Many herbal medicines and compositions are clinically effective but challenged by its safety risks, i.e., aconitine (AC) from aconite species. The combined use of Radix glycyrrhizae (licorice) with Radix aconite L. effectively eliminates toxicity of the later while increasing efficacy. In this study, a boiling-stable 31-kDa protein (namely GP) was purified from licorice and self-assembled into nanoparticles (206.2 ± 2.0 nm) at pH 5.0, 25 °C. The aconitine-encapsulated GP nanoparticles (238.2 ± 1.2 nm) were prepared following the same procedure and tested for its toxicity by intraperitoneal injection on ICR mouse (n = 8). Injection of GP-AC nanoparticles and the mixed licorice-aconite decoction, respectively, caused mild recoverable toxic effects and no death, while the aconitine, particle-free GP-AC mixture and aconite decoction induced sever toxic effects and 100 % death. Encapsulation of poisonous alkaloids into self-assembled herbal protein nanoparticles contributes to toxicity attenuation of combined use of herbs, implying a prototype nanostructure and a universal principle for the safer clinical applications of herbal medicines.
Like any typical food system, bone soup (or broth), a traditional nourishing food in many cultures, contains a colloid dispersion of self-assembled micro/nano-particles. Food ingestion results in the direct contact of food colloidal MNPs with immune cells. Will they ever interact with each other? To answer the question, MNPs and NPs were separated from porcine bone soup and labeled with Nile Red, and their uptake by murine oral macrophages and its consequent effects were investigated. Colloidal particle samples of UF-MNPs and SEC-NP were prepared from porcine bone soup by ultrafiltration (UF) and size-exclusion chromatography, respectively. Their mean hydrodynamic diameters were 248 ± 10 nm and 170 ± 1 nm with dominant composition of protein and lipid. Particles in both samples were found to be internalized by oral macrophages upon co-incubation at particle/cell ratios of 14,000/1. In normal oral macrophages, the particle uptake exerted influence neither on the cellular cytosolic membrane potential (V mem ) nor mitochondrial superoxide level, as were indicated with fluorescent dyes of DiBAC 4 (3) and MitoSOX Red, respectively. However, when oral macrophages were challenged by peroxyl radical inducer AAPH, the engulfment of UF-MNPs and SEC-NPs mitigated the peroxyl radical induced membrane hyperpolarization effect by up to 70%, and the suppression on the oxygen respiration in mitochondria by up to 100%. Those results provide evidence of the direct interaction between food colloidal particles with immune cells, implying a possible new mode of food-body interaction.
Colloidal particles are essential components of sun-dried Isatis indigotica Fort. roots (Ban-Lan-Gen in Chinese, BLG) decoction. Nanoparticles (NPs) were isolated from BLG decoction with size exclusion chromatography and characterized. Their average diameter is ∼120 nm, reversibly responding to pH and temperature changes. They promoted the growth of normal cells but suppressed that of cancerogenic cells and macrophages. Two constitutive glycated proteins were identified from the NPs, namely BLGP1 and BLGP2. Their N-terminal amino acid sequences were V-X-R-E-V-V-K-D-I and V-V-R-E-V-V-K-D-I-A-G-A-V-Q-T-N-E-Q-Y. Their full-length cDNA sequences were cloned to obtain the highly homological amino acid sequences of non-glycated proteins, whose theoretical molecular weights are 21831.64 Da and 21841.67 Da. Using pepsin hydrolysis and mass spectrometry, four possible glycation adducts were identified in BLGP1, whereas one in BLGP2. To conclude, bioactive nanoparticles isolated from the herbal decoction are intelligent nanoassemblies composed of a new boiling-stable protein. Glycation plays a critical role in heat-induced formation of these nanoassemblies. The novel, intelligent, safe and stable nano-carriers for drug delivery may be developed using BLG NPs as prototype.
The antidiabetic effects of Ge-Gen-Qin-Lian-Tang decoction (GQD) have been proven clinically. In a pharmacological study conducted on STZ-induced diabetic rats, the constitutive aggregates/sediments of Ge-Gen-Qin-Lian-Tang decoction exhibited stronger hypoglycemic and antioxidant activities compared to the soluble compositions. This study aims to demonstrate the pharmacological properties of aggregates derived from GQD by measuring permeability of the active monomer phytochemicals (e.g., baicalin) in a Caco-2 cell monolayer and determine the cellular viability, intracellular redox status (MDA and SOD), and insulin secretion of pancreatic β-cell line, INS-1, following STZ-induced oxidative stress. The aggregates were separated into three fractions, namely, “MA (microaggregates),” “400 g supernatant,” and “MNA (micro-/nanoaggregates),” by centrifugation at 400 ×g and 15000 ×g, respectively. Aggregates in the sediment increased baicalin absorption, showed little toxicity to β-cells, elevated intracellular SOD levels, and significantly suppressed oxidative damage effects on cellular viability and functions. The “MA” fraction had a larger particle size and provided higher antioxidant cellular protection than “MNA” in vitro, implying that the sediments may be the active components in the herbal decoction. The actions of these micro-/nanoaggregates may provide a new perspective for understanding the antidiabetic effects of herbal decoctions and aid in interpretation of synergistic actions between the multiple components.
Wave–current interactions are crucial to suspended-sediment dynamics, but the roles of the associated physical mechanisms, the depth-dependent wave radiation stress, Stokes drift velocity, vertical transfer of wave-generated pressure transfer to the mean momentum equation (form drag), wave dissipation as a source term in the turbulence kinetic energy equation, and mean current advection and refraction of wave energy, have not yet been fully understood. Therefore, in this study, a computationally fast wave model developed by Mellor et al., a Finite Volume Coastal Ocean Model (FVCOM) hydrodynamics model, and the sediment model developed by the University of New South Wales are two-way coupled to study the effect of each wave–current interaction mechanism on suspended-sediment dynamics near shore during strong wave events in a tidally dominated and semiclosed bay, Jiaozhou Bay, as a case study. Comparison of Geostationary Ocean Color Imager data and model results demonstrates that the inclusion of just the combined wave–current bottom stress in the model, as done in most previous studies, is clearly far from adequate to model accurately the suspended-sediment dynamics. The effect of each mechanism in the wave–current coupled processes is also investigated separately through numerical simulations. It is found that, even though the combined wave–current bottom stress has the largest effect, the combined effect of the other wave–current interactions, mean current advection and refraction of wave energy, wave radiation stress, and form drag (from largest to smallest effect), are comparable. These mechanisms can cause significant variation in the current velocities, vertical mixing, and even the bottom stress, and should obviously be paid more attention when modeling suspended-sediment dynamics during strong wave events.
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