Bioactive compounds from Huashi Baidu decoction possess both antiviral and anti-inflammatory effects against COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health concern, and effective antiviral reagents are urgently needed. Traditional Chinese medicine theory-driven natural drug research and development (TCMT-NDRD) is a feasible method to address this issue as the traditional Chinese medicine formulae have been shown effective in the treatment of COVID-19. Huashi Baidu decoction (Q-14) is a clinically approved formula for COVID-19 therapy with antiviral and anti-inflammatory effects. Here, an integrative pharmacological strategy was applied to identify the antiviral and anti-inflammatory bioactive compounds from Q-14. Overall, a total of 343 chemical compounds were initially characterized, and 60 prototype compounds in Q-14 were subsequently traced in plasma using ultrahigh-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. Among the 60 compounds, six compounds (magnolol, glycyrrhisoflavone, licoisoflavone A, emodin, echinatin, and quercetin) were identified showing a dose-dependent inhibition effect on the SARS-CoV-2 infection, including two inhibitors (echinatin and quercetin) of the main protease (Mpro), as well as two inhibitors (glycyrrhisoflavone and licoisoflavone A) of the RNA-dependent RNA polymerase (RdRp). Meanwhile, three anti-inflammatory components, including licochalcone B, echinatin, and glycyrrhisoflavone, were identified in a SARS-CoV-2-infected inflammatory cell model. In addition, glycyrrhisoflavone and licoisoflavone A also displayed strong inhibitory activities against cAMP-specific 3',5'-cyclic phosphodiesterase 4 (PDE4). Crystal structures of PDE4 in complex with glycyrrhisoflavone or licoisoflavone A were determined at resolutions of 1.54 Å and 1.65 Å, respectively, and both compounds bind in the active site of PDE4 with similar interactions. These findings will greatly stimulate the study of TCMT-NDRD against COVID-19.

Differentiation of Mountain- and Garden-Cultivated Ginseng with Different Growth Years Using HS-SPME-GC-MS Coupled with Chemometrics.

Although there are differences in the appearance of Mountain-Cultivated Ginseng (MCG) and Garden-Cultivated Ginseng (GCG), it is very difficult to distinguish them when the samples are processed to slices or powder. Moreover, there is significant price difference between them, which leads to the widespread adulteration or falsification in the market. Thus, the authentication of MCG and GCG is crucial for the effectiveness, safety, and quality stability of ginseng. In the present study, a headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) coupled with chemometrics approach was developed to characterize the volatile component profiles in MCG and GCG with 5-,10-,15-growth years, and subsequently to discover differentiating chemical markers. As a result, we characterized, for the first time, 46 volatile components from all the samples by using the NIST database and the Wiley library. The base peak intensity chromatograms were subjected to multivariate statistical analysis to comprehensively compare the chemical differences among the above samples. MCG5-,10-,15-years and GCG5-,10-,15-years samples were mainly divided into two groups by unsupervised principal component analysis (PCA), and 5 potential cultivation-dependent markers were discovered based on orthogonal partial least squares-discriminant analysis (OPLS-DA). Moreover, MCG5-,10-,15-years samples were divided into three blocks, and 12 potential growth-year-dependent markers enabled differentiation. Similarly, GCG5-,10-,15-years samples were also separated into three groups, and six potential growth-year-dependent markers were determined. The proposed approach could be applied to directly distinguish MCG and GCG with different growth years and to identify the differentiation chemo-markers, which is an important criterion for evaluating the effectiveness, safety, and quality stability of ginseng.

Platycodin D ameliorates hyperglycaemia and liver metabolic disturbance in HFD/STZ-induced type 2 diabetic mice.

In this work, we investigated the ameliorative effects of platycodin D (PD), a major active chemical ingredient isolated from the roots of Platycodon grandiflorum (PG), on high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes (T2D) mice. PD treatment (2.5 and 5.0 mg kg-1) improved HFD-induced body weight gain. PD administration also decreased the fasting blood glucose (FBG) level and improved glucose and insulin tolerance levels. These data collectively showed that PD could maintain glucose homeostasis. In addition, the diabetic mice with PD treatment also showed fewer pathological changes in liver tissues and improved hepatic functional indexes with respect to the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and recovery of abnormal liver function caused by T2D. Except for these, PD decreased the decomposition of hepatic glycogen. The results from western blot analysis showed that PD treatment might regulate the hepatic gluconeogenesis pathway with the increased phosphorylation/expression of AMPK and decreased expressions of PCK1 and G6Pase. In the aspect of lipid metabolism, PD decreased the whole-body lipid levels, including total cholesterol (TC), triglycerides (TG), and high-density lipoprotein (HDL), and reduced the hepatic fat accumulation induced by T2D through the AMPK/ACC/CPT-1 fatty acid anabolism pathway. In addition, the results of molecular docking showed that PD may have a potential direct effect on AMPK and other key glycolipid metabolism proteins. To summarize, PD modulation of hepatic glycolipid metabolism abnormalities is promising for T2D therapy in the future.

Systematic identification of chemical components in Fufang Shuanghua oral liquid and screening of potential active components against SARS-CoV-2 protease.

Coronavirus disease (COVID-19) caused by SARS-COV-2 infection has been widely prevalent in many countries and has become a common challenge facing mankind. Traditional Chinese medicine (TCM) has played a prominent role in this pandemic, and especially TCM with the function of "heat-clearing and detoxifying" has shown an excellent role in anti-virus. Fufang Shuanghua oral liquid (FFSH) has been used to treat the corresponding symptoms of influenza such as fever, nasal congestion, runny nose, sore throat, and upper respiratory tract infections in clinic, which are typical symptoms of COVID-19. The content of chlorogenic acid, andrographolide and dehydrated andrographolide as the quality control components of FFSH is not less than 1.0 mg/mL, 60 µg/mL and 60 µg/mL respectively. In this study, UPLC-Q-TOF-MS/MS was employed to describe the chemical profile of FFSH. Virtual screening and fluorescence resonance energy transfer (FRET) were used to screen the effective components of FFSH acting on SARS-CoV-2 main protease (Mpro). As a result, 214 compounds in FFSH were identified or preliminarily characterized by UPLC-Q-TOF-MS/MS, and 61 active ingredients with potential inhibitory effects on Mpro were selected through receptor-based and ligand-based virtual screening. In particular, quercetin, forsythoside A, and linoleic acid showed a good inhibitory effect on Mpro in FRET evaluation with IC50 values of 26.15 µM, 22.26 µM and 47.09 µM respectively, and had a strong binding affinity with the receptor Mpro (6LU7) in molecular docking. CYS145 and HIS41 were the main amino acid residues affected by small molecules in the protein binding domain. In brief, we characterized, for the first time, 214 chemical components in FFSH, and three of them, including quercetin, forsythoside A and linoleic acid, were screened out to exert beneficial anti-COVID-19 effects through CYS145 and HIS41 sites, which may provide a new research strategy for TCM to develop new therapeutic drugs against COVID-19.

Retraction: The PI3K/Akt and NF-κB signaling pathways are involved in the protective effects of Lithocarpus polystachyus (sweet tea) on APAP-induced oxidative stress injury in mice.

[This retracts the article DOI: 10.1039/D0RA00020E.].

The PI3K/Akt and NF-κB signaling pathways are involved in the protective effects of Lithocarpus polystachyus (sweet tea) on APAP-induced oxidative stress injury in mice.

Acetaminophen (APAP)-induced acute liver injury (ALI) is a health issue that has gradually attracted attention, and is often regarded as a model of drug-induced hepatotoxicity. The leaves of Lithocarpus polystachyus Rehd. (named as "sweet tea", ST) usually serve as tea drink and folk medicine for healthcare in the southwest part of China. In previous reports, it has been proven to protect various animal models, except for APAP-induced liver injury model. Therefore, this study initially explored the protective effect of ST leaf extract (STL-E) on hepatotoxicity induced by APAP in ICR mice. STL-E of 50 and 100 mg kg-1 were given to each group for 7 days. ALI was intraperitoneally induced by APAP treatment (i.p. 250 mg per kg body weight). Biochemical markers, levels of inflammatory factors, histopathological staining and western blotting were used to analyze the inflammation and apoptosis of liver tissues. Interestingly, the treatment with STL-E significantly attenuated APAP-induced liver injury (p < 0.05). Moreover, STL-E partially mitigated APAP-induced liver injury by effectively activating the PI3K/Akt pathway and inhibiting the NF-κB pathway. In a word, STL-E protected liver against APAP-induced hepatotoxicity by inhibiting the PI3K/Akt-mediated apoptosis signal pathway and inhibiting the NF-κB-mediated signaling pathway.

Effect of Astragalus Polysaccharide on the Expression of VEGF and EGFR in Mice with Lewis Transplantable Lung Cancer.

The aim of this study was to determine the effect of Astragalus polysaccharide (APS) on the expression of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) in mice with Lewis transplantable lung cancer. It was an experimental study carried out from June 2017 to January 2018 at the College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, China. Forty male SPF-level C57BL/6J mice were selected and inoculated with Lewis lung cancer cell suspension in the right axilla of the mice to establish a lung-cancer mouse model. The mice were randomly divided into a model control group and APS groups with high, middle and low dosages, respectively, 10 in each group. After inoculation of Lewis tumor cell suspension for 2 days, mice in the model control group were injected intraperitoneally with 50 mL/kg of 0.9% sodium chloride solution, whereas, mice in the APS groups with high, middle and low dosages were intraperitoneally injected with APS at 100, 50, 25 mg/kg, respectively. The research results showed that APS can effectively inhibit the growth and metastasis of Lewis lung cancer in mice, improve immune organ function, inhibit the protein expression of VEGF and EGFR in tumor tissues, and have a concentration-effect relationships.