Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: Role of endogenous opioids, KATP-channels and adenosine

AbstractThis study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with l-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of KATP channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10–100mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, KATP-channels and adenosine receptors

The Transition From Undernutrition to Overnutrition Under Adverse Environments and Poverty: The Risk for Chronic Diseases

Nutritional transition is an important public health issue in developing countries, where switch from undernutrition to overnutrition/obesity is rapidly occurring, often within two or three generations. Such transition is related to changes in lifestyle, with people having more access to western high-caloric diets. In developing countries, settings of poverty, poor sanitation and hygiene are still common, where children are exposed to numerous enteric pathogens, pollutants, and other biohazards. Populations living under such adverse environments and facing the nutritional transition may have increased risks for chronic illnesses in later life, including diabetes, cardiovascular, and neurodegenerative diseases. This opinion paper summarizes novel findings and recent literature addressing the nutrition transition under adverse environments, including the gut microbiota-brain axis dysfunction and their lasting effects with deleterious consequences for later development