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Astragaloside IV (AS-IV) is one of the main active components extracted from the Chinese medicinal herb Astragali and serves as a marker for assessing the herb’s quality. AS-IV is a tetracyclic triterpenoid saponin in the form of lanolin ester alcohol and exhibits various biological activities. This review article summarizes the chemical structure of AS-IV, its pharmacological effects, mechanism of action, applications, future prospects, potential weaknesses, and other unexplored biological activities, aiming at an overall analysis. Papers were retrieved from online electronic databases, such as PubMed, Web of Science, and CNKI, and data from studies conducted over the last 10 years on the pharmacological effects of AS—IV as well as its impact were collated. This review focuses on the pharmacological action of AS-IV, such as its anti-inflammatory effect, including suppressing inflammatory factors, increasing T and B lymphocyte proliferation, and inhibiting neutrophil adhesion-associated molecules; antioxidative stress, including scavenging reactive oxygen species, cellular scorching, and regulating mitochondrial gene mutations; neuroprotective effects, antifibrotic effects, and antitumor effects.

Protamine sulfate (PS), the only U.S. Food and Drug Administration (FDA)-approved heparin antagonist, is encumbered by several drawbacks. R15, a synthetic polyarginine peptide, has proven to be a promising protamine substitute in prior studies. PS and R15 undergo biotransformation to active metabolites, underscoring the need for an analytical method that quantifies their total anti-heparin activity in vivo . Here, we reported the development and validation of such a method and described the pharmacokinetic profiles of PS and R15 in rats. Total anti-heparin activity in plasma was quantified by fortifying each sample with a fixed concentration of heparin and subsequently measuring the residual heparin. The method was fully validated for PS and R15 in accordance with Chinese bioanalytical guidance from Chinese Pharmacopoeia, confirming acceptable selectivity, precision and accuracy, stability, and dilution integrity. Pharmacokinetic profiles were then characterized in rats following single intravenous bolus administrations of PS at 300 U·kg ⁻ ¹ and R15 at 300, 900, and 2700 U·kg ⁻ ¹. An assay for quantifying total anti- heparin activity in rat plasma was successfully validated for both PS and R15. After a single intravenous dose of 300 U·kg -1 , R15 sustained anti-heparin activity for a markedly longer period (51.93 min vs. 3.94 min) and achieved an 18-fold higher of areaunder the curves (AUC = 632 min·μg·mL -1 vs. 35.89 min·μg·mL -1 ) with 19-fold higher mean residence time (MRT = 54.95 min vs. 2.59 min). Clearance (CL) for R15 and PS was 2.73 mL·min -1 ·kg -1 vs. 53.65 mL·min -1 ·kg -1 , whereas the apparent volume of distribution (V d ) was of similar level (194 mL·kg -1 vs. 268 mL·kg -1 ), consistent with limited tissue distribution and prolonged intravascular retention. The extended exposure afforded by R15 is clinically advantageous because it mitigates the well-documented “heparin rebound” observed after rapid protamine clearance, thereby reducing the need for repeat dosing. R15 exhibited dose-dependent nonlinear pharmacokinetics, demonstrating saturable elimination processes typical of nonlinear pharmacokinetics. The validated assay, coupled with the in vivo rat pharmacokinetic study, provides a solid foundation for advancing R15’s preclinical development.

The symptoms of coronavirus disease 2019 (COVID-19) range from severe lung disease to milder manifestations, such as cough and throat irritation. As a bisbenzylisoquinoline alkaloid, cepharanthine (CEP) has various pharmacological properties, such as antifibrotic, anti-inflammatory, antioxidant, and antiviral effects. However, its poor solubility and low bioavailability hinder subsequent drug development. Inclusion complex technology is a well-established drug delivery method that improves drug bioavailability. Therefore, in our study, we encapsulated CEP with β-cyclodextrin and formulated it into oral tablets. Oral tablets can be absorbed through sublingual and buccal mucosa, improving CEP bioavailability, facilitating convenient dosing, and thereby enhancing its therapeutic efficacy. The cepharanthine–β-cyclodextrin (CEP–β-CD) inclusion complex was prepared using the co-grinding method. It was characterized using scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry to assess its physicochemical properties. Subsequently, the quality of the CEP–β-CD oral tablets was evaluated according to the relevant requirements of the 2020 edition of the Chinese Pharmacopoeia. Furthermore, the pharmacokinetic characteristics of the oral tablets were assessed in beagles. Finally, the anti-inflammatory effects of the CEP–β-CD oral tablets were evaluated in alveolar macrophage MH-S cells and a mouse pneumonia model. Our results suggest that the formulation of the CEP–β-CD inclusion complex into oral tablets is a promising preventive and therapeutic approach for lung injury caused by COVID-19.

Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.

Background: Traumatic hemorrhage management is challenging due to the need to control severe bleeding and support tissue repair. An ideal material would possess both hemostatic and wound-healing properties. Methods: Silkworm cocoon-derived carbon dots (SC-CDs) were synthesized via a hydrothermal method. After physical and chemical characterization using techniques such as HR-TEM and XPS, their hemostatic efficacy was assessed in rat liver injury, tail transection, and mouse coagulation disorder models. Moreover, the effects of the SC-CDs on platelet aggregation and activation were evaluated. The potential of the SC-CDs to promote wound healing was investigated through cell scratch assays and a mouse full-thickness skin defect model. Results: The SC-CDs showed a high quantum yield (12.9% ± 0.42%), with low hemolytic activity and cytotoxicity. In the hemostasis models, the SC-CDs significantly reduced the bleeding time and volume. In the rat liver injury model, the bleeding time was shortened from 152.67 ± 4.16 s (Control) to 55.33 ± 9.50 s (p < 0.05). In the rat tail transection model, the bleeding volume was reduced from 1.71 ± 0.16 g (Control) to 0.4 ± 0.11 g (p < 0.05). In the mouse coagulation disorder model, an 8 mg/kg dose reduced the bleeding volume to 11.80% ± 0.39% of that of the Control (p < 0.05). Mechanistic studies suggested enhanced platelet activation and aggregation. In the wound healing experiments, the SC-CDs reduced the wound area (88.53 ± 11.78 mm2 (Control) vs. 70.07 ± 6.71 mm2 (SC-CDs), p < 0.05) and promoted fibroblast migration (24 h scratch width: 372.34 ± 9.06 μm (Control) vs. 259.49 ± 36.75 μm (SC-CDs), p < 0.05). Conclusions: SC-CDs show promise for hemorrhage management and tissue regeneration, with potential applications in cases of internal bleeding or coagulation disorders.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 μm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model’s establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

DR5, a receptor with the highest affinity for TRAIL under physiological conditions, selectively induces apoptosis in specific target cells such as tumor and aberrant immune cells, while minimally affecting normal cells. The TRAIL-DR5 signaling pathway is a crucial regulatory mechanism when the body responds to various exogenous interference factors, including viruses, chemicals, and radiation. This pathway plays a vital role in maintaining physiological homeostasis and in the pathological development of various diseases. Different modulations of DR5, such as upregulation, activation, and antagonism, hold significant potential for therapeutic applications in tumors, cardiovascular diseases, autoimmune diseases, viral infections, and radiation injuries. This article provides an overview of the current research progress on DR5, including the status and prospects of its clinical applications.

Uncontrolled hemorrhage from trauma or surgery can lead to death. In this study, chitosan/kaolin (CSK) and chitosan/montmorillonite (CSMMT) composites were prepared from chitosan (CS), kaolin (K), and montmorillonite (MMT) as raw materials to control bleeding. The physiochemical properties and surface morphology of CSK and CSMMT composites were analyzed by Fourier transform infrared spectrometry (FT-IR), X-ray diffraction (XRD), scanning electron microscopy (SEM), zeta potentials, and X-ray fluorescence (XRF). The hemostatic mechanism was measured in vitro by activated partial thromboplastin time (APTT), prothrombin time (PT), in vitro clotting time, erythrocyte aggregation, and thromboelastogram (TEG). The hemostasis ability was further verified by using tail amputation and arteriovenous injury models in rats. The biocompatibility of CSK and CSMMT was evaluated by in vitro hemolysis, cytotoxicity assays, as well as acute toxicity test and skin irritation tests. The results show that CSK and CSMMT are promising composite materials with excellent biocompatibility and hemostatic properties that can effectively control bleeding.

The physicochemical properties and potential hemostatic application of Wenchang kaolin and Maoming kaolin were inspected and evaluated. Chemical composition analysis, Fourier transform infrared (FTIR) spectroscopy, surface area determination, X-ray diffraction, particle size, scanning electron microscopy (SEM) observations, and zeta potential analysis were performed to quantify the physical and chemical properties of the two kaolins. The results showed that both kaolins have typical FTIR bands of kaolinite with a weight fraction for kaolinite over 90 wt%. Larger conglobate aggregates of Maoming kaolin demonstrated wider particle size distributions with two peaks at 3.17 and 35.57 μm, while the book-like Wenchang kaolin had narrow particle size distribution, with a frequent size of 5.64 μm. Furthermore, thrombelastography, the whole blood clotting tests (WBCT), plasma recalcification time (PRT) measurement, and MTT assay were performed to measure the clotting activities and biocompatibility of the two kaolins. The results showed that both kaolins could promote blood coagulation with good cytocompatibility, while Wenchang kaolin had a better procoagulant activity than Maoming kaolin. These findings demonstrated Wenchang kaolin to be a more suitable local source material for application as a hemostatic agent.

Inhalation of aerosolized uranium is recognized as a principal mode of exposure, posing significant risks of damage to the lungs, kidneys, and other vital organs. To enhance nuclide elimination from the body, chelating agents are employed; however, single-component chelators often exhibit limited spectral activity and low effectiveness, resulting in toxicologically relevant concentrations. We have developed a composite chelating agent composed of 3,4,3-Li(1,2-HOPO), DFP, and HEDP in optimized ratios, demonstrating marked improvements in eliminating inhaled uranium. The selection of these components was initially guided by an agarose gel dynamics method, focusing on uranium binding and removal efficacy. Optimization of the formula was conducted through response surface methodology in a cellular model. The compound’s ability to enhance survival rates in mice subjected to acute uranium inhalation was confirmed, showing a dose-dependent improvement in survival in severely affected mice. Comparative assessments indicated that this multifaceted chelating agent substantially surpasses the uranium tissue clearance achieved by individual chelating agents.