Current Pharmaceutical Biotechnology - Volume 19, Issue 5, 2018

Background: This review is intended to draw the attention of pharmaceutical and biotechnological communities to the untapped potential of the Scutellaria genus. Skullcaps, as they are more widely known, are found in one of the oldest materia medica in the world, that of ancient Chinese pharmacology, and their numerous wide range of medicinal bioactivities have been studied both in vivo and in vitro. For thousands of years, chemical compounds from the Scutellaria species have been safely used as antitumor, antibacterial, antiviral, anti-inflammatory, antioxidant or hepatoprotective factors. Objective: As these effects are well known, reflected in the presence of Scutellaria plants in national pharmacopoeias, it is clear that the plant has yet enormous unexploited potential. The European pharmacological market has turned to the resources of Scutellaria only in the last two decades, and although the construction and clinical processing of a new drug is a long process, the general impression is that very few medical products in pharmacies have been inspired by the phytochemistry of skullcaps. Conclusion: This paper presents the current state of knowledge on the wealth of Scutellaria chemical compounds with treatment applications, its tissue culture and biotechnological achievements, especially in the context of the production of secondary metabolites.

Background: Increased demand for compounds that are derived from natural source are gaining more and more importance. Plumbagin is a plant naphthoquinone which is present in several families, including Iridaceae, Plumbaginaceae, Ebenceae, Drosophyllaceae, Nepenthaceae and Droseraceae. Plumbagin possesses high therapeutic efficacy and minimal side effects. It has various pharmaceutical activities which include anticancer, antibacterial, anti-inflammatory, antioxidant, antifungal, neuroprotective and hypolipidemic activities. In natural habitat, production of plumbagin is low due to species variations and environmental changes, considering importance of this bioactive compound, alternative techniques for its enhanced production needs to be devised. In the present review, various production techniques and scale-up strategies for plumbagin production are discussed. Objectives: Aim of this review is to provide an insight into the chemistry of plumbagin, its pharmaceutical activities, perspective of cell suspension culture, root culture, hairy root culture and scale up strategies for its production. Methodology: All the data compiled and presented here were obtained from various E-resources like Pubmed, Science Direct, and Google Scholar up to February 2018. Result: This review comprises isolation, extraction and quantification method for plumbagin, its pharmaceutical activities, various tissue culture production techniques and scale-up strategies for enhanced production. Conclusion: Plumbagin is an important phytocompound which shows potential towards treatments of various diseases. Demand for the production of plumbagin continuously increasing worldwide due to its pharmacological properties. To fulfil commercial demand of plumbagin alternative technologies need to be investigated. Biotechnological approaches like cell suspension culture, root suspension culture and hairy root culture are alternative techniques for plumbagin production. These techniques provide continuous supply of bioactive compounds. However, research on various aspects of tissue culture production techniques is in preparatory stage and requires culture and process optimization for development of a commercially practical process.

Background: Replacement therapies have revolutionized treatment paradigms in metabolic diseases by restoring defective enzymes and supplementing missing downstream metabolites. Through most of the 20th century, no targeted therapies existed for these conditions, the only treatment options available focusing on symptoms rather than the underlying disorders. Improved understanding of the molecular pathways underlying metabolic disease has allowed not only supplementation of missing metabolites and reduction of upstream substrates, but replacement of defective or missing enzymes. Objective: Modern genetic technologies have facilitated steady progress in recombinant enzyme innovation, providing treatments that replicate not only endogenous enzymes, but also their posttranslational modifications to optimize their delivery and function. The advent of the gene therapy revolution brings a possibility of new therapeutic opportunities in which the enzymes at the core of metabolic diseases may not only be added back, but genetically replaced. Conclusion: With the next generation of treatments approaching, this review examines the recent decades of replacement therapy innovation in metabolic disease and discusses the challenges and opportunities for the next generation of treatments.

Background: Insulin (INS) has been used in the treatment of diabetes mellitus. Due to its large molecular weight and short half-life, it has been usually administered subcutaneously accompanied with side effects such as the possibility of hypoglycemia episodes, weight gain and inadequate post-meal glucose control. Objective: In order to overcome these limitations, alternative delivery routes of insulin are expected to provide better safety and compliance for the patient. Non-invasive insulin delivery system represents one of the most challenging goals for pharmaceutical industry. Nasal insulin delivery has been extensively studied as an alternative to subcutaneous injection for the treatment of diabetes. The pharmacokinetic profile of nasal insulin is similar to that obtained by intravenous injection. Result & Conclusion: This review discusses the most recent developments in nasal insulin administration technology. Firstly, the structure and physiology of the nasal cavity are introduced. Then, the advantages and disadvantages of nasal administration are discussed. Next, the methods of enhancing nasal insulin absorption and the dosage forms for insulin nasal administration are described. Furthermore, new therapeutic indications of nasal insulin administration were also investigated. Finally, the future development and respective technology of nasal insulin administration are prospected.

Background: Plants of the genus Campomanesia belong to the family Myrtaceae and are very abundant in Cerrado areas. Teas from leaves of species of this genus are used for intestinal infections, combating obesity, stomach pathology, fever and among others. Objective: The present study evaluated the chemical composition and antioxidant potential, cytotoxicity and genotoxicity of ethanolic extract from leaves of Campomanesia pubescens (Mart. ex DC.) O.Berg. Method: For the evaluation of antioxidant activity, the free radical DPPH and for determination of phenolic compounds Folin-Ciocalteau reagent were used. Identification of the substances was performed by HPLC-DAD by comparison of the retention times with standards analyzed under the same conditions and by evaluation of molecular absorption spectra in the ultraviolet and visible region. The cytotoxicity, genotoxicity were evaluated using Allium cepa bioassay. Results: In the ethanolic extract 7-hydroxy-6-methyl-5-methoxyflavanone, 5,7-dihydroxy-6-methylflavanone, 5,7-dihydroxy-8-methylflavanone, 2´,4´-dihydroxy-6´-methoxychalcone, 5,7-dihydroxy-6,8- dimethylflavanone, 2´,4´-dihydroxy-5´-methyl-6´-methoxychalcone and 2´,4´-dihydroxy-3´,5´-dimethyl-6´- methoxychalcone were identified. The extract showed antioxidant activity and cytotoxic effects on cell division and increased chromosomal alterations in Allium cepa test. Conclusion: These results showed antioxidant activity and suggest the cytotoxic and genotoxic effects in Allium cepa of ethanolic extract obtained from the leaves of Campomanesia pubescens.

Background: Bioconjugates prepared from photoactive molecules and metal nanoparticles are suitable for the development of new optoelectronic devices and for theranostic applications in medicine. Methods: We produced a bioconjugate of R-phycoerythrin (R-PE), a photosynthetic pigment of red algae, with Ag0 nanoparticles (Ag0 NPs) synthesized in its tunnel cavities by mixing aqueous solutions of AgNO3 and R-PE without exogenous reductant. In freshly prepared bioconjugate (Ag0R-PE), the diameter of Ag0 NPs measured in electron microscopic images was 6.5 ± 0.5 nm, being commensurate with the length of R-PE tunnel cavity, and they were found to emit bright visible fluorescence. Result: The initial aggregation temperature (T0) of freshly prepared Ag0R-PE was decreased, compared to that of native R-PE (33 vs. 44°C). Upon the ripening of Ag0 NPs, their fluorescence was almost entirely quenched, and giant surface-enhanced Raman scattering was recorded. The bioconjugate self-assembled into nanorods 25 ± 5 nm long and could withstand heating to 90°C. Further heating (90°C → 100°C) resulted in the formation of filaments which are 0.5 ± 0.2 μm long and spherical aggregates 60 ± 10 nm in diameter. Conclusion: These data can contribute to the development of practical applications for the Ag0R-PE bioconjugate.

Background: The aim of this study was to investigate anti-apoptotic effects of luteolin on angiotensin II-stimulated murine peritoneal macrophages and to explore its mechanisms. Methods and Results: The viability and cytotoxicity of murine peritoneal macrophages were assessed using the Cell Counting Kit-8 assay and measuring lactate dehydrogenase levels, respectively. Apoptotic rates were determined using Annexin V/propidium iodide staining. Protein expression was examined by western blotting, and markers of macrophage phenotypes were analyzed by flow cytometry and ELISA. Luteolin decreased the apoptotic rate of angiotensin II-stimulated macrophages. This effect was associated with increased Bcl-2 and caspase-3 levels as well as decreased Bax and cleaved caspase-3 levels. Additionally, luteolin reduced the expression of M1 macrophage phenotype markers (IL-6, TNF-α, iNOS, CD16/32) and increased the expression of M2 macrophage phenotype markers (Dectin-1, IL-10, Arg-1, CD206). Moreover, luteolin blocked Akt phosphorylation on residues 308 and 473, which were up-regulated in presence of angiotensin II. The effects of luteolin were similar to those of LY294002, a specific PI3K/Akt pathway inhibitor. Conclusions: These results indicated that luteolin has anti-apoptotic effects on angiotensin II-stimulated macrophages via macrophage polarization, which might be associated with PI3K/Akt signaling.