Interfacial Denaturation at the Droplet Simplifies the Formation of Drug-Loaded Protein Nanocapsules to Enhance Immune Response of Cells.

Nanocapsules enable multicomponent encapsulation of therapeutic cargoes with high encapsulation content and efficiency, which is vital for cancer immunotherapy. In the past, chemical crosslinking is used to synthesize nanocapsules, which can impede the regulatory approval process. Therefore, a new class of protein nanocapsules is developed by eliminating the need for chemical crosslinking by utilizing protein denaturation through a process that is referred to as "baking at the droplet interface". Such protein nanocapsules with antigens incorporated in the shell and a combination of encapsulated drugs showed an enhancement in the immune response of cells.

Synthesis and Biochemical Evaluation of Baicalein Prodrugs.

Baicalein (5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a flavonoid analog from Scutellaria baicalensis, possesses several pharmacological activities including antioxidant, antiproliferative, and anti-inflammatory activities. We previously reported that baicalein inhibits the thymic stromal lymphopoietin (TSLP)/TSLP receptor (TSLPR) signaling pathways and can be used as an active ingredient in the treatment of asthma and atopic dermatitis. However, baicalein is rapidly metabolized to baicalin and baicalein-6-O-glucuronide in vivo, which limits its preclinical and clinical use. In this study, we designed, synthesized, and evaluated baicalein prodrugs that protect the OH group at the 7-position of the A ring in baicalein with the amino acid carbamate functional group. Comprehensive in vitro and in vivo studies identified compound 2 as a baicalein prodrug candidate that improved the plasma exposure of baicalein in mouse animal studies. Our results demonstrated that this prodrug approach could be further adopted to discover oral baicalein prodrugs.

Fighting Diabetes Mellitus: Pharmacological and Non-pharmacological Approaches.

BACKGROUND: The increasing worldwide prevalence of diabetes mellitus confers heavy public health issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost scientific challenges. OBJECTIVES: This article aims to provide an overview of current pharmacological and non-pharmacological approaches available for the management of diabetes mellitus. METHODS: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes, glucagon-like peptide-1, glucose homeostasis, etc. Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors- cyclic adenosine monophosphate, 5'-adenosine monophosphate-activated protein kinase, sodium-glucose cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods designed to mitigate diabetes are summarized and discussed. CONCLUSION: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2 inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent the most important strategies in diabetes management. These approved diabetes medications work via targeting the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is insufficient to achieve positive outcomes.

Metabolism and Pharmacokinetics of SP-8356, a Novel (1S)-(-)-Verbenone Derivative, in Rats and Dogs and Its Implications in Humans.

(1S,5R)-4-((E)-3,4-dihydroxy-5-methoxystryryl)-6,6-dimethylbicylco[3.1.1]hept-3-en-2-one (SP-8356) is a novel (1S)-(-)-verbenone derivative that is currently in preclinical development for the treatment of ischemic stroke and atherosclerosis. This report aimed at characterization of the metabolism and pharmacokinetic properties of SP-8356. Following intravenous dose in rats and dogs, plasma concentrations of SP-8356 declined rapidly with high clearance (CL) and short half-life; after oral administration in both species, its plasma levels were below the quantitation limit. Fourteen circulating metabolites, formed by mono-oxygenation, demethylation, glucuronidation, catechol O-methylation, sulfation and oxidation (bioactivation) followed by glutathione (GSH) conjugation, were tentatively identified in both species. Urinary excretion of SP-8356 appeared to be minimal in rats, compared to its metabolites. GSH conjugate of SP-8356 was also formed during incubation with rat liver S9 fraction consistent with oxidative bioactivation; this bioactivation was almost completely inhibited by the cofactors for glucuronidation, sulfation and methylation, indicating that it may be abolished by competing metabolic reactions in the body. The human pharmacokinetics of SP-8356 was predicted to be similar to that of the animals based on the current in vitro metabolic stability results. In summary, rapid phase II metabolism appears to be mainly responsible for its suboptimal pharmacokinetics, such as high CL and low oral absorption. Because of competing metabolic reactions, potential safety risks related to SP-8356 bioactivation may be low.

Antioxidant Activity and Main Chemical Components of a Novel Fermented Tea.

In the present study, we aimed to develop a novel fermented tea (NFT) product and to evaluate their in vitro antioxidant potential and chemical composition. We found that NFT contained a high level of total phenolic compounds (102.98 mg gallic acid equivalents/g extract) and exhibited diverse antioxidant activities, such as scavenging of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and hydroxyl radicals, as well as reducing power. The total catechins in NFT were comparable to those of Lipton black tea (LBT), but lower than those of Boseong green tea (BGT) or Tieguanyin oolong tea (TOT). Among all catechins tested, epigallocatechin (EGC) and epigallocatechin-3-O-gallate (EGCG) were the predominant compounds in NFT. In particular, the contents of total theaflavins (TFs), theaflavin (TF), theaflavin-3-gallate (TF3G), and theaflavin-3'-gallate (TF3'G) in NFT were significantly higher than that of BGT, TOT, or LBT. NFT had the highest level of total essential amino acid and γ-aminobutyric acid (GABA) compared with BGT, TOT and LBT. Furthermore, the sensory evaluation results showed that NFT had satisfactory color, aroma, taste, and overall acceptability scores. Our results highlight the potential usefulness of this novel fermented tea as a nutraceutical food/ingredient with special functional activities.