Hesperitin derivative-11 suppress hepatic stellate cell activation and proliferation by targeting PTEN/AKT pathway.
Hesperitin derivative (HD-11) is a monomeric compound derived from Hesperidin, which is a naturally occurring flavanone glycoside that exerts extensive clinical effects such as anti-inflammatory, anti-oxidant and anti-angiogenic. However, the role and fundamental mechanism of HD-11 in hepatic fibrosis are still unrevealed. In this study, HD-11 not only alleviates ECM deposition in rats with liver fibrosis, but also reduces the expression of α-SMA and col1a1 in TGF-β1-induced HSC-T6 cells. Moreover, it was demonstrated that HD-11 significantly promoted the expression of PTEN in vivo and in vitro. In order to evaluate the involvement of HD-11 in TGF-β1-induced HSC-T6 activation, a specific blocking agent of PTEN (bpv) and PTEN small interfering (si)-RNA-mediated silencing were used. Interestingly, HD-11 treatment couldn't inhibit α-SMA and col1a1 expression on the basis of PTEN knockdown. On the contrary, over-expression of PTEN had an opposite effect on the expression of α-SMA and col1a1 in TGF-β1-induced HSC-T6 cells after treatment of HD-11. In addition, HD-11 remarkably inhibited the expression of p-AKT in vivo and in vitro. Taken together, all the above results indicate that HD-11 may play the part of an effective modulator of PTEN/AKT signaling pathway.
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Wan-Xia
WX
Li
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Xin
X
Chen
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Yang
Y
Yang
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Hui-Min
HM
Huang
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Hai-di
HD
Li
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Cheng
C
Huang
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China.
Xiao-Ming
XM
Meng
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China; Institute for Liver Diseases of Anhui Medical University (ILD-AMU), Anhui Medical University, Hefei 230032, China; Anhui Institute of Innovative Drugs, Anhui Medical University, Hefei 230032, China; The Key laboratory of Anti-inflammatory and Immune medicines, Ministry of Education, China. Electronic address: lj@ahmu.edu.cn.
Jun
J
Li
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006569:Hesperidin / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
D000199:Actins; D000410:Alanine Transaminase; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001219:Aspartate Aminotransferases; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D006569:Hesperidin; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat; C487216:Pten protein, rat; C013015:hesperetin
AKT; Hesperidin derivative-11; Liver fibrosis; PTEN