Search Results (33)

The General Movements Assessment provides early insight into motor development’s range of motion; however, its relationship with joint kinematics, such as hip abduction range of motion, remains underexplored. This study analyzed hip abduction kinematics during General Movements, evaluating potential sex differences and variations in movement patterns (Fidgety vs. Writhing), and aimed to provide quantitative data that complement qualitative pediatric assessments. This cross-sectional observational study analyzed video recordings of spontaneous motor activity in 32 infants under three months of corrected age. Hip abduction range of motion was extracted using biomechanical analysis during General Movements. Interrater reliability was evaluated using Fleiss’s Kappa. Correlations were assessed using Pearson’s test, and a two-way ANOVA examined the effects of sex and the type of movements on range of motion. Interrater reliability for movement classification was excellent (Kappa = 0.909, p < 0.001). No significant correlations were found between sex or General Movements type and hip abduction range of motion (p > 0.68). Two-way ANOVA showed no significant effects of sex, movement pattern, or their interaction on range of motion in either hip (right: p = 0.726, left: p = 0.823), with small effect sizes (η² < 0.013). A minor asymmetry favoring the right hip was observed but was not clinically significant. Sex and General Movements type did not significantly influence hip abduction range of motion in infants under three months. Early joint mobility appears consistent across sexes and movement patterns, supporting its reliability as a biomechanical marker of typical development. Full article

An essential oil dominated by germacrene D (19.3% by GC) was isolated from the fresh fruit of Amorpha fruticosa L. (Fabaceae). Agglomerative clustering and k-means clustering were employed to compare the composition of the oil with the existing literature data, suggesting that the A. fruticosa used in this study represents a new chemotype. The essential oil was evaluated for its antinociceptive activity using the acetic acid-induced writhing test in rats at doses of 400, 200, and 100 mg/kg. All tested doses reduced the number of writhes induced by the intraperitoneal injection of acetic acid. The 400 mg/kg dose of the oil demonstrated a 54.4% inhibition, which was statistically different from the positive control, aspirin, which showed 90.2% inhibition at a dose of 200 mg/kg. Since the injection of acetic acid produces the release of prostaglandins, such as PGE2α and PGF2α, as well as sympathetic nervous system mediators in peritoneal fluids, the results suggest that the inhibition of prostaglandin release might represent one of the possible mechanisms of action exerted by the oil. Full article

Background:Asarum heterotropoides and Asarum sieboldii are commonly used in traditional Chinese medicine. However, little is known about how they differ in terms of essential oil (EO) and ethanol extract (EE) content and composition. Moreover, the effect of various geographical locations on the essential oil (EO), ethanol extract (EE), and asarinin content of different Asarum samples remains unknown. We tested four root-drying methods, i.e., soil removal and shade drying (P1), water washing and shade drying (P2), and water washing and drying at 30 °C (P3) and 40 °C (P4). We used LC-MS and GC-MS to investigate these differences. We also investigated the pharmacodynamic effects of EO and EE. Results: Overall, the EO, EE and asarinin contents of the analysed samples were 19.21–51.53 μL.g⁻¹, 20.00–45.00 μL.g⁻¹, and 1.268–2.591 mg.g⁻¹, respectively. P1 treatment yielded the lowest volatile oil content compared to the other three treatments. GC-MS analysis revealed 78 EO components. Among the six major EO components, eucarvone, 3,5-dimethoxytoluene, and methyl eugenol were higher in A. heterotropoides than in A. sieboldii. However, the latter had a higher myristicin content. LC-MS analysis identified 888 EE components in roots and leaves of A. heterotropoides and A. sieboldii; 317 differentially accumulated metabolites were identified. EO and EE showed a dose-dependent reduction in the degree of swelling and an increase in the inhibition rate of drug concentration on acetic acid writhing in mice. Asarum EO proved to be more effective than EE in the pharmacodynamic study. Conclusions: We conclude that Asarum species show inter- and intra-specific differences in EO and EE content and composition, which may influence the pharmacodynamics of Asarum root extracts. Full article

The design, synthesis, and evaluation of novel non-steroidal anti-inflammatory drugs (NSAIDs) with better activity and lower side effects are big challenges today. In this work, two 5-acetamido-2-hydroxy benzoic acid derivatives were proposed, increasing the alkyl position (methyl) in an acetamide moiety, and synthesized, and their structural elucidation was performed using ¹H NMR and ¹³C NMR. The changes in methyl in larger groups such as phenyl and benzyl aim to increase their selectivity over cyclooxygenase 2 (COX-2). These 5-acetamido-2-hydroxy benzoic acid derivatives were prepared using classic methods of acylation reactions with anhydride or acyl chloride. Pharmacokinetics and toxicological properties were predicted using computational tools, and their binding affinity (kcal/mol) with COX-2 receptors (Mus musculus and Homo sapiens) was analyzed using docking studies (PDB ID 4PH9, 5KIR, 1PXX and 5F1A). An in-silico study showed that 5-acetamido-2-hydroxy benzoic acid derivates have a better bioavailability and binding affinity with the COX-2 receptor, and in-vivo anti-nociceptive activity was investigated by means of a writhing test induced by acetic acid and a hot plate. PS3, at doses of 20 and 50 mg/kg, reduced painful activity by 74% and 75%, respectively, when compared to the control group (20 mg/kg). Regarding the anti-nociceptive activity, the benzyl showed reductions in painful activity when compared to acetaminophen and 5-acetamido-2-hydroxy benzoic acid. However, the proposed derivatives are potentially more active than 5-acetamido-2-hydroxy benzoic acid and they support the design of novel and safer derivative candidates. Consequently, more studies need to be conducted to evaluate the different pharmacological actions, the toxicity of possible metabolites that can be generated, and their potential use in inflammation and pain therapy. Full article

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC₅₀ = 1.09 mg/mL and IC₅₀ = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC₅₀ = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out. Full article

Wild Vitex agnus-castus (VAC) is a Mediterranean plant that is rich in bioactive metabolites. This study aimed to validate, for the first time, the beneficial use of VAC fruits and fruit decoctions (VFDs) through in vitro and in vivo trials. Forty-one volatile components were detected in VAC fruits, with 1,8-cineole (30.3%) comprising the majority. The antioxidant activity of VFD was measured by using different in vitro methods (EC₅₀ of 0.16 mg/mL by β-carotene bleaching inhibition assay) and by measuring the DNA protection power. Using the disc diffusion assay, the antimicrobial activity of VFD was evaluated, and it exhibited a noticeable anticandidal activity. VFD did not cause any toxicity or mortality in rats treated with doses > 200 mg/kg. Using the acetic acid writhing test, the antinociceptive activity of VFD was measured. Our results showed that VFD at 200 mg/kg exhibited a higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). Its gastroprotective ability was assessed by HCl/ethanol-induced gastric lesions, which were remarkably inhibited (84.62%) by intraperitoneal administration of VFD. This work helps to validate the popular use of VAC to treat nociceptive, inflammatory, and gastric disorders and encourages researchers to further investigate the identification of pharmacological compounds from this species. Full article

Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora’s flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV–visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm⁻¹, 1000 cm⁻¹, 1500 cm⁻¹, and 1650 cm⁻¹ reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections. Full article

The goal of this work was to investigate the impact of the flavoring of some aromatic plants/spices, including rosemary (R), lemon (L) and orange (O) at the concentration of 5% and 35% (w/w) added by 2 methods (conventional maceration and direct flavoring), on quality attributes, chemical changes and oxidative stability of extra virgin olive oil (EVOO). Six flavored oils were obtained (EVOO + O, O + O, EVOO + R, O + R, EVOO + L and O + L). The physicochemical parameters (water content, refractive index, acidity and peroxide value, extinction coefficient, fatty acids, volatile aroma profiles, Rancimat test, phenols and pigments composition) of the flavored oils were investigated. Based on the results obtained, it was observed that flavoring with a conventional process provided increased oxidative stability to the flavored oils, especially with rosemary (19.38 ± 0.26 h), compared to that of unflavored oil. The volatile profiles of the different flavored oils revealed the presence of 34 compounds with the dominance of Limonene. The fatty acid composition showed an abundance of mono-unsaturated fatty acids followed by poly-unsaturated ones. Moreover, a high antioxidant activity, a significant peripheral analgesic effect (77.7% of writhing inhibition) and an interesting gastroprotective action (96.59% of ulcer inhibition) have been observed for the rosemary-flavored oil. Indeed, the flavored olive oils of this study could be used as new functional foods, leading to new customers and further markets. Full article

α-conotoxin AuIB is the only one of the 4/6 type α-conotoxins (α-CTxs) that inhibits the γ-aminobutyric acid receptor B (GABA_BR)-coupled N-type calcium channel (Ca_V2.2). To improve its inhibitory activity, a series of variants were synthesized and evaluated according to the structure–activity relationships of 4/7 type α-CTxs targeting GABA_BR-coupled Ca_V2.2. Surprisingly, only the substitution of Pro7 with Arg results in a 2–3-fold increase in the inhibition of GABA_BR-coupled Ca_V2.2 (IC₅₀ is 0.74 nM); substitutions of position 9–12 with basic or hydrophobic amino acid and the addition of hydrophobic amino acid Leu or Ile at the second loop to mimic 4/7 type α-CTxs all failed to improve the inhibitory activity of AuIB against GABA_BR-coupled Ca_V2.2. Interestingly, the most potent form of AuIB[P7R] has disulfide bridges of “1–4, 2–3” (ribbon), which differs from the “1–3, 2–4” (globular) in the isoforms of wildtype AuIB. In addition, AuIB[P7R](globular) displays potent analgesic activity in the acetic acid writhing model and the partial sciatic nerve injury (PNL) model. Our study demonstrated that 4/6 type α-CTxs, with the disulfide bridge connectivity “1–4, 2–3,” are also potent inhibitors for GABA_BR-coupled Ca_V2.2, exhibiting potent analgesic activity. Full article

We performed molecular dynamics simulations of DNA polymer chains confined in helical nano-channels under compression in order to explore the potential of knot-factories with helical geometry to produce knots with a preferred handedness. In our simulations, we explore mutual effect of the confinement strength and compressive forces in a range covering weak, intermediate and strong confinement together with weak and strong compressive forces. The results find that while the common metrics of polymer chain in cylindrical and helical channels are very similar, the DNA in helical channels exhibits greatly different topology in terms of chain knottedness, writhe and handedness of knots. The results show that knots with a preferred chirality in terms of average writhe can be produced by using channels with a chosen handedness. Full article

Saffron is the most expensive spice in the world. In addition to its culinary utilization, this spice is used for medicinal purposes such as in pain management. In this study, the analgesic activity of Crocus sativus stigma extract (CSSE) was evaluated in rodents and its possible physiological mechanism was elucidated. The anti-nociceptive effect of CSSE was evaluated using three animal models (hot plate, writhing, and formalin tests). The analgesic pathways involved were assessed using various analgesia-mediating receptors antagonists. The oral administration of CSSE, up to 2000 mg/kg, caused no death or changes in the behavior or in the hematological and biochemical blood parameters of treated animals nor in the histological architecture of the animals’ livers and kidneys. CSSE showed a central, dose-dependent, anti-nociceptive effect in response to thermal stimuli; and a peripheral analgesic effect in the test of contortions induced by acetic acid. The dual (central and peripheral) analgesic effect was confirmed by the formalin test. The anti-nociceptive activity of CSSE was totally or partially reversed by the co-administration of receptor antagonists, naloxone, atropine, haloperidol, yohimbine, and glibenclamide. CSSE influenced signal processing, by the modulation of the opioidergic, adrenergic, and muscarinic systems at the peripheral and central levels; and by regulation of the dopaminergic system and control of the opening of the ATP-sensitive K⁺ channels at the spinal level. The obtained data point to a multimodal mechanism of action for CSSE: An anti-inflammatory effect and a modulation, through different physiological pathways, of the electrical signal generated by the nociceptors. Further clinical trials are required to endorse the potential utilization of Moroccan saffron as a natural painkiller. Full article

Coumaric acid (CouH), an antioxidant molecule assimilated by food consumption, was intercalated into layered double hydroxide (LDH) nanocarrier, having zinc and aluminium ions in the layers (LDH-Cou), to evaluate its pharmacological activity through in vitro and in vivo assays in mice. Therefore, the following tests were performed: coumarate delivery in saline solution, fibroblasts’ cell viability using neutral red, peritonitis induced by carrageenan, formalin test, acetic-acid-induced writhing, and tail-flick assay, for the non-intercalated CouH and the intercalated LDH-Cou system. Furthermore, different pharmacological pathways were also investigated to evaluate their possible anti-inflammatory and antinociceptive mechanisms of action, in comparison to traditionally used agents (morphine, naloxone, caffeine, and indomethacin). The LDH-Cou drug delivery system showed more pronounced anti-inflammatory effect than CouH but not more than that evoked by the classic non-steroidal anti-inflammatory drug (NSAID) indomethacin. For the analgesic effect, according to the tail-flick test, the treatment with LDH-Cou expressively increased the analgesia duration (p < 0.001) by approximately 1.7–1.8 times compared to CouH or indomethacin. Thus, the results pointed out that the LDH-Cou system induced in vivo analgesic and anti-inflammatory activities and possibly uses similar mechanisms to that observed for classic NSAIDs, such as indomethacin. Full article

Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This study aimed to evaluate the long-lasting neurobehavioral and nociceptive consequences in adult offspring rats and mice exposed to morphine during intrauterine/lactation periods. Pregnant rats and mice were exposed subcutaneously to morphine (10 mg/kg/day) during 42 consecutive days (from the first day of pregnancy until the last day of lactation). Offspring were weighed on post-natal days (PND) 1, 5, 10, 15, 20, 30, and 60, and behavioral tasks (experiment 1) or nociceptive responses (experiment 2) were assessed at 75 days of age (adult life). Morphine-exposed female rats displayed increased spontaneous locomotor activity. More importantly, both males and female rats perinatally exposed to morphine displayed anxiety- and depressive-like behaviors. Morphine-exposed mice presented alterations in the nociceptive responses on the writhing test. This study showed that sex difference plays a role in pain threshold and that deleterious effects of morphine during pre/perinatal periods are nonrepairable in adulthood, which highlights the long-lasting clinical consequences related to anxiety, depression, and nociceptive disorders in adulthood followed by intrauterine and lactation morphine exposure. Full article

F-polynomials for virtual knots were defined by Kaur, Prabhakar and Vesnin in 2018 using flat virtual knot invariants. These polynomials naturally generalize Kauffman’s affine index polynomial and use smoothing in the classical crossing of a virtual knot diagram. In this paper, we introduce weight functions for ordered orientable virtual and flat virtual links. A flat virtual link is an equivalence class of virtual links with respect to a local symmetry changing a type of classical crossing in a diagram. By considering three types of smoothing in classical crossings of a virtual link diagram and suitable weight functions, there is provided a recurrent construction for new invariants. It is demonstrated by explicit examples that newly defined polynomial invariants are stronger than F-polynomials. Full article

This study aims to investigate the potential analgesic properties of the crude extract of Monochoria hastata (MH) leaves using in vivo experiments and in silico analysis. The extract, in a dose-dependent manner, exhibited a moderate analgesic property (~54% pain inhibition in acetic acid-induced writhing test), which is significant (** p < 0.001) as compared to the control group. The complex inflammatory mechanism involves diverse pathways and they are inter-connected. Therefore, multiple inflammatory modulator proteins were selected as the target for in silico analysis. Computational analysis suggests that all the selected targets had different degrees of interaction with the phytochemicals from the extract. Rutin (RU), protocatechuic acid (PA), vanillic acid (VA), and ferulic acid (FA) could regulate multiple targets with a robust efficiency. None of the compounds showed selectivity to Cyclooxygenase-2 (COX-2). However, regulation of COX and lipoxygenase (LOX) cascade by PA can reduce non-steroidal analgesic drugs (NSAIDs)-related side effects, including asthma. RU showed robust regulation of cytokine-mediated pathways like RAS/MAPK and PI3K/NF-kB by inhibition of EGFR and IKBα (IKK), which may prevent multi-organ failure due to cytokine storm in several microbial infections, for example, SARS-CoV-2. Further investigation, using in vivo and in vitro experiments, can be conducted to develop multi-target anti-inflammatory drugs using the isolated compounds from the extract. Full article