Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice

Chen, Shaoru; Li, Feng; Ding, Mo-Yu; Wang, Decai; Zhao, Qi; Wang, Ying; Zhou, Guo‐Chun

doi:10.1016/j.bmc.2018.09.002

Cited by 14 publications

(7 citation statements)

References 43 publications

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“…24 Interestingly, in carbon tetrachloride-induced acute hepatic damage, compound 24, a STAT3 inhibitor, significantly down-regulated the level of IL-6. 25 These above data indicate that inhibition of STAT3 plays a protective effect in the intervention of inflammation. In addition, it should be noted that inhibition of STAT3 plays pro-inflammatory roles.…”

Section: Discussionmentioning

confidence: 83%

Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

et al. 2021

Innate Immun

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Increasing evidence indicates that signal transducer and activator of transcription 3 (STAT3), a vital transcription factor, plays crucial roles in the regulation of inflammation. STAT3 has become a novel therapeutic target for intervention in inflammation-related disorders. However, it remains unclear whether STAT3 plays a part in acute hepatic damage. To investigate the effects of STAT3 here, LPS/d-GalN-induced hepatic damage was induced in mice, the STAT3 inhibitor Stattic was administered, and the degree of liver injury, inflammation, and hepatocyte apoptosis were investigated. The results showed that Stattic mitigated the hepatic morphologic abnormalities and decreased the level of aminotransferase in LPS/D-GalN-insulted mice. The results also indicated that Stattic decreased the levels of TNF-α and IL-6, prevented the activation of the caspase cascade, suppressed cleavage of PARP, and decreased the quantity of TUNEL-positive cells. These results suggest that Stattic provided protective benefits in LPS/d-GalN-induced hepatic damage, and the protective effects might be associated with its anti-inflammatory and anti-apoptotic effects. Therefore, STAT3 might become a novel target for intervening in inflammation-based and apoptosis-based hepatic disorders.

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Section: Discussionmentioning

confidence: 83%

Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

et al. 2021

Innate Immun

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“…First, small molecular compounds have been found to directly inhibit STAT3 activity and function, and have been developed for cancer treatment and prevention, such as Stattic. The second method was to block the activation of STAT3 by inhibiting the upstream signaling proteins, including cell surface receptor inhibitors PD153035, LCB03‐0110, and HJC0152, as well as phosphokinase inhibitors AG490, WP‐1066, and LS‐104 (Chai et al, 2016; Chen et al, 2018; Desroses et al, 2018). Third, after the immune regulatory factors were suppressed, the cells could generate a powerful antitumor immune response (Pei et al, 2019; Su, Banerjee, White, & Kortylewski, 2018).…”

Section: Discussionmentioning

confidence: 99%

Trilobolide‐6‐O‐isobutyrate suppresses hepatocellular carcinoma tumorigenesis through inhibition of IL‐6/STAT3 signaling pathway

Zhou

Mao

Fan

et al. 2021

Phytotherapy Research

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Currently available therapies for hepatocellular carcinoma (HCC), with a high morbidity and high mortality, are only marginally effective and with sharp adverse side effects, which makes it compulsory to explore novel and more effective anticancer molecules. Chinese medicinal herbs exhibited prominent anticancer effects and were applied to supplement clinical cancer treatment. Here, we reported a compound, trilobolide-6-O-isobutyrate (TBB), isolated from the flowers of Wedelia trilobata with a markedly cytotoxic effect on HCC cells. We found that TBB time-and dosedependently inhibited HCC cells' growth and colony formation in vitro. Moreover, TBB induced cell cycle arrest at the G2/M phase, mitochondrial caspase-dependent apoptosis, and suppressed migration and invasion, as well as the glycolysis of HCC cells. Mechanistically, our data indicated that TBB inhibited the STAT3 pathway activation by directly interacting with the TYR 640/657 sites of the STAT3 protein and decreasing the level of p-STAT3. TBB also regulated the expression of PCNA, Ki67, Cyclin B1, Cyclin E, Bax, Bcl2, MMP2/9, and PGK1 through the inhibition of the IL-6/ STAT3 signaling pathway. Lastly, we confirmed that TBB effectively eliminated tumor growth without causing overt toxicity to healthy tissues in the xenograft tumor model. The exploration of anticancer activity and the underlying mechanism of TBB suggested its usage as a promising chemotherapeutic agent for HCC.

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“…84 Wang et al reported that Compound 24, an andrographolide derivative, attenuated hepatic pathological damage by inhibiting STAT3 activation in CCl 4 -induced acute liver damage. 28 19-propionyl isoandrographolide treatment inhibited high-fat diet fed-induced liver injury in rats. 85 Methotrexate is an antirheumatic medication.…”

Section: Liver Diseasesmentioning

confidence: 96%

“…[25][26][27] In this section, we summarize the andrographolide derivatives that have been identified in the past 3 years. These important derivatives include 14-tert-butyl dimethyl silicon-epoxyandrographolide; 28 3-(thiophene-2-carbonyl)−14-deoxy-11, 12 didehydroandrographolide; 29 3-dehydroandrographolide (3-DA); 30 3, 19-diacetyl-14-deoxy-11, 12-didehydroandrographolide (SRS27); 31 3-(2-methoxy-4-nitrophenyl)-andrographolie; 32 3, 14, 19-triacetyl andrographolide (CX-10); 33 AGP-26a (12β-isomer); 34 AGP-26b (12αisomer); 34 14-alpha-lipoic acylandrographolide (AL-1); 35 19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide; 36 and 19-triisopropyl andrographolide. 37 To some extent, these andrographolide derivatives address the issue of andrographolide's low oral bioavailability.…”

Section: Andrographolide and Its Derivativesmentioning

confidence: 99%

“…Andrographolide may decrease oxidative stress and hepatic damage in ethanol‐exposed rats by reducing NF‐κB and TNF‐α activation 84 . Wang et al reported that Compound 24, an andrographolide derivative, attenuated hepatic pathological damage by inhibiting STAT3 activation in CCl 4 ‐induced acute liver damage 28 . 19‐propionyl isoandrographolide treatment inhibited high‐fat diet fed‐induced liver injury in rats 85 .…”

Section: Andrographolide In Inflammatory Diseasesmentioning

confidence: 99%

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Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

Liu

You

et al. 2021

Medicinal Research Reviews

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Andrographolide, a well-known natural lactone having a range of pharmacological actions in traditional Chinese medicine. It has long been used to cure a variety of ailments. In this review, we cover the pharmacokinetics and pharmacological activity of andrographolide which supports its further clinical application in cancers and inflammatory diseases. Growing evidence shows a good therapeutic effect in inflammatory diseases, including liver diseases, joint diseases, respiratory system diseases, nervous system diseases, heart diseases, inflammatory bowel diseases, and inflammatory skin diseases. As a result, the effects of andrographolide on immune cells and the processes that underpin them are discussed. The preclinical use of andrographolide to different organs in response to malignancies such as colorectal, liver, gastric,

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Andrographolide derivative as STAT3 inhibitor that protects acute liver damage in mice

Cited by 14 publications

References 43 publications

Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

Stattic alleviates acute hepatic damage induced by LPS/d-galactosamine in mice

Trilobolide‐6‐O‐isobutyrate suppresses hepatocellular carcinoma tumorigenesis through inhibition of IL‐6/STAT3 signaling pathway

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

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