Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery.

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines-fluticasone propionate (FP) and salmeterol xinafoate (SAL)-for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency- > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.

Development and Characterization of Transdermal Patches Using Novel Thymoquinone-L-Arginine-Based Polyamide Nanocapsules for Potential Use in the Management of Psoriasis.

Thymoquinone (TQ) is a phytochemical compound present in Nigella sativa and has potential benefits for treating dermatological conditions such as psoriasis. However, its clinical use is limited due to its restricted bioavailability, caused mainly by its low solubility and permeability. To overcome this, a new transdermal drug delivery system is required. Nanoparticles are known to enhance material solubility and permeability, and hence, this study aimed to synthesize TQ-loaded L-arginine-based polyamide (TQ/Arg PA) nanocapsules incorporated into transdermal patches for prolonged delivery of TQ. To achieve this, Eudragit E polymer, plasticizers, and aloe vera as penetration enhancer were used to develop the transdermal patch. Furthermore, novel TQ/Arg-PA was synthesized via interfacial polymerization, and the resultant nanocapsules (NCs) were incorporated into the matrix transdermal patch. The Arg-PA NCs' structure was confirmed via NMR and FTIR, and optimal TQ/Arg-PA NCs containing formulation showed high entrapment efficiency of TQ (99.60%). Molecular and thermal profiling of TQ/Arg-PA and the transdermal patch revealed the effective development of spherical NCs with an average particle size of 129.23 ± 18.22 nm. Using Franz diffusion cells and synthetic membrane (STRAT M®), the in vitro permeation profile of the prepared patches demonstrated an extended release of TQ over 24 h, with enhanced permeation by 42.64% when aloe vera was employed. In conclusion, the produced formulation has a potential substitute for corticosteroids and other drugs commonly used to treat psoriasis due to its effectiveness, safety, and lack of the side effects typically associated with other drugs.

Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation.

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats' model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-ß, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug.

Addressing 10 Myths About Pediatric Palliative Care.

With advances in biomedical sciences, a growing number of conditions affecting children have evolved from being considered life-limiting to almost chronic diseases. However, improvements in survival rates often come at a cost of increased medical complexity and lengthy hospitalizations, which can be associated with a poorer quality of life. This is where pediatric palliative care (PPC) can play a significant role. PPC is a specialty of healthcare that focuses on the prevention and relief of suffering in children with serious conditions. Unfortunately, despite the well-identified need for PPC services across pediatric specialties, multiple misconceptions persist. Common myths about palliative care are identified and deconstructed in light of the most recent evidenced-based references in the field to provide guidance to healthcare providers to address these. PPC is often associated with end-of-life care, loss of hope, and cancer. Some healthcare providers and parents also believe that information like diagnosis should be withheld from children for their emotional protection. These examples of misconceptions hinder the integration of pediatric palliative care and its additional layer of support and clinical expertise. PPC providers have advanced communication skills, are able to instill hope in the face of uncertainty, are trained to initiate and implement individualized pain and symptom management plans, and understand how to improve the quality of life in children with serious illnesses. Improved awareness about the scope of PPC is needed to ensure that children benefit from the maximum expertise and support throughout their complex health trajectories.

Prevalence and Knowledge of Respiratory Symptoms Among the General Public in the Southern Area of Najran, Saudi Arabia: A Cross-Sectional Health Survey Study.

Objective: To investigate the knowledge, prevalence of chronic respiratory disorders, and utilization of their medications among the adults at Najran region, Saudi Arabia. Methods: An online cross-sectional survey was carried out in Najran region, Saudi Arabia. A self-administered questionnaire was distributed among a random sample of the general population, aged 18 or above between March and December 2022. The survey instrument included questions regarding history and exposure, physician diagnosed-disorders, respiratory symptoms, allergy, use of medications and possible risk-related factors. Results: This research had a total of 712 individuals. Nearly one-third of the participants in the survey (n = 218; 30.6%) said that they or a member of their family suffer from respiratory ailments. The majority of research participants (n = 167; 76.8%) identified asthma as their primary respiratory condition. A total of 32.0% of participants (n = 70) reported dealing with dust or chemicals such as paints, fertilizers, and cleaning products on a daily basis at work or at home. Around 62.0% of the participants (n = 134) said that exposure to gases, fragrances, and other such substances negatively impacts their health. Almost 78.0% (n = 169) of them indicated that summer weather affects their health, whereas 63.0% (n = 138) reported that winter cold affects their health. Participants aged 41-50 years were 38.0% less likely to have CRDs compared to others (p < 0.05). Conclusion: This study is among the first few studies that explored the knowledge, prevalence of chronic respiratory disorders, and utilization of their medications among the adults at Najran region, Saudi Arabia. In the southern area of Najran, respiratory symptoms are frequent among the inhabitants of Saudi Arabia. More research is required to discover avoidable risk factors and create countermeasures for them. It is recommended that healthcare personnel increase their efforts to educate their patients about respiratory illness prevention methods.

Physicians' Knowledge, Attitudes, and Perception Toward Pediatric Palliative Care in Saudi Arabia: A National Exploratory Survey.

Background: Pediatric palliative care (PPC) helps maintain the quality of life for both children and their families. It has been identified as an important goal within the global health agenda. In Saudi Arabia, the discipline remains in its infancy, as illustrated by the absence of PPC programs in academic and health care institutions. Aim: The aim was to conduct a pilot study assessing physicians' knowledge, attitudes, and perceptions toward PPC. Method: Data were gathered through a self-administered questionnaire sent to physicians working in Saudi Arabia. Results: One hundred twelve completed the survey (male 54.2%, n = 50). A total of 40.8% (n = 42) had 20 years or more of experience, 42.9% (n = 48) were from the hematology-oncology specialty, and 68.5% (n = 74) received no training in PPC. Half suggested that children should be informed of their condition but mostly when reaching 12 or 15 years of age. Various physicians reported that the most appropriate time to discuss a transition to palliative care goals is when diagnosing an incurable condition or when despite all efforts, a condition continues to progress and death is expected. Conclusion: Multiple gaps were identified. PPC basic concepts should be included in the formal medical curriculum (e.g., pain management, communication, and ethical considerations at the end of life). There is also a significant need to develop further both primary and specialized palliative care.

Taste Masking of Promethazine Hydrochloride Using l-Arginine Polyamide-Based Nanocapsules.

Promethazine hydrochloride (PMZ), a potent H1-histamine blocker widely used to prevent motion sickness, dizziness, nausea, and vomiting, has a bitter taste. In the present study, taste masked PMZ nanocapsules (NCs) were prepared using an interfacial polycondensation technique. A one-step approach was used to expedite the synthesis of NCs made from a biocompatible and biodegradable polyamide based on l-arginine. The produced NCs had an average particle size of 193.63 ± 39.1 nm and a zeta potential of −31.7 ± 1.25 mV, indicating their stability. The NCs were characterized using differential scanning calorimetric analysis and X-ray diffraction, as well as transmission electron microscopy that demonstrated the formation of the NCs and the incorporation of PMZ within the polymer. The in vitro release study of the PMZ-loaded NCs displayed a 0.91 ± 0.02% release of PMZ after 10 min using artificial saliva as the dissolution media, indicating excellent taste masked particles. The in vivo study using mice revealed that the amount of fluid consumed by the PMZ-NCs group was significantly higher than that consumed by the free PMZ group (p < 0.05). This study confirmed that NCs using polyamides based on l-arginine and interfacial polycondensation can serve as a good platform for the effective taste masking of bitter actives.

Mechanistic modelling of targeted pulmonary delivery of dactinomycin iron oxide-loaded nanoparticles for lung cancer therapy.

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments. Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5-0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Assessment of vaping devices as an alternative respiratory drug delivery system.

The respiratory system has generated significant interest as an alternative drug delivery route. However, because of the limitations encountered with the present inhalation devices, alternative options could present an ideal opportunity to enhance therapeutic effectiveness and patient compliance. Vaping devices have been extensively used to deliver nicotine. This manuscript aimed to conduct an in vitro evaluation of the performance of commonly used vaping devices to assess their effectiveness in delivering fluticasone propionate (FP) to the lungs. Vaping devices were assessed for aerodynamic performance using the NGI. The e-liquid containing FP was made using glycerin and propylene glycol. The results showed the superiority of the vape-tank and vape-coil over the vape-pod. The vape-tank delivered the highest amount of nicotine. The e-liquid containing the FP was assessed and the results were compared with a marketed FP pressurized metered-dose inhaler (pMDI). The results of the respirable dose (RD) ranged from 22.10 µg for the vape pod, to 50.38 µg for the vape-tank; whereas the marketed pMDI value was 44.54 µg despite the lower content of FP per actuation in the vaping devices (100 µg versus 125 µg). Interestingly, the vaping devices showed a significantly lower level of oropharyngeal deposition than the pMDI (10% versus 50%), and hence, the potential for fewer side effects than those encountered with the chronic use of inhalers. Despite the effectiveness of the vape tank and coil in delivering a high percentage of FP, which makes them a promising alternative for delivering an effective yet user-friendly dosage of respiratory drugs, their safety and toxicity need to be established.

Tamoxifen Citrate Containing Topical Nanoemulgel Prepared by Ultrasonication Technique: Formulation Design and In Vitro Evaluation.

The present study aims to design and develop a nanoemulgel formulation of Tamoxifen citrate (TAM), a water-insoluble, potent anticancer drug, using the spontaneous emulsification method to improve topical delivery, achieve high accumulation at the tumour site, and spare the healthy tissues. The oil-based selection was related to the TAM solubility, while the surfactant and co-surfactant were chosen based on the droplets' thermodynamic stability and size. Afterwards, a pseudo-ternary phase diagram was built for the most promising formulation using two oils, olive and sesame, with a varied mix of Tween 40 as the surfactant and Trascutol HP as the co-surfactant (Smix), by the optimisation of experiments. The nanoemulsion (NE) formulations that were prepared were found to have an average droplet size of 41.77 ± 1.23 nm and 188.37 ± 3.53 nm, with suitable thermodynamic stability and physicochemical properties. Both olive and sesame oils are natural food additives due to their associated antioxidant effects; therefore, they showed no toxicity profile on breast cell lines (MCF-7, ATCC number HTB-22). The TAM-NE preparations revealed a prolonged and doublings superior cumulative percentage of in vitro release of TAM compared to TAM plain gel suspension over 24 h. The release data suggested that the Higuchi model was the best fitting kinetical model for the developed formulations of NE1, NE9, and NE18. The extended release of the drug as well as an acceptable amount of the drug permeated TAM via nanogel preparations suggested that nanoemulgel (NEG) is suitable for the topical delivery of TAM in breast cancer management. Thus, this work suggests that a nanogel of TAM can improve anticancer properties and reduce systemic adverse effects compared to a suspension preparation of TAM when applied in the treatment of breast cancer.

Medication errors in Najran, Saudi Arabia: Reporting, responsibility, and characteristics: A cross-sectional study.

Background: Medication error is a preventable adverse effect of medical care, whether or not it is evident or harmful to the patient. Disclosure of medication errors and improvement of patient safety are inexorably related, and they provide one of the strongest reasons to report and disclose errors, including near misses in which no harm comes to the patient. This study aimed to identify medication errors at the southern province of Saudi Arabia. Methods: A cross-sectional retrospective study was conducted by reviewing all medical records in the King Khaled Hospital in Najran, Saudi Arabia. Medication errors related information were extracted from the electronic medical system for the duration between 2018 and 2020. Results: During the study period of 2018 to 2020, a total of 4860 medication errors were identified. More than half of the reported medication errors (66.9%) were linked to ordering, prescribing, or transcribing medications. The most commonly reported medication errors connected to ordering/prescribing/transcribing were inappropriate dosage, dosage units, and therapeutic duplication of medication. The most commonly reported medication errors linked to administration were missing documentation during administration, not performing independent double-checks during the administration of high alert medications, and the administration of look-alike sound-alike (LASA) medications. The intensive care unit (ICU), female medical ward, and male medical ward were the most commonly reported locations for medication errors. Pharmacists detected more than half of the reported medication errors. Physicians were found to be responsible for 66.0% of reported medication errors, followed by nurses. Conclusion: Medication errors are common in hospital settings in Saudi Arabia's southern provinces. Efforts should be made to improve drug ordering, prescribing, and transcription in hospital settings. To guarantee optimum practices, the entire medical team should take responsibility for the patient's optimal medication administration.

Implementing a nurse-led paediatric palliative care service.

BACKGROUND: Children with life-limiting illnesses are living longer. They have complex care needs and require specialised knowledge and skills, yet paediatric palliative care is still at its infancy in most settings worldwide. AIMS: To describe the process of implementing a nurse-led paediatric palliative care programme in a large tertiary hospital in Saudi Arabia. METHODS: The steps that led to the implementation of this new nurse-led programme will be described through a 1-year analysis of collected data. FINDINGS: A total of 107 children received services from the paediatric palliative care programme for over one year, with cancer being the predominant diagnosis (n=71, 66.3%). More than half of the children had a do not attempt resuscitation (DNAR) order (n=54, 50.5%). The most frequently encountered issues were the family's difficulty in coping with the disease (n=80, 74.7%) and a child's uncontrolled pain (n=72, 67.3%). The most frequent interventions were family support and counselling (n=71, 66.3%), family education about symptom management (n=69, 64,5%) and adjusted analgesics (n=60, 56%). Children in the terminal stage of their disease had significantly more issues. CONCLUSION: Effective paediatric palliative care can be successfully implemented in a healthcare setting even when resources are limited. A nurse-led service was found to be a viable option for the delivery of palliative care to children with serious illnesses.

Knowledge and Attitudes toward Autism Spectrum Disorder in Saudi Arabia.

AIMS: The diagnosis of autism spectrum disorder (ASD) is not easy as there is no direct test that exists to establish such a diagnosis. Increasing community and healthcare professional knowledge of the ASD spectrum is crucial because it will encourage parents of ASD children to seek screening and diagnosis from a specialist, allowing for better early detection and treatment. This study explored the knowledge of the general population in Saudi Arabia regarding ASD and assessed variables associated with an accurate understanding of ASD. METHODS: A total of 769 participants were involved in this cross-sectional study, which was conducted in Saudi Arabia between November 2021 and February 2022 using an online survey tool to explore the knowledge of the general population in Saudi Arabia regarding typical child development and ASD. A binary logistic regression analysis was used to determine factors affecting participants' knowledge of autism. RESULTS: Overall, the study participants showed a weak level of knowledge about autism with a mean score of 5.9 (SD: 3.1), comprising 34.7% of the total maximum obtainable score. Participants with a middle income category of 5000-7500 SR are less likely to be knowledgeable about autism compared to others (OR: 0.60 (95% CI: 0.39-0.92)) (p-value = 0.020). CONCLUSION: The participants in our study showed limited knowledge about autism. Government funds should be made available to facilitate educational services for ASD children. More funding and resources should be allocated by the government to provide assistance for children with special needs, and changes in public facilities are required to meet the demands of ASD patients. Through an informed educational effort, various media platforms should assist in improving the community's understanding of ASD and their attitude toward ASD patients. Educational campaigns should focus on enhancing the public's knowledge about ASD treatment and etiology.

Correction: Naser et al. Knowledge and Practices during the COVID-19 Outbreak in the Middle East: A Cross-Sectional Study. Int. J. Environ. Res. Public Health 2021, 18, 4699.

The authors would like to make the following corrections about the published paper [...].

Novel Thymoquinone Nanoparticles Using Poly(ester amide) Based on L-Arginine-Targeting Pulmonary Drug Delivery.

Thymoquinone (TQ), the main active constituent of Nigella sativa, has demonstrated broad-spectrum antimicrobial, antioxidant, and anti-inflammatory effects, which suggest its potential use in secondary infections caused by COVID-19. However, clinical deployment has been hindered due to its limited aqueous solubility and poor bioavailability. Therefore, a targeted delivery system to the lungs using nanotechnology is needed to overcome limitations encountered with TQ. In this project, a novel TQ-loaded poly(ester amide) based on L-arginine nanoparticles was prepared using the interfacial polycondensation method for a dry powder inhaler targeting delivery of TQ to the lungs. The nanoparticles were characterized by FTIR and NMR to confirm the structure. Transmission electron microscopy and Zetasizer results confirmed the particle diameter of 52 nm. The high-dose formulation showed the entrapment efficiency and loading capacity values of TQ to be 99.77% and 35.56%, respectively. An XRD study proved that TQ did not change its crystallinity, which was further confirmed by the DSC study. Optimized nanoparticles were evaluated for their in vitro aerodynamic performance, which demonstrated an effective delivery of 22.7-23.7% of the nominal dose into the lower parts of the lungs. The high drug-targeting potential and efficiency demonstrates the significant role of the TQ nanoparticles for potential application in COVID-19 and other respiratory conditions.

Novel Fluticasone Propionate and Salmeterol Fixed-Dose Combination Nano-Encapsulated Particles Using Polyamide Based on L-Lysine.

One of the key challenges in developing a dry powder inhaler (DPI) of an inhalable potent fixed-dose combination (FDC) is the ability of the formulation to generate an effective and reproducible aerosol able to reach the lower parts of the lungs. Herein, a one-step approach is presented to expedite the synthesis of nanoaggregates made from a biocompatible and biodegradable polyamide based on L-lysine amino acid employing market-leading active pharmaceutical ingredients (fluticasone propionate (FP) and salmeterol xinafoate (SAL)) for the management of asthma. The nanoaggregates were synthesized using interfacial polycondensation that produced nanocapsules with an average particle size of 226.7 ± 35.3 nm and zeta potential of -30.6 ± 4.2 mV. Differential scanning calorimetric analysis and x-ray diffraction, as well as scanning electron microscopy of the produced FDC, revealed the ability of the produced nanocapsules to encapsulate the two actives and display the best aerodynamic performance. The FDC nanocapsules displayed 88.5% and 98.5% of the emitted dose for FP and SAL, respectively. The fine particle fraction of the nominated dose was superior to the marketed product (Seretide Diskus®, Brentford, United Kingdom). The in-vitro release study showed an extended drug release profile. Our findings suggest that nanoaggregates using polyamides based on L-lysine and interfacial polycondensation can serve as a good platform for pulmonary drug delivery of FDC systems.

Design, Characterization, and Antimicrobial Evaluation of Copper Nanoparticles Utilizing Tamarixinin a Ellagitannin from Galls of Tamarix aphylla.

The application of plant extracts or plant-derived compounds in the green synthesis of metal nanoparticles (NPs) was researched. Determining the exact metabolite implicated in the formation of NPs would necessitate comprehensive investigations. Copper nanoparticles (CuNPs) are gaining a lot of attention because of their unique properties and effectiveness against a wide range of bacteria and fungi, as well as their potential for usage in catalytic, optical, electrical, and microelectronics applications. In the course of this study, we aimed to formulate CuNPs utilizing pure tamarixinin A (TA) ellagitannin isolated from Tamarix aphylla galls. The main particle size of the formed CuNPs was 44 ± 1.7 nm with zeta potential equal to -23.7 mV, which emphasize the stability of the CuNPs. The X-ray diffraction spectroscopy showed a typical centered cubic crystalline structure phase of copper. Scanning electron microscopy images were found to be relatively spherical and homogeneous in shape. The antimicrobial properties of TA, as well as its mediated CuNPs, have been evaluated through well diffusion assays against four bacterial, Bacillus subtilis NCTC 10400, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, and two fungal, Candida albicans and Aspergillus flavus, strains. The distinctive antimicrobial activities were noted against the fungal strains and the Gram-negative bacterial strains P. aeruginosa ATCC 27853, and E. coli ATCC 25922. In conclusion, CuNPs mediated by TA can be applied for combating a wide range of bacterial and fungal species especially C. albicans, Asp. flavus, and P. aeruginosa in a variety of fields.

Ellagitannins and simple phenolics from the halophytic plant Tamarix nilotica.

Three new [nilotinins M8‒M10 (1‒3)] and two known [tamarixinin A (4) and gemin D (5)] ellagitannins and seven simple phenolics [gallic acid (6), methyl gallate (7), 3,4-di-O-methylgallic acid (8), ellagic acid (9), 3-O-methylellagic acid (10), methyl ferulate 3-O-sulphate (11), and 7,4'-di-O-methylkaempferol (12)] were isolated from the halophytic plant Tamarix nilotica (Ehrenb.) Bunge (Tamaricaceae). Their structures were determined based on intensive spectroscopic studies and comparisons with reported data. Compounds 4, and 6-8 were evaluated for their cytotoxicity against lung adenocarcinoma cell line (A549) and anti-leishmanial activity against Leishmania major. Compounds 4, 6 and 7 showed promising cytotoxic properties against A549 (IC50 29 ± 2.3, 10.5 ± 0.7, and 20.7 ± 1.9 µg/mL), while compounds 4 and 7 showed higher growth-inhibitory effects against L. major promastigotes (IC50 40.5 ± 2.7 and 38.4 ± 2.5 µg/mL), as compared with the standards doxorubicin (IC50 0.42 µg/mL) and miltefosine (IC50 9.43 µg/mL), respectively.

Antileishmanial and lung adenocarcinoma cell toxicity of Withania somnifera (Linn.) dunal root and fruit extracts.

This study aims to evaluate the anti-Leishmania major and the lung adenocarcinoma (A549) cytotoxicity of Withania somnifera root and fruit. The total extracts were obtained by homogenisation in aqueous MeOH, and the sub-extracts [n-hexane, ethyl acetate (EtOAc), n-butanol (n-BuOH), and methanol (MeOH)] were obtained by flash chromatography. The activity evaluation showed that n-BuOH sub-extracts from root and fruit exhibited noticeable antileishmanial promastigote properties. The n-hexane and EtOAc sub-extracts from both organs, and the MeOH sub-extract from the fruit exerted mild to moderate effects on the promastigotes. In-vitro growth-inhibitory test results on axenic amastigote and cytotoxicity testing on macrophages (RAW264.7), the parasite-host at the amastigote stage, revealed that the activity was mainly concentrated in the root EtOAc and n-BuOH sub-extracts and to a lesser extent the fruit MeOH and EtOAc, and the root n-hexane sub-extracts. Only the roots' EtOAc and n-BuOH sub-extracts demonstrated low cytotoxicity on the A549 cell line.

Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers.

Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the C. macrocarpa leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the C. macrocarpa leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side effects.