In Vitro Cytotoxicity and Bioavailability of Ginsenoside-Modified Nanostructured Lipid Carrier Containing Curcumin.

Our aim was to investigate the cellular uptake, in vitro cytotoxicity and bioavailability of ginsenoside-modified nanostructured lipid carrier loaded with curcumin (G-NLC). The formulation was prepared by melt emulsification technique, in which water was added to the melted lipids and homogenized to give a uniform suspension of NLC (without ginsenoside) and G-NLC. Cellular uptake of curcumin in two colon cancer cell lines (HCT116 and HT29) was increased when administered using both NLC and G-NLC compared to control (curcumin dissolved into DMSO) as measured by fluorescence microscopy. Ginsenoside modification resulted in 2.0-fold and 1.4-fold increases in fluorescence intensity in HCT116 and HT29 cell lines, respectively, compared to plain NLC. In vitro cytotoxicity (assessed by MTT assay) had a dose-dependent relationship with curcumin concentration for both NLC and G-NLC. Although G-NLC was taken up more readily in HCT116 cells, ginsenoside modification did not produce a significant increase in cytotoxic effect; a significant increase was observed in HT29 cells. Oral administration of G-NLC in ten colon cancer patients produced an appreciable plasma level of unbound curcumin (2.9 ng/mL). In conclusion, introduction of ginsenoside into NLC enhanced the cellular uptake and cytotoxicity of curcumin as well as its oral bioavailability, and this strategy can be used to improve clinical outcomes in the treatment of colon cancer with similar genotype to HT29.

Skin permeation and retention of topical bead formulation containing tranexamic acid.

The objective of this study is to develop a topical bead formulation of tranexamic acid (TA) which can be used concomitantly with laser treatment. The bead formulation of TA (TAB) was successfully prepared by fluidized bed drying method. Physicochemical properties of the TAB were evaluated in terms of chemical stability of TA and differential scanning calorimetry. TA in the bead was stable up to six months at 25°C and existed as amorphous state. In vitro skin permeation and in vivo skin retention of TA in the beads were significantly higher compared to a commercial product. When the bead was dissolved into distilled water and applied concomitantly with laser treatment, the amount of TA retained in the skin in the in vivo study was inversely proportional to the energy levels of laser treatment, indicating absorption into subcutaneous tissue and drainage to systemic circulation. Therefore, when laser treatment is used concomitantly with TAB, energy level should be very carefully monitored to avoid possible adverse events associated with systemic side effects of TA.

Quercetin-Loaded Solid Lipid Nanoparticle Dispersion with Improved Physicochemical Properties and Cellular Uptake.

The objective of this study was to formulate and characterize properties of solid lipid nanoparticle (SLN) dispersion containing quercetin. SLN was prepared by ultrasonication method using tripalmitin and lecithin as lipid core and then the surface was coated with chitosan. Entrapment efficiency was greater than 99%, and mean particle size of SLN was 110.7 ± 1.97 nm with significant increase in the coated SLN (c-SLN). Zeta potential was proportionally increased and reached plateau at 5% of chitosan coating with respect to tripalmitin. Differential scanning calorimetry showed disappearance of endothermic peak of quercetin in SLNs, indicating conversion of crystalline state to amorphous state. FTIR study of SLNs showed no change in the spectrum of quercetin, which indicates that the lipid and chitosan were not incompatible with quercetin. When coating amount was greater than 2.5% of tripalmitin, particle size and zeta potential were very stable even at 40°C up to 90 days. All SLN dispersions showed significantly faster release profile compared to pure quercetin powder. At pH 7.0, the release rate was increased in proportion to the coating amount. Interestingly, at pH 3.0, chitosan coating of 5.0% or greater decreased the rate. Cellular uptake of quercetin was performed using Caco-2 cells and showed that all SLN dispersions were significantly better than quercetin dispersed in distilled water. However, cellular uptake of quercetin from c-SLN was significantly lower than that from uncoated SLN.

Ginseng and ginsenosides on cardiovascular and pulmonary diseases; Pharmacological potentials for the coronavirus (COVID-19).

Since its outbreak in late 2019, the Coronavirus disease 2019 (COVID-19) pandemic has profoundly caused global morbidity and deaths. The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has major complications in cardiovascular and pulmonary system. The increased rate of mortality is due to delayed detection of certain biomarkers that are crucial in the development of disease. Furthermore, certain proteins and enzymes in cellular signaling pathways play an important role in replication of SARS-CoV-2. Most cases are mild to moderate symptoms, however severe cases of COVID-19 leads to death. Detecting the level of biomarkers such as C-reactive protein, cardiac troponin, creatine kinase, creatine kinase-MB, procalcitonin and Matrix metalloproteinases helps in early detection of the severity of disease. Similarly, through downregulating Renin-angiotensin system, interleukin, Mitogen-activated protein kinases and Phosphoinositide 3-kinases pathways, COVID-19 can be effectively controlled and mortality could be prevented. Ginseng and ginsenosides possess therapeutic potential in cardiac and pulmonary complications, there are several studies performed in which they have suppressed these biomarkers and downregulated the pathways, thereby inhibiting the further spread of disease. Supplementation with ginseng or ginsenoside could act on multiple pathways to reduce the level of biomarkers significantly and alleviate cardiac and pulmonary damage. Therefore, this review summarizes the potential of ginseng extract and ginsenosides in controlling the cardiovascular and pulmonary diseases by COVID-19.

Gintonin upregulates cytokine production and expression of NKp30, NKp44 and NKp44 related to natural killer cell activity on immunosuppressive rat.

The objective of the study is to estimate the potential of gintonin, as an immune enhancing agent through natural killer cell (NK cell) activity in cyclophosphamide (CY)-induced immunosuppressive animals. Accumulated results reveals that, gintonin attenuated CY-induced immunosuppression and it might modulate NK cell activity to boost the immunity.

Bone marrow stem cells incubated with ellipticine regenerate articular cartilage by attenuating inflammation and cartilage degradation in rabbit model.

BACKGROUND: Ellipticine (Ellip.) was recently reported to have beneficial effects on the differentiation of adipose-derived stem cells into mature chondrocyte-like cells. On the other hand, no practical results have been derived from the transplantation of bone marrow stem cells (BMSCs) in a rabbit osteoarthritis (OA) model. OBJECTIVES: This study examined whether autologous BMSCs incubated with ellipticine (Ellip.+BMSCs) could regenerate articular cartilage in rabbit OA, a model similar to degenerative arthritis in human beings. METHODS: A portion of rabbit articular cartilage was surgically removed, and Ellip.+BMSCs were transplanted into the lesion area. After two and four weeks of treatment, the serum levels of proinflammatory cytokines, i.e., tumor necrosis factor α (TNF-α) and prostaglandin E2 (PGE2), were analyzed, while macroscopic and micro-computed tomography (CT) evaluations were conducted to determine the intensity of cartilage degeneration. Furthermore, immuno-blotting was performed to evaluate the mitogen-activated protein kinases, PI3K/Akt, and nuclear factor-κB (NF-κB) signaling in rabbit OA models. Histological staining was used to confirm the change in the pattern of collagen and proteoglycan in the articular cartilage matrix. RESULTS: The transplantation of Ellip.+BMSCs elicited a chondroprotective effect by reducing the inflammatory factors (TNF-α, PGE2) in a time-dependent manner. Macroscopic observations, micro-CT, and histological staining revealed articular cartilage regeneration with the downregulation of matrix-metallo proteinases (MMPs), preventing articular cartilage degradation. Furthermore, histological observations confirmed a significant boost in the production of chondrocytes, collagen, and proteoglycan compared to the control group. Western blotting data revealed the downregulation of the p38, PI3K-Akt, and NF-κB inflammatory pathways to attenuate inflammation. CONCLUSIONS: The transplantation of Ellip.+BMSCs normalized the OA condition by boosting the recovery of degenerated articular cartilage and inhibiting the catabolic signaling pathway.

Ginsenoside improves physicochemical properties and bioavailability of curcumin-loaded nanostructured lipid carrier.

The aim of this study was to develop a ginsenoside-modified nanostructured lipid carrier (G-NLC) dispersion containing curcumin. The NLC was prepared by melt emulsification with slight modification process. Different G-NLC dispersion systems were prepared using lipid carrier matrix composed of ginsenoside, phosphatidylcholine, lysophosphatidylcholine, and hydrogenated bean oil. TEM image of the nanoparticles in the NLC dispersion showed core/shell structure, and there was corona-like layer surrounding the particles in the G-NLC. The mean particle size of G-NLC dispersion was in the range of about 300-500 nm and stayed submicron size up to 12 months. The in vitro release of curcumin was faster in pH 1.2 compared to pH 6.8 and it showed linear release pattern after lag time of 1 h. When the G-NLC dispersion was orally administered to rats, Cmax of the free curcumin was 15.2 and 32.3 ng/mL at doses of 50 and 100 mg/kg, respectively, while it was below quantification limit when curcumin was administered as of dispersion in distilled water. Based on these results, it is certain that ginsenoside modulated the NLC dispersion, leading to enduring shelf-life of the dispersion system and enhanced bioavailability. These results strongly suggest that ginsenoside holds a promising potential as a pharmaceutical excipient in the pharmaceutical industries to increase the utility of various bioactives.