Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARγ and inhibiting TGFβ1

Qiao, Hong; Han, Hongcan; Hong, Dongsheng; Ren, Zihua; Chen, Yan; Zhou, Chang‐Xin

doi:10.3109/13880209.2010.493179

Cited by 38 publications

(24 citation statements)

References 41 publications

(45 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a high-fat diet-induced obesity model of mice, baicalin attenuates liver dysfunction by inhibiting CaMKK/AMPK/ACC pathway and protein kinase B/glycogen synthase kinase 3 beta pathway [15, 16]. Recently, baicalin is shown to protect the carbon tetrachloride-induced liver injury model of the rat by activating PPAR γ and inhibiting TGF β 1 [17]. Here, we demonstrated the protective effect of baicalin in a cholestatic mice model was mediated via NRF2 transcription factor and its downstream target in addition to modulation of oxidative stress-generating enzymes and inflammation.…”

Section: Introductionmentioning

confidence: 99%

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Shen

Feng

Pān

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL) in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA), and connective tissue growth factor (CTGF); increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2); increased oxidative stress and reactive oxygen species- (ROS-) inducing enzymes (NOX2 and iNOS); dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity). Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.

show abstract

Section: Introductionmentioning

confidence: 99%

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Shen

Feng

Pān

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…In view of baicalin's serving as a role of PPARγ activator [18], [19], We speculated that baicalin might modulate iNOS expression via activation of PPARγ pathway. SR-202 was used to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, baicalin ameliorates experimental chemical colitis [11], [12], [13] and small intestinal injury in severe acute pancreatitis [14], [15]. Baicalin has been reported to repress p38 phosphorylation [16], [17] and activate PPARγ [18], [19] to attenuate inflammation. Therefore, in this experiment we explored whether baicalin would regulate iNOS and NO expression in small intestinal mucosa via modulation of p38 and/or PPARγ pathways in a rat model of acute endotoxemia.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory Effect of Baicalin on iNOS and NO Expression in Intestinal Mucosa of Rats with Acute Endotoxemia

et al. 2013

View full text Add to dashboard Cite

The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways.

show abstract

“…Extensive studies have revealed that baicalin exhibits strong anti-oxidant [11], anti-inflammatory [12], and hepato-protective [13], [14] activities. Baicalin is also a component in a wide range of vegetables, fruits, and beverages derived from plants [15], [16].…”

Section: Introductionmentioning

confidence: 99%

Contribution of Baicalin on the Plasma Protein Binding Displacement and CYP3A Activity Inhibition to the Pharmacokinetic Changes of Nifedipine in Rats In Vivo and In Vitro

et al. 2014

View full text Add to dashboard Cite

Baicalin purified from the root of Radix scutellariae is widely used in clinical practices. This study aimed to evaluate the effect of baicalin on the pharmacokinetics of nifedipine, a CYP3A probe substrate, in rats in vivo and in vitro. In a randomised, three-period crossover study, significant changes in the pharmacokinetics of nifedipine (2 mg/kg) were observed after treatment with a low (0.225 g/kg) or high (0.45 g/kg) dose of baicalin in rats. In the low- and high-dose groups of baicalin-treated rats, C max of total nifedipine decreased by 40%±14% (P<0.01) and 65%±14% (P<0.01), AUC0–∞ decreased by 41%±8% (P<0.01) and 63%±7% (P<0.01), Vd increased by 85%±43% (P<0.01) and 224%±231% (P<0.01), and CL increased by 97%±78% (P<0.01) and 242%±135% (P<0.01), respectively. Plasma protein binding experiments in vivo showed that C max of unbound nifedipine significantly increased by 25%±19% (P<0.01) and 44%±29% (P<0.01), respectively, and there was a good correlation between the unbound nifedipine (%) and baicalin concentrations (P<0.01). Furthermore, in vitro results revealed that baicalin was a competitive displacer of nifedipine from plasma proteins. In vitro incubation experiments demonstrated that baicalin could also competitively inhibit CYP3A activity in rat liver microsomes in a concentration-dependent manner. In conclusion, the pharmacokinetic changes of nifedipine may be modulated by the inhibitory effects of baicalin on plasma protein binding and CYP3A–mediated metabolism.

show abstract

Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARγ and inhibiting TGFβ1

Abstract: (2011) Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARγ and inhibiting TGFβ1, Pharmaceutical Biology, 49:1, 38-45,

Cited by 38 publications

References 41 publications

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Inhibitory Effect of Baicalin on iNOS and NO Expression in Intestinal Mucosa of Rats with Acute Endotoxemia

Contribution of Baicalin on the Plasma Protein Binding Displacement and CYP3A Activity Inhibition to the Pharmacokinetic Changes of Nifedipine in Rats In Vivo and In Vitro

Contact Info

Product

Resources

About