of SARS-CoV-2 antibodies in radio and TV workers during the second wave of COVID-19 in Brazil.

Would carvacrol be a supporting treatment option effective in minimizing the deleterious effects of COVID-19?

The pathophysiological process of the disease, Covid-19, is mediated by innate immunity, with the presence of macrophages responsible for secreting type 1 and 6 interleukins (IL), tumor necrosis factor (TNF) leading to dilation of endothelial cells with a consequent increase in capillary permeability. The treatment of this disease has been much discussed, but the variability in the clinical picture, the difficulties for diagnosis and treatment, especially of those patients who have the most severe clinical condition of the disease. Immunization is an effective tool for controlling the spread and overload of health services, but its effectiveness involves high investments in the acquisition of inputs, development of vaccines, and logistics of storage and distribution. These factors can be obstacles for countries with lower economic, technological, and infrastructure indexes. Reflecting on these difficulties, we raised the possibility of adjuvant therapies with imminent research feasibility, as is the case with the use of carvacrol, a monoterpenic phenol whose has biological properties that serve as a barrier to processes mediated by free radicals, such as irritation and inflammation, due to its antioxidant action. Many authors highlighted the activity of carvacrol as a potent suppressor of COX-2 expression minimizing the acute inflammatory process, decreasing the release of some pro-inflammatory mediators such as IL-1ß, TNF-α, PGE2. Anyway, the benefits of carvacrol are numerous and the therapeutic possibilities too. With this description, the question arises: would carvacrol be a supporting treatment option, effective in minimizing the deleterious effects of Covid-19? There is still a lot to discover and research.

(-)-linalool-Loaded Polymeric Nanocapsules Are a Potential Candidate to Fibromyalgia Treatment.

Fibromyalgia (FM) is a chronic disease that has as main characteristic generalized musculoskeletal pain, which can cause physical and emotional problems to patients. However, pharmacological therapies show side effects that hamper the adhesion to treatment. Given this, (-)-linalool (LIN), a monoterpene with several therapeutic properties already reported in scientific literature as anti-depressive, antinociceptive, anti-inflammatory, and antihyperalgesic also demonstrated therapeutic potential in the treatment of FM. Nevertheless, physicochemical limitations as high volatilization and poor water-solubility make its use difficult. In this perspective, this present research had performed the incorporation of LIN into polymeric nanocapsules (LIN-NC). Size, morphology, encapsulation efficiency, cytotoxicity, and drug release were performed. The antihyperalgesic effect of LIN-NC was evaluated by a chronic non-inflammatory muscle pain model. The results demonstrated that the polymeric nanocapsules showed particle size of 199.1 ± 0.7 nm with a PDI measurement of 0.13 ± 0.01. The drug content and encapsulation efficiency were 13.78 ± 0.05 mg/mL and 80.98 ± 0.003%, respectively. The formulation did not show cytotoxicity on J774 macrophages. The oral treatment with LIN-NC and free-LIN increased the mechanical withdrawal threshold on all days of treatment in comparison with the control group. In conclusion, LIN-NC is a promising proposal in the development of phytotherapy-based nanoformulations for future clinical applications.

Characterization of ß-cyclodextrin/myrtenol complex and its protective effect against nociceptive behavior and cognitive impairment in a chronic musculoskeletal pain model.

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with ß-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into ß-cyclodextrin cavity. The interaction between myrtenol and ß-cyclodextrin was confirmed by molecular docking. Hence, the SC ß-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and ß-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the ß-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, ß-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.

Volatile profiling and UHPLC-QqQ-MS/MS polyphenol analysis of Passiflora leschenaultii DC. fruits and its anti-radical and anti-diabetic properties.

Twenty-four phenolic compounds including daidzein, epicatechin and artepillin C were identified in Passiflora leschenaultii DC. fruit by UHPLC-QqQ-MS/MS analysis. The aroma profile has been studied using the HS-SPME/GC-MS which revealed 67 volatile compounds including 13 terpenes, 18 alcoholics, 15 esters, ketones and phenolic acids. Further, the proximate composition, anti-radical and anti-diabetic activities of fruit pulp were also determined. The fresh fruit pulp of P. leschenaultii registered higher total phenolic (691.90 mg GAE/g extract) and tannin (313.81 mg GAE/g extract) contents and it also exhibited maximum DPPH (IC50 of 6.69 µg/ml) and ABTS+ (9760.44 µM trolox equivalent/g extract) scavenging activities. The fresh fruit pulp showed a strong inhibition towards the α-Amylase and α-Glucosidase (IC50 of 32.20 and 19.81 µg/mL, respectively) enzymes. Thus, the work stipulates that phenolic compounds rich P. leschenaultii fruit can serve as a potential nutraceutical, antioxidative and anti-diabetic agent in food and pharmaceutical formulations.

Inflammatory modulation of fluoxetine use in patients with depression: A systematic review and meta-analysis.

There is growing evidence that there is a relationship between major depressive disorder (MDD), also simply known as "depression", and inflammatory processes. Selective serotonin inhibitors, such as fluoxetine, are used as a first-line treatment for depression, and it is hypothesized that its use can reduce levels of proinflammatory cytokines. The aim of this systematic review and meta-analysis is to enable a better understanding of how treatment with the antidepressant fluoxetine modulates inflammation, and the roles of the main cytokines in this process. Risk of bias (RoB) in the included studies was assessed using the Cochrane Risk of Bias Assessment tool for Non-randomized studies (RoBANS). In the meta-analysis, standardized mean difference (SMD) was used as a summary statistic and grouped statistics using the generic inverse variation method in RevMan 5 with random effects model. Heterogeneous changes in cytokine levels were also evaluated from the SMD forest plot of individual studies. After analysis, we observed that fluoxetine was able to decrease TNF-α levels (SMD ± 0.90, 95% CI = 0.16, 1.165, Z ± 2.40, p = 0.02), but not change IL-6 levels (SMD ± 0.37, 95% CI = 0.21, 0.95, Z ± 1.25, p = 0.21).Fluoxetine acts by modulating neuroimmunology, and not only by acting only on the independent restoration of neurotransmission and neuroinflammation pathways.

Anti-inflammatory and antioxidant activity of carvacrol in the respiratory system: A systematic review and meta-analysis.

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta-analysis to assess the anti-inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE-PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti-inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta-analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)-1ß, IL-4, IL-8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL-6 and tumor necrosis factor alpha (TNF-α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti-inflammatory effects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation.

Therapeutic bullfrog oil-based nanoemulsion for oral application: Development, characterization and stability.

The aim of this study was to develop, optimize, and characterize a stable therapeutic bullfrog oil based nanoemulsion for oral application using a rational experimental design approach. The optimized oral nanoemulsion contained 0.2 % sodium benzoate and 0.02 % propyl-paraben as preservatives; 0.1 % sucralose and 0.4 % acesulfam K as sweeteners and 0.1 % tutti-frutti as flavoring to mask the unpleasant organoleptic characteristics of bullfrog oil. The oral O/W-nanoemulsion showed the droplet size, PDI, zeta potential, and pH of 410 ± 8 nm, 0.20 ± 0.02, -38 ± 2.5 mV, and 6.43 ± 0.05, respectively. The optimized oral nanoemulsion showed a milky single-phase and optimal physical stability at 25 °C for 90 days. Indeed, higher oxidation induction time and lower formation of peroxides in the oral nanoemulsion were responsible for improving its stability. A therapeutic delivery system containing bullfrog oil for oral application was successfully developed and optimized with ideal thermo-oxidative stability.

Anticonvulsant, sedative, anxiolytic and antidepressant activities of the essential oil of Annona vepretorum in mice: Involvement of GABAergic and serotonergic systems.

Annona vepretorum is an endemic species of the Caatinga biome, known in Northeastern Brazil as "araticum" and/or "pinha da Caatinga". In the present study it was evaluated the neuropharmacological potential of the essential oil obtained from the leaves of Annona vepretorum, as well as of the inclusion complexes of oil obtained with cyclodextrin. Thus, were used neuropharmacological tests already consolidated in the literature like open-field, elevated plus maze, rota-rod, tail suspension test, thiopental-induced sleep test, among others. The acute treatment of essential oil (EO) has anxiolytic, sedative, antiepileptic and antidepressant effects. The anxiolytic and anticonvulsant effects seems to be related to the GABAergic system, probably in the receptor subtypes that mediate the effects of the benzodiazepines, to generate anxiolytic activity. The sedative effect seems to be involved with other signaling pathways. The antidepressant effect of EO seems to be related to its action on serotonergic receptors. It was verified that some behavioral parameters were improved with the oil complexed with ß-cyclodextrin, but this effect was not uniform for all the doses and tests used. Further studies are needed in order to use other options for drug delivery systems. Thus, the essential oil of Annona vepretorum is a promising agent with neurobiological activity and a potential target for drug discovery, since the natural products such as medicinal plants have been a source of new therapeutic proposals.

Pharmacological Effects of Carvacrol in In vitro Studies: A Review.

Carvacrol has a high therapeutic potential, with in vitro studies showing promising results in different cellular models using a variety of methodological designs. Therefore, the objective of this study was to conduct a systematic review to analyze the pharmacological effects of carvacrol in in vitro studies. A comprehensive search of the literature was made using four databases: Science Direct, Scopus, MEDLINE-PubMed, and Web of Science using different combinations of the following keywords: carvacrol, drug therapy, therapeutic uses, in vitro study. The search of the databases was for studies conducted in the period up to and including September 2016. A total of 3,269 studies were initially identified, with only 31 meeting the inclusion criteria. The included studies contained a variety of in vitro models able to determine the properties of Carvacrol. The following properties of Carvacrol were identified: antimicrobial (7 studies), bactericidal (4), bactericidal and antifungal (1), antiinflammatory (4), anticancer (4), mutagenic (4), antioxidant (3), antifungal (3), antidepressant (1), as a modulator of nerve impulses (1) and an immunological modulator (1). The In vitro studies with Carvacrol included in this review showed a diversity of models and confirmed the therapeutic potential of this product in relation to several diseases.

Physicochemical Characterization and Antinociceptive Effect of ß-cyclodextrin/Lippia pedunculosa Essential Oil in Mice.

BACKGROUND: Some research studies have shown that Lippia pedunculosa essential oil (EOLP) has interesting biological activities. However, its low water solubility is the main challenge to achieve its therapeutic potential. In this context, Cyclodextrins (CDs) have been widely used in order to overcome this problem due to your capability to improve the physicochemical properties of drugs. OBJECTIVE: In this perspective, the main goal of this study was to investigate how the improvement of the physicochemical properties of inclusion complexes (EOLP and ß-CD) enhance the antinociceptive effect in mice. METHODS: To achieve that, we prepared samples by Physical Mixture (PM), Paste Complexation (PC) and Slurry Complexation (SC) methods, followed by their physicochemical characterization. In addition, it was evaluated if the use of ß-CD enhances the antinociceptive effect of EOLP in mice. RESULTS: The analysis showed that rotundifolone (72.02%) was the major compound of EOLP and we found out based on DSC results that ß-CD protected it from oxidation. In addition, TG techniques demonstrated that the best inclusion methods were PC and SC, due to their greater weight loss (10.8 and 11.6%, respectively) in the second stage (171-312°C), indicating that more complexed oil was released at the higher temperature than oil free. Other characteristics, such as changes in the typical crystalline form, and reduced particle size were observed by SEM and laser diffraction, respectively. The SC was the most effective complexation method, once the presence of rotundifolone was detected by FTIR. Based on that, SC method was used in all mice tests. In this regard, the number of paw licks was reduced for both compounds (all doses), but EOLP was more effective in reducing the nociceptive behavior. CONCLUSION: Therefore, CDs seem not to be a good tool to enhance the pharmacological properties of EOs rich in peroxide compounds such as rotundifolone.

Evaluation of Aristolochia indica L. and Piper nigrum L. methanol extract against centipede Scolopendra moristans L. using Wistar albino rats and screening of bioactive compounds by high pressure liquid chromatography: a polyherbal formulation.

The present study was aimed to explore the anti-venom activity of Aristolochia indica and Piper nigrum plants against the centipede (Scolopendra moristans) envenomation in animal model. In vtiro phytochemical, antioxidant and blocking of proteolysis were carried out by using standard spectrophotometric methods. In vivo anti-venom activity of methanol extracts was determined using Wistar albino rats after fixing lethal and effective doses. The electrolytes, lipid, liver, kidney, hematological parameters were analyzed and histopathology of skin and liver were also examined. Anti-skin cancer by MTT method and HPLC analysis were also carried out. The CAIPN extract showed higher total phenolics (150.65 ± 0.08 mg GAE/g extract) and flavonoids (158.97 ± 0.93 mg RE/g extract) content. Further, the same extract revealed the higher molybdenum reducing, inhibition of lipid peroxidation (80.08 ± 0.22%), DPPH radical scavenging (3.05 µg/mL), and blocking of proteolysis activities (96.45 ± 0.04%). The parameters like hypersensitivity, electrolytes, lipids, blood components, liver and kidney marker of the CAIPN methanol extract (200 mg/kg) treated envenomated rats was remarkable and same as in the normal animals. Such status was also achieved by RBAI and SPN at 600 mg/kg. The histopathological scoring of skin and liver confirmed the venom neutralizing activity of CAIPN. Also, the CAIPN methanol extract was notable in anti-skin cancer activity (208 µg/mL). The presence of the ferulic acid (04 ± 0.09 µg/mg) and quercetin (35.30 ± 0.30 µg/mg) like compounds was confirmed by HPLC analysis. Hence, the present investigation results conclude that the CAIPN was significant in their action and this polyherbal formulation could be considered as a new source for the pharmaceutical industries to develop a new effective, ecofriendly anti-venom drug.

UHPLC-QqQ-MS/MS identification, quantification of polyphenols from Passiflora subpeltata fruit pulp and determination of nutritional, antioxidant, α-amylase and α-glucosidase key enzymes inhibition properties.

The diabetic key enzymes inhibition, nutritional, antioxidant activity and bioactive compounds identification of Passiflora subpeltata fruit pulp were investigated. Fifteen polyphenolic compounds including protocatechuic acid, ferulic acid, vanillic acid, epicatechin, p-coumaric acid, cinnamic acid, eriodictyol and quercetin-3-glucoside were identified in the pulp of this species by using UHPLC-QqQ-MS/MS analysis. The total carbohydrates and crude protein contents in fruit pulp were 2.62 mg glucose equivalent/g sample fruit pulp and 8.80 mg BSA equivalent/g sample fruit pulp, respectively. The fresh fruit pulp of P. subpeltata contained high total phenolic (724.76 mg GAE/g sample) content and it revealed very high DPPH• (IC50 of 5.667 µg/mL) and ABTS+• (6794.96 µM trolox equivalent/g sample) scavenging activities. In the key enzymes assays useful for diabetic inhibition the fresh fruit pulp characterized maximum inhibition of α-amylase and α-glucosidase IC50 of 18.69 and 32.63 µg/mL, respectively. Thus, these results lead to conclude that this fruit specie could be very useful source in nutraceutical products preparations for Type 2 diabetic suffering humans.

Amorphous solid dispersions of hecogenin acetate using different polymers for enhancement of solubility and improvement of anti-hyperalgesic effect in neuropathic pain model in mice.

Hecogenin acetate (HA) is an acetylated sapogenin that has shown potential antihyperalgesic activity, inhibiting descending pain and acting in opioid receptors. However, HA exhibits poor aqueous solubility, which may limit its application. This study aims to develop amorphous solid dispersions (ASD) using five hydrophilic polymers, to characterize them and to evaluate their antihyperalgesic activity. Physicochemical characterization was performed by X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM) and Fourier Transformed Infrared (FTIR) spectroscopy. In order to evaluate the hyperalgesia of the ASD, sciatic nerve crush injury (NCI) was induced in mice followed by administration of the ASD, where three parameters were evaluated: mechanical and thermal hyperalgesia as well as grip strength. XRD and SEM showed that ASD of HA with HPMC obtained by kneading (KND) presented an amorphous profile, unlike the others polymers, indicating interaction between HA and HPMC. FTIR analysis evidenced the strong interaction between HA and HPMC. Although the results of mechanical hyperalgesia were slightly improved on the groups treated with ASD of HA with HPMC, the thermal hyperalgesia showed that the incorporation of HA into HPMC matrix significantly improved its antinociceptive activity.