Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice
Acute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from <i>Betula platyphylla</i> that ha...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/13/6871 |
| _version_ | 1797411906446688256 |
|---|---|
| author | Ziqi Zhou Ji-Won Choi Joon Yeon Shin Dong-Uk Kim Bitna Kweon Hyuncheol Oh Youn-Chul Kim Ho-Joon Song Gi-Sang Bae Sung-Joo Park |
| author_facet | Ziqi Zhou Ji-Won Choi Joon Yeon Shin Dong-Uk Kim Bitna Kweon Hyuncheol Oh Youn-Chul Kim Ho-Joon Song Gi-Sang Bae Sung-Joo Park |
| author_sort | Ziqi Zhou |
| collection | DOAJ |
| description | Acute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from <i>Betula platyphylla</i> that has been shown to have anti-inflammatory effects. In this study, we aimed to investigate the effects of BA on AP and elucidate the potential underlying mechanisms. AP was induced in mice through six intraperitoneal injections of cerulein. After the last cerulein injection, the mice were sacrificed. Our results revealed that pre- and post-treatment with BA significantly reduced the severity of pancreatitis, as evidenced by a decrease in histological damage in the pancreas and lung, serum amylase and lipase activity and pancreatic myeloperoxidase activity. Furthermore, BA pretreatment reduced proinflammatory cytokine production, augmentation of chemokines, and infiltration of macrophages and neutrophils in the pancreas of AP mice. In addition, mice that were pretreated with BA showed a reduction in Iκ-Bα degradation and nuclear factor-kappa B (NF-κB) binding activity in the pancreas. Moreover, BA reduced the production of proinflammatory cytokines and NF-κB activation in pancreatic acinar cells (PACs). These findings suggest that BA may have prophylactic and therapeutic effects on AP via inhibition of the NF-κB signaling pathway. |
| first_indexed | 2024-03-09T04:53:08Z |
| format | Article |
| id | doaj.art-7f1feb796da24ad19f92c20c6fd679ad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:53:08Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7f1feb796da24ad19f92c20c6fd679ad2023-12-03T13:08:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-06-012213687110.3390/ijms22136871Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in MiceZiqi Zhou0Ji-Won Choi1Joon Yeon Shin2Dong-Uk Kim3Bitna Kweon4Hyuncheol Oh5Youn-Chul Kim6Ho-Joon Song7Gi-Sang Bae8Sung-Joo Park9Department of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaDepartment of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaDepartment of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaHanbang Cardio-Renal Syndrome Research Center, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaDepartment of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaInstitute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaInstitute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaDepartment of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaHanbang Cardio-Renal Syndrome Research Center, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaDepartment of Herbology, School of Korean Medicine, Wonkwang University, 460 Iksandaero, Iksan 54538, Jeonbuk, KoreaAcute pancreatitis (AP) is an inflammatory disorder, involving acinar cell death and the release of inflammatory cytokines. Currently, there are limited effective therapeutic agents for AP. Betulinic acid (BA) is a pentacyclic triterpenoid extracted from <i>Betula platyphylla</i> that has been shown to have anti-inflammatory effects. In this study, we aimed to investigate the effects of BA on AP and elucidate the potential underlying mechanisms. AP was induced in mice through six intraperitoneal injections of cerulein. After the last cerulein injection, the mice were sacrificed. Our results revealed that pre- and post-treatment with BA significantly reduced the severity of pancreatitis, as evidenced by a decrease in histological damage in the pancreas and lung, serum amylase and lipase activity and pancreatic myeloperoxidase activity. Furthermore, BA pretreatment reduced proinflammatory cytokine production, augmentation of chemokines, and infiltration of macrophages and neutrophils in the pancreas of AP mice. In addition, mice that were pretreated with BA showed a reduction in Iκ-Bα degradation and nuclear factor-kappa B (NF-κB) binding activity in the pancreas. Moreover, BA reduced the production of proinflammatory cytokines and NF-κB activation in pancreatic acinar cells (PACs). These findings suggest that BA may have prophylactic and therapeutic effects on AP via inhibition of the NF-κB signaling pathway.https://www.mdpi.com/1422-0067/22/13/6871acute pancreatitisbetulinic acidacinar cellinflammationnuclear factor-kappa B |
| spellingShingle | Ziqi Zhou Ji-Won Choi Joon Yeon Shin Dong-Uk Kim Bitna Kweon Hyuncheol Oh Youn-Chul Kim Ho-Joon Song Gi-Sang Bae Sung-Joo Park Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice International Journal of Molecular Sciences acute pancreatitis betulinic acid acinar cell inflammation nuclear factor-kappa B |
| title | Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice |
| title_full | Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice |
| title_fullStr | Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice |
| title_full_unstemmed | Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice |
| title_short | Betulinic Acid Ameliorates the Severity of Acute Pancreatitis via Inhibition of the NF-κB Signaling Pathway in Mice |
| title_sort | betulinic acid ameliorates the severity of acute pancreatitis via inhibition of the nf κb signaling pathway in mice |
| topic | acute pancreatitis betulinic acid acinar cell inflammation nuclear factor-kappa B |
| url | https://www.mdpi.com/1422-0067/22/13/6871 |
| work_keys_str_mv | AT ziqizhou betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT jiwonchoi betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT joonyeonshin betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT dongukkim betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT bitnakweon betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT hyuncheoloh betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT younchulkim betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT hojoonsong betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT gisangbae betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice AT sungjoopark betulinicacidamelioratestheseverityofacutepancreatitisviainhibitionofthenfkbsignalingpathwayinmice |