Dryocrassin ABBA is an orally active phloroglucinol derivative with antiviral and antibacterial activities[1][2]. Dryocrassin ABBA not only exhibits inhibitory activity against the neuraminidases (NAs) of the H7N9 influenza virus, with an IC50 of 3.6μM[2]; but also inhibits the SrtA enzyme of Staphylococcus aureus (S. aureus), with an IC50 of 24.17μM[3].
In vitro, pretreatment of mouse bone marrow-derived DCs (mBM-DCs) with 10 or 20μM Dryocrassin ABBA 1h before lipopolysaccharide (LPS) stimulation significantly reduced the LPS-induced emission of tumor necrosis factor-a, interleukin-6, and interleukin-12p70 without affecting cell viability[4].Treatment of HepG2 cells with 25, 50, and 75μg/mL Dryocrassin ABBA for 48h inhibited the growth of HepG2 cells in a concentration-dependent manner[5].
In vivo, oral administration of Dryocrassin ABBA with different concentration(12.5, 18, and 33mg/kg) for 7 days on SPF BALB/C female mice inoculated intra-nasally with H5N1 viruses significantly reduced mortality, prolonged survival rate, and increased body weight throughout the infection period. Moreover, 33 and 18mg/kg Dryocrassin ABBA have decreased lung index and virus loads, and significantly increased MCP-1 and IL-10 while significantly decreased IL-12, IL-6, IFN-γ and TNF-α compared to the untreated group[6]. Subcutaneous injection of Dryocrassin ABBA(100mg/kg) every 12h for 96h can attenuate injury and inflammation of mouse lung tissues caused by S. aureus and increase survival of mice[7].
References:
[1] Jin, Y. H., Jeon, S., Lee, J., Kim, S., Jang, M. S., Park, C. M., Song, J. H., Kim, H. R., & Kwon, S. (2022). Anticoronaviral Activity of the Natural Phloroglucinols, Dryocrassin ABBA and Filixic Acid ABA from the Rhizome of Dryopteris crassirhizoma by Targeting the Main Protease of SARS-CoV-2. Pharmaceutics, 14(2), 376.
[2] Hou, B., Liu, Z., Yang, X. B., Zhu, W. F., Li, J. Y., Yang, L., Reng, F. C., Lv, Y. F., Hu, J. M., Liao, G. Y., & Zhou, J. (2019). Total synthesis of dryocrassin ABBA and its analogues with potential inhibitory activity against drug-resistant neuraminidases. Bioorganic & medicinal chemistry, 27(17), 3846–3852.
[3] Zhang, B., Wang, X., Wang, L., Chen, S., Shi, D., & Wang, H. (2016). Molecular Mechanism of the Flavonoid Natural Product Dryocrassin ABBA against Staphylococcus aureus Sortase A. Molecules (Basel, Switzerland), 21(11), 1428.
[4] Fu, R. H., Wang, Y. C., Liu, S. P., Shih, T. R., Lin, H. L., Chen, Y. M., Tsai, R. T., Tsai, C. H., Shyu, W. C., & Lin, S. Z. (2014). Dryocrassin suppresses immunostimulatory function of dendritic cells and prolongs skin allograft survival. Cell transplantation, 23(4-5), 641–656.
[5] Jin, Z., Wang, W. F., Huang, J. P., Wang, H. M., Ju, H. X., & Chang, Y. (2016). Dryocrassin ABBA Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells Through a Caspase-Dependent Mitochondrial Pathway. Asian Pacific journal of cancer prevention : APJCP, 17(4), 1823–1828.
[6] Ou, C., Zhang, Q., Wu, G., Shi, N., & He, C. (2015). Dryocrassin ABBA, a novel active substance for use against amantadine-resistant H5N1 avian influenza virus. Frontiers in microbiology, 6, 592.
[7] Li, B., Jin, Y., Xiang, H., Mu, D., Yang, P., Li, X., Zhong, L., Cao, J., Xu, D., Gong, Q., Wang, T., Wang, L., & Wang, D. (2019). An Inhibitory Effect of Dryocrassin ABBA on Staphylococcus aureus vWbp That Protects Mice From Pneumonia. Frontiers in microbiology, 10, 7.
Dryocrassin ABBA是一种可口服的、具有抗病毒和抗菌活性的间苯三酚衍生物[1][2]。Dryocrassin ABBA不仅对H7N9流感病毒的神经氨酸酶（NAs）具有抑制作用，IC50值为3.6μM[2]；而且对金黄色葡萄球菌（S. aureus）的SrtA酶也有抑制作用，IC50为24.17μM[3]。
在体外实验中，在脂多糖（LPS）刺激前1h用10或20μM Dryocrassin ABBA预处理小鼠骨髓源性树突状细胞（mBM-DCs）可显著降低LPS诱导的肿瘤坏死因子-a、白细胞介素-6和白细胞介素-12p70的释放，且不影响细胞活力[4]。以25、50和75μg/mL Dryocrassin ABBA处理HepG2细胞 48h 后，HepG2细胞的生长以浓度依赖性的方式受到抑制[5]。
在体内，对经鼻内接种H5N1病毒的SPF级BALB/C雌性小鼠口服不同浓度（12.5、18和33mg/kg）的Dryocrassin ABBA 7天，可显著降低死亡率，延长存活率，并增加整个感染期的体重。此外，与未处理组相比，33和18mg/kg Dryocrassin ABBA处理还可显著降低肺指数和病毒载量，且显著升高MCP-1和IL-10，显著降低IL-12、IL-6、IFN-γ和TNF-α[6]。在96h内每隔12h给感染黄色葡萄球菌的小鼠皮下注射Dryocrassin ABBA (100mg/kg)，可减轻金黄色葡萄球菌对小鼠肺组织的损伤和炎症，提高小鼠的存活率[7]。