| In vitro: |
| Int Immunopharmacol. 2004 Aug;4(8):1039-49. | | Platycodin D and D3 isolated from the root of Platycodon grandiflorum modulate the production of nitric oxide and secretion of TNF-alpha in activated RAW 264.7 cells.[Pubmed: 15222978] | Platycodon D (PD) and D3 (PD3) isolated from Platycodon grandiflorum has been previously reported to show anti-inflammatory activities in rats.
METHODS AND RESULTS:
In this study, the production of proinflammatory cytokines, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) was examined in a macrophage like cell line, RAW 264.7 cells, in the presence of PD and PD3, oligosaccharide derivatives of oleanolic acid. RAW 264.7 cells activated with lipopolysaccharide (LPS; 1 microg/ml) and recombinant interferon-gamma (rIFN-gamma; 50 U/ml) were treated with various doses of PD and PD3 for 24 h. Supernatants were analyzed for the production of NO and TNF-alpha using Griess reagent and enzyme-linked immunosorbent assay (ELISA), respectively. NO was inhibited in a dose-dependent manner by PD and PD3 (IC50 of Platycodin D approximately 15 uM, IC50 PD3 approximately 55 uM). The expression of inducible NOS (iNOS) was inhibited by these compounds, as measured by Western blot analysis, as well as the expression of iNOS mRNA, as measured by Northern blot analysis. RAW 264.7 cells were treated at various times after LPS and activation with PD. Treatment with PD up to 8 h after activation showed significant inhibition of NO, indicating that early signal transduction of NOS synthesis may be inhibited by PD. In contrast to NO, secretion of TNF-alpha as well as expression of TNF-alpha mRNA was increased by PD and PD3. TNF-alpha secretion from RAW 264.7 cells was measured at various times after LPS and rIFN-gamma activation. Secretion of TNF-alpha was also increased up to 8 h postactivation, suggesting that PD may stimulate TNF-alpha synthesis or inhibit degradation of TNF-alpha mRNA. Oleanolic acid was without effect on both the production of NO and secretion of TNF-alpha.
CONCLUSIONS:
These data suggest a dichotomous regulation of these important proinflammatory mediators by PD and PD3. |
|
| In vivo: |
| Evid Based Complement Alternat Med. 2014;2014:954508. | | The Effects of Platycodin D, a Saponin Purified from Platycodi Radix, on Collagen-Induced DBA/1J Mouse Rheumatoid Arthritis.[Pubmed: 24511322] | The object of this study is to observe the effects of Platycodin D, a saponin purified from Platycodi Radix, on mice collagen-induced arthritis (CIA).
METHODS AND RESULTS:
A daily dose of 200, 100, and 50 mg/kg Platycodin D was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) was measured from histopathological changes in the spleen, left popliteal lymph node, third digit, and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the Platycodin D-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in Platycodin D-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the Platycodin D group. Finally, the production of IL-6 and TNF- α , involved in rheumatoid arthritis pathogenesis, was suppressed by treatment with Platycodin D.
CONCLUSIONS:
Taken together, these results suggest that Platycodin D is a promising new effective antirheumatoid arthritis agent, exerting anti-inflammatory, antioxidative and immunomodulatory effects in CIA mice. | | Int Immunopharmacol. 2015 Jul;27(1):138-47. | | Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro.[Pubmed: 25981110] | Platycodin D (PLD) is the major triterpene saponin in the root of Platycodon grandiflorum (Jacq.) with various pharmacological activities. The purpose of the present study was to evaluate the protective effects and possible mechanisms of PLD on acute lung injury (ALI) both in vivo and in vitro.
METHODS AND RESULTS:
In vivo, we used two ALI models, lipopolysaccharide (LPS)-induced ALI and bleomycin (BLE)-induced ALI to evaluate the protective effects and possible mechanisms of PLD. Female BALB/c mice were randomly divided into the following groups: control group, LPS group, LPS plus pre-treatment with dexamethasone (2 mg/kg) group, LPS plus pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), LPS plus post-treatment with dexamethasone (2 mg/kg) group, LPS plus post-treatment with PLD groups (50 mg/kg, 100 mg/kg), BLE group, BLE plus pre-treatment with dexamethasone (2 mg/kg) group, BLE plus pre-treatment with PLD groups (50 mg/kg, 100 mg/kg), BLE plus post-treatment with dexamethasone (2 mg/kg) group, and BLE plus post-treatment with PLD groups (50 mg/kg, 100 mg/kg). PLD was orally administered before or after LPS or BLE challenge with mice. Mice were sacrificed, and lung tissues and bronchoalveolar fluid (BALF) were prepared for further analysis. Our results showed that PLD significantly decreased lung wet-to-dry weight ratio (lung W/D weight ratio), total leukocyte number and neutrophil percentage in the BALF, and myeloperoxidase (MPO) activity of lung in a dose-dependent manner. Besides, cytokine levels, including interleukin (IL)-6, tumor neurosis factor (TNF)-α were also found significantly inhibited in BALF. Furthermore, PLD effectively inhibited the expressions of nuclear factor κB (NF-κB), Caspase-3 and Bax in the lung tissues, as well as restored the expression of Bcl-2 in the lungs and improved the superoxide dismutase (SOD) activity in BALF. In vitro, we used LPS-challenged cell model to evaluate the protective effects and possible mechanisms of PLD. MLE-12 cells were stimulated with LPS in the presence and absence of PLD. The levels of TNF-α, IL-6 and the expressions of NF-κB, Caspase-3, and Bax were remarkably down-regulated, while the expression of bcl-2 was significantly up-regulated in PLD treatment groups in MLE-12 cells.
CONCLUSIONS:
These results showed that the administration of PLD improved ALI both in vivo and in vitro, possibly through suppressing apoptosis and inflammation. | | Phytomedicine . 2019 Jan;52:254-263. | | Platycodin D, a novel activator of AMP-activated protein kinase, attenuates obesity in db/db mice via regulation of adipogenesis and thermogenesis[Pubmed: 30599906] | | Abstract
Background: Platycodi Radix (root of Platycodon grandiflorum) and its active compound Platycodin D (PD) has been previously shown to possess anti-obesity properties, but the underlying mechanisms remain poorly understood.
Purpose: The present study was aimed to evaluate the anti-obese effect of PD and reveal its mechanism of action.
Study design/methods: Genetically obese db/db mice were orally treated with PD for 4 weeks, and body weight gain, adipose tissue weight, serum parameters were measured. Then, assays on adipogenic factors, thermogenic factors, and AMP-activated protein kinase (AMPK) pathway were performed in PD-treated 3T3-L1 murine adipocytes, human adipose-derived mesenchymal stem cells (hAMSCs), and primary cultured brown adipocytes.
Results: PD treatment attenuated body weight gain, suppressed white adipose tissue weight and improved obesity-related serum parameters in db/db mice. Two major adipogenic factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) were decreased by PD treatment in WAT of db/db mice, 3T3-L1 adipocytes and hAMSCs. In BAT of db/db mice and primary cultured brown adipocytes, PD treatment elevated the expressions of uncoupled protein 1 (UCP1) and peroxisome proliferator-activated receptor γ coactivator 1 α (PCG1α), the key regulators of BAT-associated thermogenesis. In addition, PD activated AMPKα both in vivo and in vitro. However, when AMPK was inhibited by compound C, PD treatment failed to suppress adipogenic factors and increase thermogenic factors.
Conclusions: PD improved obesity in db/db mice by AMPK-associated decrease of adipogenic markers including PPARγ and C/EBPα. PD increased thermogenic factors such as UCP1 and PGC1α in db/db mice and primary cultured brown adipocytes. AMPK inhibition nullified the effects of PD, suggesting its anti-adipogenic and thermogenic actions were dependent on AMPK pathway activation.
Keywords: AMP-activated protein kinase pathway; Adipogenesis; Obesity; Platycodin D; Thermogenesis. |
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