Search Results (9)

The Quality by Design (QbD) concept has been widely applied to the optimization of traditional Chinese medicine production processes recently. This work focused on optimizing the critical purification process of Scutellaria baicalensis extract used in the preparation of Zhusheyong Shuanghuanglian. Considering the impact of noise parameters and changes in herbal properties, an experimental design method was employed for optimization. Multiple batches of Scutellaria baicalensis decoction were prepared in this research, and quantitative models of Scutellaria baicalensis herbal properties, critical process parameters (CPPs), and process evaluation indicators were established. The R² of the quantitative models were all higher than 0.80. According to the model, the yield of baicalin was identified as a critical material property (CMA). The pH of first acid precipitation (X₁), first temperature holding time (X₂), pH of alkalization (X₃), ethanol amount (X₄), and end pH of ethanol washing (X₅) were CPPs. Considering the difficulty in controlling the end pH of the ethanol washing, it was considered to be a noise parameter. The Monte Carlo probability-based method was used to calculate the design space, determining the range of controllable parameters, which was successfully validated through experiments. Normal operation ranges for controllable parameters are recommended as follows: X₁ of 0.8–2.2, X₂ of 25–35 min, X₃ of 6.5–7.5, and X₄ of 0.8–1.2 g/g. Full article

Steroid hormones, recognized as emerging environmental contaminants, have garnered increasing attention in recent years. The present work studied the distribution characteristics in the environment, bioaccumulation in aquatic products, and the associated environmental and health risks of typical steroid hormones from commercial freshwater aquaculture farms operating under different aquaculture modes (monoculture and polyculture). Totals of 9 and 14 steroid hormones were detected in water and sediment samples, with concentrations ranging from 0.66 ± 0.17 ng/L to 40.5 ± 5.08 ng/L and from 0.36 ± 0.08 ng/g to 123 ± 19.9 ng/g, respectively. Hazard index (HI) calculations indicated that all sampling locations were identified as medium or high risk for both water and sediment matrices. Nineteen steroids were detected in at least one type of tissue, with the concentrations in the bile, plasma, muscle, liver, and gill ranging from <LOQ to 52.6 ± 4.82 ng/L, from <LOQ to 41.9 ± 4.80 ng/L, from 0.36 ± 0.07 ng/g to 321 ± 19.1 ng/g, from <LOQ to 1140 ± 107 ng/g, and from 0.36 ± 0.03 ng/g to 1450 ± 239 ng/g, respectively. Furthermore, four synthetic steroid hormones exhibited significant bioaccumulation across various tissues, such as MLA in bile and 5α-DHP in muscle, liver, and gill (BAF > 5000 L/kg). Notably, despite low estimated daily intakes (EDIs) (0.43–6.43 ng/day/person to 18.7 ng/day/person) and hazard quotients (HQs) (below 4.188 × 10⁻⁷), the high bioaccumulation factors (BAFs) underscore the necessity for stringent regulatory measures by local governments. Additionally, a comparison of EDI results across different aquaculture modes and fish species revealed that steroid hormone-related health risks to humans are influenced by both the fish species and the aquaculture mode. This study indicated that the consumption of poly-cultured fish (e.g., bighead carp) may pose a greater steroid-related health risk, compared to the consumption of mono-cultured fish. Full article

Local feature extractions have been verified to be effective for person re-identification (re-ID) in recent literature. However, existing methods usually rely on extracting local features from single part of a pedestrian while neglecting the relationship of local features among different pedestrian images. As a result, local features contain limited information from one pedestrian image, and cannot benefit from other pedestrian images. In this paper, we propose a novel approach named Local Relation-Aware Graph Convolutional Network (LRGCN) to learn the relationship of local features among different pedestrian images. In order to completely describe the relationship of local features among different pedestrian images, we propose overlap graph and similarity graph. The overlap graph formulates the edge weight as the overlap node number in the node’s neighborhoods so as to learn robust local features, and the similarity graph defines the edge weight as the similarity between the nodes to learn discriminative local features. To propagate the information for different kinds of nodes effectively, we propose the Structural Graph Convolution (SGConv) operation. Different from traditional graph convolution operations where all nodes share the same parameter matrix, SGConv learns different parameter matrices for the node itself and its neighbor nodes to improve the expressive power. We conduct comprehensive experiments to verify our method on four large-scale person re-ID databases, and the overall results show LRGCN exceeds the state-of-the-art methods. Full article

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, there have been more than 10 million reported cases, more than 517,000 deaths in 215 countries, areas or territories. There is no effective antiviral medicine to prevent or treat COVID-19. Natural products and traditional medicine products with known safety profiles are a promising source for the discovery of new drug leads. There is increasing number of publications reporting the effect of natural products and traditional medicine products on COVID-19. In our review, we provide an overview of natural products and their derivatives or mimics, as well as traditional medicine products, which were reported to exhibit potential to inhibit SARS-CoV-2 infection in vitro, and to manage COVID-19 in vivo, or in clinical reports or trials. These natural products and traditional medicine products are categorized in several classes: (1) anti-malaria drugs including chloroquine and hydroxychloroquine, (2) antivirals including nucleoside analogs (remdesivir, favipiravir, β-D-N4-hydroxycytidine, ribavirin and among others), lopinavir/ritonavir and arbidol, (3) antibiotics including azithromycin, ivermectin and teicoplanin, (4) anti-protozoal drug, emetine, anti-cancer drug, homoharringtonine, and others, as well as (5) traditional medicine (Lian Hua Qing Wen Capsule, Shuang Huang Lian Oral Liquid, Qingfei Paidu Decoction and Scutellariae Radix). Randomized, double-blind and placebo-controlled large clinical trials are needed to provide solid evidence for the potential effective treatment. Currently, drug repurposing is a promising strategy to quickly find an effective treatment for COVID-19. In addition, carefully combined cocktails need to be examined for preventing a COVID-19 pandemic and the resulting global health concerns. Full article

In recent years, hypersensitivity reactions to the Shuanghuanglian injection have attracted broad attention. However, the componential chief culprits inducing the reactions and the underlying mechanisms involved have not been completely defined. In this study, we used a combination of approaches based on the mouse model, human umbilical vein endothelial cell monolayer, real-time cellular monitoring, immunoblot analysis, pharmacological inhibition, and molecular docking. We demonstrated that forsythoside A and forsythoside B contributed to Shuanghuanglian injection-induced pseudoallergic reactions through activation of the RhoA/ROCK signaling pathway. Forsythoside A and forsythoside B could trigger dose-dependent vascular leakage in mice. Moreover, forsythoside A and forsythoside B slightly elicited mast cell degranulation. Correspondingly, treatment with forsythoside A and forsythoside B disrupted the endothelial barrier and augmented the expression of GTP-RhoA, p-MYPT1, and p-MLC2 in a concentration-dependent manner. Additionally, the ROCK inhibitor effectively alleviated forsythoside A/forsythoside B-induced hyperpermeability in both the endothelial cells and mice. Similar responses were not observed in the forsythoside E-treated animals and cells. These differences may be related to the potential of the tested compounds to react with RhoA-GTPγS and form stable interactions. This study innovatively revealed that some forsythosides may cause vascular leakage, and therefore, limiting their contents in injections should be considered. Full article

Cutaneous eruption is a common drug-adverse reaction, characterised by keratinocytes inflammation and apoptosis. Shuanghuanglian injeciton (SHLI) is a typical Chinese medicine injection, which is used to treat influenza. It has been reported that SHLI has the potential to induce cutaneous adverse eruptions. However, the mechanisms remain unclear. Since desmoglein 1 (DSG1) shows a crucial role in maintaining skin barrier function and cell susceptibility, we assume that DSG1 plays a critical role in the cutaneous eruptions induced by SHLI. In our study, retinoic acid (RA) was selected to downregulate the DSG1 expression, and lipopolysaccharide (LPS) was first used to identify the susceptibility of the DSG1-deficiency Hacat cells. Then, SHLI was administrated to normal or DSG1-deficient Hacat cells and mice. The inflammatory factors and apoptosis rate were evaluated by RT-PCR and flow cytometry. The skin pathological morphology was observed by hematoxylin and eosin (HE) staining. Our results show that treated only with SHLI could not cause IL-4 and TNF-α mRNA increases in normal Hacat cells. However, in the DSG1-deficient Hacat cells or mice, SHLI induced an extreme increase of IL-4 and TNF-α mRNA levels, as well as in the apoptosis rate. The skin tissue showed a local inflammatory cell infiltration when treated with SHIL in the DSG1-deficient mice. Thus, we concluded that DSG1 deficiency was a potential causation of SHLI induced eruptions. These results indicated that keratinocytes with DSG1 deficiency were likely to induce the cutaneous eruptions when stimulated with other medicines. Full article

The Shuang-Huang-Lian (SHL) oral liquid is a combined herbal prescription used in the treatment of acute upper respiratory tract infection, acute bronchitis and pneumonia. Multiple constituents are considered to be responsible for the therapeutic effects of SHL. However, the quantitation of the multi-components from multiple classes is still unsatisfactory because of the high complexity of constituents in SHL. In this study, an accurate, rapid, and specific UPLC-MS/MS method was established for simultaneous quantification of 18 compounds from multiple classes in SHL oral liquid formulations. Chromatographic separation was performed on a HSS T3 (1.8 μm, 2.1 mm × 100 mm) column, using a gradient mobile phase system of 0.1% formic acid in acetonitrile and 0.1% formic acid in water at a flow rate of 0.2 mL·min⁻¹; the run time was 23 min. The MS was operated in negative electrospray ionization (ESI⁻) for analysis of 18 compounds using multiple reaction monitoring (MRM) mode. UPLC-ESI⁻-MRM-MS/MS method showed good linear relationships (R² > 0.999), repeatability (RSD < 3%), precisions (RSD < 3%) and recovery (84.03–101.62%). The validated method was successfully used to determine multiple classes of hydrophilic and lipophilic components in the SHL oral liquids. Finally, principal component analysis (PCA) was used to classify and differentiate SHL oral liquid samples attributed to different manufacturers of China. The proposed UPLC-ESI⁻-MRM-MS/MS coupled with PCA has been elucidated to be a simple and reliable method for quality evaluation of SHL oral liquids. Full article

In the present study, the rationality for the antiviral effect (H1N1 virus) of Flos Lonicerae Japonicae (FLJ, named JinYinHua)-Fructus forsythiae (FF, named LianQiao) herb couple preparations improved by chito-oligosaccharide (COS) was investigated. We found that the improvement of antiviral activity for four preparations attributed to the enhancement of bioavailability for the FLJ-FF herb couple in vivo, and that caffeic acid derivatives are the most important type of components for antiviral activity. The anti-Influenza virus activity-half maximal inhibitory concentration (IC₅₀), not area under concentration (AUC) was considered as the weighting factor for integrating the pharmacokinetics of caffeic acid derivatives. It was found that the integral absorption, both in vitro and in vivo, especially that in Shuang-Huang-Lian, can be improved significantly by COS, an absorption enhancer based on tight junction. The results indicated that the antiviral activity in four preparations improved by COS was mainly attributed to the integral absorption enhancement of caffeic acid derivatives. Full article

Shuang–Huang–Lian injectable powder (SHL)—a classical purified herbal preparation extracted from Scutellaria baicalensis, Lonicera japonica, and Forsythia suspense—has been used against human adenovirus III (HAdV₃) for many years. The combination herb and its major bioactive compounds, including chlorogenic acid, baicalin, and forsythia glycosides A, are effective inhibitors of the virus. However, no comprehensive studies are available on the antiviral effects of SHL against HAdV₃. Moreover, it remains unclear whether the mixture of chlorogenic acid, baicalin, and forsythia glycosides A (CBF) has enhanced antiviral activity compared with SHL. Therefore, a comparative study was performed to investigate the combination which is promising for further antiviral drug development. To evaluate their antivirus activity in parallel, the combination ratio and dose of CBF were controlled and consistent with SHL. First, the fingerprint and the ratio of CBF in SHL were determined by high performance liquid chromatography. Then, a plaque reduction assay, reverse transcription polymerase chain reaction (PCR), real-time polymerase chain reaction (qPCR), and enzyme-linked immunosorbent assay (ELISA) were used to explore its therapeutic effects on viral infection and replication, respectively. The results showed that SHL and CBF inhibited dose- and time-dependently HAdV₃-induced plaque formation in A549 and HEp-2 cells. SHL was more effective than CBF when supplemented prior to and after viral inoculation. SHL prevented viral attachment, internalization, and replication at high concentration and decreased viral levels within and out of cells at non-toxic concentrations in both cell types. Moreover, the expression of tumor necrosis factor alpha (TNF)-α, interleukin (IL)-1ß, and IL-6 was lower and the expression of interferon (IFN)-γ was higher in both cell types treated with SHL than with CBF. In conclusion, SHL is much more effective and slightly less toxic than CBF. Full article