Involvement of a neutrophil-mast cell axis in the effects of Piper malacophyllum (C. PESL) C. DC extract and its isolated compounds in a mouse model of dysmenorrhoea.
Nara Lins Meira QuintãoJaqueline Pavesi ReisLarissa BenvenuttiRoberta NunesFernanda Capitanio GoldoniManuela Somensi CozerPriscila de SouzaRita de Cássia Melo Vilhena de Andrade Fonseca da SilvaJessica MelatoCarlos Rafael VazJuliana Cristina Pereira WhitakerFlavia Werner JesuínoMariana Couto CostaMaria Verônica Dávila PastorAngela MalheirosChristiane Meyre-SilvaJosé Roberto SantinPublished in: Inflammopharmacology (2022)
The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6-8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour.
Keyphrases
- oxidative stress
- mouse model
- anti inflammatory
- high fat diet induced
- induced apoptosis
- diabetic rats
- dendritic cells
- chronic pain
- rheumatoid arthritis
- blood pressure
- immune response
- physical activity
- mass spectrometry
- insulin resistance
- wild type
- endoplasmic reticulum stress
- adipose tissue
- endothelial cells
- cell cycle arrest
- drug induced