Green synthesis of Fe and Zn-NPs, phytochemistry and pharmacological evaluation of Phlomis cashmeriana Royle ex Benth.

This investigation portrays the phytochemical screening, green synthesis, characterization of Fe and Zn nanoparticles, their antibacterial, anti-inflammation, cytotoxicity, and anti-thrombolytic activities. Four dissimilar solvents such as, n-hexane, chloroform, ethyl acetate and n-butanol were used to prepare the extracts of Phlomis cashmeriana Royle ex Benth. This is valued medicinal plant (Family Lamiaceae), native to mountains of Afghanistan and Kashmir. In the GC-MS study of its extract, the identified phytoconstituents have different nature such as terpenoids, alcohol and esters. The synthesized nanoparticles were characterized by SEM, UV, XRD, and FT-IR. The phytochemical analysis showed that the plant contains TPC (total phenolic content) 297.51 mg GAE/g and TFC (total flavonoid content) 467.24 mg CE/g. The cytotoxicity values have shown that the chloroform, n-butanol and aqueous extracts were more toxic than other extracts. The anti-inflammatory potential of n-butanol and aqueous extracts was found higher than all other extracts. Chloroform and n-hexane extracts have low MIC values against both E. coli and S. aureus bacterial strains. Chloroform and aqueous extracts have great anti-thrombolytic potential than all other extracts. Overall, this study successfully synthesized the nanoparticles and provides evidence that P. cashmeriana have promising bioactive compounds that could serve as potential source in the drug formulation.

Potential anticancer and antioxidant lauric acid-based hydrazone synthesis and computational study toward the electronic properties.

The modification of natural products is one of the key areas of synthetic organic chemistry for obtaining valuable chemical building blocks that have medicinal significance. In this study, lauric acid-based hydrazones, namely (E)-N'-(2-nitrobenzylidene)dodecanehydrazide (NBDH), (E)-N'-(naphthalen-1-ylmethylene)dodecanehydrazide (NMDH), and (E)-N'-(4-fluorobenzylidene)dodecanehydrazide (FBDH), were synthesized and characterized using spectroscopic techniques. The newly synthesized lauric acid-based hydrazones were screened for their anticancer and antioxidant potential. The antioxidants showed their activity by inhibiting the oxidative chain reactions that produce reactive oxygen species. The antioxidant activity showed that NBDH exhibited the maximum DPPH inhibitory activity when compared with that of NMDH and FBDH, whereas the anticancer activity showed that FBDH exhibited maximum percent viability when compared to that of NBDH and NMDH. The reactivity and biological needs of the synthesized compounds NBDH, NMDH, and FBDH were met by performing geometrical, FT-IR vibrational, UV-visible, global reactivity parameters (GRP), MEP, FMO, NBO, ELF, LOL, and nonlinear optical (NLO) analysis at the DFT/B3LYP/6-311+G(d,p) level. NBO analysis confirmed the existence of extended conjugation and intramolecular charge transfer among NBDH, NMDH, and FBDH, which have the lowest gap in π → π*, which are in line with the FMO results where successful charge transfer occurred from the highest occupied molecular orbital (HOMO) to the lowest unoccupied molecular orbital (LUMO). GRP analysis confirmed the potential of NBDH, NMDH, and FBDH for biological, electronic, and NLO applications. It is clear from the comparative analysis of the urea molecule that NBDH, NMDH, and FBDH all comprise fine NLO properties.

Synthesis, Characterization, and Enzyme Inhibition Properties of 1,2,4-Triazole Bearing Azinane Analogues.

Considering the importance of acetylcholine esterase (AChE, BchE) and α-glucosidase in the treatment of Alzheimer's disease and diabetes mellitus, the synthesis of novel azinane triazole-based derivatives as effective acetylcholinesterase (AchE), α-glucosidase, urease, lipoxygenase (LOX), and butyrylcholinesterase (BChE) inhibitors is described. Azinane analogue (2) was merged with 1,2,4-triazole to acquire 1-(4-toluenesulfonyl)-4-(3-mercapto-4-methyl-4H-1,2,4-triazol-5-yl) piperidine (8) through a list of intermediates including 1-(4-toluenesulfonyl)-4-(ethoxycarbonyl) piperidine (3), 1-(4-toluenesulfonyl)-4-(2-hydrazinocarbonyl)piperidine (5), and 1-(4-toluenesulfonyl)-4-[1-(methyl amino thiocarbonyl)-2-hydrazinocarbonyl]piperidine (7). The target molecules, 1-(4-toluenesulfonyl)-4-[3-(N-alkyl/phenyl/aryl-2-ethanamoyl thio)-4-methyl-4H-1,2,4-triazol-5-yl] piperidine (12a-o), were achieved through the reaction of 8 with N-alkyl/phenyl/aryl-2-bromo ethanamides (11a-o) as electrophiles. These electrophiles were accomplished by a benign reaction of alkyl/phenyl/aryl amines (9a-o) and 2-bromo ethanoyl bromide (10). The spectral study of IR, 1D-NMR, and EI-MS corroborated the synthesized compounds. Methyl phenyl and methyl phenyl-substituted derivatives 12d and 12m with IC50 = 0.73 ± 0.54; 36.74 ± 1.24; 19.35 ± 1.28; 0.017 ± 0.53; and 0.038 ± 0.50 µM are found to be the most potent AChE, α-glucosidase, urease, and BChE inhibitors. The high inhibition potential of synthesized molecules against AChE, α-glucosidase, urease, and BChEenzymes inferred their role in enzyme inhibition properties.

Role of Drug Delivery System in Improving the Bioavailability of Resveratrol.

Resveratrol (RSV) is a natural polyphenolic compound known for its therapeutic activities but has limited bioavailability. The aim of our study was to explore various drug-delivering methods that are being employed to achieve target-oriented delivery and therapeutic performance of RSV. To improve the bioavailability and pharmacokinetic properties of RSV, efforts are being made to produce efficient formulations accompanying efficient drug delivery strategies. Several clinical trial studies have been conducted on RSV isomers, and the majority of studies indicated that trans-RSV had better clinical potential and therapeutic effectiveness in various types of complications such as colorectal cancer, metabolic syndrome, hypertension, obesity, neurodegenerative diseases, diabetes, hepatic disease, cardiac disorders, and breast cancer. However, multiple research studies enable us to understand various strategies that can enhance the systemic availability and efficacy of topical RSV formulations. In this article, we emphasize the hurdles of RSV delivery processes. We summarized that the micro- particulate system works efficiently for delivering liquid and solid microparticles of RSV. Another technique in which a coating encloses particles is called microencapsulation. This technique reduces the degradation of pharmaceutical compounds. Similarly, the cyclodextrin system is mainly used for poorly soluble drugs. On the other hand, the vesicular system is another micro-particulate system that can encapsulate hydrophilic and hydrophobic drugs. However, the RSV nanosponge formulations have advanced nano drug delivery systems, making it possible to use RSV for its antioxidant potential.

Natural Immunity Boosters as Therapeutic Interventions in the Era of the COVID-19 Pandemic.

COVID-19, a pandemic caused by SARS-CoV-2, has been spread all over the world and is responsible for serious fatalities. SARS-CoV-2 belongs to the family of ß-coronavirus that affects pulmonary gas exchange and triggers cytokines storm. Vigorous inflammation, hyper-coagulation, a decrease in the lymphocytic count, and an increase in the neutrophilic count are observed in the second week after the onset of the disease. Fever, dry cough, sneezing, shortness of breath, and respiratory distress are the symptoms of COVID-19. The use of sanitizers, social distancing, vaccination, wearing gloves and face masks, and other preventative measures are all important in preventing coronavirus outbreaks. People with weak immunity are more susceptible to coronavirus. Various natural immunity boosters are known for their immune boosting properties; among them are vitamin C, D, and B complex, medicinal mushrooms, plant-based stuff, and minerals play important roles by increasing the beneficial flora of the human body. All these natural immunity boosters improve the innate and adaptive immune response against coronavirus. Hence, we conclude that the use of natural immunity boosters prevents the attack of coronavirus and makes a person stronger against the suspected attack of COVID-19 and/or other viral diseases.

Pharmacological evaluation of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension through in-vivo and in vitro-assays.

OBJECTIVE: This study determines the efficacy and probable underlying mode of action to the folk usage of Euphorbia hirta, Fagonia indica and Capparis decidua in hypertension. METHODS: The aqueous-methanol extracts of E. hirta (EH.Cr), F. indica (FI.Cr) and C. decidua (CD.Cr) were tested for antihypertensive effects in rats using non-invasive and in-vasive blood pressure measuring apparatus. In-vitro assays were carried out using isolated rat aortae using PowerLab station. RESULTS: EH.Cr, FI.Cr and CD.Cr at 500 mg/kg (orally) caused a fall in the mean systolic blood pressure in arsenic-induced hypertensive and normotensive rats, similar to nifedipine. In rat aortae, EH.Cr, CD.Cr and FI.Cr reversed low (20 mM), high (80 mM) K+ and phenylephrine (P.E)-driven contractions, while F. indica partially inhibited high K+ contractions. In the presence of TEA, F. indica remained unable to relax low K+ contractions. EH.Cr and CD.Cr moved Ca++ concentrations response curves to the right, like nifedipine. All fractions of EH.Cr and CD.Cr except aqueous, pet-ether and chloroform fractions of FI.Cr displayed Ca++ antagonistic activity. FI.Cr, its ethyl acetate and aqueous fraction exhibited TEA-sensitive potassium channel activation. On baseline tension, test materials also produced phentolamine-sensitive vasospasm. CONCLUSION: E. hirta, F. indica and C. decidua possess antihypertensive activity in arsenic-induced hypertensive rats possibly mediated via endothelium-dependent vasorelaxation. In normotensive rats, E. hirta and C. decidua showed antihypertensive activities through endothelium-dependent and Ca++ antagonistic pathways, while F. indica exhibited potassium channel activation and Ca++ antagonistic like effects in its vasorelaxation. Additional weaker vasospastic effects were derived through α-adrenergic like pathways.

Assessment of knowledge, attitude and practice of Pakistani population about the risk factors, causes, complications and management of diabetes mellitus.

OBJECTIVE: To compare the knowledge, attitude and practice regarding diabetes mellitus among diabetics and non-diabetics. METHODS: The cross-sectional study was conducted at the Government College University, Faisalabad, Pakistan, from December 2017 to April 2018, and comprised subjects recruited randomly from different cities of Punjab, Pakistan. Data was collected using a predesigned structured questionnaire regarding socio-demographic characteristics, general knowledge about diabetes, perception regarding indication, risk factors, diagnosis, and complications, and practices followed for treatment and management of diabetes. RESULTS: Of the 2,000 subjects, 972(48.6%) had family history of diabetes, 1338(66.9%) were living in urban areas, 1068(53.4%) were university graduates, 804(40.2%) were employed and 1152(57.6%) belonged to socio-economically balanced families. Composite knowledge score was significantly associated with age and socio-economic status (p<0.05). A highly significant association was observed regarding family history (p<0.001), level of education (p<0.0001) and occupation (p<0.001) with composite knowledge score. CONCLUSIONS: The knowledge level about diabetes was seen to be average.

Mini-Review: molecular elucidations of hutchinson-gilford progeria syndrome: A hope for managing horrors of premature aging in children.

Hutchinson-Gilford Progeria syndrome (or Progeria) is an exceptionally rare genetic disorder in children. It is caused by a rare point mutation in the lamin gene. It encodes lamin A protein, resulting in the de-shaping of nuclear membrane. This altered structure of the nuclear membrane renders the nucleus unstable. The shortened lifespan of the nucleus makes the cell liable for rapid ageing. Children are healthy by appearance when they are born but the signs appear after 12-24 months of age. Cardiovascular system is greatly affected which became a reason for the death of most of the patients of progeria. Stiffened joints disturb the bone movements; and alopecia affects the appearance of the patient. Rate of occurrence of the disease is one per four hundred thousand of people, though both sexes are equally affected.

REVIEW- Contemporary evidence on the dynamic role of probiotics in liver diseases.

Currently probiotics are considered as an emerging therapeutic strategy in the treatment of many liver disorders. The use of probiotics beyond infection of intestinal flora is a very helpful approach. The optimistic effect of probiotics has been observed in treating the hepatic cirrhosis, hepatic encephalopathy, viral hepatitis, irritable bowel syndrome, non-alcoholic fatty liver and alcoholic liver disease. The characterize mechanisms of probiotics are still unknown but may involve in, maintaining a microbial barrier against potential pathogens, reducing the production of bacterial toxins, modulating the immune system, intestinal permeability, and the inflammatory response. Its safety issues, effectiveness, food supplements as its source are still to be studied. However, studies revealed that probiotic therapy in hepatocellular carcinoma and in portal hypertension are still weak. Larger clinical studies are required before probiotics can be recommended as a treatment modality in liver diseases.

Delivery of Therapeutic Proteins: Challenges and Strategies.

Recent advances in genetic engineering and pharmaceutical biotechnology have made possible to combat life-threatening diseases with efficient delivery of therapeutic proteins. These advancements have increased the significance of therapeutic proteins in pharmaceutical market, but their therapeutic delivery to the targeted site is still a major obstacle to achieve desired therapeutic outcomes. In most cases, majority of the therapeutic proteins are usually administered via oral routes which encounter many problems notably enzymatic degradation, poor solubility and nonlinear pharmacokinetics. Besides this route, many other routes like mucosal, intra-nasal, intra-vaginal, pulmonary and transdermal have also been used for the delivery of therapeutic proteins. In order to keep these therapeutic proteins safe from enzymatic degradation and improve their therapeutic efficacy, several strategies have been designed and investigated various therapeutic delivery routes for efficient delivery of therapeutic proteins to the targeted site with minimal side effects. In this article, we have comprehensively summarized the recent advances and developments that have been adopted for delivery systems of these therapeutic proteins via invasive and/or non-invasive routes.