Background: Glycyrrhetinic acid-mediated brucine self-assembled nanomicelles enhance the anti-hepatitis B properties of brucine by improving its water solubility, short half-life, toxicity, and side effects. Brucine (B) is an indole alkaloid extracted from the seeds of Strychnos nux-vomica (Loganiaceae). Purpose: To assess the efficacy of the Brucine-Glycyrrhetnic acid-Polyethylene glycol-3,3’-dithiodipropionic acid-Glycerin monostearate (B-GPSG) in treating hepatitis B, its potential to protect against acute liver injury caused by d-galactosamine and its anti-hepatoma activities were studied. Research Design: The concentration of B-GPSG used in the in vivo and in vitro experiments was 0.63 mg/mL. The rats injected with d-GalN (450 mg/kg) were used as liver injury models. The rats were separated into normal, model, positive, positive control, B-PSG and B-GPSG groups. Hepatoma cells expressing HBV HepG2.2.15 were used for in vitro experiments. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, plate cloning, Hoechst staining and flow cytometry were conducted to explore the mechanism of B-GPSG against hepatitis B. Results: Compared with the model group, the liver coefficient of B-GPSG group decreased (4.59 ± 0.17 vs 5.88 ± 0.42), the content of MDA in rat liver homogenate decreased (12.54 ± 1.81 vs 23.05 ± 2.98), the activity of SOD increased, the activity of ALT and AST in rat serum decreased. In vitro, the IC50 values of B-GPSG group decreased. B-GPSG group effectively inhibited the proliferation and migration of HepG2.2.15 cells. Conclusions: The hepatoprotective effects of B-GPSG nanomicelles, which are attributed to their GA-mediated liver targeting and synergistic actions with brucine, suggest their therapeutic potential against hepatitis B. This development opens up new possibilities for the application of traditional Chinese medicine and nanomedicine in anti-hepatitis B.
WangYLiuYYuanJL, et al.Research progress of drug-induced liver injury. Chin J Pharm Econ2013; 5: 52–54.
2.
MaKLiuYL. Research progress of drug-induced liver injury caused by Traditional Chinese Medicine. Guangming J Chin Med2015; 30: 907–911.
3.
LiuCYChenKFChenPJ. Treatment of liver cancer. Cold Spring Harb Perspect Med2015; 5: a021535.
4.
ChenDShenDHZhuJY. Research progress in clinical pathology of hepatocellular carcinoma. Chin J Diagnostic Patho2017; 24: 945–952.
5.
AsraniSKDevarbhaviHEatonJ, et al.Burden of liver diseases in the world. J Hepatol2019; 70: 151–171.
6.
ChenWLLinCHHuangCC, et al.Chinese herbal medicine reduces acute hepatitis exacerbation in patients with hepatitis B virus infection: a case-control study in Taiwan. Compl Ther Med2019; 42: 248–254.
7.
GuoWNZhuBAiL, et al.Animal models for the study of hepatitis B virus infection. Zool Res2018; 39: 25–31.
8.
XiangJZhangHYLiD, et al.Study on the mechanism of brucine in the treatment of early mouse knee osteoarthritis. J Chengdu Med Univ2021; 16: 561–565.
9.
GuoYYLiCCSunS, et al.Study on antitumor mechanism of brucine based on network pharmacology. Acta Chin Med2022; 37: 844–849.
10.
QinJYangLShengX, et al.Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in vivo. Oncol Lett2018; 15: 6137–6146.
11.
FrediansyahASofyantoroFAlhumaidS, et al.Microbial natural products with antiviral activities, including anti-SARS-CoV-2: a review. Molecules2022; 27(13): 4305.
12.
LiangJKWuZLWuGH, et al.The anti-hepatoma mechanism of glycyrrhetinic acid and its research progress as liver targeting ligand. J China Pharm2017; 28: 3150–3154.
13.
JiaLGaoYQiaoMX, et al.Preparation and targeting study of glycyrrhetinic acid-LCA liposomes. J Shenyang Pharm Univ2022; 39: 521–528.
14.
WangHFangZZMengR, et al.Glycyrrhizin and glycyrrhetinic acid inhibits alpha-naphthyl isothiocyanate-induced liver injury and bile acid cycle disruption. Toxicology2017; 386: 133–142.
15.
SpecialeAMuscaràCMoloniaMS, et al.Recent advances in glycyrrhetinic acid-functionalized biomaterials for liver cancer-targeting therapy. Molecules2022; 27: 1775.
16.
YangWZhangYWangJ, et al.Glycyrrhetinic acid-cyclodextrin grafted pullulan nanoparticles loaded doxorubicin as a liver targeted delivery carrier. Int J Biol Macromol2022; 216: 789–798.
17.
HuangPWangDSuY, et al.Combination of small molecule prodrug and nanodrug delivery: amphiphilic drug-drug conjugate for cancer therapy. J Am Chem Soc2014; 136: 11748–11756.
18.
SongQWangXWangY, et al.Reduction responsive self-assembled nanoparticles based on disulfide-linked drug-drug conjugate with high drug loading and antitumor efficacy. Mol Pharm2015; 13: 190–201.
19.
TianFDahmaniFZQiaoJ, et al.A targeted nanoplatform co-delivering chemotherapeutic and antiangiogenic drugs as a tool to reverse multidrug resistance in breast cancer. Acta Biomater2018; 15: 398–412.
20.
GuanQXZhangXZhangY, et al.Design, synthesis, and characterization of glycyrrhetinic acid-mediated multifunctional liver-targeting polymeric carrier materials. Mater Res2020; 35: 1236–1248.
21.
YuanBZhangNJingM. MTT method and LDH method to evaluate the cytotoxicity of nanosilver antibacterial gel in vitro. Chin Medical Device Information2022; 28: 24–31.
22.
MaZJiangZXJiangZ. The effect of PHLDA2 on proliferation, invasion, migration and apoptosis of hepatocellular carcinoma cells. Acta Anat Sin2020; 51: 398–404.
23.
JiangYYBaoXLiH, et al.Effects of ZWF on migration, cell cycle and apoptosis of A549 cells. West China J. Pharm Times2020; 35: 167–170.
24.
LiQSuRBaoX, et al.Glycyrrhetinic acid nanoparticles combined with ferrotherapy for improved cancer immunotherapy. Acta Biomater2022; 144: 109–120.
25.
ZhuXLWangSSLiLH, et al.Preparation and characterization of glycyrrhetinic acid-modified nano graphene oxide drug delivery system. Zhongguo Zhongyao Zazhi2019; 44(21): 4621–4626.
26.
GuanQZhouXYangF, et al.A novel strategy against hepatitis B virus: glycyrrhetnic acid conjugated multi-component synergistic nano-drug delivery system for targeted therapy. J Biomater Appl2022; 12: 8853282221139132.
