Peiminine

Immunopharmacol Immunotoxicol. 2015;37(4):351-8.

Antiallergic effects of peiminine through the regulation of inflammatory mediators in HMC-1 cells.[Pubmed: 26121924]

Peiminine is the main biologically active component derived from Fritillaria ussuriensis. Peiminine was investigated in various pulmonary diseases, but its antiallergic effect and the related mechanism have not been reported yet.
METHODS AND RESULTS:
The present study aimed to evaluate the effect of Peiminine on mast cell-mediated allergic inflammation in HMC-1 cells. The pro-inflammatory cytokine production was measured using ELISA, reverse transcription-polymerase chain reaction and nuclear factor-kappaB (NF-κB), mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Peiminine inhibits the production of the pro-inflammatory cytokine, such as interleukin (IL)-6, IL-8, tumor necrosis factor-alpha (TNF-α) and IL-1beta (IL-1β). It was shown to have inhibitory effects on MAPKs phosphorylation and NF-B expression in human mast cells (HMC)-1 using Western blot. HMC-1 cells were observed for confirmation of histamine release. Passive cutaneous anaphylaxis (PCA) reactions were evaluated using an animal model and Peiminine demonstrated inhibitory effects on IgE-dependent anaphylaxis.
CONCLUSIONS:
These results suggest that Peiminine has regulatory potential for allergic inflammatory reactions mediated by HMC-1 cells.

Biochem Biophys Res Commun. 2015 Jun 19;462(1):38-45.

The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death.[Pubmed: 25935480 ]

Autophagy is evolutionarily conservative in eukaryotic cells that engulf cellular long-lived proteins and organelles, and it degrades the contents through fusion with lysosomes, via which the cell acquires recycled building blocks for the synthesis of new molecules.
METHODS AND RESULTS:
In this study, we revealed that Peiminine induces cell death and enhances autophagic flux in colorectal carcinoma HCT-116 cells. We determined that Peiminine enhances the autophagic flux by repressing the phosphorylation of mTOR through inhibiting upstream signals. Knocking down ATG5 greatly reduced the Peiminine-induced cell death in wild-type HCT-116 cells, while treating Bax/Bak-deficient cells with Peiminine resulted in significant cell death.
CONCLUSIONS:
In summary, our discoveries demonstrated that Peiminine represses colorectal carcinoma cell proliferation and cell growth by inducing autophagic cell death.

Mol Med Rep. 2013 Apr;7(4):1103-10.

Peiminine ameliorates bleomycin-induced acute lung injury in rats.[Pubmed: 23404624]

The aim of this study was to investigate whether or not Peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury.
METHODS AND RESULTS:
Rats were randomly divided into 4 groups. In 3 groups, intratracheal bleomycin (5 mg/kg) was used to induce acute lung injury, followed by administration of either carboxymethyl cellulose (control group, n=14), dexamethasone (DXS group, n=14) or Peiminine (Peiminine group, n=10). In the fourth group (sham-operated, n=12), normal saline was instilled instead of bleomycin, followed by administration of carboxymethyl cellulose. Drugs were administered intragastrically for 28 days. Lung sections were stained with hematoxylin and eosin (H&E) and Masson's trichrome, to grade the degree of alveolitis and pulmonary fibrosis. The lung index was calculated as the ratio of lung to body weight. Serum levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were obtained using a radioimmunoassay. Immunocytochemical methods were employed to assess the expression of transforming growth factor-β (TGF-β), connective tissue growth factor (CTGF), NF-κB, extracellular signal-related kinase (ERK1/2), Fas and FasL in lung tissue. Peiminine and DXS significantly reduced alveolar inflammation and pulmonary interstitial inflammation in rats with bleomycin-induced lung injury. These protective effects were associated with significant (P<0.05) decreases in the levels of IFN-γ in serum and of TGF-β, CTGF, ERK1/2, NF-κB and FasL in lung tissue. No effects were observed on serum TNF-α or IL-4.
CONCLUSIONS:
In conclusion, Peiminine inhibits lung inflammation and pulmonary fibrosis in a rat model of bleomycin-induced lung injury, by reducing circulating IFN-γ levels and inhibiting signal transduction pathways involving TGF-β, CTGF, ERK1/2, NF-κB and FasL.