Opuntia monacantha: Validation of the anti-inflammatory and anti-arthritic activity of its polyphenolic rich extract in silico and in vivo via assessment of pro- and anti-inflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Opuntia monacantha belongs to the cactus family Cactaceae and is also known by cochineal prickly pear, Barbary fig or drooping prickly pear. It was traditionally used to treat pain and inflammation. O. monacantha cladodes showed pharmacological effects such as antioxidant potential owing to the presence of certain polysaccharides, flavonoids, and phenols. AIM OF THE STUDY: This research aimed to evaluate the anti-inflammatory as well as the anti-arthritic potential of ethanol extract of Opuntia monacantha (E-OM). MATERIALS AND METHODS: In vivo edema in rat paw was triggered by carrageenan and used to evaluate anti-inflammatory activity, while induction of arthritis by Complete Freund's Adjuvant (CFA) rat model was done to measure anti-arthritic potential. In silico studies of the previously High performance liquid chromatography (HPLC) characterized metabolites of ethanol extract was performed by using Discovery Studio 4.5 (Accelrys Inc., San Diego, CA, USA) within active pocket of glutaminase 1 (GLS1) (PDB code: 3VP1; 2.30 Å). RESULTS: EOM, particularly at 750 mg/kg, caused a reduction in the paw edema significantly and decreased arthritic score by 80.58% compared to the diseased group. It revealed significant results when histopathology of ankle joint was examined at 28th day as it reduced inflammation by 18.06%, bone erosion by 15.50%, and pannus formation by 24.65% with respect to the diseased group. It restored the altered blood parameters by 7.56%, 18.47%, and 3.37% for hemoglobin (Hb), white blood count (WBC), and platelets, respectively. It also reduced rheumatoid factor RF by 13.70% with concomitant amelioration in catalase (CAT) and superoxide dismutase (SOD) levels by 19%, and 34.16%, respectively, in comparison to the diseased group. It notably decreased mRNA expression levels of COX-2, IL-6, TNF-α, IL-1, NF-κß and augmented the levels of IL-4 and IL-10 in real time PCR with respect to the diseased group and piroxicam. HPLC analysis previously performed showed that phenolic acids and flavonoids are present in E-OM. Molecular docking studies displayed pronounced inhibitory potential of these compounds towards glutaminase 1 (GLS1), approaching and even exceeding piroxicam. CONCLUSIONS: Thus, Opuntia monacantha could be a promising agent to manage inflammation and arthritis and could be incorporated into pharmaceuticals.

Mining of Marburg Virus Proteome for Designing an Epitope-Based Vaccine.

Marburg virus (MARV) is one of the most harmful zoonotic viruses with deadly effects on both humans and nonhuman primates. Because of its severe outbreaks with a high rate of fatality, the world health organization put it as a risk group 4 pathogen and focused on the urgent need for the development of effective solutions against that virus. However, up to date, there is no effective vaccine against MARV in the market. In the current study, the complete proteome of MARV (seven proteins) was analyzed for the antigenicity score and the virulence or physiological role of each protein where we nominated envelope glycoprotein (Gp), Transcriptional activator (VP30), and membrane-associated protein (VP24) as the candidates for epitope prediction. Following that, a vaccine construct was designed based on CTL, HTL, and BCL epitopes of the selected protein candidates and to finalize the vaccine construct, several amino acid linkers, ß-defensin adjuvant, and PADRE peptides were incorporated. The generated potential vaccine was assessed computationally for several properties such as antigenicity, allergenicity, stability, and other structural features where the outcomes of these assessments nominated this potential vaccine to be validated for its binding affinity with two molecular targets TLR-8 and TLR-4. The binding score and the stability of the vaccine-receptor complex, which was deeply studied through molecular docking-coupled dynamics simulation, supported the selection of our designed vaccine as a putative solution for MARV that should be validated through future wet-lab experiments. Here, we describe the computational approach for designing and analysis of this potential vaccine.

GC-MS/MS Quantification of EGFR Inhibitors, ß-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of Thonningia sanguinea.

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, ß-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of -19.93 and -16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments.

Exploring the Activity of Fungal Phenalenone Derivatives as Potential CK2 Inhibitors Using Computational Methods.

Cancer represents one of the most prevalent causes of global death. CK2 (casein kinase 2) activation boosted cancer proliferation and progression. Therefore, CK2 inhibition can have a crucial role in prohibiting cancer progression and enhancing apoptosis. Fungi have gained vast interest as a wealthy pool of anticancer metabolites that could particularly target various cancer progression-linked signaling pathways. Phenalenones are a unique class of secondary metabolites that possess diverse bioactivities. In the current work, the CK2 inhibitory capacity of 33 fungal phenalenones was explored using computational studies. After evaluating the usefulness of the compounds as enzyme inhibitors by ADMET prediction, the compounds were prepared for molecular docking in the CK2-α1 crystal structure (PDB: 7BU4). Molecular dynamic simulation was performed on the top two scoring compounds to evaluate their binding affinity and protein stability through a simulated physiological environment. Compound 19 had a superior binding affinity to the co-crystallized ligand (Y49). The improved affinity can be attributed to the fact that the aliphatic chain makes additional contact with Asp120 in a pocket distant from the active site.

Phytoconstituents and Pharmacological Activities of Indian Camphorweed (Pluchea indica): A Multi-Potential Medicinal Plant of Nutritional and Ethnomedicinal Importance.

Pluchea indica (L.) Less. (Asteraceae) commonly known as Indian camphorweed, pluchea, or marsh fleabane has gained great importance in various traditional medicines for its nutritional and medicinal benefits. It is utilized to cure several illnesses such as lumbago, kidney stones, leucorrhea, inflammation, gangrenous and atonic ulcer, hemorrhoids, dysentery, eye diseases, itchy skin, acid stomach, dysuria, abdominal pain, scabies, fever, sore muscles, dysentery, diabetes, rheumatism, etc. The plant or its leaves in the form of tea are commonly used for treating diabetes and rheumatism. The plant is a rich source of calcium, vitamin C, dietary fiber, and ß-carotene. Various biomolecules have been isolated from P. indica, including thiophenes, terpenes, quinic acids, sterols, lignans, phenolics, and flavonoids. The current review reports detailed information about the phytoconstituents and pharmacological relevance of P. indica and the link to its traditional uses. The reported studies validated the efficacy and safety of P. indica, as well as supported its traditional uses for treating various ailments and promoting health and well-being. Thus, this could encourage the development of this plant into a healthy food supplement or medicine for the prevention and treatment of various diseases. However, further studies on the drug interactions, mechanism of action, pharmacokinetics, toxicology, and metabolism, as well as clinical trials, should be carried out.

Thiophenes-Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors.

Naturally, thiophenes represent a small family of natural metabolites featured by one to five thiophene rings. Numerous plant species belonging to the family Asteraceae commonly produce thiophenes. These metabolites possessed remarkable bioactivities, including antimicrobial, antiviral, anti-inflammatory, larvicidal, antioxidant, insecticidal, cytotoxic, and nematicidal properties. The current review provides an update over the past seven years for the reported natural thiophene derivatives, including their sources, biosynthesis, spectral data, and bioactivities since the last review published in 2015. Additionally, with the help of the SuperPred webserver, an AI (artificial intelligence) tool, the potential drug target for the compounds was predicted. In silico studies were conducted for Cathepsin D with thiophene derivatives, including ADMET (drug absorption/distribution/metabolism/excretion/and toxicity) properties prediction, molecular docking for the binding interaction, and molecular dynamics to evaluate the ligand-target interaction stability under simulated physiological conditions.

Anticancer Effects of New Ceramides Isolated from the Red Sea Red Algae Hypnea musciformis in a Model of Ehrlich Ascites Carcinoma: LC-HRMS Analysis Profile and Molecular Modeling.

Different classes of phytochemicals were previously isolated from the Red Sea algae Hypnea musciformis as sterols, ketosteroids, fatty acids, and terpenoids. Herein, we report the isolation of three fatty acids-docosanoic acid 4, hexadecenoic acid 5, and alpha hydroxy octadecanoic acid 6-as well as three ceramides-A (1), B (2), and C (3)-with 9-methyl-sphinga-4,8-dienes and phytosphingosine bases. Additionally, different phytochemicals were determined using the liquid chromatography coupled with electrospray ionization high-resolution mass spectrometry (LC-ESI-HRMS) technique. Ceramides A (1) and B (2) exhibited promising in vitro cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line when compared with doxorubicin as a positive control. Further in vivo study and biochemical estimation in a mouse model of Ehrlich ascites carcinoma (EAC) revealed that both ceramides A (1) and B (2) at doses of 1 and 2 mg/kg, respectively, significantly decreased the tumor size in mice inoculated with EAC cells. The higher dose (2 mg/kg) of ceramide B (2) particularly expressed the most pronounced decrease in serum levels of vascular endothelial growth factor -B (VEGF-B) and tumor necrosis factor-α (TNF-α) markers, as well as the expression levels of the growth factor midkine in tumor tissue relative to the EAC control group. The highest expression of apoptotic factors, p53, Bax, and caspase 3 was observed in the same group that received 2 mg/kg of ceramide B (2). Molecular docking simulations suggested that ceramides A (1) and B (2) could bind in the deep grove between the H2 helix and the Ser240-P250 loop of p53, preventing its interaction with MDM2 and leading to its accumulation. In conclusion, this study reports the cytotoxic, apoptotic, and antiangiogenic effects of ceramides isolated from the Red Sea algae Hypnea musciformis in an experimental model of EAC.

Commonly used agent for acute pain management of sickle cell anemia in Saudi Emergency Department: A narrative review.

INTRODUCTION: Sickle-cell disease (SCD) is one of the most common hematologic inherited disorders in Saudi Arabia. Vaso-occlusive pain crisis in SCD is a major cause for emergency visits and patients' pain may be undertreated. This study presents a narrative literature review of current agents used to manage acute pain crisis in SCD patients presenting to the emergency department in hospitals of Saudi Arabia. METHOD: We conducted a narrative review on relevant published articles about sickle cell disease pain crisis management in Saudi Arabia and included seven relevant studies based on our inclusion criteria. RESULTS: Using our search strategy, we included 7 studies Out of 4052. Studies included were conducted in different locations in the country. Four studies were in the Eastern region while only one in Western and One in Central regions. Those studies included around 2441 patients, in total. Morphine was used in 5 studies out of the 7 included. Pethidine was used in 4. One study used Isoxsuprine and another study used tinzaparin. CONCLUSION: We found that continuous administration of IV morphine accompanied by oral analgesics including NSAIDs and acetaminophen is the most commonly used practice for treating SCD patients presenting with a vaso-occlusive pain crisis. Possible effectiveness of tinzaparin, isoxsuprine, and pethidine as therapeutic options may be considered. However, there was no recommendation for a certain agent to be prescribed. We recommend conducting further clinical randomized-controlled trials.

Selective cytotoxic activity and protective effects of sodium ascorbate against hepatocellular carcinoma through its effect on oxidative stress and apoptosis in vivo and in vitro.

Objectives: Hepatocellular carcinoma (HCC) is characterized by elevated in oxidative stress and inflammatory cytokines, which enhance destructive effects of the tumor. Therefore, we conducted this study to investigate the protective effects of sodium ascorbate against thioacetamide-induced HCC in rats through studying its effect on the apoptotic pathway in rats. In addition, in vitro activity of sodium ascorbate was investigated on HepG2 and compared with cisplatin.Methods: HCC was experimentally induced by injecting rats with 200 mg/kg thioacetamide intraperitoneally twice weekly for 16 weeks. Part of HCC rats was concomitantly treated with 100 mg/kg sodium ascorbate intraperitoneally during the 16-week period. Hepatic tissues were used for the determination of NFκB, Nrf2, TNF-α, caspase-3, caspase-8 and caspase-9.Results: Sodium ascorbate significantly attenuated HCC-induced reduction in the expression of NrF2 associated with a reduction in concentrations of hydrogen peroxide and superoxide anion. In addition, sodium ascorbate blocked HCC-induced increase in the expression of NFκB and TNF-α. Sodium ascorbate slightly increased the activity of caspase-3, -8 and -9 in vitro but inhibited their activities in vivo.Conclusion: In spite of the antioxidant and anti-inflammatory activity of sodium ascorbate, it produced selective cytotoxic activity via direct activation of the apoptotic pathway in cancer cells without affecting the apoptotic pathway in normal hepatic cells.

The Impact of COVID-19 Outbreak on Reassessing the Need for Drive Thru Community Pharmacy: Cross-Sectional Study.

INTRODUCTION: Community pharmacies spread all over Saudi Arabia. Customers face some of the logistic problems, such as parking availability and privacy. This study was aimed to evaluate the need, awareness, perception, and barriers of the drive-thru community pharmacy services. METHODS: A cross-sectional study was conducted between January 1, 2020, and February 1, 2020, based on a questionnaire that was published on WhatsApp and Twitter. RESULTS: From 1001 participants who completed the questionnaire, 54% of them are female and 70% between the age group of 18 and 30 years. The most common reason to visit the pharmacy among the participants is to purchase over-the-counter medications (36.4%). Although (86.5%) reported that there is no pharmacy provide drive-thru service in their city, 78% of participants think that this service will help all the community component. Participants believe that the drive-thru service will help in reducing car parking problems and traffic violations (83.8% and 86.3%, respectively) and will help in keeping patient privacy and (82.2%). CONCLUSION: Establishing community pharmacy with drive-thru service is very important to ensure a more convenient service to customers and to assist all ages, women, and special needs. Giving the recent declaration to live with coexisting COVID-19 pandemic, further procedures should be implemented to support this recommendation.