bims-antpol 2024-06-16 papers

Issue of 2024–06–16
four papers selected by
Rick Sheridan, EMSKE Phytochem

Int J Nanomedicine. 2024 ;19 5139-5156

Combined Hydroxyethyl Starch Luteolin Nanocrystals for Effective Anti-Hyperuricemia Effect in Mice Model.

Han Luo, Xiaofei Wang, Mengqi Fang, Huifan Yu, Lili Gui, Zhengkun Wu, Jianyong Sheng, Fei Li.

Introduction: Although flavonoid compounds exhibit various pharmacological activities, their clinical applications are restricted by low oral bioavailability owing to their poor solubility. Nanocrystals (NCs) represent an excellent strategy for enhancing the oral bioavailability of flavonoids. Hydroxyethyl starch (HES), a biomaterial compound used as a plasma expander, could be an ideal stabilizer material for preparing flavonoid NCs.
Methods: HES was used to stabilize flavonoid nanocrystals (NCs), using luteolin (LUT) as a model drug. After full characterization, the freeze-drying and storage stability, solubility, intestinal absorption, pharmacokinetics, and in vivo anti-hyperuricemic effect of the optimized HES-stabilized LUT NCs (LUT-HES NCs) were investigated.
Results: Uniformed LUT-HES NCs were prepared with mean particle size of 191.1±16.8 nm, zeta potential of about -23 mV, drug encapsulation efficiency of 98.52 ± 1.01%, and drug loading of 49.26 ± 0.50%. The freeze-dried LUT-HES NCs powder showed good re-dispersibility and storage stability for 9 months. Notably, compared with the coarse drug, LUT-HES NCs exhibited improved saturation solubility (7.49 times), increased drug dissolution rate, enhanced Caco-2 cellular uptake (2.78 times) and oral bioavailability (Fr=355.7%). Pharmacodynamic studies showed that LUT-HES NCs remarkably lowered serum uric acid levels by 69.93% and ameliorated renal damage in hyperuricemic mice.
Conclusion: HES is a potential stabilizer for poorly soluble flavonoid NCs and provides a promising strategy for the clinical application of these compounds. LUT-HES NCs may be an alternative or complementary strategy for hyperuricemia treatment.

Keywords: Hydroxyethyl starch; anti-hyperuricemia; luteolin; nanocrystals; oral bioavailability; stabilizer

DOI: https://doi.org/10.2147/IJN.S464948

Chem Biol Drug Des. 2024 Jun;103(6): e14567

Study on the mechanism of quercetin in Sini Decoction Plus Ginseng Soup to inhibit liver cancer and HBV virus replication through CDK1.

Liyuan Hao, Shenghao Li, Guo Chen, Aiyu Nie, Liang Zeng, Zhonghui Xiao, Xiaoyu Hu.

BACKGROUND: To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms.
METHODS: The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified in vitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell.
RESULTS: The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor.
CONCLUSIONS: Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.

Keywords: CCNB1; CDK1; HBV‐related HCC; SNRS; quercetin

DOI: https://doi.org/10.1111/cbdd.14567

Food Funct. 2024 Jun 10.

Polyphenols in edible plant leaves: an overview of their occurrence and health properties.

Anthony Masiala, Audrey Vingadassalon, Guylène Aurore.

Edible plant leaves (EPLs) constitute a major renewable functional plant biomass available all year round, providing an essential source of polyphenols in the global diet. Polyphenols form a large family of antioxidant molecules. They protect against the harmful effects of free radicals, strengthen immunity and stimulate the body's natural defenses thanks to their antibacterial and antiviral functions. This study refers to phenolic compounds from 50 edible plant leaves divided into four categories: green leafy vegetables, underutilized leafy vegetables, leafy spices and leafy drinks. It provides data on the identification, occurrence and pharmacological functions of polyphenols contained in EPLs, and provides a better understanding of trends and gaps in their consumption and study. Certain EPLs, such as moringa (Moringa oleifera Lam.), tea (Camellia sinensis L.) and several leafy spices of the Lamiaceae family, reveal important characteristics and therapeutic potential. The polyphenol composition of EPLs makes them functional plants that offer relevant solutions in the fight against obesity, the management of food insecurity and the prevention of chronic diseases.

DOI: https://doi.org/10.1039/d4fo00509k

Microb Pathog. 2024 Jun 06. pii: S0882-4010(24)00179-7. [Epub ahead of print] 106712

Antiviral activity and underlying mechanisms of baicalin against porcine reproductive and respiratory syndrome virus in vitro.

Weichen Chang, Jing Wang, Feifan Wu, Hongying Zhang, Mingfan Yang.

Porcine reproductive and respiratory syndrome (PRRS) is a major challenge for the global swine industry, causing huge economic losses worldwide. To date, there are no effective measures to prevent and control the spread of PRRS virus (PRRSV). Baicalin (BA) is a natural flavonoid with various pharmacological effects, including antiviral, anti-inflammatory, antioxidant and immunomodulatory. Here, we demonstrate that BA exhibits potent anti-PRRSV activity in vitro, BA concentrations in the range of 5-20 μg/mL significantly inhibited PRRSV infection in a dose-dependent manner and were independent of PRRSV strain. Mechanistically, BA inhibited PRRSV replication by directly interacting with virions, thereby affecting multiple stages of the virus life cycle. Meanwhile, the preventive effect of BA on PRRSV could be realized by inhibiting CD151 and CD163 expression. Furthermore, BA reduced the PRRSV-induced expression of PAMs cytokines (IFN-α, IL-6, IL-8, and TNF-α), suggesting that BA-induced antiviral cytokines may help BA inhibit PRRSV infection. Taken together, BA can be used as an inhibitor of PRRSV infection in vitro, which provides a theoretical basis for the clinical application of BA and the prevention and control of PRRSV infection, which is worthy of further in vivo studies in swine.

Keywords: Antiviral effect; Baicalin; Cytokine; Porcine reproductive and respiratory syndrome virus