PMID- 34956386 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211228 IS - 1741-427X (Print) IS - 1741-4288 (Electronic) IS - 1741-427X (Linking) VI - 2021 DP - 2021 TI - Procyanidin B2 Alleviates Palmitic Acid-Induced Injury in HepG2 Cells via Endoplasmic Reticulum Stress Pathway. PG - 8920757 LID - 10.1155/2021/8920757 [doi] LID - 8920757 AB - Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome featuring ectopic lipid accumulation in hepatocytes. NAFLD has been a severe threat to humans with a global prevalence of over 25% yet no approved drugs for the treatment to date. Previous studies showed that procyanidin B2 (PCB2), an active ingredient from herbal cinnamon, has an excellent hepatoprotective effect; however, the mechanism remains inconclusive. The present study aimed to investigate the protective effect and underlying mechanism of PCB2 on PA-induced cellular injury in human hepatoma HepG2 cells. Our results showed that PA-induced oxidative stress, calcium disequilibrium, and subsequent endoplasmic reticulum stress (ERS) mediated cellular injury, with elevated protein levels of GRP78, GRP94, CHOP, and hyperphosphorylation of PERK and IRE1alpha as well as the increased ratio of Bax/Bcl-2, which was restored by PCB2 in a concentration-dependent manner, proving the excellent antiapoptosis effect. In addition, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, increased cell viability and decreased protein levels of GRP78 and CHOP, which is similar to PCB2, and thapsigargin (TG), the ER stress agonist, exhibited conversely meanwhile partly counteracted the hepatic protection of PCB2. What is more, upregulated protein expression of p-IKKalpha/beta, p-NF-kappaB p65, NLRP3, cleaved caspase 1, and mature IL-1beta occurred in HepG2 cells in response to PA stress while rescued with the PCB2 intervention. In conclusion, our study demonstrated that PA induces ERS in HepG2 cells and subsequently activates downstream NLRP3 inflammasome-mediated cellular injury, while PCB2 inhibits NLRP3/caspase 1/IL-1beta pathway, inflammation, and apoptosis with the presence of ERS, thereby promoting cell survival, which may provide pharmacological evidence for clinical approaches on NAFLD. CI - Copyright (c) 2021 Yi-Ming Li et al. FAU - Li, Yi-Ming AU - Li YM AUID- ORCID: 0000-0001-9475-2374 AD - The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China. FAU - Zhao, Shao-Yang AU - Zhao SY AUID- ORCID: 0000-0001-8521-0223 AD - The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China. AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China. FAU - Zhao, Huan-Huan AU - Zhao HH AUID- ORCID: 0000-0002-5274-5595 AD - Nutrition Department, Linyi People's Hospital, Linyi 276000, China. FAU - Wang, Bao-Hua AU - Wang BH AUID- ORCID: 0000-0001-9520-6009 AD - The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China. AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China. FAU - Li, Sai-Mei AU - Li SM AUID- ORCID: 0000-0002-5119-1412 AD - The First School of Clinical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510000, China. AD - The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510000, China. LA - eng PT - Journal Article DEP - 20211216 PL - United States TA - Evid Based Complement Alternat Med JT - Evidence-based complementary and alternative medicine : eCAM JID - 101215021 PMC - PMC8702323 COIS- All authors declare no conflicts of interest. EDAT- 2021/12/28 06:00 MHDA- 2021/12/28 06:01 PMCR- 2021/12/16 CRDT- 2021/12/27 06:26 PHST- 2021/08/29 00:00 [received] PHST- 2021/11/21 00:00 [revised] PHST- 2021/11/26 00:00 [accepted] PHST- 2021/12/27 06:26 [entrez] PHST- 2021/12/28 06:00 [pubmed] PHST- 2021/12/28 06:01 [medline] PHST- 2021/12/16 00:00 [pmc-release] AID - 10.1155/2021/8920757 [doi] PST - epublish SO - Evid Based Complement Alternat Med. 2021 Dec 16;2021:8920757. doi: 10.1155/2021/8920757. eCollection 2021.