Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation

Yin, Wanling; Han, Jing; Zhang, Zhijun; Han, Zaomu; Wang, Siyuan

doi:10.1038/s41598-018-24565-y

Cited by 42 publications

(25 citation statements)

References 33 publications

(40 reference statements)

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“…Overall, our findings indicate interplay of molecules in human thyroid cancer cells following aloperine treatment, which mediates both autophagy and apoptosis, and these molecules may be effective targets in developing anticancer therapies. In addition, aloperine exhibits multiple pharmacological activities, including anti-inflammatory, antiallergenic, antiviral, antimicrobial, and antinociceptive effects against renal and neuronal injuries as well as pulmonary fibrosis [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Here, we demonstrate autophagy regulation by aloperine.…”

Section: Discussionmentioning

confidence: 51%

“…Aloperine, a quinolizidine alkaloid isolated from Sophora alopecuroides , reportedly exhibits multiple pharmacological activities, including anti-inflammatory, antiallergenic, antiviral, antimicrobial, antinociceptive, and antitumor effects; moreover, it exhibits protective effects against renal and neuronal injuries as well as pulmonary fibrosis [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20]. Aloperine exerts antitumor effects against multiple human cancers, including multiple myeloma; colon, breast, prostate, and thyroid cancers; and osteosarcoma [1,7,12,15,18,20].…”

Section: Introductionmentioning

confidence: 99%

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Autophagy Modulation in Human Thyroid Cancer Cells following Aloperine Treatment

Shen

Chen

et al. 2019

IJMS

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Aloperine, an alkaloid isolated from Sophora alopecuroides, exhibits multiple pharmacological activities including anti-inflammatory, antioxidant, antiallergic, antinociceptive, antipathogenic, and antitumor effects. Furthermore, it exerts protective effects against renal and neuronal injuries. Several studies have reported antitumor effects of aloperine against various human cancers, including multiple myeloma; colon, breast, and prostate cancers; and osteosarcoma. Cell cycle arrest, apoptosis induction, and tumorigenesis suppression have been demonstrated following aloperine treatment. In a previous study, we demonstrated antitumor effects of aloperine on human thyroid cancer cells through anti-tumorigenesis and caspase-dependent apoptosis induction via the Akt signaling pathway. In the present study, we demonstrated the modulation of the autophagy mechanism following the incubation of multidrug-resistant papillary and anaplastic human thyroid cancer cells with aloperine; we also illustrate the underlying mechanisms, including AMPK, Erk, JNK, p38, and Akt signaling pathways. Further investigation revealed the involvement of the Akt signaling pathway in aloperine-modulated autophagy in human thyroid cancer cells. These results indicate a previously unappreciated function of aloperine in autophagy modulation in human thyroid cancer cells.

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Section: Discussionmentioning

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Autophagy Modulation in Human Thyroid Cancer Cells following Aloperine Treatment

Shen

Chen

et al. 2019

IJMS

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“…50 mg/L, 100 mg/L Reduce ROS (−) Nrf2-ARE Renal injury ( Hu et al, 2016 ) In vivo In vitro Ischemia reperfusion (C57BL/6) — 50 mg/kg (i.g.) 500 μ M Reduce ROS (+) SOD (+) Bcl-2/Bax Pulmonary fibrosis ( Yin et al, 2018 ) In vivo Bleomycin (C57BL/6 — 40 mg/kg (i.g.) Inhibit proliferation and differentiation of fibroblast (−) PI3K/AKT/mTOR (−) TGF-β/Smad Immuno-regulatory Allergic airway inflammation ( Wang et al, 2018 ) In vivo OVA (BALB/c — 100 mg/kg, 200 mg/kg (i.g.)…”

Section: Antitumor Effect Of Aloperinementioning

confidence: 99%

A Review on Recent Advances in Aloperine Research: Pharmacological Activities and Underlying Biological Mechanisms

Zhou

Sun

et al. 2020

Front. Pharmacol.

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Aloperine, a quinolizidine-type alkaloid, was first isolated from the seeds and leaves of herbal plant, Sophora alopecuroides L. Empirically, Sophora alopecuroides L. is appreciated for its anti-dysentry effect, a property that is commonly observed in other Sophora Genus phytomedicines. Following the rationale of reductionism, subsequent biochemical analyses attribute such anti-dysentry effect to the bactericidal activity of aloperine. From then on, the multiple roles of aloperine are gradually revealed. Accumulating evidence suggests that aloperine possesses multiple pharmacological activities and holds a promising potential in clinical conditions including skin hyper-sensitivity, tumor and inflammatory disorders etc.; however, the current knowledge on aloperine is interspersed and needs to be summarized. To facilitate further investigation, herein, we conclude the key pharmacological functions of aloperine, and most importantly, the underlying cellular and molecular mechanisms are clarified in detail to explain the functional mode of aloperine.

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“…Following xation, the lungs were embedded in para n and sectioned. The sections were then stained with hematoxylin and eosin (H&E), Masson's trichrome stain and Sirius red as previously described 23 . Fibrosis was scored on a scale of 0-8 using the Ashcroft scoring method 24 .…”

Section: Pathological Staining and Histopathologic Assessmentmentioning

confidence: 99%

Tartrate-resistant acid phosphatase 5 serves as a viable target against pulmonary fibrosis by modulating β-catenin signaling

Hu¹,

Yu²,

Wang³

et al. 2020

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrated that the levels of ACP5 were increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 were noted in the sera of IPF patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protected mice from BLM-induced lung injury and fibrosis and reduced the differentiation and proliferation of fibroblasts. Mechanistic studies revealed that Acp5 was upregulated by TGF-β1 in a TGFβR1/Smad3-dependent manner, after which Acp5 dephosphorylated p-β-catenin at Ser33 and Thr41, inhibiting the degradation of β-catenin and subsequently enhancing β-catenin signaling in the nucleus, which promoted the differentiation and proliferation of fibroblast. Notably, the treatment of mice with BLM-induced fibrosis with Acp5 siRNA-loaded liposomes robustly reversed lung fibrosis. Collectively, these data indicate that Acp5 plays an essential role in the initiation and progression of pulmonary fibrosis; therefore, strategies aimed at silencing Acp5 could be novel therapeutic approaches against pulmonary fibrosis in a clinical setting.

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Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation

Cited by 42 publications

References 33 publications

Autophagy Modulation in Human Thyroid Cancer Cells following Aloperine Treatment

Autophagy Modulation in Human Thyroid Cancer Cells following Aloperine Treatment

A Review on Recent Advances in Aloperine Research: Pharmacological Activities and Underlying Biological Mechanisms

Tartrate-resistant acid phosphatase 5 serves as a viable target against pulmonary fibrosis by modulating β-catenin signaling

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