Activation of PPARγ by baicalin attenuates pulmonary hypertension in an infant rat model by suppressing HMGB1/RAGE signaling

Abstract

Pulmonary hypertension (PH) is a vascular disease, and proinflammatory factors are strongly implicated in its pathogenesis, causing right ventricular (RV) hypertrophy and heart failure. Baicalin exhibits potent anti‐inflammation activity. This study aimed to investigate the curative effects of baicalin in an infant rodent model of PH and to further explore the underlying mechanisms. A PH model in infant rats was induced by hypoxia and the resulting rats were administered baicalin in incremental dosages. Invasive hemodynamic methods were used to measure mean pulmonary arterial pressure (mPAP) and RV end‐diastolic pressure (RVEDP). RV hypertrophy was assessed by mass pathology and histology. ELISAs were used to determine concentrations of high‐mobility group box 1 (HMGB1), secretory receptor for advanced glycation end products (sRAGE), interleukin 6 (IL6) and transforming growth factor β (TGFβ1) in bronchoalveolar lavage fluid (BALF). Electrophoretic mobility shift and phosphorylation in nuclear extracts were used to evaluate the activation of peroxisome proliferator‐activated receptor γ (PPARγ). Western blotting was used to detect the expression levels of heme oxygenase 1 (HO1), HMGB1, RAGE, IL6 and TGFβ1 in lung tissue. Baicalin administration significantly attenuated mPAP, RVEDP and RV hypertrophy in infant rats with PH. HMGB1, sRAGE, IL6 and TGFβ1 levels in BALF were also reduced by baicalin treatment. Baicalin activated PPARγ, which promoted expression of HO1. Furthermore, expression levels of HMGB1, RAGE, IL6 and TGFβ1 in lung tissue were dramatically decreased by baicalin in a dosage‐dependent manner. Baicalin showed curative effects in infant rats with PH. Activation of PPARγ that inhibited HMGB1/RAGE inflammatory signaling was involved.

C. quinoa and S. hispanica L. Seeds Provide Immunonutritional Agonists to Selectively Polarize Macrophages

“…These changes seem to highlight a metabolic orientation skewing towrads oxidative metabolism. The cellular response and association between high mobility group protein B1 (HMGB1) (P09429), (TGF)-β1 [28] and peroxisome proliferator-activated receptor (PPAR)-γ [29] occur in an environment (P63151, P0CG48, Q9Y263) dominated by TLR4 signaling towards downstream MyD88/TRIF signaling [30]. However, these biological responses do not appear to mediate mitochondrial dysfunction (O95831-3, P08758, P39656 and P04843) as LPS does.…”

In vitro and in vivo activities of flavonoids – apigenin, baicalin, chrysin, scutellarin – in regulation of hypertension – a review for their possible effects in pregnancy-induced hypertension

“…It was observed that after oral administration in the doses from 10 mg/kg/day to 30 mg/kg/day baicalin significantly attenuated pulmonary arterial pressure, and right ventricular hypertrophy in infant rats. Few biomarkers such as advanced glycation end products, IL 6, TGFβ1 in bronchoalveolar lavage fluid (BALF) were also reduced after baicalin treatment [53]. Furthermore, in this study it was shown that HMGB1/RAGE signaling can be taken into account as a molecular point of action for baicalin.…”

“…Baicalin has been widely studied in several in vitro and in vivo models and showed many activities such as: anti-viral [42], anti-oxidative via several pathways [43], neuroprotective and enhancin cognitive functions [44,45], anti-inflammatory [46], anti-cancer [47,48], and hepatoprotection [49]. In recent years, many studies showed anti-hypertensive properties of baicalin [46,[50][51][52][53][54][55][56][57][58][59][60], and also cardioprotective [50], antiplatelet, anticoagulant, and profibrinolytic activities [61].…”

“…Baicalin is intensively studied in various animal models of hypertension, atherosclerosis and myocardial ischaemic injury, but most studies were carried out only in model of pulmonary hypertension (PH). Chen and Wang [53] showed in an infant rodent model of PH that baicalin exerted anti-inflammation activity. It was observed that after oral administration in the doses from 10 mg/kg/day to 30 mg/kg/day baicalin significantly attenuated pulmonary arterial pressure, and right ventricular hypertrophy in infant rats.…”

“…Furthermore, in this study it was shown that HMGB1/RAGE signaling can be taken into account as a molecular point of action for baicalin. Therefore, baicalin is mentioned as anti-inflammatory flavonoid which can play beneficial role in prevention and treatment of infant PH [53]. Luan et al [46] observed the protective effects of intragastric administration of baicalin (100 mg/kg) in rat model of monocrotaline (MCT)-induced PH.…”