Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 17, Issue 7, Pages -Publisher
MDPI
DOI: 10.3390/ijms17071036
Keywords
hepatic fibrosis; hepatic stellate cells; cell apoptosis; Demethyleneberberine; NF-B
Funding
- National Natural Science Foundation of China [81573484]
- Project of State Key Laboratory of Natural Medicines, China Pharmaceutical University [SKLNMZZC201407]
- Huahai Pharmaceutical Graduate Student Innovation Fund [CX14B-012HH]
- National Found for Fostering Talents of Basic Science (NFFTBS) [J1030830]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Demethyleneberberine (DMB) is an essential metabolite of Berberine (BBR) in vivo. Recent reports have revealed multiple novel therapeutic applications of BBR. However, the pharmacological activities of DMB remain to be elucidated. This study aimed to demonstrate the hepatoprotective and anti-fibrotic effects of DMB both in vitro and in vivo. Here we showed that DMB protects against thioacetamide (TAA)-induced hepatic fibrosis in mice and exhibits a higher safety profile as compared to BBR. Flow cytometry and Western blotting analysis showed that DMB is able to suppress the activation of hepatic stellate cells (HSCs) and induce cell apoptosis through the nuclear factor-B (NF-B) cascade. Immunohistochemical (IHC) and quantitative polymerase chain reaction (qPCR) analysis indicated that DMB also has inhibitory effects on collagen synthesis and is able to increase collagen degradation by blocking the transforming growth factor 1 (TGF-1)-Smad signaling and reducing the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs). These findings indicate that DMB has the potential to attenuate hepatic fibrosis via suppressing HSC activation.
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