Inhibitory effect of γ-ray-modified hydroxymethylated baicalins on NO production.

Baicalin, a glucuronic flavone, is the major active component in the medicinal plant Scutellaria baicalensis. Herein, baicalin was irradiated by γ-rays to afford four unusual flavanones, baicalinols A (2), B (3), and C (4) and peroxybaicaleinol (5), and two known flavones, oroxylin A (6) and baicalein (7). The structures of the hydroxymethylated products were elucidated using nuclear magnetic resonance spectroscopy and mass spectrometry, and their absolute configuration was established using electronic circular dichroism spectroscopy. Novel hydroxymethylated flavanones 2 and 3 suppressed both nitric oxide (NO) production and the expression of inducible NO synthase and showed significantly higher anti-inflammatory activities in lipopolysaccharide-stimulated macrophages than the parent compound. These newly generated hydroxymethylated flavanones can be potentially used for treating inflammatory diseases.

Urine-Derived Stem Cell-Secreted Klotho Plays a Crucial Role in the HK-2 Fibrosis Model by Inhibiting the TGF-ß Signaling Pathway.

Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.

Pharmacokinetic/Pharmacodynamic Modeling To Predict the Antiplatelet Effect of the Ticagrelor-Loaded Self-Microemulsifying Drug Delivery System in Rats.

Ticagrelor (TCG) has been used as an antiplatelet agent for acute coronary syndrome patients. The aim of this research was to establish a population pharmacokinetic/pharmacodynamic (PK/PD) model of TCG and to apply the model for predicting the PD response of the TCG-loaded self-microemulsifying drug delivery system (TCG-SME) in rats. Pure TCG and TCG-SME (2, 5, and 10 mg/kg of TCG) were orally administered to male Sprague-Dawley rats. Plasma samples were collected at scheduled time-points and then analyzed for TCG plasma concentrations and antiplatelet effects. The inhibition of platelet aggregation of TCG was measured as a PD response. The PK profiles of pure TCG and TCG-SME could be well-explained with a two-compartment PK model. The accuracy of the PK model was assessed with a goodness-of-fit plot and conditional weight residual error (CWRES). Also, the visual predictive check was investigated based on the predictions. A population PK/PD model for pure TCG was established as an indirect response Emax model linked to the two-compartment PK model of pure TCG. The PK/PD model proposed a suitable fitting to link the plasma concentration of TCG simultaneously with platelet aggregation. Based on the PK data of TCG-SME, as well as the established PK/PD model of pure TCG, the PD profiles of TCG-SME were simulated. TCG-SME was more effective in inducing the antiplatelet effect than pure TCG at equivalent doses of TCG. The accuracy of the simulation was verified by comparing the simulated PD profile with the profile observed in rats. The observations were close to the model simulations. In addition, the values of CWRES were almost within ±2. In conclusion, the PK/PD modeling approach can provide a way for predicting mathematically the PD responses from PK profiles of other TCG formulations and a conceptual prediction for future clinical assessment.

Consensus on Current Injectable Treatment Strategies in the Asian Face.

BACKGROUND: The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. METHODS: The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. RESULTS: The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to[55 years are presented. CONCLUSIONS: In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

An EGF- and Curcumin-Co-Encapsulated Nanostructured Lipid Carrier Accelerates Chronic-Wound Healing in Diabetic Rats.

Nanostructured lipid carriers (NLC) are capable of encapsulating hydrophilic and lipophilic drugs. The present study developed an NLC containing epidermal growth factor (EGF) and curcumin (EGF-Cur-NLC). EGF-Cur-NLC was prepared by a modified water-in-oil-in-water (w/o/w) double-emulsion method. The EGF-Cur-NLC particles showed an average diameter of 331.8 nm and a high encapsulation efficiency (81.1% and 99.4% for EGF and curcumin, respectively). In vitro cell studies were performed using two cell types, NIH 3T3 fibroblasts and HaCaT keratinocytes. The results showed no loss of bioactivity of EGF in the NLC formulation. In addition, EGF-Cur-NLC improved in vitro cell migration, which mimics the wound healing process. Finally, EGF-Cur-NLC was evaluated in a chronic wound model in diabetic rats. We found that EGF-Cur-NLC accelerated wound closure and increased the activity of antioxidant enzymes. Overall, these results reveal the potential of the NLC formulation containing EGF and curcumin to promote healing of chronic wounds.

Bioanalytical Method Development and Validation of Veratraldehyde and Its Metabolite Veratric Acid in Rat Plasma: An Application for a Pharmacokinetic Study.

A simple, sensitive, and rapid UHPLC-MS/MS method was developed for the simultaneous determination of veratraldehyde and its metabolite veratric acid in rat plasma. Cinnamaldehyde was used as an internal standard (IS) and the one-step protein precipitation method with 0.2% formic acid in acetonitrile (mobile phase B) was used for the sample extraction. Reversed C18 column (YMC-Triart C18 column, 50 mm × 2.0 mm, 1.9 µm) was used for chromatographic separation and was maintained at 30 °C. The total run time was 4.5 min and the electrospray ionization in positive mode was used with the transition m/z 167.07 → 139.00 for veratraldehyde, m/z 183.07 → 139.00 for veratric acid, and m/z 133.00 → 55.00 for IS. The developed method exhibited good linearity (r2 ≥ 0.9977), and the lower limits of quantification ranged from 3 to 10 ng/mL for the two analytes. Intra-day precision and accuracy parameters met the criteria (within ±15%) during the validation. The bioanalytical method was applied for the determination of veratraldehyde and veratric acid in rat plasma after oral and percutaneous administration of 300 and 600 mg/kg veratraldehyde. Using the analytical methods established in this study, we can confirm the absorption and metabolism of veratraldehyde in rats for various routes.

Hybrid polymeric microspheres for enhancing the encapsulation of phenylethyl resorcinol.

Phenylethyl resorcinol (PR) has been known to allow the whitening effect by inhibiting formation of tyrosinase. PR has solubility of 4.05 ± 0.02 mg/g for water and log P of 3.017, proposed an amphiphilic substance. Hybrid PLGA microspheres with oil (HPMSs) have been used to improve encapsulation efficiency (EE) of hydrophilic molecules and control the release of them. The solubility (618.3 ± 22.29 mg/g) of PR was the highest in CapryolTM 90. The formulations (F6 and F`6) were selected after evaluation with EE and the released % (w/w) at 8 h. HPMSs showed 40% (w/w) increase of EE compared to that in CPMSs. Retention study on rat skin at 12 h resulted in that PR of HPMSs was remained more than that of CPMSs in dermal layer forming the melanin. HPMSs showed 1.4-fold increase of tyrosinase inhibition significantly in melanoma cells than that of the PR solution at 24 h.

Consensus on Current Injectable Treatment Strategies in the Asian Face.

BACKGROUND: The desire for and use of nonsurgical injectable esthetic facial treatments are increasing in Asia. The structural and anatomical features specific to the Asian face, and differences from Western populations in facial aging, necessitate unique esthetic treatment strategies, but published recommendations and clinical evidence for injectable treatments in Asians are scarce. METHOD: The Asian Facial Aesthetics Expert Consensus Group met to discuss current practices and consensus opinions on the cosmetic use of botulinum toxin and hyaluronic acid (HA) fillers, alone and in combination, for facial applications in Southeastern and Eastern Asians. Consensus opinions and statements on treatment aims and current practice were developed following discussions regarding pre-meeting and meeting survey outcomes, peer-reviewed literature, and the experts' clinical experience. RESULTS: The indications and patterns of use of injectable treatments vary among patients of different ages, and among Asian countries. The combination use of botulinum toxin and fillers increases as patients age. Treatment aims in Asians and current practice regarding the use of botulinum toxin and HA fillers in the upper, middle, and lower face of patients aged 18 to >55 years are presented. CONCLUSIONS: In younger Asian patients, addressing proportion and structural features and deficiencies are important to achieve desired esthetic outcomes. In older patients, maintaining facial structure and volume and addressing lines and folds are essential to reduce the appearance of aging. This paper provides guidance on treatment strategies to address the complex esthetic requirements in Asian patients of all ages. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Anatomical and histological study of the arterial distribution in the columellar area, and the clinical implications.

PURPOSE: The aim of this study was to elucidate the distribution of the columellar artery (CoA) in the mobile nasal septum by means of detailed dissection and histological observation. METHODS: Fifteen Korean cadavers were examined; five specimens were dissected to observe the ramification pattern of the CoA from the superior labial artery (SLA), and the noses of ten specimens were quick-frozen in isopropanol cooled with liquid nitrogen and then cryosectioned at a thickness of 40 µm. RESULTS: The arterial vasculature of the CoA in the columella was supplied by the SLA and entered the columella via the columellolabial junction. The vessels of the CoA proceeded anteriorly, inferior to the medial crus of the lower lateral cartilage (MC) at the midline, at the basal and posterior portions of the septum. The vessels traveled closer to the MC than the epidermis. There were very few vessels in the area between the left and right MCs, which was usually packed only with loose connective tissue. More anteriorly, there were more abundant vessels between the MC and the epidermis, with a dispersed distribution. In axial sections, multiple vessels were dispersed in front of the MC, with the pattern varying among the specimens. Furthermore, tiny vessels were also detected in the vicinity of the septal cartilage posterior to the MC. The microdistribution near to the MC was almost consistent. CONCLUSION: The anatomical findings of the CoA in this study will be useful for safe manipulations during various medical interventions in the columella.

Combinational Pulsing of TAAs Enforces Dendritic Cell-Based Immunotherapy through T-Cell Proliferation and Interferon-γ Secretion in LLC1 Mouse Model.

NSCLC, the most common type of lung cancer, is often diagnosed late due to minimal early symptoms. Its high risk of recurrence or metastasis post-chemotherapy makes DC-based immunotherapy a promising strategy, offering targeted cancer destruction, low side effects, memory formation, and overcoming the immune evasive ability of cancers. However, the limited response to DCs pulsed with single antigens remains a significant challenge. To overcome this, we enhanced DC antigen presentation by pulsing with TAAs. Our study focused on enhancing DC-mediated immune response specificity and intensity by combinatorial pulsing of TAAs, selected for their prevalence in NSCLC. We selected four types of TAAs expressed in NSCLC and pulsed DCs with the optimal combination. Next, we administered TAAs-pulsed DCs into the LLC1 mouse model to evaluate their anti-tumor efficacy. Our results showed that TAAs-pulsed DCs significantly reduced tumor size and promoted apoptosis in tumor tissue. Moreover, TAAs-pulsed DCs significantly increased total T cells in the spleen compared to the unpulsed DCs. Additionally, in vitro stimulation of splenocytes from the TAAs-pulsed DCs showed notable T-cell proliferation and increased IFN-γ secretion. Our findings demonstrate the potential of multiple TAA pulsing to enhance the antigen-presenting capacity of DCs, thereby strengthening the immune response against tumors.

A new incorporation method of metallic precursors into a nafion film via a drying process for the preparation of metallic nanocatalysts/nafion.

A new simple drying process was developed in order to prepare a metallic nanocatalysts/Nafion for self-humidifying membrane in a proton-exchange membrane fuel cell (PEMFC). Metallic precursors such as platinum(ll) bis(acetylacetonate) or palladium(ll) bis(acetylacetonate) was sublimed and simultaneously penetrated into the surface of a Nafion film. And then it was reduced to Pt or Pd nanoparticles beneath the film surface without a special reducing agent in a glass reactor of N2 atmosphere at 180 degrees C for 5, 10, 30 and 60 min, respectively. The morphology and distribution of the Pt or Pd nanoparticles were observed by transmission electron microscopy (TEM) and elemental analysis was carried out by an energy dispersive spectroscopy (EDS), and we found that the penetration depth of the metallic nanoparticles and the particle sizes increased with increasing exposure time to the metallic precursors, and the particle size at the surface area was larger than that at the deeper area.

A new deposition method for the preparation of Pt-Pd nanocatalysts on a nafion coated carbon black via the reduction of metallic precursors in a drying process.

A simple method for the synthesis of Pt-Pd nanocatalysts was developed for a proton-exchange membrane fuel cell (PEMFC), which was loaded on a nafion coated carbon black via the sequential reduction of palladium(II) bis(acetylacetonato) and platinum(II) bis(acetylacetonato) in a drying process. Metallic precursors were sublimed and reduced on a nafion coated carbon black which was spray coated on a gas diffusion layer (GDL) in a glass reactor of N2 atmosphere at 180 degrees C for various times. The morphology and distribution of the Pt and Pd nanoparticles were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and we found that the loading weight, number density and particle size of Pt-Pd nanoparticles increased with increasing exposure time at 180 degrees C.

Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the ß-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. ß-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.

Nipple reduction using circumcision and wedge excision technique.

BACKGROUND: The definition of nipple hypertrophy does not exist, and the cause of the deformity remains unknown. However, many patients are uncomfortable with nipple hypertrophy and seek plastic surgeons for correction. Many techniques have been introduced till now to correct nipple hypertrophy, but they are difficult to perform and control the size of nipple in 3-dimensional way. This article describes a new method to reduce nipple hypertrophy in both height and width simultaneously. METHODS: Between January 2001 and December 2010, we performed nipple reduction with our own method on 257 patients (491 nipples). For reduction in height, 2 circumferential lines are drawn: one at the base of the nipple and the other along the height of the new nipple. The distance between these circles is planned according to the required height reduction. For reduction in diameter, wedge excision lines are drawn from the top to the side wall of nipple only until the new baseline, which was drawn in a circumferential pattern. One or 2 wedge(s) is/are needed to get the desirable diameter in opposite position. RESULTS: Among 257 patients, 23 underwent unilateral nipple reduction (male 1, female 22) and 234 underwent bilateral nipple reduction (male 9, female 225). The age ranged from 23 to 63 years (mean age, 34.6 years). The mean follow-up period was 30 months (range, 5-72 months). We performed a survey to evaluate long-term patient satisfaction. Of the 225 female patients, 200 who underwent bilateral nipple reduction surgery participated in our survey. This survey showed that our surgical technique is capable of producing satisfactory results. No major complications such as nipple necrosis, delayed wound healing, excessive scar, or loss of sensation were noted. CONCLUSIONS: Our new method for nipple reduction has many advantages such as short learning curve, its ability to control the height and diameter of desired nipple size, and excellent aesthetic results.

Practical Manipulation for the Preparation of Mesoporous Silica Nanoparticles for Drug Delivery Vehicles.

BACKGROUND: Optimization of MSNs is the most important process for efficient and safe drug delivery systems. OBJECTIVE: In this study, the physicochemical properties of MSNs were evaluated using various compositions of individual reagents. METHODS: MSNs were synthesized according to a modified Stöber method. The physicochemical properties of MSNs were evaluated. Spherical uniform particles were observed in the scanning electron microscope (SEM) and transmission electron microscopy (TEM) image and the meso-structure of MSNs was confirmed. The amorphous and specific hexagonal structure of MSNs was confirmed through Xray diffraction (XRD) and SAXRD. RESULTS: The particle size and surface area according to changes in amounts of reagents ranged from 34.5 ± 2.3 to 216.0 ± 17.1 nm and from 549.79 to 1154.26 m2/g, respectively. A linear relationship was found between the surface area of MSNs and the adsorption rate of methylene blue (MB). MSNs exhibited no apparent cytotoxic effect on Caco-2 cell up to 200 µg/mL. The amounts of tetramethyl ammonium silicate and tetraethyl ortho silicate (TEOS), NaOH, and hexadecyl trimethyl ammonium bromide (CTAB) were adjusted to control the particle size and surface area of MSNs, and it was found that the amounts of synthetic reagents affected the physicochemical properties such as particle size and surface area of MSNs. MSNs with a large surface area adsorbed a large amount of MB. CONCLUSION: These results indicated that drug adsorption is related to the surface area of MSNs. MSNs did not show cytotoxicity to Caco-2 cells. MSNs may be a promising nanomaterial that could be applied as a carrier for various drugs.

Novel aminopyridazine derivative of minaprine modified by radiolysis presents potent anti-inflammatory effects in LPS-stimulated RAW 264.7 and DH82 macrophage cells.

Radiation molecularly transforms naturally occurring products by inducing the methoxylation, hydroxylation, and alkylation of parent compounds, thereby affecting the anti-inflammatory capacities of those compounds. Minaprine (1) modified by ionizing radiation generated the novel hydroxymethylation hydropyridazine (2), and its chemical structure was determined based on NMR and HRESIMS spectra. Compared to the original minaprine, the novel generated product showed a highly enhanced anti-inflammatory capacity inhibited nitric oxide (NO) and prostaglandin E2 (PGE2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 and DH82 macrophage cells. In addition, minaprinol (2) effectively inhibited cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS) at the protein level and pro-inflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10) production in macrophages.

In vivo safety and biodistribution profile of Klotho-enhanced human urine-derived stem cells for clinical application.

BACKGROUND: Urine-derived stem cells (UDSCs) can be easily isolated from urine and possess excellent stem cell characteristics, making them a promising source for cell therapeutics. Due to their kidney origin specificity, UDSCs are considered a superior therapeutic alternative for kidney diseases compared to other stem cells. To enhance the therapeutic potential of UDSCs, we developed a culture method that effectively boosts the expression of Klotho, a kidney-protective therapeutic factor. We also optimized the Good Manufacturing Practice (GMP) system to ensure stable and large-scale production of clinical-grade UDSCs from patient urine. In this study, we evaluated the in vivo safety and distribution of Klotho-enhanced UDSCs after intravenous administration in accordance with Good Laboratory Practice (GLP) regulations. METHODS: Mortality and general symptoms were continuously monitored throughout the entire examination period. We evaluated the potential toxicity of UDSCs according to the administration dosage and frequency using clinical pathological and histopathological analyses. We quantitatively assessed the in vivo distribution and retention period of UDSCs in major organs after single and repeated administration using human Alu-based qPCR analysis. We also conducted long-term monitoring for 26 weeks to assess the potential tumorigenicity. RESULTS: Klotho-enhanced UDSCs exhibited excellent homing potential, and recovered Klotho expression in injured renal tissue. Toxicologically harmful effects were not observed in all mice after a single administration of UDSCs. It was also verified that repeated administration of UDSCs did not induce significant toxicological or immunological adverse effects in all mice. Single and repeated administrated UDSCs persisted in the blood and major organs for approximately 3 days and cleared in most organs, except the lungs, within 2 weeks. UDSCs that remained in the lungs were cleared out in approximately 4-5 weeks. There were no significant differences according to the variation of sex and administration frequency. The tumors were found in the intravenous administration group but they were confirmed to be non-human origin. Based on these results, it was clarified that UDSCs have no tumorigenic potential. CONCLUSIONS: Our results demonstrate that Klotho-enhanced UDSCs can be manufactured as cell therapeutics through an optimized GMP procedure, and they can be safely administered without causing toxicity and tumorigenicity.

Development of a long-acting tablet with ticagrelor high-loaded nanostructured lipid carriers.

Ticagrelor (TCG), an antiplatelet agent, has low solubility and permeability; thus, there are many trials to apply the pharmaceutical technology for the enhancement of TCG solubility and permeability. Herein, we have developed the TCG high-loaded nanostructured lipid carrier (HL-NLC) and solidified the HL-NLC to develop the oral tablet. The HL-NLC was successfully fabricated and optimized with a particle size of 164.5 nm, a PDI of 0.199, an encapsulation efficiency of 98.5%, and a drug loading of 16.4%. For the solidification of HL-NLC (S-HL-NLC), the adsorbent was determined based on the physical properties of the S-HL-NLC, such as bulk density, tap density, angle of repose, Hausner ratio, Carr's index, and drug content. Florite R was chosen because of its excellent adsorption capacity, excellent physical properties, and solubility of the powder after manufacturing. Using an S-HL-NLC, the S-HL-NLC tablet with HPMC 4 K was prepared, which is showed a released extent of more than 90% at 24 h. Thus, we have developed the sustained release tablet containing the TCG-loaded HL-NLC. Moreover, the formulations have exhibited no cytotoxicity against Caco-2 cells and improved the cellular uptake of TCG. In pharmacokinetic study, compared with raw TCG, the bioavailability of HL-NLC and S-HL-NLC was increased by 293% and 323%, respectively. In conclusion, we successfully developed the TCG high-loaded NLC tablet, that exhibited a sustained release profile and enhanced oral bioavailability.

Antiviral Lipid Nanocarrier Loaded with Remdesivir Effective Against SARS-CoV-2 in vitro Model.

Introduction: The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral efficacy of the antiviral agent remdesivir (RDS). Results: We developed a nanosized spherical RDS-NLC in which the RDS was encapsulated in an amorphous form. The RDS-NLC significantly potentiated the antiviral efficacy of RDS against SARS-CoV-2 and its variants (alpha, beta, and delta). Our study revealed that NLC technology improved the antiviral effect of RDS against SARS-CoV-2 by enhancing the cellular uptake of RDS and reducing SARS-CoV-2 entry in cells. These improvements resulted in a 211% increase in the bioavailability of RDS. Conclusion: Thus, the application of NLC against SARS-CoV-2 may be a beneficial strategy to improve the antiviral effects of antiviral agents.

Protective effect of the aqueous extract from the root of Platycodon grandiflorum on cholestasis-induced hepatic injury in mice.

CONTEXT: The root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae) has been widely studied for its hepatoprotective effects against various hepatotoxicants. OBJECTIVE: The present study evaluated the protective effect of the standardized aqueous extract of P. grandiflorum (BC703) on cholestasis-induced hepatic injury in mice. MATERIALS AND METHODS: BC703 is a standardized aqueous extract of P. grandiflorum in reference to platycodin D (at least 0.8%). The mice were allocated into five groups as follows: Sham-operated, bile duct ligation (BDL) alone, and BDL with BC703 (1, 5, and 10 mg/kg BW) treated group. BC703 was given for 3 consecutive days before BDL operation. The animals were sacrificed by CO2 anesthesia post-24 h of BDL operations. RESULTS AND DISCUSSION: Serum alanine aminotransferase and serum aspartate aminotransferase increased to 395.2 ± 90.0 and 266.0 ± 45.6 Unit/L in the BDL alone group and decreased with BC703 in a dose-dependent manner. Especially the 10 mg/kg of BC703-treated mice showed a 77% decrease of serum alanine aminotransferase and 56% of aspartate aminotransferase as compared with BDL alone. Decreased antioxidant enzyme levels in BDL alone group were elevated in BC703-treated groups ranging from 7 to 29% for glutathione and from 13 to 25% for superoxide dismutase. BC703 treatment also attenuated malondialdehyde (from 3 to 32%) and nitric oxide levels (from 32 to 50%) as compared with BDL alone. Histopathological studies further confirmed the hepatoprotective effect of BC703 in BDL-induced cholestesis. CONCLUSION: BC703 could attenuate liver injury by BDL in mice, and test results indicate that BC703 might be useful in cholestatic liver injury.