Andrographolide Prevents High-Fat Diet–Induced Obesity in C57BL/6 Mice by Suppressing the Sterol Regulatory Element-Binding Protein Pathway

Ding, Lili; Li, Jinmei; Song, Bei; Xu, Xiao; Huang, Wendong; Zhang, Bin-Feng; Tang, Xiaowen; Qi, Meng; Yang, Qiming; Yang, Qiaoling; Yang, Li; Wang, Zhengtao

doi:10.1124/jpet.114.217968

Cited by 61 publications

(48 citation statements)

References 42 publications

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“…Both results are in agreement with our observations and suggest that reduced HTC, also observed by Ding et al . 16 , and liver inflammation in ANDRO-treated mice fed with CDAA diet compared with vehicle-treated animals fed with the same diet may be related, at least in part, to modulation of hepatic inflammasome. Of note, since the CDAA diet feeding model is of more intense and long-term model of NASH, with all liver features of the disease compared to more ‘metabolic’ models such as high-fat diet fed mice or short-term nutritional models such as methionine-choline-deficient diet-induced NASH, we were able to also document an anti-fibrotic action of ANDRO in the setting of NASH.…”

Section: Discussionmentioning

confidence: 99%

“…Of note, a recent report by Ding et al . 16 showed that ANDRO was effective in preventing fat accumulation in liver of high-fat diet fed mice through regulation of sterol regulatory element-binding proteins (SREBPs) target genes. However, these authors did not explore further the effects of ANDRO on either inflammation or fibrosis in their animals due to shortcomings of the experimental models used.…”

Section: Introductionmentioning

confidence: 99%

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Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Cabrera

Wree

Povero

et al. 2017

Sci Rep

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Therapy for nonalcoholic steatohepatitis (NASH) is limited. Andrographolide (ANDRO), a botanical compound, has a potent anti-inflammatory activity due to its ability to inhibit NF-κB. ANDRO has been also shown to inhibit the NLRP3 inflammasome, a relevant pathway in NASH. Our aim was to evaluate the effects of ANDRO in NASH and its influence on inflammasome activation in this setting. Thus, mice were fed a choline-deficient-amino-acid–defined (CDAA) diet with/without concomitant ANDRO administration (1 mg/kg, 3-times/week). Also, we assessed serum levels of alanine-aminotransferase (ALT), liver histology, hepatic triglyceride content (HTC) and hepatic expression of pro-inflammatory, pro-fibrotic and inflammasome genes. Inflammasome activation was also evaluated in fat-laden HepG2 cells. Our results showed that ANDRO administration decreased HTC and attenuated hepatic inflammation and fibrosis in CDAA-fed mice. ANDRO treatment determined a strong reduction in hepatic macrophage infiltration and reduced hepatic mRNA levels of both pro-inflammatory and pro-fibrotic genes. In addition, mice treated with ANDRO showed reduced expression of inflammasome genes. Finally, ANDRO inhibited LPS-induced interleukin-1β expression through NF-κB inhibition in fat-laden HepG2 cells and inflammasome disassembly. In conclusion, ANDRO administration reduces inflammation and fibrosis in experimental NASH. Inflammasome modulation by a NF-κB-dependent mechanism may be involved in the therapeutic effects of ANDRO.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Cabrera

Wree

Povero

et al. 2017

Sci Rep

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“…They are implicated in complicated pathogenic processes such as endoplasmic reticulum stress, inflammation and autophagy, and as a result, they contribute to obesity, dyslipidemia, diabetes mellitus, AS and NAFLD (20). AG regulated SREBP and other metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity in mice with high fat diet (HFD)-induced obesity (21). Decrease of pathological lesions contain AS and NAFLD in ApoE knockout (ApoE -/-) mice with HFD can be controlled by regulating the lipid metabolism and inflammatory (22).…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Shi

et al. 2020

Preprint

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Mechanisms relating the gut bacteria to Nonalcoholic Fatty Liver Disease (NAFLD) have been proposed containing the dysbiosis-induced dysregulation of hepatic lipid metabolism that allows for the translocation of microbial components and leads to hepatic inflammation and steatosis. Andrographolide (AG) regulates inflammation mediated by NF-κB pathway which also play a key role in reduction of inflammation and fibrosis in experimental nonalcoholic steatohepatitis (NASH), yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that ApoE knockout (Apoe -/-) mice fed a high-fat diet (HFD) supplemented with AG regulates levels of biochemical index and inflammatory cytokines associated with gut microbe. Moreover, HEPG2 cells induced by ox-LDL were used as validation in vitro. H&E staining and Oil-Red staining were respectively used for tissue and cells morphology. Gut microbiota were examined by 16S rRNA sequencing. Expression of NF-κB, C/EBPβ and PPAR-γ in liver and HEPG2 cells were detected by western blot and qRT-PCR. The results showed, among others, that AG alleviate hepatic steatosis and fat content in HEPG2 cells, while it induced decreased levels of Bacteroides, and increased levels of Faecalibaculum, Akkermansia. We further identified that inhibition of NF-κB/C/EBPβ/PPAR-γ pathway of hepatic steatosis model in vivo and vitro by AG also contributes to prevention of HFD-induced inflammation and dislipidemia. Importantly, as result of pearson correlation, Bacteroides may be the most relevant one fundamentally involved in the mechanism of AG attenuates NAFLD. Together, our findings uncover an interaction between AG and gut microbiota as a novel mechanism for the anti-NAFLD effect of AG acting through prevention of microbial dysbiosis, dislipidemia and inflammation.Importance HFD due to gut microbial dysbiosis is a major contributor to the pathogenesis of dislipidemia and inflammation, which primarily mediates the development of NAFLD. A treatment strategy to reduce both dislipidemia and inflammation appears to be an effective approach for addressing the issue of NAFLD. Andrographolide (AG) is the major effect component in traditional Chinese medicine Chuan-xin-lian (Andrographis). Little is known about the role of gut microbiota in the anti-NAFLD effect of AG. 16S rRNA gene sequencing revealed that AG significantly decreased Bacteroides and increased Faecalibaculum, Akkermansia. By using vivo and vitro experiment, we prove that gut microbiota plays a key role in AG-induced protective against high-fat-diet-induced dislipidemia and inflammation. Moreover, NF-κB/C/EBPβ/PPAR-γ pathway inhibition was partially involved in the beneficial effect of AG. Together, these data suggest that the gut microbiome is a critical factor for the anti-NAFLD effects of AG.

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“…A s a l a b d a n e d i t e r p e n o i d i s o l a t e d f r o m Andrographispaniculata, andrographolide has been widely used in treatment of various human diseases including different types of cancers (7), obesity (8), oxidative damage (9), and so on. Andrographolide is also a safe and effective drug for treatment of various inflammatory diseases (10).…”

Section: Introductionmentioning

confidence: 99%

Andrographolide attenuates viral myocarditis through interactions with the IL‑10/STAT3 and P13K/AKT/NF‑κβ signaling pathways

Zhao¹,

Wang

et al. 2018

Exp Ther Med

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As a cardiac disease caused by the inflammation of the heart muscle, viral myocarditis (VMC) causes dilated cardiomyopathy, congestive heart failure and even death. With anti-inflammatory activities, andrographolide has been used in the treatment of various human diseases. In the present study, therapeutic effects of andrographolide on VMC were investigated using a VMC mouse model. Measurement of physiological indexes and echocardiographic examination was performed to explore the effects of andrographolide on cardiac function in mice with VMC. Levels of TNF-α, hs-CRP and cTnl in serum were measured by enzyme-linked immunosorbent assay (ELISA). Effects of andrographolide on the expression of L-10, STAT3, NF-κβ p65 and NF-κβ p50 were investigated by western blot analysis. Results indicated that andrographolide treatment reduced serum levels of TNF-α, hs-CRP and cTnl, increased the expression levels of IL-10 and STAT3 and reduced the expression levels of NF-κβ p65 and NF-κβ p50 and the phosphorylation levels of phosphoinositide 3-kinase (P13K) and AKT in the heart tissues of mice with VMC. In addition, andrographolide also increased the expression level of Iκβα in heart tissue. Therefore, it was concluded that andrographolide may inhibit the progression of VMC by interacting with the IL-10/STAT3 and NF-κβ signaling pathways.

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Andrographolide Prevents High-Fat Diet–Induced Obesity in C57BL/6 Mice by Suppressing the Sterol Regulatory Element-Binding Protein Pathway

Cited by 61 publications

References 42 publications

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Andrographolide Ameliorates Inflammation and Fibrogenesis and Attenuates Inflammasome Activation in Experimental Non-Alcoholic Steatohepatitis

Gut Microbiota Mediates the Protective Effects of Andrographolide Inhibits Inflammation and Nonalcoholic Fatty Liver Disease(NAFLD) in High-Fat Diet induced ApoE(-/-) Mice

Andrographolide attenuates viral myocarditis through interactions with the IL‑10/STAT3 and P13K/AKT/NF‑κβ signaling pathways

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