Baicalin attenuates hepatic injury in non-alcoholic steatohepatitis cell model by suppressing inflammasome-dependent GSDMD-mediated cell pyroptosis

Shi, Huilian; Zhang, Yanliang; Xing, Jing; Liu, Lina; Qiao, Fei; Li, Jun; Chen, Yuanyuan

doi:10.1016/j.intimp.2020.106195

Cited by 49 publications

(29 citation statements)

References 26 publications

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“…Recent studies have shown that pyroptosis, as an in ammation-related and controllable cell death method with potential therapeutic implications of NAFLD [23], accelerates the process of hepatic in ammation and brosis [24,25]. Noticeably, pyroptosis is the indispensable pathogenesis in the development of NAFLD model [23,26], more importantly, suppression of in ammasome-dependent GSDMD-mediated cell pyroptosis could attenuate hepatic injury in liver diseases [27]. Therefore, we focused on the in uence of JZLGD on pyroptosis in this study.…”

Section: Discussionmentioning

confidence: 99%

Jiangzhi Ligan Decoction Alleviated Nonalcoholic Fatty Liver Disease Induced by High-Fat-Diet in Rats via GSDMD-mediated Canonical/Non-canonical Pyroptosis Pathway

Zhang

Yin

Jiang

et al. 2021

Preprint

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Background Hepatoprotective effects of Chinese herbal formula Jiangzhi Ligan Decoction (JZLGD) against nonalcoholic fatty liver disease (NAFLD) have been demonstrated, but its mechanism is not clear. The aim of this study was to evaluate the protective effects of against high-fat diet (HFD) induced NAFLD in rat, and to further explore the potential molecular mechanism. Methods SD rats were assigned to five different groups: normal control group, NAFLD model group and JZLGD-treated NAFLD group (3 doses of JZLGD: 2.3, 4.6, 9.2 g/kg of body weight, respectively). All the rats were fed a HFD for 18 weeks except the normal control group(a normal diet). After 12 weeks, rats in JZLGD-treated NAFLD group were administered different doses of JZLGD by oral gavage once daily for another period of 6 weeks, and the rest were given the same dosage of normal saline. After the intervention, blood and liver from each sample were carefully removed and analyzed accordingly. Results We found that JZLGD significantly reduced the liver index, levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum. Furthermore, pathological examinations showed that JZLGD markedly reduced liver lipid droplets and improved liver lipid accumulation, NAFLD activity score and ballooning pathology scoring were also decreased. The detection of cytokines showed that JZLGD could significantly reduced the levels of serum inflammatory factors IL-1β, IL-18, tumor necrosis factor α (TNF-α) and IL-6, protected HFD rats from inflammation. In addition, NAFLD treatment, exhibited significant reduction in serum triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL) and free fatty acid (FFA) when compared to NAFLD control rats. JZLGD intervention also reduced the level of serum lipopolysaccharide (LPS) and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1, caspase-11, GSDMD, GSDMD N-terminus (GSDMD-N), IL-1β, IL-18 in the liver. Conclusion These results demonstrate the hepatoprotective effects of JZLGD in NAFLD mice, the effects may be mediated via downregulation of NLRP3 /caspase-1/GSDMD mediated canonical pyroptosis pathway and LPS /caspase-11/GSDMD mediated non-canonical pyroptosis pathway.

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Section: Discussionmentioning

confidence: 99%

Jiangzhi Ligan Decoction Alleviated Nonalcoholic Fatty Liver Disease Induced by High-Fat-Diet in Rats via GSDMD-mediated Canonical/Non-canonical Pyroptosis Pathway

Zhang

Yin

Jiang

et al. 2021

Preprint

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“…Our study revealed that BA played a part in the treatment of SCIRI and that the underlying mechanism involves promoting autophagy to dampen pyroptosis and ERS mediated apoptosis. Baicalein reportedly attenuates hepatic injury in nonalcoholic steatohepatitis by suppressing pyroptosis (Shi et al, 2020). Pyroptosis, a specific pro-inflammatory programmed cell death, is characterized by the swelling and rupture of cells and the lysis and release of pro-inflammatory molecules (Xing et al, 2020;Zheng and Li, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Baicalein reportedly attenuates hepatic injury in nonalcoholic steatohepatitis by suppressing pyroptosis ( Shi et al., 2020 ). Pyroptosis, a specific pro-inflammatory programmed cell death, is characterized by the swelling and rupture of cells and the lysis and release of pro-inflammatory molecules ( Xing et al., 2020 ; Zheng and Li, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that baicalein can induce autophagy to prevent hepatocellular injury (Liu et al, 2016). It can block NLRP3-GSDMD signaling to reduce pyroptosis and thereby protect the liver (Shi et al, 2020). In addition, baicalein can inhibit CHOP expression, suggesting that BA can suppress ER stress-induced apoptosis by inhibiting the CHOP pathway (Choi et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement

et al. 2020

Front. Pharmacol.

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Background: Spinal cord ischemia-reperfusion injury (SCIRI) is the main complication after the repair of a complex thoracoabdominal aortic aneurysm. Many clinical treatments are not ideal due to the complex pathophysiological process of this injury. Baicalein (BA), a component derived from the roots of the herb Scutellaria baicalensis, may contribute to the successful treatment of ischemia/reperfusion injury. Purpose: In the present study, the effects of BA on spinal cord ischemia-reperfusion injury and the underlying mechanisms were assessed. Materials and Methods: Spinal cord ischemia was induced in C57BL/6 mice by blocking the aortic arch. Fifty-five mice were then randomly divided into four groups: Sham, SCIR+Vehicle, SCIR+BA, and SCIR+BA +3MA groups. At 0 and 24 h pre-SCIRI and at 24 h and 7 days post-SCIRI, evaluations with the Basso mouse scale (BMS) were performed. On postoperative 24 h, the spinal cord was harvested to assess pyroptosis, endoplasmic reticulum stress mediated apoptosis and autophagy. Results: BA enhanced the functional recovery of spinal cord ischemia-reperfusion injury. In addition, BA attenuated pyroptosis, alleviated endoplasmic reticulum stress-mediated apoptosis, and activated autophagy. However, the effects of BA on the functional recovery of SCIRI, pyroptosis and endoplasmic reticulum stress-mediated apoptosis were reversed by the inhibition of autophagy. Conclusions: In general, our findings revealed that BA enhances the functional recovery of spinal cord ischemia-reperfusion injury by dampening pyroptosis and alleviating endoplasmic reticulum stress-mediated apoptosis, which are mediated by the activation of autophagy.

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“…It could regulate the levels of AST, ALT and TG in the serum, and the levels of GSH and MDA in liver tissues. For non-alcoholic fatty liver, Baicalin down-regulated the NLRP3–GSDMD pathway to inhibit liver cell death, but induced cytotoxicity with a doses of 32 μM [ 102 ].…”

Section: Pharmacological Effects (Shown In Table 2 mentioning

confidence: 99%

Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review

et al. 2020

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Scutellaria baicalensis Georgi. (SB) is a common heat-clearing medicine in traditional Chinese medicine (TCM). It has been used for thousands of years in China and its neighboring countries. Clinically, it is mostly used to treat diseases such as cold and cough. SB has different harvesting periods and processed products for different clinical symptoms. Botanical researches proved that SB included in the Chinese Pharmacopoeia (1st, 2020) was consistent with the medicinal SB described in ancient books. Modern phytochemical analysis had found that SB contains hundreds of active ingredients, of which flavonoids are its major components. These chemical components are the material basis for SB to exert pharmacological effects. Pharmacological studies had shown that SB has a wide range of pharmacological activities such as antiinflammatory, antibacterial, antiviral, anticancer, liver protection, etc. The active ingredients of SB were mostly distributed in liver and kidney, and couldn't be absorbed into brain via oral absorption. SB’s toxicity was mostly manifested in liver fibrosis and allergic reactions, mainly caused by baicalin. The non-medicinal application prospects of SB were broad, such as antibacterial plastics, UV-resistant silk, animal feed, etc. In response to the Coronavirus Disease In 2019 (COVID-19), based on the network pharmacology research, SB’s active ingredients may have potential therapeutic effects, such as baicalin and baicalein. Therefore, the exact therapeutic effects are still need to be determined in clinical trials. SB has been reviewed in the past 2 years, but the content of these articles were not comprehensive and accurate. In view of the above, we made a comprehensive overview of the research progress of SB, and expect to provide ideas for the follow-up study of SB.

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Baicalin attenuates hepatic injury in non-alcoholic steatohepatitis cell model by suppressing inflammasome-dependent GSDMD-mediated cell pyroptosis

Cited by 49 publications

References 26 publications

Jiangzhi Ligan Decoction Alleviated Nonalcoholic Fatty Liver Disease Induced by High-Fat-Diet in Rats via GSDMD-mediated Canonical/Non-canonical Pyroptosis Pathway

Jiangzhi Ligan Decoction Alleviated Nonalcoholic Fatty Liver Disease Induced by High-Fat-Diet in Rats via GSDMD-mediated Canonical/Non-canonical Pyroptosis Pathway

Baicalein Attenuates Pyroptosis and Endoplasmic Reticulum Stress Following Spinal Cord Ischemia-Reperfusion Injury via Autophagy Enhancement

Applications, phytochemistry, pharmacological effects, pharmacokinetics, toxicity of Scutellaria baicalensis Georgi. and its probably potential therapeutic effects on COVID-19: a review

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