Indole-3-guanylhydrazone hydrochloride mitigates long-term cognitive impairment in a neonatal sepsis model with involvement of MAPK and NFκB pathways.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. GENERAL SIGNIFICANCE: 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.

d-Limonene Ameliorates Myocardial Infarction Injury by Reducing Reactive Oxygen Species and Cell Apoptosis in a Murine Model.

Myocardial infarction (MI) leads to high mortality, and pharmacological or percutaneous primary interventions do not significantly inhibit ischemia/reperfusion injuries, particularly those caused by oxidative stress. Recently, research groups have evaluated several naturally occurring antioxidant compounds for possible use as therapeutic alternatives to traditional treatments. Studies have demonstrated that d-limonene (DL), a monoterpene of citrus fruits, possesses antioxidant and cardiovascular properties. Thus, this work sought to elucidate the mechanisms of protection of DL in an isoproterenol-induced murine MI model. It was observed that DL (10 µmol) attenuated 40% of the ST elevation, reduced the infarct area, prevented histological alterations, abolished completely oxidative stress damage, restored superoxide dismutase activity, and suppressed pro-apoptotic enzymes. In conclusion, the present study demonstrated that DL produces cardioprotective effects from isoproterenol-induced myocardial infarction in Swiss mice through suppression of apoptosis.

Phytomedicines containing Matricaria species for the treatment of skin diseases: A biotechnological approach.

Skin diseases have a notable impact on the life of the affected and in their health conditions. In order to allow a more effective and economical treatment for such disorders, new therapeutic approaches have been continuously investigated. Due to its high therapeutic and phytochemical potential, Matricaria species emerges as a pleasant alternative, since it is an important source of bioactive secondary metabolites suitable for the treatment of varied skin diseases. Therefore, this review aimed to catalog inventions that have used Matricaria species as the active component for skin disease treatment in order to assess the status of the technological development of the fitomedicines. For this, a search of patents was performed in four specialized patent database, which have reported the discovery of pharmaceutical bioproducts that used Matricaria species in its composition for skin treatment. Therefore, it is possible to notice that the pharmaceutical industry has driven efforts and investment to produce medicines for the dermatopathies, using species of this genus as an active principle. Besides, a trend of growth has been identified for the last years, which is accompanied by the continuous publication of scientific articles on the subject. It is known that a long journey is traversed between the scientific findings and their applications in the pharmaceutical market, creating the perspective that new Matricaria-based medicines may reach the pharmaceutical market in the coming years.

Effects of Carvacrol, Thymol and essential oils containing such monoterpenes on wound healing: a systematic review.

OBJECTIVES: The treatment of wounds accounts for a considerable fraction of health expenses as well as serious socioeconomic problems. The use of natural substances stands out as a source of new therapeutic discoveries for the wound healing. Thus, this review compiled scientific findings on the applicability of carvacrol and thymol, or essential oils containing at least one of these compounds, for the treatment of wounds. METHODS: This review was performed at PubMed, SCOPUS, Web of Science databases using keywords as wound healing, thymol/carvacrol and essential oils. Thirteen studies were selected for discussion. KEY FINDINGS: Thymol/carvacrol was able to act in the three phases of wound healing. In the first phase, they showed modulatory effect of the inflammatory cytokines, oxidative stress and antimicrobial power. In the second phase, they promoted re-epithelialization, angiogenesis and development of granulation tissue. Finally, in the third phase, they improve the collagen deposition and modulated the growth of fibroblasts and keratinocytes. CONCLUSIONS: These compounds present a high potential for the development of new therapeutic for wound repair. However, dose, efficacy and safety of these compounds for the treatment of wounds, as well as the mechanisms by which those effects can be observed, are challenges for future studies.

Borneol, a bicyclic monoterpene alcohol, reduces nociceptive behavior and inflammatory response in mice.

Borneol, a bicyclic monoterpene, has been evaluated for antinociceptive and anti-inflammatory activities. Antinociceptive and anti-inflammatory activities were studied by measuring nociception by acetic acid, formalin, hot plate, and grip strength tests, while inflammation was prompted by carrageenan-induced peritonitis. The rotarod test was used to evaluate motor coordination. Borneol produced a significant (P < 0.01) reduction of the nociceptive behavior at the early and late phases of paw licking and reduced the writhing reflex in mice (formalin and writhing tests, resp.). When the hot plate test was conducted, borneol (in higher dose) produced an inhibition (P < 0.05) of the nociceptive behavior. Such results were unlikely to be provoked by motor abnormality. Additionally, borneol-treated mice reduced the carrageenan-induced leukocytes migration to the peritoneal cavity. Together, our results suggest that borneol possess significant central and peripheral antinociceptive activity; it has also anti-inflammatory activity. In addition, borneol did not impair motor coordination.