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BACKGROUND: Cardiopulmonary resuscitation (CPR) is a procedure performed in an emergency when the heart stops. Early initiation of CPR can save many lives. Thus, the aim of the present study was to assess the level of awareness toward CPR in a community-based study in Northern Saudi Arabia. MATERIALS AND METHODS: This is a cross-sectional survey conducted in the city of Hail, Northern Saudi Arabia. Data about CPR were obtained from 442 Saudi volunteers living in the city of Hail. RESULTS: A family history of ischemic heart disease was indicated in 148/442 (33.5%) of the participants. On asking the participants whether they have previous information about CPR, about 258/442 (58.4%) persons indicated “Yes,” 118/442 (26.6%) replied “May be,” and the remaining 66/442 (15%) replied “No.” CONCLUSION: The study showed a high level of awareness about CPR, which might be attributed to the majority of highly educated participants. Effective and sustainable public CPR training programs are needed to be implemented to preserve better knowledge and awareness of CPR in the general population.

Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and -6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and -23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).

Conventional RA treatments required prolonged therapy courses that have been accompanied with numerous side effects impairing the patient's quality of life. Therefore, microneedles combined with nanotechnology emerged as a promising alternative non-invasive, effective and self-administrating treatment option. Hence, the main aim of this study is to reduce the side effects associated with systemic teriflunomide administration through its encapsulation in solid lipid nanoparticles (TER-SLNs) and their administration through transdermal route using AdminPen™ hollow microneedles array in the affected joint area directly. In vitro characterization studies were conducted including particle size, zeta potential, encapsulation efficiency and in vitro drug release. Also, ex vivo insertion properties of AdminPen™ hollow microneedles array was carried out. Besides, in vivo evaluation in rats with antigen induced arthritis model were also conducted by assessment of joint diameter, histopathological examination of the dissected joints and testing the levels of TNF-α, IL1B, IL7, MDA, MMP 3, and NRF2 at the end of the experiment. The selected TER-SLNs formulation was about 155.3 nm with negative surface charge and 96.45 % entrapment efficiency. TER-SLNs had a spherical shape and provided sustained release for nearly 96 h. In vivo results demonstrated that nanoencapsulation along with the use of hollow microneedles had a significant influence in improving TER anti-arthritic effects compared with TER suspension with no significant difference from the negative control group., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Chemotherapeutic agents are used to treat a wide range of cancer types, but they cause serious side effects which must be managed after treatment. Cyclophosphamide (CYP) is one of chemotherapeutic drugs that causes hemorrhagic cystitis (HC) induced by acrolein., Objective: The current investigation intended to uncover the role of chrysin (CHR) in CYP-induced HC in rats and explore the signaling pathway beyond this effect., Analysis: process: A single dose of CYP (200 mg/kg/IP) was injected, meanwhile CHR (25, 50 and 100 mg/kg, P.O) was administered respectively for 7 days prior to CYP administration and resume for 7 days afterwards. Urinary bladder tissue was then isolated from all rats to assess oxidative stress and inflammatory biomarkers. Moreover, histopathological examinations were performed., Results: Treatment with CHR showed a marked alleviation in oxidative stress biomarkers induced by CYP. Furthermore, CHR treatment presented a dose-dependent boost in the anti-inflammatory; IL-10 levels and a drop in the pro-inflammatory biomarkers; IL-1β, IL-6, and TNF-α. Additionally, stabilization of the PARP-1 protein expression was also detected thus preventing DNA damage. Similarly, CHR restored the urinary bladder cGMP levels. Notably, CHR treatment was accompanied with inhibition in NF-κB/p38-MAPK, NO/PARP-1 and STAT-3 signaling pathways inflammatory cascades. All these findings conformed with the histopathological examinations as well as iNOS immunostaining in the urinary bladder tissue., Conclusion: Co-administration of CHR and CYP attained uro-protective therapeutic potential to guard against HC as well as spot the tangled mechanism of CHR in attenuating the HC induced by CYP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Gastric ulcer is a common gastrointestinal ailment that affects many people worldwide. NSAIDs induced ulcers are the second most common etiology of gastric ulcers. Coconut oil has well-known potential anti-ulcerogenic characteristics. This work aimed to develop and optimize diclofenac potassium (a highly used model drug of NSAIDs) as self-nanoemulsifying delivery system containing coconut oil (DFP-COSNEDS) to overcome its ulcerogenic effect. A mixture design was applied for formula optimization and investigation of the effect of different formulation factors on the droplet size (DS) and polydispersity index (PDI) of the prepared DFP-COSNEDS. The optimized formulae showed good self-emulsification characters and better drug dissolution compared with the drug suspension. The ulcer protection was assessed in-vivo using 7 groups of adult male Wistar rats. Oxidative stress parameters (MDA, GSH, and SOD), inflammatory mediators (PGE-2, TNF-α, and IL-6) and peroxisome proliferator-activated receptor-γ (PPAR-γ) gene expression were measured. The results revealed that pure coconut oil and DFP-COSNEDS containing 25 % of coconut oil showed close figures to normal group and better values than famotidine (FAM) group. In conclusion, coconut oil showed high potential for gastric-protection activity against DFP induced ulcer. DFP-COSNEDS offers dual benefits of improving DFP dissolution and alleviating its ulcerogenic effect., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The neuroprotective capacity of morin hydrate (MH), a potent antioxidant flavonoid, and calpeptin (CP), a calpain inhibitor, was documented against different insults but not Huntington's disease (HD). Accordingly, we aim to assess the neuroprotective potential of MH and/or CP in a 3-nitropropionic acid (3-NP)-induced HD model. The 3-NP-treated rats were post-treated with saline, MH, CP, or MH + CP for a week. Post-treatment with MH and/or CP amended motor function (beam walking test) and short-/ long-term spatial memory (novel object recognition test) and improved cortical microscopic architecture. On the molecular level, MH, and to a lesser extent CP, inhibited the cortical content/expression of glutamate, calpain, and Kidins220 and abated the inflammatory molecules, nuclear factor (NF)-κB, tumor necrosis factor-α, and interleukin-1β, as well as lipid peroxidation. However, MH, but barely CP, activated the molecules of the neuroprotective trajectory; viz., brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (TrkB), protein kinase B (AKT), and cAMP response element-binding protein (CREB). Compared to the single treatments, the combination regimen mediated further reductions in the cortical contents of glutamate, calpain, and Kidins220, effects that extended to entail the anti-inflammatory/anti-oxidant potentials of MH and to a greater extent CP. However, the combination of MH strengthened the fair effect of CP on the survival signaling pathway BDNF/TrkB/AKT/CREB. In conclusion, MH, CP, and especially their combination, afforded neuroprotection against HD through curbing the glutamate/calpain axis, Kidins220, as well as NF-κB-mediated neuroinflammation/oxidative stress, besides activating the BDNF/TrkB/AKT/CREB hub that was partly dependent on calpain inhibition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Preparation and evaluation of a non-invasive intranasal luteolin delivery for the management of cognitive dysfunction in Alzheimer's disease (AD) using novel chitosan decorated nanoparticles. Development of luteolin-loaded chitosomes was followed by full in vitro characterization. In vivo efficacy was evaluated using a sporadic Alzheimer's disease (SAD) animal model via intracerebroventricular injection of 3 mg/kg streptozotocin (ICV-STZ). Treatment groups of luteolin suspension and chitosomes (50 mg/kg) were then intranasally administered after 5 h of ICV-STZ followed by everyday administration for 21 consecutive days. Behavioral, histological, immunohistochemical, and biochemical studies were conducted. Chitosomes yielded promising quality attributes in terms of particle size (PS) (412.8 ± 3.28 nm), polydispersity index (PDI) (0.378 ± 0.07), Zeta potential (ZP) (37.4 ± 2.13 mv), and percentage entrapment efficiency (EE%) (86.6 ± 2.05%). Behavioral findings showed obvious improvement in the acquisition of short-term and long-term spatial memory. Furthermore, histological evaluation revealed an increased neuronal survival rate with a reduction in the number of amyloid plaques. Biochemical results showed improved antioxidant effects and reduced pro-inflammatory mediators' levels. In addition, a suppression by half was observed in the levels of both Aβ aggregation and hyperphosphorylated-tau protein in comparison to the model control group which in turn confirmed the capability of luteolin-loaded chitosomes (LUT-CHS) in attenuating the pathological changes of AD. The prepared nanoparticles are considered a promising safe, effective, and non-invasive nanodelivery system that improves cognitive function in SAD albino mice as opposed to luteolin suspension.

Impaired memory and cognitive function are the main features of Alzheimer's disease (AD). Unfortunately, currently available treatments cannot cure or delay AD progression. Moreover, the blood-brain barrier hampers effective delivery of treatment to the brain. Therefore, we aimed to evaluate the impact of intranasally delivered luteolin on AD using bile-salt-based nano-vesicles (bilosomes). Different bilosomes were prepared using 2 3 -factorial design. The variables were defined by the concentration of surfactant, the molar ratio of cholesterol:phospholipid, and the concentration of bile salt. Results demonstrated optimized luteolin-loaded bilosomes with particle size (153.2 ± 0.98 nm), zeta potential (-42.8 ± 0.24 mV), entrapment efficiency% (70.4 ± 0.77%), and % drug released after 8 h (80.0 ± 1.10%). In vivo experiments were conducted on an AD mouse model via intracerebroventricular injection of 3 mg/kg streptozotocin. We conducted behavioral, biochemical marker, histological, and immune histochemistry assays after administering a luteolin suspension or luteolin bilosomes (50 mg/kg) intranasally for 21 consecutive days. Luteolin bilosomes improved short-term and long-term spatial memory. They also exhibited antioxidant properties and reduced levels of proinflammatory mediators. They also suppressed both amyloid β aggregation and hyperphosphorylated Tau protein levels in the hippocampus. In conclusion, luteolin bilosomes are an effective, safe, and non-invasive approach with superior cognitive function capabilities compared to luteolin suspension.

Five flavonoids were isolated from the ethyl acetate fraction of leaves of Sophora secundiflora ; formononetin (1) , 5-hydroxy-4'-methoxyflavone (2) , genistein (3) , 5-hydroxy-8-(1-hydroxy-1-methyl-ethyl)-2-(4-hydroxyphenyl)-4 H -furo-[2, 3- h ]-chromen-4-one (4) and ononin (5) . Additionally, LC-ESI-MS/MS analysis of the ethyl acetate fraction of S. secundiflora leaves had led to tentative identification of eighteen compounds. Formononetin, S. tomentosa and S. secundiflora leaves methanolic extract were evaluated in vivo for their neuroprotective activity where formononetin and S. tomentosa showed promising neuroprotective activity with reduction in acetylcholine esterase (AchE) enzyme activity and elevation of acetylcholine (Ach) and glutathione(GSH) brain levels and attenuation of dopamine (DA), nor-adrenaline (NA) and malonedialdehyde (MDA) brain level significantly, However S. secundiflora leaves methanolic extract didn't attenuate the AchE enzyme activity, DA and NA brain levels.

The current work aims to utilize a quality by design (QbD) approach to develop and optimize nanovesicular carriers of a hydrophobic drug. Rosuvastatin calcium was used as a model drug, which suffers poor bioavailability. Several tools were used in the risk assessment study as Ishikawa diagrams. The critical process parameters (CPP) were found to be the particle size, polydispersity index, zeta potential, and entrapment efficiency. A factorial design was used in risk analysis, which was complemented with an artificial neural network (ANN); to assure its accuracy. A design space was established, with an optimized nanostructured lipid carrier formula containing 3.2% total lipid content, 0.139% surfactant, and 0.1197 mg % drug. The optimized formula showed a sustained drug release up to 72 h. It successfully lowered each of the total cholesterol, low-density lipoprotein, and triglycerides and elevated the high-density lipoprotein levels, as compared to the standard drug. Thus, the concurrent use of the factorial design with ANN using the QbD approach permitted the exploration of the experimental regions for a successful nanovesicular carrier formulation and could be used as a reference for many nanostructured drug delivery studies during their pharmaceutical development and product manufacturing.

Designing nanocarriers with actions directed at a specific organ or tissue is a very promising strategy since it can significantly reduce the toxicity of a bioactive drug. In this study, an organometallic dendrimer was used to synthesize a biocompatible drug delivery system by attaching aspirin to the periphery of the dendrimer. Our goal is to enhance the bioavailability and anticancer activity of aspirin and reduce its toxicity through successive generations of organoiron dendrimers. The biological activity of aspirin-based dendrimer complexes was evaluated. The result of antimicrobial activity of the synthesized dendrimers also demonstrated an increase in their antimicrobial activity with increased generation of the dendrimers for most types of microorganisms. This study reveals for the first time that organoiron dendrimers linked with aspirin exhibit an excellent Gram-negative activity comparable to the reference drug Gentamicin. All synthesized dendrimers were tested for their anticancer activity against breast cancer cell lines (MCF-7), hepatocellular cell lines (Hep-G2), and a non-cancer cell line, Human Embryonic Kidney (HEK293), using the MTT cell viability assay and compared against a standard anticancer drug, Doxorubicin. Compounds G3-D9-Asp and G4-D12-Asp exhibited noticeable activity against both cell lines, both of which were more effective than aspirin itself. In addition, the in vivo anti-inflammatory activity and histopathology of swollen paws showed that the designed aspirin-based dendrimers displayed significant anti-inflammatory activity; however, G2-D6-Asp showed the best anti-inflammatory activity, which was more potent than the reference drug aspirin during the same period. Moreover, the coupling of aspirin to the periphery of organoiron dendrimers showed a significant reduction in the toxicity of aspirin on the stomach.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the lining of the synovial joints and approximately affects 0.5 - 1% of the total population imposing a socioeconomic burden. The current study aimed at investigating the novel possible beneficial effects of using zinc oxide nanoparticles (ZnO NPs) on such devastating disease. The complete Freund's adjuvant (CFA) model was used to mimic RA in rats where ZnO NPs were given orally (2 mg/kg/day) daily for 14 days; and diclofenac Na, the standard drug, was given intraperitoneally (1 mg/kg/day) the day after CFA, daily for 14 days. Our results displayed that ZnO NPs attenuated adjuvant-induced increased production of inflammatory mediators interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), and total leukocyte count. Besides, they ameliorated autoimmunity through suppression of anti-citrullinated protein auto antibodies (anti-CCP) levels in rats. In conclusion our results highlight the benefits which could be obtained of nanoparticles either alone or in combination with the known anti-arthritic and/or anti-inflammatory agents, giving rise to new protocols to maximize the control of RA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hepatic encephalopathy (HE) is a debilitating and life-threatening disease. Results from acute or chronic liver failure and is characterized by abnormal cerebral and neurological alterations. This study aimed at investigating the effect of allicin, the major functional component in freshly crushed garlic extract, on thioacetamide (TAA)-induced HE in rats. Induction of HE by a single dose of TAA (300 mg/kg; I.P.) was associated with a marked elevation in the serum levels of alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, total protein, blood urea nitrogen and serum ammonia besides reduction in the serum level of albumin. Moreover, it was accompanied with an increase in the hepatic and brain levels of inflammatory mediators; TNF-α and IL-1β as well as elevation of the hepatic and brain levels of oxidative stress biomarkers; reduced glutathione and lipid peroxidation evidenced by malondialdeyde. Oral administration of allicin (50, 100 and 200 mg/kg; P.O.) for 6 days prior to TAA injection restored the serum liver function, hepatic and brain levels of inflammatory mediators as well as oxidative stress biomarkers in a dose-dependent manner. From our results, it can be concluded that allicin has a protective effect on TAA-induced HE in rats in a dose-dependent manner due to its powerful antioxidant and anti-inflammatory properties., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism., (© 2021. American Association of Pharmaceutical Scientists.)

Ethnopharmacological Relevance: Pulicaria incisa sub. candolleana E. Gamal-Eldin (Asteraceae) was traditionally used by Bedouins as a refreshing tea and as hypoglycemic, in gastrointestinal ailments, sinusitis and headache. Recently a great correlation has been established between liver cirrhosis and gastrointestinal dysfunction reflected by abdominal bloating, pain, diarrhea, constipation, besides decreased food intake. So far, the hepatoprotective effect of P. incisa sub. candolleana E. Gamal-Eldin was not studied before although other Pulicaria species have previously shown hepatoprotective and antioxidant effects., Aim of the Study: In this study, we aimed to identify the phytochemical constituents of the P. incisa sub. candolleana E. Gamal-Eldin hydroethanolic extract (PICE), as well as to evaluate the hepatoprotective, anti-inflammatory and antioxidant activities in methotrexate (MTX)- intoxicated rats. Besides, the molecular interaction between the isolated compounds and cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) were assessed by in-silico screening., Material and Methods: The main phytoconstituents were characterized using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Vacuum liquid chromatography (VLC) aided by preparative high-performance liquid chromatography (HPLC) were also used to isolate the major phenolics from the hydroethanolic extract. Their structures were elucidated using different spectroscopic analysis methods, including 1D and 2D nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI/MS). The hepatoprotective activity of three doses (100, 250, 500 mg/kg) of PICE in MTX-intoxicated rats was assessed and compared to silymarin as a standard. Additionally, in silico docking study on cyclooxygenase-2 (COX-2) and phospholipase 2 (PLA-2) was performed to justify the anti-inflammatory activity of the isolated compounds., Results: Thirteen compounds were tentatively identified, including flavonoids and phenolic acids. Four main isolated compounds were identified as, eugenol-1-O-β-glucoside, 5-O-caffeoylquinic acid, 3, 5-di-O-caffeoylquinic acid and quercetin-3-O-β-glucoside. Treatment of MTX-intoxicated rats with the 250 mg/kg extract reversed the altered levels of biochemical markers of liver damage, ameliorated the oxidant status and reduced the inflammatory mediators, similar to treatment with silymarin. Quercetin-3-O-β-glucoside showed the best docking energy score of -19.12 kcal/mol against COX-2, forming four binding interactions with residues Leu 353, Arg 121, Tyr 356 and Ala 528, followed by 3,5-di-O-caffeoylquinic acid (-18.01 kcal/mol)., Conclusion: This study reveals P. incisa sub. candolleana as a rich source of phenolics including flavonoids, supporting its anti-inflammatory and hepatoprotective effects and suggesting its usage as a promising candidate in inflammatory conditions., (Copyright © 2020 Elsevier B.V. All rights reserved.)

To search for effective and selective COX-2 inhibitors, four novel series of tetrazole derivatives were designed based on bioisosteric replacement of SO 2 NH 2 in celecoxib with tetrazole ring incorporating different central moieties as chalcone (2a-f), isoxazole (3a-c) or pyrazole (4a-c & 5a-c). Target tetrazoles were synthesized and their structures were confirmed by spectroscopic techniques and elemental analyses. All target compounds were more selective for COX-2 isozyme than COX-1 when compared to standard drugs indomethacin and celecoxib. Compounds 3b, 3c, 4b, 4c, 5b and 5c exhibited potent in vitro COX-2 inhibitory activity (IC 50  = 0.039-0.065 μM). Trimethoxy derivatives 3c, 4c and 5c acquired superior COX-2 selectivity index values (SI = 297.67-317.95) and were 1.1 fold higher than celecoxib (SI = 282.22). The most active six compounds were evaluated for their in vivo anti-inflammatory activity and serum levels of PGE 2 , TNF-α and IL-6 in addition to their ulcerogenic liability and histopathological profile. At a dose of 50 mg/Kg, compounds 3c and 5c showed better anti-inflammatory activity (% edema inhibition = 29.209-42.643) than celecoxib (% edema inhibition = 28.694-40.114) at different time intervals and were less ulcerogenic (UI = 0.123 and 0.11 in sequent) than celecoxib (UI = 0.167). Also, they displayed potent inhibitory effect on the production of PGE 2 (% inhibition = 81.042 and 82.724 in sequent) greater than celecoxib (% inhibition = 79.666). Compound 5c decreased rat serum concentrations of both TNF-α (% inhibition = 55.349) and IL-6 (% inhibition = 61.561) in a comparable or better activity to celecoxib as reference drug. Finally, docking poses of the most active compounds showed strong binding interactions and effective overall docking energy scores explaining their remarkable COX-2 inhibitory activity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To enhance bioavailability of timolol (TML) and utilize alternatives for traditional eye drops for more patient compliance, this study was aiming to develop biodegradable orally dissolving strips (ODSs) of TML for treatment of primary open-angle glaucoma (POAG)., Methods: Novel ODSs of TML were formulated and optimized using solvent casting method according to full factorial design (3 1 .2 2 ). TML ODSs were characterized with respect to many parameters. In-vivo test was carried out using four groups of 24 New Zealand albino rabbits. POAG was induced by subconjunctival treatment of betamethasone. Histopathological examination and oxidative stress markers assay were carried out., Key Findings: The optimized formula (F9) exhibited a remarkably 15-s disintegration time and 96% dissolution rate after 10 min. The results revealed a potent significant inhibitory effect of the optimized TML ODS to reduce IOP in induced rabbits in comparison with control rabbits and TML eye drops-treated rabbits. The formula showed also high activity against oxidative stress and absence of histopathological changes in iridocorneal angle and cornea., Conclusion: The ODSs could be a promising alternative delivery system for eye drops with more compliance to enhance delivery and therapeutic activity of TML in treatment of POAG., (© 2020 Royal Pharmaceutical Society.)

Skin health is vital for a healthy body. Herbal remedies have long been used for skin care, and their global use has tremendously increased over the past three decades. Although cellulite is seen as a normal condition by the medical community, it is considered a serious cosmetic concern for most affected women. Many topical anti-cellulite creams are available on the market, but unfortunately, their efficacy has not been proven scientifically. Microneedles (MNs) represent a new approach to enhance the permeation of loaded medication through the skin. In this study, the anti-cellulite effects of Vitex agnus-castus and Tamarindus indica extracts were compared using safe and effective polymeric MNs. This delivery system offers a painless alternative to the combined treatment strategy of microneedling devices and anti-cellulite products. The selected standardized extracts were evaluated for their mineral, phenolic and flavonoid contents, which are correlated to a promising antioxidant effect, as demonstrated by an in vitro radical scavenging activity assay. 3D-printing techniques were chosen for fabrication of a micromold, which is inexpensive for mass production. To ensure that MNs were sufficiently strong to perforate the skin without breaking, axial failure force was measured using a micro-mechanical test machine. The anticellulite effects of MNs were assessed using an in vivo diet-induced obesity guinea pig model. Skin properties, histopathology and inflammatory markers were examined. MNs loaded with plant extracts were statistically comparable in normalizing the oxidative state and reducing inflammation, while myeloperoxidase levels were more significantly reduced by T. indica than by V. agnus-castus. This novel delivery system opens the door for new transdermal strategies for cellulite management.

Vascular dementia is considered a vascular cognitive impairment disease caused by neuronal degeneration in the brain. Several studies have supported the hypothesis that oxidative stress and endothelial dysfunction are the main pathogenic factors in vascular dementia. This current study aims to determine the possible neuroprotective effects of zafirlukast, piracetam and the combination of piracetam and zafirlukast on L-methionine-induced vascular dementia in rats. Male Wistar albino rats were divided into five groups. Group I was the normal control, and group II received L-methionine (1700 mg/kg, P.O.) for 32 days. The remaining groups received zafirlukast (20 mg/kg, P.O.), piracetam (600 mg/kg, P.O.) or their combination (zafirlukast 20 mg/kg + piracetam 600 mg/kg, P.O.) for 32 days after L-methionine administration. Afterwards, the cognitive and memory performances of the rats were investigated using the novel object recognition (NOR) test; rats were then sacrificed for histopathological and biochemical analyses. L-methionine-induced vascular dementia altered rats' behaviours and the brain contents of different neurotransmitters and acetylcholinesterase activity while increasing levels of oxidative stress and causing notable histopathological alterations in brain tissues. The treatment of vascular dementia with zafirlukast and the combination improved neurochemical, behavioural and histological alterations to a comparable level to those of piracetam. Thus, zafirlukast, piracetam and the combination of both drugs can be considered as potential therapeutic strategies for the treatment of vascular dementia induced by L-methionine. To the best of our knowledge, this study is the first to explore the neuroprotective effects of zafirlukast and piracetam on L-methionine-induced vascular dementia., (© 2019 Société Française de Pharmacologie et de Thérapeutique.)

Platelet-rich plasma (PRP) accelerates wound healing, as it is an excellent source of growth factors. PRP was separated from whole human blood by centrifugation. PRP powder and wafers were prepared by lyophilization, with the wafers prepared using sodium carboxymethylcellulose (Na CMC). The PRP wafers showed porous structures, as indicated by scanning electron microscopy (SEM) images, and the ability of the wafer to absorb exudates and thus promote wound healing was tested with the hydration capacity test. The platelet count was tested and indicated that the presence of PRP in the wafers had no effect on the platelet count. An antimicrobial activity test was carried out, showing that PRP had antibacterial activity against Gram-negative bacteria. Compared with lyophilized PRP powder and PRP-free wafers, PRP wafers showed the highest percent of wound size reduction on induced wounds in rats. Histopathological examination of rat skin showed that the PRP wafers achieved the shortest healing time, followed by the lyophilized PRP powder and finally the PRP-free wafers. The present study revealed that PRP can be formulated as a wafer, which is a promising pharmaceutical delivery system that can be used for enhanced wound-healing activity and improved the ease of application compared to lyophilized PRP powder.

Background: Natural antioxidants and anti-inflammatory agents have the ability to restore normal balance to destructed liver cells. The genus Erythrina has attracted attention for its broad spectrum of physiological activities and its rich polyphenolic and alkaloid contents., Hypothesis/purpose: The major phytoconstituents of Erythrina × neillii, an ornamental coral tree and a hybrid between E. herbacea and E. humeana that was not previously studied, were investigated. The hepatoprotective effect and underlying mechanisms were also assessed., Study Design and Methods: The main phytoconstituents in the different fractions of the alcoholic leaf extract (dichloromethane and ethyl acetate) were identified using high resolution high-performance liquid chromatography coupled with mass spectrometry (HR-HPLC-MS-MS) based on the fragmentation pattern and molecular formula of the identified compounds and on previous literature. In addition, the hepatoprotective, anti-inflammatory and antioxidant activities of three doses of E. × neillii alcoholic leaf extract (100, 250, 500 mg/kg) were investigated in methotrexate (MTX)-intoxicated rats and were compared with those of silymarin-treated rats. Liver function parameters were obtained, and a histopathological study was performed. In addition, the anti-inflammatory mediators and the antioxidant system in the liver tissues were assessed., Results: The dichloromethane extract revealed an abundance of alkaloids (25), in addition to tentatively identifying flavone (1), flavanone (1) and three fatty acids. Additionally, thirty-six compounds belonging to different classes of phytoconstituents with a predominance of flavonoids (21), O/C-flavone and flavonol glycosides, followed by alkaloids (9), fatty acids (4) and (2), and phenolic glycoside were identified in the ethyl acetate extract. Compared with MTX, alcoholic leaf extract (500 mg/kg) ameliorated the MTX-induced alterations by improving several biochemical marker levels, fighting oxidative stress in serum and liver tissues, and decreasing inflammatory mediators; this finding was further confirmed by the histopathological study., Conclusion: This study reveals E. × neillii, a rich source of flavonoids and alkaloids, which could be further exploited to provide a promising and safe antihepatotoxic agent source., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Background: The current study aimed to evaluate the mechanisms involved in protection against doxorubicin-induced cardiac and renal toxicities upon treatment with eicosapentaenoic acid and vitamin E., Methods: Rats were randomly assigned to 4 groups: normal control, doxorubicin inducted control, eicosapentaenoic acid treated group and a final group pretreated with vitamin E. Lipid peroxidation, reduced glutathione (GSH) and tumor necrosis factor-alpha (TNF-α) contents as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities were assessed. Moreover, hearts were used for immunohistochemical detection of the pro-apoptotic protein cytochrome c expression, while the kidneys were used for detection of inducible nitric oxide synthase (iNOS) expression., Results: Eicosapentaenoic acid and vitamin E produced significant protection from doxorubicin-induced cardiac and renal toxicities. The suggested mechanisms for protection included decreased cytochrome c and iNOS expression as well as markedly decreased lipid peroxides and TNF-α contents accompanied with increased GSH content as compared to the doxorubicin control group. Moreover, there was marked increase in GPx and SOD activities accompanied by significant suppression of MPO activity., Conclusion: The present study demonstrated the potent protective effects of eicosapentaenoic acid and vitamin E from doxorubicin induced cardiac and renal toxicities through their potent anti-oxidant, anti-inflammatory and anti-apoptotic properties. Hence, eicosapentaenoic acid and vitamin E could be promising protective agents against doxorubicintoxicity., (© 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Hepatic injury is a major side effect associated with methotrexate (MTX) therapy resulting from inflammatory reactions and oxidative stress induction. Therefore, liver fibrosis incidence is augmented with long-term MTX therapy. Alpha lipoic acid (ALA) is a naturally occurring compound with potent antioxidant activity. This study explored the hepatoprotective mechanisms of ALA against MTX-induced hepatic injury in rats. Hepatic injury was induced in MTX group by 20 mg/kg body weight ip. injection of MTX. ALA group was pretreated with ALA 60 mmol/kg body weight ip. for five days followed by a single dose of MTX in the sixth day. Blood samples and liver tissues were then obtained to assess several biochemical parameters as serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), reduced glutathione (GSH), total antioxidant capacity (TAC) and lipid peroxidation. Nuclear factor E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway was studied by determining the extent of mRNA Nrf2 expression and the level of HO-1. Hepatic stellate cells (HSCs) activation was evaluated by estimating the expression of α-smooth muscle actin (α-SMA) and hydroxyproline content. Also, tumor necrosis factor alpha (TNF-α), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and caspase-3 were assessed by ELISA in addition to histopathological examination of liver samples. Results showed that ALA pretreatment improved liver function since serum ALT, AST and ALP levels were reduced. Additionally, ALA restored GSH and TAC levels when compared to MTX group and decreased lipid peroxidation. ALA exerted its antioxidant effect via Nrf2/HO-1 pathway as well as it showed anti-inflammatory and antiapoptotic effects by reducing TNF-α, iNOS, COX-2 and caspase-3 levels in liver tissue homogenate. Finally, ALA suppressed HSCs activation by decreasing α-SMA expression and hydroxyproline content in liver. It was concluded that ALA has hepatoprotective effects against MTX-induced hepatic injury mediated by Nrf2/HO-1 pathway as well as anti-inflammatory and antiapoptotic properties., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)