Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway
Rhubarb is a well-known herb worldwide and includes approximately 60 species of the <i>Rheum</i> genus. One of the representative plants is <i>Rheum palmatum</i>, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopo...
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/23/9044 |
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| author | Yong Joo Park Kwang Ho Lee Mi Seon Jeon Yong Hoon Lee Yoon Joo Ko Changhyun Pang Bonglee Kim Kyu Hyuck Chung Ki Hyun Kim |
| author_facet | Yong Joo Park Kwang Ho Lee Mi Seon Jeon Yong Hoon Lee Yoon Joo Ko Changhyun Pang Bonglee Kim Kyu Hyuck Chung Ki Hyun Kim |
| author_sort | Yong Joo Park |
| collection | DOAJ |
| description | Rhubarb is a well-known herb worldwide and includes approximately 60 species of the <i>Rheum</i> genus. One of the representative plants is <i>Rheum palmatum</i>, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of <i>R. palmatum</i> inhibited hepatic stellate cell (HSC) activation by transforming growth factor β1 (TGF-β1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-<i>O</i>-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-<i>O</i>-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-<i>O</i>-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-<i>O</i>-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-β1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-<i>O</i>-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-<i>O</i>-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-<i>O</i>-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation. |
| first_indexed | 2024-03-10T14:29:46Z |
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| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-10T14:29:46Z |
| publishDate | 2020-11-01 |
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| spelling | doaj.art-279421d072a447449a5c7b78ae82c7082023-11-20T22:41:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012123904410.3390/ijms21239044Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling PathwayYong Joo Park0Kwang Ho Lee1Mi Seon Jeon2Yong Hoon Lee3Yoon Joo Ko4Changhyun Pang5Bonglee Kim6Kyu Hyuck Chung7Ki Hyun Kim8School of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaLaboratory of Nuclear Magnetic Resonance, National Center for Inter-University Research Facilities (NCIRF), Seoul National University, Gwanak-gu, Seoul 08826, KoreaSchool of Chemical Engineering, Sungkyunkwan University, Suwon 16419, KoreaDepartment of Pathology, College of Korean Medicine, Kyung Hee University, Seoul 02453, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaSchool of Pharmacy, Sungkyunkwan University, Suwon 16419, KoreaRhubarb is a well-known herb worldwide and includes approximately 60 species of the <i>Rheum</i> genus. One of the representative plants is <i>Rheum palmatum</i>, which is prescribed as official rhubarb due to its pharmacological potential in the Korean and Chinese pharmacopoeia. In our bioactive screening, we found out that the EtOH extract of <i>R. palmatum</i> inhibited hepatic stellate cell (HSC) activation by transforming growth factor β1 (TGF-β1). Chemical investigation of the EtOH extract led to the isolation of chrysophanol 8-<i>O</i>-glucoside, which was determined by structural analysis using NMR spectroscopic techniques and electrospray ionization mass spectrometry (ESIMS). To elucidate the effects of chrysophanol 8-<i>O</i>-glucoside on HSC activation, activated LX-2 cells were treated for 48 h with chrysophanol 8-<i>O</i>-glucoside, and α-SMA and collagen, HSC activation markers, were measured by comparative quantitative real-time PCR (qPCR) and western blotting analysis. Chrysophanol 8-<i>O</i>-glucoside significantly inhibited the protein and mRNA expression of α-SMA and collagen compared with that in TGF-β1-treated LX-2 cells. Next, the expression of phosphorylated SMAD2 (p-SMAD2) and p-STAT3 was measured and the translocation of p-STAT3 to the nucleus was analyzed by western blotting analysis. The expression of p-SMAD2 and p-STAT3 showed that chrysophanol 8-<i>O</i>-glucoside strongly downregulated STAT3 phosphorylation by inhibiting the nuclear translocation of p-STAT3, which is an important mechanism in HSC activation. Moreover, chrysophanol 8-<i>O</i>-glucoside suppressed the expression of p-p38, not that of p-JNK or p-Erk, which can activate STAT3 phosphorylation and inhibit MMP2 expression, the downstream target of STAT3 signaling. These findings provided experimental evidence concerning the hepatoprotective effects of chrysophanol 8-<i>O</i>-glucoside against liver damage and revealed the molecular basis underlying its anti-fibrotic effects through the blocking of HSC activation.https://www.mdpi.com/1422-0067/21/23/9044<i>Rheum palmatum</i>chrysophanol 8-<i>O</i>-glucosidehepatic stellate cellshepatic fibrosisSTAT3 |
| spellingShingle | Yong Joo Park Kwang Ho Lee Mi Seon Jeon Yong Hoon Lee Yoon Joo Ko Changhyun Pang Bonglee Kim Kyu Hyuck Chung Ki Hyun Kim Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway International Journal of Molecular Sciences <i>Rheum palmatum</i> chrysophanol 8-<i>O</i>-glucoside hepatic stellate cells hepatic fibrosis STAT3 |
| title | Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway |
| title_full | Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway |
| title_fullStr | Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway |
| title_full_unstemmed | Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway |
| title_short | Hepatoprotective Potency of Chrysophanol 8-<i>O</i>-Glucoside from <i>Rheum palmatum</i> L. against Hepatic Fibrosis via Regulation of the STAT3 Signaling Pathway |
| title_sort | hepatoprotective potency of chrysophanol 8 i o i glucoside from i rheum palmatum i l against hepatic fibrosis via regulation of the stat3 signaling pathway |
| topic | <i>Rheum palmatum</i> chrysophanol 8-<i>O</i>-glucoside hepatic stellate cells hepatic fibrosis STAT3 |
| url | https://www.mdpi.com/1422-0067/21/23/9044 |
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