Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma

Li, Hui; Bi, Qianyu; Cui, Hongxia; Lv, Chuanfeng; Wang, Meng

doi:10.1186/s12906-020-03187-w

Cited by 17 publications

(12 citation statements)

References 21 publications

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“…Mice sensitized with OVA as the T celldependent antigen 41 have shown allergic airway inflammation that is dependent on Th2 responses in asthma. 42,43 Consistent with previous reports, 44,45 the expression levels of Beclin-1 and LC3-II increased in the lung tissues of the OVA-induced asthmatic group as compared to PBS mice (Figure S5B). As expected, TSLP neutralization in OVA-injected mice showed a significant reduction in these levels (p < .05, Figure S5B).…”

Section: Tslp Regulates Autophagy In a Murine Asthma Modelsupporting

confidence: 89%

TSLP up‐regulates inflammatory responses through induction of autophagy in T cells

et al. 2022

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Thymic stromal lymphopoietin (TSLP), a type I cytokine belonging to the IL‐2 cytokine family, promotes Th2‐mediated inflammatory responses. The aim of this study is to investigate whether TSLP increases inflammatory responses via induction of autophagy using a murine T cell lymphoma cell line, EL4 cells, and lipopolysaccharide (LPS)‐injected mice. TSLP increased expression levels of autophagy‐related factors, such as Beclin‐1, LC3‐II, p62, Atg5, and lysosome associated membrane protein 1/2, whereas these factors increased by TSLP disappeared by neutralization of TSLP in EL4 cells. TSLP activated JAK1/JAK2/STAT5/JNK/PI3K, while the blockade of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways reduced the expression levels of Beclin‐1, LC3‐II, and p62 in TSLP‐stimulated EL4 cells. In addition, TSLP simultaneously increased levels of inflammatory cytokines via induction of autophagy by activation of JAK1/JAK2/STAT5/JNK/PI3K signaling pathways. In an LPS‐induced acute liver injury (ALI) mouse model, exogenous TSLP increased expression levels of Beclin‐1 and LC3‐II, whereas functional deficiency of TSLP by TSLP siRNA resulted in lower expression of Beclin‐1, LC3‐II, and inflammatory cytokines, impairing their ability to form autophagosomes in ALI mice. Thus, our findings show a new role of TSLP between autophagy and inflammatory responses. In conclusion, regulating TSLP‐induced autophagy may be a potential therapeutic strategy for inflammatory responses.

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Section: Tslp Regulates Autophagy In a Murine Asthma Modelsupporting

confidence: 89%

TSLP up‐regulates inflammatory responses through induction of autophagy in T cells

et al. 2022

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“…This review has compiled the effects of Rhy with a particular focus on the CNS. However, Rhy impacts, among others, the cardiovascular and immune systems [ 3 , 10 , 84 , 297 ] (see also Section 2.1 and Section 2.7 ). Rhy was indeed shown to have antihypertensive roles via anti-sympathetic and vasodilatory effects that are mainly linked to ion channels [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

et al. 2021

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Uncaria rhynchophylla is a plant highly used in the traditional Chinese and Japanese medicines. It has numerous health benefits, which are often attributed to its alkaloid components. Recent studies in humans show that drugs containing Uncaria ameliorate sleep quality and increase sleep time, both in physiological and pathological conditions. Rhynchophylline (Rhy) is one of the principal alkaloids in Uncaria species. Although treatment with Rhy alone has not been tested in humans, observations in rodents show that Rhy increases sleep time. However, the mechanisms by which Rhy could modulate sleep have not been comprehensively described. In this review, we are highlighting cellular pathways that are shown to be targeted by Rhy and which are also known for their implications in the regulation of wakefulness and sleep. We conclude that Rhy can impact sleep through mechanisms involving ion channels, N-methyl-d-aspartate (NMDA) receptors, tyrosine kinase receptors, extracellular signal-regulated kinases (ERK)/mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K)/RAC serine/threonine-protein kinase (AKT), and nuclear factor-kappa B (NF-κB) pathways. In modulating multiple cellular responses, Rhy impacts neuronal communication in a way that could have substantial effects on sleep phenotypes. Thus, understanding the mechanisms of action of Rhy will have implications for sleep pharmacology.

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“…Allergic asthma is linked with variable expiratory airflow and is characterized by the airway inflammation, bronchoconstriction, oxidative stress, collagen deposition, and mucus [ 4 ]. Our previous study has demonstrated that 40 mg/kg Rhy treatment by gavage protects murine airway against OVA-induced damages of allergic asthma by mitigating inflammation, airway remodeling, and oxidative stress [ 16 , 17 ]. In the current study, 20 mg/kg Rhy-SLNs or Rhy were subjected to OVA-induced mice to compare their therapeutic effects.…”

Section: Discussionmentioning

confidence: 99%

“…Rhynchophylline (Rhy) is the major active ingredient of Uncaria rhynchophylla and possesses anti-inflammatory, vasodilatory, and anti-hypertensive functions [13][14][15]. In our previous study, we have found that Rhy markedly attenuates the allergic bronchial asthma, as evidenced by the alleviation of airway inflammation, airway remodeling, and oxidative stress [16]. The protective role of Rhy in asthma is mediated by repressing the smad and mitogen-activated protein kinase (MAPK) signaling transductions [17].…”

Section: Introductionmentioning

confidence: 99%

Solid lipid nanoparticle delivery of rhynchophylline enhanced the efficiency of allergic asthma treatment via the upregulation of suppressor of cytokine signaling 1 by repressing the p38 signaling pathway

Li²,

Cui

et al. 2021

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Allergic asthma is one of the most common chronic airway diseases, and there is still a lack of effective drugs for the treatment of allergic asthma. The purpose of this work is to formulate rhynchophylline (Rhy)-solid lipid nanoparticles (SLNs) to improve their therapeutic efficacy in a mice allergic model of asthma. A solvent injection method was employed to prepare the Rhy-SLNs. Physicochemical characterization of Rhy-SLNs was measured, and the release assessment was investigated, followed by the release kinetics. Next, a model of murine experimental asthma was established. Mice were subcutaneously injected with 20 μg ovalbumin mixed with 1 mg aluminum hydroxide on days 0, 14, 28, and 42 and administrated aerosolized 1% ovalbumin (w/v) by inhalation from day 21 to day 42. Mice were intraperitoneally injected with 20 mg/kg Rhy-SLNs or Rhy at one hour before the airway challenge with ovalbumin. The results showed that Rhy-SLNs revealed a mean particle size of 62.06 ± 1.62 nm with a zeta potential value of -6.53 ± 0.04 mV and 82.6 ± 1.8% drug entrapment efficiency.The release curve of Rhy-SLNs was much higher than the drug released in phosphate buffer saline at 0, 1, 1.5, 2, 4, or 6 h. Moreover, Rhy-SLNs exerted better effects on inhibiting ovalbumin-induced airway inflammation, oxidative stress, airway remodeling (including collagen deposition and mucus gland hyperplasia) than Rhy in murine experimental asthma. Subsequently, we found that Rhy-SLNs relieved allergic asthma via the upregulation of the suppressor of cytokine signaling 1 by repressing the p38 signaling pathway.

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Suppression of autophagy through JAK2/STAT3 contributes to the therapeutic action of rhynchophylline on asthma

Cited by 17 publications

References 21 publications

TSLP up‐regulates inflammatory responses through induction of autophagy in T cells

TSLP up‐regulates inflammatory responses through induction of autophagy in T cells

Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation

Solid lipid nanoparticle delivery of rhynchophylline enhanced the efficiency of allergic asthma treatment via the upregulation of suppressor of cytokine signaling 1 by repressing the p38 signaling pathway

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