Platycodin D and D3 Increase Airway Mucin Release in vivo and in vitro in Rats and Hamsters

Platycodin D is a major pharmacological constituent of Platycodi radix and has showed various pharmacological activities through oxidative stress defense mechanisms. Here, possible antitumor, anticachexia, and immunomodulatory activities of platycodin D were observed on the H520 tumor cell-bearing athymic nude mice after confirming thein vitrocytotoxicity. Platycodin D was orally administered at dose levels of 200, 100, and 50 mg/kg, once a day for 35 days from 15 days after implantation. The results were compared with gemcitabine 160 mg/kg intraperitoneally treated mice (7-day intervals). Platycodin D showed favorable cytotoxic effects on the H520 cells, and also dose-dependently decreased the tumor volumes and weights with increases of apoptotic cells (caspase-3 and PARP immunopositive cells), iNOS and TNF-αimmunoreactivities, decreases of COX-2 immunoreactivities in tumor masses. Platycodin D also showed dose-dependent immunostimulatory and anticachexia effects. Gemcitabine showed favorable cytotoxity against H520 tumor cell and relatedin vivoantitumor effects but aggravated the cancer related cachexia and immunosuppress in H520 tumor cell-bearing athymic nude mice. Taken together, it is considered that oral treatment of platycodin D has potent antitumor activities on H520 cells through direct cytotoxic effects, increases of apoptosis in tumor cells, and immunostimulatory effects and can be control cancer related cachexia.

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Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro

International Immunopharmacology ◽

10.1016/j.intimp.2015.05.005 ◽

2015 ◽

Vol 27 (1) ◽

pp. 138-147 ◽

Cited By ~ 35

Author(s):

Weiwei Tao ◽

Qiang Su ◽

Hanqin Wang ◽

Shen Guo ◽

Yanyan Chen ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Platycodin D ◽

Apoptosis And Inflammation

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Platycodin D Induces Tumor Growth Arrest by Activating FOXO3a Expression in Prostate Cancer in vitro and in vivo

Current Cancer Drug Targets ◽

10.2174/1568009614666141128104642 ◽

2015 ◽

Vol 14 (9) ◽

pp. 860-871 ◽

Cited By ~ 11

Author(s):

Rui Zhou ◽

Zongliang Lu ◽

Kai Liu ◽

Jing Guo ◽

Jie Liu ◽

...

Keyword(s):

Prostate Cancer ◽

Tumor Growth ◽

Growth Arrest ◽

Platycodin D

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THE EFFECT OF LEUKOTRIENE C4 ON MUCIN RELEASE INTO THE CAT TRACHEA in vivo AND in vitro

British Journal of Pharmacology ◽

10.1111/j.1476-5381.1982.tb09310.x ◽

1982 ◽

Vol 77 (3) ◽

pp. 391-393 ◽

Cited By ~ 65

Author(s):

A.C. PEATFIELD ◽

PRISCILLA J. PIPER ◽

P.S. RICHARDSON

Keyword(s):

Leukotriene C4 ◽

Mucin Release

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Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene

Oncology Reports ◽

10.3892/or.2016.4935 ◽

2016 ◽

Vol 36 (3) ◽

pp. 1447-1456 ◽

Cited By ~ 8

Author(s):

Ya Kong ◽

Zong-Liang Lu ◽

Jia-Jia Wang ◽

Rui Zhou ◽

Jing Guo ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Growth ◽

Platycodin D ◽

Breast Cancer Growth

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Potentiating TMEM16A channel function has no effect on airway goblet cells or bronchial and pulmonary vascular smooth muscle function

10.1101/2020.04.17.046177 ◽

2020 ◽

Author(s):

Henry Danahay ◽

Roy Fox ◽

Sarah Lilley ◽

Holly Charlton ◽

Kathryn Adley ◽

...

Keyword(s):

Smooth Muscle ◽

Muscle Contraction ◽

Goblet Cell ◽

Pulmonary Arteries ◽

Smooth Muscle Contraction ◽

Cell Numbers ◽

Channel Function ◽

Mucin Release

AbstractThe calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.

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Platycodin D Suppresses Type 2 Porcine Reproductive and Respiratory Syndrome Virus In Primary and Established Cell Lines

Viruses ◽

10.3390/v10110657 ◽

2018 ◽

Vol 10 (11) ◽

pp. 657 ◽

Cited By ~ 8

Author(s):

Mingxin Zhang ◽

Taofeng Du ◽

Feixiang Long ◽

Xia Yang ◽

Yankuo Sun ◽

...

Keyword(s):

Virus Production ◽

In Vivo Studies ◽

Progeny Virus ◽

Respiratory Syndrome Virus ◽

Dependent Manner ◽

Triterpenoid Saponins ◽

Platycodin D

Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pork industry as it continues to cause significant economic loss worldwide. Currently, vaccination strategies provide very limited protection against PRRSV transmission. Consequently, there is an urgent need to develop new antiviral strategies. Platycodin D (PD) is one of the major bioactive triterpenoid saponins derived from Platycodon grandiflorum, a traditional Chinese medicine used as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Here, we demonstrate that PD exhibits potent activity against PRRSV infection in Marc-145 cells and primary porcine alveolar macrophages. PD exhibited broad-spectrum inhibitory activities in vitro against high pathogenic type 2 PRRSV GD-HD strain and GD-XH strain as well as classical CH-1a and VR2332 strains. PD at concentrations ranging 1–4 μM significantly inhibited PRRSV RNA synthesis, viral protein expression and progeny virus production in a dose-dependent manner. EC50 values of PD against four tested PRRSV strains infection in Marc-145 cells ranged from 0.74 to 1.76 μM. Mechanistically, PD inhibited PRRSV replication by directly interacting with virions therefore affecting multiple stages of the virus life cycle, including viral entry and progeny virus release. In addition, PD decreased PRRSV- and LPS-induced cytokine (IFN-α, IFN-β, IL-1α, IL-6, IL-8 and TNF-α) production in PAMs. Altogether, our findings suggested that PD is a potent inhibitor of PPRSV infection in vitro. However, further in vivo studies are necessary to confirm PD as a potential novel and effective PPRSV inhibitor in swine.

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Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines

Cells ◽

10.3390/cells11010134 ◽

2022 ◽

Vol 11 (1) ◽

pp. 134

Author(s):

Liyan Zhu ◽

Ziyi Han ◽

Yanfei He ◽

Hongxiang Sun

Keyword(s):

Inflammatory Response ◽

Mechanisms Of Action ◽

C2c12 Cells ◽

C2c12 Myoblast ◽

Adjuvant Activity ◽

In Vivo Models ◽

Platycodin D ◽

Caspase 1

Platycodin D (PD) is a potent adjuvant with dual Th1 and Th2 potentiating activity, but its mechanisms of action remain unclear. Here, the C2C12 myoblast cell line and mice were used as in vitro and in vivo models to identify potential signaling pathways involved in the adjuvant activity of PD. PD induced a transient cytotoxicity and inflammatory response in the C2C12 cells and in mouse quadricep muscles. A comparative analysis of microarray data revealed that PD induced similar gene expression profiles in the C2C12 cells and in the quadricep muscles, and triggered rapid regulation of death, immune, and inflammation-related genes, both in vivo and in vitro. It was further demonstrated that caspase-1-dependent pyroptosis was involved in the PD-induced cytotoxicity and inflammatory response in the C2C12 cells via the Ca2+–c-jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK)–NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway. Consistently, the in vivo analysis revealed that a local blockage of NLRP3 and caspase-1 inhibited PD-induced cytokine production and immune cell recruitment at the injection site, and impaired the adjuvant activity of PD on antigen-specific immune responses to model antigen ovalbumin (OVA) in mice. These findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.

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