Gastrodin ameliorates Concanavalin A-induced acute hepatitis via the IL6/JAK2/STAT3 pathway.

AIMS: Gastrodin, the main active ingredient of Gastrodia elata Blume, has been shown to protect against many inflammatory diseases. Our study aimed to investigate the anti-inflammatory role of gastrodin in concanavalin A (ConA)-induced acute hepatitis in mice and to explore its precise mechanism. METHODS: C57BL/6 mice were administered with gastrodin (50 or 100mg/kg) for 3 days prior to intravenous injection of ConA to induce acute autoimmune hepatitis (AIH). Serum aminotransferases levels and cytokine levels were measured. Liver tissue histology was conducted to assess the degree of liver injury. Splenocytes pretreated with gastrodin were stimulated with ConA to observe splenocyte proliferation. RESULTS: Gastrodin greatly reduced the level of serum aminotransferases, inflammatory cytokine such as IL-6 and TNF-α and histopathological damage in ConA-induced hepatitis. Besides, gastrodin had an inhibitory effect on liver apoptosis, and autophagy. Furthermore, gastrodin inhibited the proliferation of splenocytes in vitro. The protein expression of p-JAK2 and p-STAT3 was markedly affected by gastrodin pretreatment. CONCLUSIONS: The present study indicated that gastrodin pretreatment exerted protective effects against ConA-induced acute hepatitis, partly through the inhibition of the IL6/JAK2/STAT3 pathway. Further studies are recommended to determine the potential therapeutic role of gastrodin in acute AIH.

Isorhamnetin Inhibits Liver Fibrosis by Reducing Autophagy and Inhibiting Extracellular Matrix Formation via the TGF-ß1/Smad3 and TGF-ß1/p38 MAPK Pathways.

OBJECTIVE: Liver fibrosis is a consequence of wound-healing responses to chronic liver insult and may progress to liver cirrhosis if not controlled. This study investigated the protection against liver fibrosis by isorhamnetin. METHODS: Mouse models of hepatic fibrosis were established by intraperitoneal injection of carbon tetrachloride (CCl4) or bile duct ligation (BDL). Isorhamnetin 10 or 30 mg/kg was administered by gavage 5 days per week for 8 weeks in the CCl4 model and for 2 weeks in the BDL model. Protein and mRNA expressions were assayed by western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction. RESULTS: Isorhamnetin significantly inhibited liver fibrosis in both models, inhibiting hepatic stellate cell (HSC) activation, extracellular matrix (ECM) deposition, and autophagy. The effects were associated with downregulation of transforming growth factor ß1 (TGF-ß1) mediation of Smad3 and p38 mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSION: Isorhamnetin protected against liver fibrosis by reducing ECM formation and autophagy via inhibition of TGF-ß1-mediated Smad3 and p38 MAPK signaling pathways.

The Role of miR-1183: A Potential Suppressor in Hepatocellular Carcinoma via Regulating Splicing Factor SRSF1.

Purpose: Hepatocellular carcinoma (HCC) is a severe global health problem, causing many deaths of patients all over the world. Serine and arginine-rich splicing factor 1 (SRSF1) functions as an important oncogenic role in tumorigenesis and progression in HCC. Therefore, therapies targeting SRSF1 may provide promising therapeutic approaches. MiRNAs are virtually involved at the post-transcriptional level and bind to 3' untranslated region (3'-UTR) of their target messenger RNA (mRNA) to suppress expression. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to detect the expression of SRSF1 and miR-1183 in HCC cell lines. CCK8 assay, colony formation assay and wound healing assay were used to detect the function of miR-1183 in HCC cell lines in vitro. Luciferase reporter assay and Western blot were applied to detect the regulation of particular molecules. Xenograft tumor assay was used to detect the function of miR-1183 in HCC cell lines in vivo. Immunohistochemistry (IHC) was used to detect the expression of SRSF1 in HCC tissues and Xenograft tumors. Results: In this study, we identified that miR-1183 was downregulated in HCC cell lines. Functional assays indicated that miR-1183-upregulation cells show weakened proliferation ability and migration ability in vitro and inhibit subcutaneous tumor formation in vivo. With respect to the underlying mechanism, we found that miR-1183 function as a tumor suppressor by specifically binding to SRSF1. Conclusion: This study is the first to demonstrate that miR-1183 function as an important tumor-suppressing role by binding to the 3'-UTR of SRSF1 mRNA and suppressing its protein level in HCC cells in vitro and in vivo. Further, miR-1183 may be a potential target in the prognosis and treatment of HCC.

Proanthocyanidin Alleviates Liver Ischemia/Reperfusion Injury by Suppressing Autophagy and Apoptosis via the PPARα/PGC1α Signaling Pathway.

Background and Aims: Hepatic ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon in clinical practice, which usually occurs in liver transplantation, liver resection, severe trauma, and hemorrhagic shock. Proanthocyanidin (PC), exerted from various plants with antioxidant, antitumor, and antiaging activity, were administrated in our study to investigate the underlying mechanism of its protective function on IRI. Methods: Two doses of PC (50 mg/kg, 100 mg/kg) were given to BALB/c mice by intragastric administration for 7 days before partial (70%) warm IR surgery. Serum and liver tissues were collected 2, 8, and 24 h after reperfusion for relevant experiments. Results: The results of transaminase and hematoxylin and eosin staining indicated that PC pretreatment significantly alleviated IRI in mice. Serum total superoxide dismutase increased and malondialdehyde decreased in PC pretreatment groups. Enzyme-linked immunosorbent assays, western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry showed that inflammation, apoptosis, and autophagy in PC preprocessing groups were significantly inhibited and were dose-dependent. The protein, mRNA expression, and immunohistochemical staining results of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) in the PC pretreatment groups were significantly upregulated compared with the IR group in a dose-dependent manner. Conclusions: PC pretreatment suppressed inflammation, apoptosis, and autophagy via the PPAR-α signaling pathway to protect against IRI of the liver in mice.

miR-22-3p/PGC1ß Suppresses Breast Cancer Cell Tumorigenesis via PPARγ.

In this study, we found that miR-22-3p expression was decreased in breast cancer (BC) cell lines and tissues. Overexpression of miR-22-3p inhibited the proliferation and migration of BC cells in vitro and in vivo, while depletion of miR-22-3p exhibited the opposite effect. Importantly, miR-22-3p could directly target PGC1ß and finally regulate the PPARγ pathway in BC. In conclusion, miR-22-3p/PGC1ß suppresses BC cell tumorigenesis via PPARγ, which may become a potential biomarker and therapeutic target.