Alzheimer’s disease is a prevalent cause of dementia in the elderly population. The existing treatments in this issue are limited in efficacy besides having several adverse effects. Therefore, developing new therapeutic strategies is a major concern of scientists. This disease is closely linked to gut microflora through the brain–gut–microbiota axis. Targeting gut microbiota by pre-, pro-, and synbiotics supplementation can be effective for its treatment. Herein, we discuss the protecting effects of pre-, pro-, and synbiotics products against Alzheimer’s disease based on comprehensive assessment of animal studies and performed clinical trials. Primarily, we briefly introduced involved pathogenesis, probable drug targets, and its correlation with gut microbiota. Subsequently, we debated preclinical and clinical research studies on the effect of pre-, pro-, and synbiotics agents on brain functionality, metabolic features, and biomarkers that are proven to have therapeutic effects. Searching the online databases revealed therapeutic capabilities of pre-, pro-, and synbiotics in Alzheimer’s disease treatment by some mechanisms such as anti-oxidative stress, anti-inflammatory, prohibiting of apoptosis and DNA damage, insulin regulation, suppressing the aggregation of beta-amyloid (Aβ) and tau proteins, which can be considered as important outcomes of this application.

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Background: Due to the complexities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an effective medicinal treatment protocol for this lethal disease with a high prevalence has not been approved yet. This study aimed to explore the efficacy of the main alkaloids of Isatis indigotica, one of the richest plant sources of alkaloids against SARS-CoV-2 targets computationally. Materials and Methods: 3D structures of the target proteins including 3CLpro; PLpro, and RdRp were downloaded from Protein Data Bank. The structures of ligands were retrieved from PubChem database or optimized by ORCA program. Ritonavir, Lopinavir, Sofosbuvir, and Remdesivir were selected as control inhibitors. Docking calculations were performed by AutoDock Vina option and top-ranked compounds were subjected to molecular dynamics simulation by Gromacs 5.1.4 simulation package. Result: The results showed that all 15 compounds had stronger interactions with PLpro in comparison to the other enzymes. Dihydroxylisopropylidenylisatisine A binds to the active site of PLpro with highest affinity (–9.3 kcal/mol) which is even more than the binding constants of Ritonavir and Lopinavir. Of the 15 compounds, Dihydroxylisopropylidenylisatisine A and Isatibisindosulfonic acid B had the highest tendency to bind to 3CLpro. Dihydroxylisopropylidenylisatisine A, Indirubin, Insatindibisindolamide A, Indigo, Insatindibisindolamide B, Isatibisindosulfonic acid B and Isatindosulfonic acid B had the highest RdRp binding affinity even more Remdesivir. Conclusion: Based on the results, the highest and weakest interaction with all three enzymes was observed for Dihydroxylisopropylidenylisatisine A and Epigoitrin, respectively. Based on these findings, Dihydroxylisopropylidenylsatistine A might be potential therapeutic candidate against SARS-CoV-2.

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The 3D printing technique is a 3D fabricating technique, which involves numerous working operations and manufacturing techniques. Nowadays, the technique is mostly used in the healthcare and pharmaceutical industries. This is not very new while the seed of this technique originated in the 1980s. The article contains background, historical development, types, global market, and examples of 3D-printed marketed preparations. This paper gives a focus in particular on 3D printing in capsules. In 3D printing, capsules will be a defining moment in capsule development and capsule applications for customized and personalized medications.

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Introduction: Animal studies indicated the protective effect of resveratrol against cerebral ischemic damages, but it has not been researched well in human ischemic stroke. In the present study, the effect of resveratrol on recovery outcomes after acute ischemic stroke was investigated among patients with ischemic stroke who were not eligible for taking recombinant tissue plasminogen activator as an accepted intervention for stroke condition. Materials and Methods: In this double-blind clinical trial, 100 patients with ischemic stroke who suffered from the territory of the middle cerebral artery were randomly allocated to either resveratrol or placebo group. In the intervention group, resveratrol was administered orally at a dose of 500 ± 10 mg daily in three 170 mg divided doses, whereas the placebo group was treated with lactose, both for 30 consequent days. Systolic and diastolic blood pressures and the National Institute of Health Stroke Scale (NIHSS) were measured at the stroke onset and during discharges. Besides, the Barthel index and Modified Rankin Scale (MRS) were performed 3 months after the intervention. Results: Resveratrol had no significant effects on NIHSS (P = 0.97), systolic (P = 0.17), and diastolic blood pressure (P = 0.42) compared with placebo. There were no significant differences in the Barthel index (P = 0.84) and MRS (P = 1.00) between the two groups 3 months after treatment. Conclusion: Resveratrol did not improve functional recovery measured by the NIHSS, MRS, and Barthel index in patients with acute ischemic stroke. In addition, it had no significant effect on blood pressure.

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Background: Cocrystal formation between an active pharmaceutical ingredient (API) and coformer is an applicable technique to change the physicochemical and pharmacokinetic properties. Computational methods can overcome the need for extensive experiments and improve the chances of success in the coformer selection. In this method, two compounds connect by non-covalent interactions that form a unique crystalline structure. Prediction of a cocrystal formation between API and coformer can help in the screening and design of new cocrystals. Methods: In this study, available data in the literature were applied to develop a prediction method based on binary logistic regression to screen cocrystal formation by sum and absolute difference of structural parameters (the number of rotatable bonds, Abraham solvation parameters, and topological polar surface area) of the two involved compounds. Results: The results showed various factors (eight structural parameters of the two compounds) could affect cocrystal formation, and the developed model can predict cocrystallization with a probability of about 90%. Conclusion: The related parameter to hydrogen bonding basicity and volume of compounds has the most significant effect on cocrystal formation.

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Background: Rifaximin, a BCS class IV drug, possesses low bioavailability due to low solubility and low permeability attributable to P-gp efflux. The studies attempted to develop pH-sensitive rifaximin tablets based on ternary solid dispersion (TSD) for spatial and temporal drug release in colon. Materials and Methods: Rifaximin TSD was prepared using Neusilin US2 as a mesoporous carrier and Poloxamer 188 as a hydrophilic carrier and P-gp inhibitor by solvent evaporation technique employing acetone at 1:5 ratio. The TSD was assessed for P-gp inhibition using the gut sac method and Caco-2 permeability studies. The TSD was compressed into tablets and coated with pH-sensitive polymers. Coating optimization was carried out using a 3² factorial design, wherein % coating and ratio of Eudragit S100:Eudragit L100 were the independent variables and % drug release at 2 h and % drug release at 8 h were the dependent variables. Results: Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy studies of rifaximin TSD suggested amorphization of the drug. Gut sac studies indicated higher mucosal to serosal permeability of rifaximin from TSD. Caco-2 permeability studies demonstrated a 4.83-fold higher permeability of rifaximin from TSD (polaxamer 25% w/w and Neusilin 55% w/w of TSD) and a significant change in efflux ratio. In-vitro release studies of the coated tablets displayed controlled and site-specific release at pH of the colon. Conclusion: Effective, stable, pH-dependent rifaximin colon-targeted tablets with enhanced dissolution, permeability, and reduced P-gp efflux were developed. The achieved merits could translate into augmented bioavailability and dose reduction. Further in-vivo studies on this novel formulation, which is cost-effective and industrially scalable, can improve the pharmacoeconomics of inflammatory bowel disease management.

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Background: Humulus lupulus L. (Hops) is one of the medicinal plants for which several effects have been reported such as sedative and hypnotic, anti-inflammatory, antioxidant, antibacterial, and anticancer. The fruits of this plant are also used for flavoring and as an aromatizer in the food and beverage industry. This study was done to evaluate the gastric anti-ulcer capacity of this plant in an animal model. Materials and Methods: Male Wistar rats were used and the gastric ulcer was induced by oral administration of indomethacin (30 mg/kg, p.o.). The ulcer-bearing rats were orally treated with hydroalcoholic extracts of the leaf (HLE) and fruit (HFE) of hops at similar doses of 50, 100, and 150 mg/kg. Ranitidine (35 mg/kg, p.o.) was used as a reference drug. Gastric acid, pepsin activity, malondialdehyde (MDA), and myeloperoxidase (MPO) were evaluated in gastric tissue, whereas this tissue was examined macroscopically and microscopically. Results: The results showed that both extracts (HLE and HFE) at a dose of 150 mg/kg reduced gastric ulcer characteristics such as number and severity, content acidity, pepsin activity, MPO, and MDA values. Also, macroscopic and microscopic images confirmed the effectiveness of the tested extracts in the healing of gastric ulcers. Conclusion: It was concluded that leaves and fruits of hops were effective in healing gastric ulcers caused by indomethacin probably by reducing gastric acid and oxidative stress, and this effect was dose-dependent. This effect along with the sedative and anti-Helicobacter pylori properties of hops can be useful in introducing this plant as an antigastric ulcer agent under clinical conditions.

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Objectives: The aim of this study is to investigate anticancer activity of Brassica oleracea var. alboglabra (BOA) against the proliferation of BGC-823 human gastric cancer cells. Materials and Methods: B. oleracea var. alboglabra was extracted by ethanol 98% at a solid-to-liquid ratio of 1:8, (w/v) for 24h at room temperature. The cytotoxic effect of vegetables was examined by MTT assay. The migration of the cancer cells was conducted by wound healing assay and visualized under an inverted microscope. The mRNA expression level was quantified by real time PCR. Major Findings: It was found that ethanol extract of BOA exhibited the inhibitory activity against the proliferation of BGC-823 cells at IC₅₀ value of 217.6 ± 2.8 µg/ml. Moreover, the treatment of BOA extract at concentration of 100 µg/ml for 24 h significantly suppressed the migration of gastric cancer cells into the gap as compared to the untreated cell group. Notably, the cytotoxic effect of BOA extract on human gastric cancer cells was found due to induction of apoptosis, mediating the up-regulation of caspase-8, -9, -3, and Bax in cancer cells. Conclusion: These results indicated that B. oleracea var. alboglabra have the potential inhibitory activity against the development of gastric cancer.

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Introduction: COVID-19 is one of the most severe, intestinal, respiratory, and systemic infections in animals and humans. The purpose of this experiment was to evaluate the effect of kelofan syrup on biochemical factors and clinical signs of patients with COVID-19. Materials and Methods: This randomized clinical trial was performed on 60 hospitalized patients with moderate or severe COVID-19. The intervention group received 7.5 cc of kelofan syrup(a traditional Persian medicine product) every 12 hours for one week and the placebo group received 7.5 cc of placebo syrup. Serum levels of white blood cells (WBCs), C - reactive protein (CRP), lactate dehydrogenase (LDH), creatinine, lymphocyte, and clinical outcomes were measured before the beginning of the intervention and on day 7. Results: Kelofan syrup enhanced the white blood cell and reduced creatinine and LDH in the syrup group. However, serum levels of WBC, lymphocyte, CRP, LDH, and creatinine(P > 0.05) in the kelofan group at the end of the study did not significantly change than in the placebo group. Also, clinical outcomes such as fever, respiratory rate, saturated oxygen, cough, dyspnea, myalgia, duration of hospitalization, and fatigue did not change significantly from in the placebo group. Conclusion: our findings indicate that kelofan syrup for seven days could not alter biochemical and clinical outcomes than in the placebo group in patients with COVID-19. However, in some clinical symptoms such as cough, dyspnea, weakness, and biochemical factors like WBC, Cr, and LDH, a significant change was observed at the end of hospitalization in the intervention group.

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Background: Falcaria vulgaris is a medicinal plant with culinary uses and widespread therapeutic applications. Despite already proven as a very promising dietary supplement, its safety and possible effects on the human body are yet to define. This study was designed to investigate the acute and subchronic toxic effects of hydroethanolic F. vulgaris in male and female Wistar rats. Experimental: To evaluate the safety of a hydroethanolic extract of F. vulgaris, acute and subchronic toxicity in Wistar rats treated with extract was investigated. For investigation of acute toxicity of F. vulgaris, both genders of rats were treated for 45 days with a single dose of the extract (4000 mg/kg) via gavage. Also for sub-chronic testing, the extract was administrated orally at the doses of 150, 300, and 450 mg/kg for 45 days. At the end of the study, the animals were sacrificed and the hematological, biochemical, and histopathological parameters were assayed. Results: After a single oral administration of F. vulgaris (4000 mg/kg), no mortality was observed in both control and groups in either sex. Also, histopathological inspection of vital organs and tissues revealed no obvious alteration in these organs. The obtained results showed a significant reduction in the weight of heart and liver in male rats that received the highest dose of the extract. The level of red blood cell distribution width (dose of 450 mg/kg) from the hematological parameters and the level of serum creatinine (dose of 150 and 450 mg/kg) from the biochemical parameters increased significantly in male rats. On the contrary, during treatment the concentration of all examined minerals remained unchanged. Histopathological inspection indicated that liver, kidney, and testis were found to be affected by subchronic exposure to F. vulgaris extract. Conclusion: The results of the acute study revealed that F. vulgaris may be nontoxic even at doses less than 4000 mg/kg body weight. However, the result of subchronic study confirmed the liver dysfunctions in Wistar rats and also suggested the significant effect of F. vulgaris on testicular tissue, which may cause serious male infertility. The ability to impair male fertility by such a medicinal plant has not been reported yet. It can be concluded that the no observed adverse effect level (NOAEL) of F. vulgaris are 150 and 450 mg/kg for male and female rats, respectively.

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Background: Pantoprazole sodium is one of the most widely used drugs for treating gastric acid–related disorders as well as is the most popular drug among various cancer therapy protocols for treating gastric disturbances pertained to the chemotherapy. The present study aims to validate high-performance liquid chromatographic (HPLC) method for the quantification of pantoprazole sodium in mice plasma and various tissue homogenates including kidney, heart, prostate, lung, pancreas, liver, and brain. Pantoprazole sodium estimation was done using 100 μL aliquot, which was injected into HPLC system, and the separation was achieved using Shimadzu C18 column at 40°C. Mobile phase composed of acetonitrile/dibasic phosphate buffer (40:60, v/v), pH = 7.4 was isocratically pumped at 1.0 mL min^-1, and detection was performed at wavelength of 290 nm. Material and Methods: All the samples including tissues and plasma were collected after 4 h of oral administration of pantoprazole sodium to Swiss albino mice (10 mg/kg, p.o.). Results: Bioanalytical method was further validated according to the standard guidelines and portrays to be selective as well as linear (r² ≥ 0.999) over the concentration range of 10–50 ng/injection. The intraday (% relative standard deviation [RSD] = 0.29%–1.21%) and inter-day precision (%RSD = 0.52%–2.88%) was found to be within the layout standards by International Council for Harmonization. Pantoprazole sodium extraction recovery was achieved between 64.15% and 78.17% demonstrating the suitability of the method. Conclusion: Bio-distribution study so carried out by bioanalytical technique can be used as an aiding tool for the quantification of pantoprazole sodium in all the studies involving the pharmacokinetic profiling of drug in various tissues of rodents.

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Aims: The study intends to monitor the consequences of lead on the body, its reversal by natural chelators (chitosan and chitosamine), and comparison of monotherapy with the combination using the synthetic ones. Materials and Methods: A total of 42 albino Wistar male rats (200–250 g) were divided into seven groups (n = 6). Except for the first group which received sodium acetate 1 g/L (drinking water, vehicle control), all groups received lead acetate 0.4 mg/kg body weight peroral (p.o.). Group II (toxic) received merely lead acetate, whereas the third and fourth groups received 0.2 g/kg (p.o.) of chitosan and chitosamine, respectively. Groups V–VII received ethylenediaminetetraacetic acid (EDTA) 495 mg/kg (p.o.). In addition, the sixth and seventh groups received chitosan and chitosamine (0.2 g/kg) (p.o.), respectively. The hematological, biochemical, oxidative stress parameters, number of porphobilinogen molecules formed/h/mL, and histopathology were assessed. The data obtained were compared using analysis of variance following Tukey’s test. Results: The results revealed a statistically significant reduction in the hemogram parameters, antioxidant enzymes, porphobilinogen molecules and an increase in oxidative stress, liver biomarkers along with malondialdehyde in the toxic group in comparison with control and treatment groups. The histopathological findings revealed a significant improvement in the chitosan and chitosamine treatment groups when compared with the toxic group, whereas the results obtained from combination therapy with respect to its monotherapy were most significant than the monotherapy alone. Conclusion: Chitosan and chitosamine are found to improve hemato- and hepatotoxicity by chelation and can be used as potent detoxifiers in heavy metal toxicities.

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