GlaxoSmithKline.

Pay-load deliveries across the skin barrier to the systemic circulation have been one of the most challenging delivery options. Necessitated requirements of the skin and facilitated skin layer cross-over delivery attempts have resulted in development of different non-invasive, non-oral methods, devices and systems which have been standardized, concurrently used and are in continuous upgrade and improvements. Iontophoresis, electroporation, sonophoresis, magnetophoresis, dermal patches, nanocarriers, needled and needle-less shots, and injectors are among some of the methods of transdermal delivery. The current review covers the current state of the art, merits and shortcomings of the systems, devices and transdermal delivery patches, including drugs’ and other payloads’ passage facilitation techniques, permeation and absorption feasibility studies, as well as physicochemical properties affecting the delivery through different transdermal modes along with examples of drugs, vaccines, genes and other payloads.

Three new compounds, (7E)-2beta,3alpha-dihydroxy-megastigm-7-en-9-one (1), 3-[5,7-dihydroxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-8-yl]-4-methoxybenzoic acid (2), and 4'-O-methyl myricetin 3-O-(6-O-alpha-L-rhamnopyranosyl)-beta-D-glucopyranoside (3), were isolated from Ginkgo biloba, together with 27 known compounds. The structures of the new compounds were determined primarily from 1D- and 2D-NMR analysis. The 4-O-methylbenzoic acid structural feature at C-8 in 2 is encountered for the first time. The antioxidant activities of 29 compounds isolated from Ginkgo biloba were evaluated on intracellular reactive oxygen species in HL-60 cells. It was found that quercetin, kampferol, and tamarixetin had antioxidant activity that was approximately 3-fold greater than that of their respective glycosides and also approximately 3-fold greater than that of a standard ascorbic acid with an IC(50) at maximum effectiveness.

The role and contributions of natural products chemistry in advancements of the physical and biological sciences, its interdisciplinary domains, and emerging of new avenues by providing novel applications, constructive inputs, thrust, comprehensive understanding, broad perspective, and a new vision for future is outlined. The developmental prospects in bio-medical, health, nutrition, and other interrelated sciences along with some of the emerging trends in the subject area are also discussed as part of the current review of the basic and core developments, innovation in techniques, advances in methodology, and possible applications with their effects on the sciences in general and natural products chemistry in particular. The overview of the progress and ongoing developments in broader areas of the natural products chemistry discipline, its role and concurrent economic and scientific implications, contemporary objectives, future prospects as well as impending goals are also outlined. A look at the natural products chemistry in providing scientific progress in various disciplines is deliberated upon.

Background: Alzheimer is a fast growing disease with imprecise chemical treatments. Increased oxidative stress, decrease in acetylcholine concentration, and appearance of amyloidal proteins are reported in pathology of Alzheimer. Chemical drugs are effective but on the cost of detrimental side effects. Purpose: Present research is based on Preparation, characterization, behavioral and biochemical evaluation of brain targeted Piperine solid lipid nanoparticles in an experimentally induced Alzheimer's model at a low dose of 2 mg/kg. Methods: Piperine solid lipid nanoparticles were prepared by Emulsification-Solvent Diffusion technique with polysorbate-80 coating to impart Brain specific targeting. Experimental Ibotenic acid induced Alzheimer's, Force swimming test, superoxide dismutase, acetylcholenesterase enzymatic assays and also Histopathology of brain cortex was conducted to evaluate the Piperine therapeutic effects in Alzheimer's Disease. Results: Piperine in solid lipid nanoformulation (2 mg/kg equivalent) reduced the SOD values by 504 ± 44.24 m units, p < 0.05, increased the acetylcholenesterase values by 29.24 ± 4.29 µg/mg, p < 0.01 and reduced immobility to 41.36 ± 3.53 s, p < 0.001 and has shown superior results than Donepezil (5 mg/kg). Histopathology studies revealed the reduced plaques and tangles. Conclusions: P-80-PIP-SLN has shown therapeutic effects in Alzheimer via reducing the oxidative stress and reducing the cholinergic degradation at 2 mg/kg dose equivalent.

Streptomyces smyrnaeus UKAQ_23, isolated from the mangrove-sediment, collected from Jubail,Saudi Arabia, exhibited substantial antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), including non-MRSA Gram-positive test bacteria. The novel isolate, under laboratory-scale conditions, produced the highest yield (561.3 ± 0.3 mg/kg fermented agar) of antimicrobial compounds in modified ISP-4 agar at pH 6.5, temperature 35 °C, inoculum 5% v/w, agar 1.5% w/v, and an incubation period of 7 days. The two major compounds, K1 and K2, were isolated from fermented medium and identified as Actinomycin X2 and Actinomycin D, respectively, based on their structural analysis. The antimicrobial screening showed that Actinomycin X2 had the highest antimicrobial activity compared to Actinomycin D, and the actinomycins-mixture (X2:D, 1:1, w/w) against MRSA and non-MRSA Gram-positive test bacteria, at 5 µg/disc concentrations. The MIC of Actinomycin X2 ranged from 1.56–12.5 µg/ml for non-MRSA and 3.125–12.5 µg/ml for MRSA test bacteria. An in-silico molecular docking demonstrated isoleucyl tRNA synthetase as the most-favored antimicrobial protein target for both actinomycins, X2 and D, while the penicillin-binding protein-1a, was the least-favorable target-protein. In conclusion, Streptomyces smyrnaeus UKAQ_23 emerged as a promising source of Actinomycin X2 with the potential to be scaled up for industrial production, which could benefit the pharmaceutical industry.

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This Paper describes an improved HPLC method for the determination of pentacyclic oxindole alkaloids in Uncaria tomentosa (Cat's Claw). Six of the isomeric compounds could be baseline separated at room temperature within less than 30 min by using 3 microm C-18 column material and a mobile phase consisting of 10 mM phosphate buffer at pH 7.0 and acetonitrile. At a wavelength of 245 nm all standard compounds could be detected at concentrations as low as 0.63 microg/ml. Different samples of U. tomentosa bark and market products containing Cat's Claw were extracted with a modified procedure ensuring the integrity of the alkaloids and analyzed successfully. The results indicated accuracy and consistency of the new method, and showed variations in the total alkaloid content in products from 0.156 to 0.962%.