Neonatal sepsis is defined as a systemic inflammatory response caused by a suspected or proven infection, occurring in the first month of life, and remains one of the main causes of morbidity and ...mortality in newborn and preterm infants. Frequently, survivors of neonatal sepsis have serious long-term cognitive impairment and adverse neurologic outcomes. There is currently no specific drug treatment for sepsis. Indole-3-guanylhydrazone hydrochloride (LQM01) is an aminoguanidine derivative that has been described as an anti-inflammatory, antihypertensive and antioxidant with potential applicability in inflammatory diseases.
We used a LPS-challenged neonatal sepsis rodent model to investigate the effect of LQM01 on cognitive impairment and anxiety-like behavior in sepsis mice survivors, and examined the possible molecular mechanisms involved.
It was found that LQM01 exposure during the neonatal period reduces anxiety-like behavior and cognitive impairment caused by lipopolysaccharides (LPS) in adult life. Additionally, treatment with LQM01 decreased pro-inflammatory cytokine levels and reduced NFκB, COX-2, MAPK and microglia activation in hippocampus of neonatal mice. Furthermore, LQM01 was also able to prevent oxidative damage in hippocampus of neonatal mice and preserve brain barrier integrity.
LQM01 attenuated inflammatory reactions in an LPS-challenged neonatal sepsis mice model through the MAPK and NFκB signaling pathways and microglia activation suppression. All these findings are associated with mitigated cognitive impairment in 70 days-old LQM01 treated-mice.
We revealed the effect of LQM01 as an anti-septic agent, and the role of crucial molecular pathways in mitigating the potential damage caused by neonatal sepsis.
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•LQM01 exposure during the neonatal period reduces anxiety-like behavior caused by LPS.•LQM01 exposure during the neonatal period reduces cognitive impairment caused LPS.•LQM01 decrease neuroinflammation caused by LPS exposure during neonate phase.•LQM01 decreased NFκB, COX-2, MAPK activation in hippocampus of mice exposure to LPS.•LQM01 decreased microglia activation an protect BBB from LPS toxicity.
H. pectinata (L.) Poit, popularly known as “sambacaitá" or “canudinho”, is a plant endemic to north-eastern Brazil. Its aerial parts, leaves and flowers have traditionally been used to treat ...gastrointestinal disorders, rhinopharyngitis, nasal congestion, bacterial and fungal infections, fever, colic, inflammation, and pain.
The aim of this review was to provide information on the botanical characteristics, ethnomedicinal uses, phytochemistry and biological-pharmacological activities of H. pectinata.
This systematic review followed the Cochrane Handbook Collaboration and the PRISMA guidelines. The review question was what are the biological-pharmacological activities of H. pectinata presented in non-clinical studies. The search for articles was conducted in the Medline (via PubMed), Embase, Web of Science, Scopus, Virtual Health Library, SciELO, Google Scholar and the Brazilian Digital Library of Theses and Dissertations databases. Two reviewers independently selected the studies that met the inclusion criteria, extracted the data, and assessed the risk of bias of the included studies.
39 articles were included in this review, of which 19 reported in vitro experiments, 16 in vivo studies and 4 in vivo and in vitro experiments. H. pectinata is a plant widely used in folk medicine in north-eastern Brazil for the treatment of various ailments, such as respiratory diseases, gastrointestinal disorders, bacterial and fungal infections, and general inflammation. Supporting its popular use, several in vitro and in vivo pharmacological investigations of the essential oil and extract of H. pectinata have demonstrated their anti-inflammatory, antinociceptive, antioxidant, antidepressant, anticancer, hepatoregenerative, healing, and antimicrobial activities. H. pectinata has been reported to contain 75 bioactive constituents, comprising 9 flavonoids, 54 terpenes, and 12 other compounds.
H. pectinata is a plant commonly used in traditional medicine. Phytochemically, it contains several bioactive constituents, including terpenes and flavonoids, and has been shown to have antinociceptive, anti-inflammatory, antimicrobial and antitumour activity, as well as hepatorregenerative and healing effects, and low toxicity.
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•H. pectinata is widely used in traditional medicine in north-eastern Brazil.•Preparations of H. pectinata are rich in alkaloids, monoterpenes, and flavonoids.•H. pectinata exhibits diverse biological activities.•H. pectinata does not present toxicity.
Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory ...or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with β-cyclodextrin (βCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-βCD (50 mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in βCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-βCD reduced (p < 0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-βCD inhibited (p < 0.05) TNF-α production in the spinal cord and stimulated (p < 0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-βCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-βCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in βCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.
•BIS and BIS-βCD reduced mechanical and thermal hyperalgesia in inflammatory and neuropathic pain.•BIS and BIS-βCD inhibited TNF-α production in the spinal cord and stimulated the release of IL-10 in the spinal cord in PLSN-mice.•BIS and BIS-βCD reduced IBA-expression in the spinal cord in the PLSN model.
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