Recently it has been suggested that the somas of the lacrimal nucleus and salivatory nuclei are, to a certain extent, anatomically intermingled all along the parvocellular reticular formation. The objective of this study was to investigate, using a physiological approach, the topographical relationship between salivatory and lacrimal cells. To this end the cell bodies of the superior (SSN) and inferior (ISN) salivatory nuclei were activated following a microinjection of NMDA. Results showed that NMDA administered to the SSN produced an increased secretion of submandibular-sublingual saliva, but not parotid saliva, concurrently with lacrimation. On the other hand, NMDA administered to the ISN produced hypersecretion of parotid, but not submandibular-sublingual saliva, concurrently with lacrimation. These secretory effects were blocked by i.p. administration of atropine but not when dihydroergotamine plus propranolol was administered, which points to the parasympathetic nature of the activated cells. Although the diffusion of the NMDA has not been evaluated directly, and it is not possible to pinpoint the anatomical specificity of the microinjections, these findings do suggest, from a functional perspective, the coexistence of salivatory and lacrimal cells in the same regions, or regions very close to one another, in the brainstem.

Piper aduncum L. is a medicinal plant whose essential oil is rich in bioactive constituents, particularly dilapiol, and has attracted interest because of its diverse pharmacological properties. However, its anti-inflammatory, antipyretic, and antinociceptive activities and the mechanisms potentially underlying these effects remain insufficiently characterized. Therefore, this study investigated the pharmacological effects of P. aduncum leaf essential oil (EOPa) and explored potential mechanisms involved in its antinociceptive activity. EOPa was obtained by hydrodistillation and chemically characterized by GC-MS and GC-FID. Its pharmacological effects were evaluated in male Swiss mice using brewer's yeast-induced pyrexia, carrageenan-induced paw edema, acetic acid-induced writhing, and the formalin test. Potential mechanisms of antinociceptive activity were investigated using naloxone, atropine, L-NAME, and glibenclamide as pharmacological antagonists/inhibitors. Chemical characterization identified dilapiol as the major constituent of EOPa (69.65 ± 2.12%). EOPa showed dose-dependent anti-inflammatory, antipyretic, and antinociceptive effects, with the most pronounced activity observed at 200 mg/kg. The essential oil reduced inflammatory edema, fever, and nociceptive responses in the experimental models. EOPa at 200 mg/kg reduced yeast-induced fever by up to 76.1% (p < 0.01), carrageenan-induced paw edema by up to 26.48% (p < 0.0001), and acetic acid-induced writhing by 65.90% (p < 0.001). In the formalin test, EOPa reduced nociceptive behavior by 39.89% during the neurogenic phase and by 70.67% during the inflammatory phase (p < 0.0001). Pretreatment with atropine and glibenclamide markedly attenuated the antinociceptive effect of EOPa, whereas naloxone and L-NAME did not significantly modify the response. These findings provide preclinical evidence that P. aduncum leaf essential oil possesses anti-inflammatory, antipyretic, and antinociceptive activities and suggest that the antinociceptive effect of EOPa involves activation of muscarinic receptors, consistent with a muscarinic agonist-like effect, and stimulation of ATP-sensitive potassium (K[+]ATP) channels, consistent with a K[+]ATP-channel-stimulating effect. Further pharmacological, toxicological, and mechanistic studies are warranted to clarify the molecular basis, active constituents, and safety profile of these effects.

Leaky gut, defined as increased intestinal permeability, has been associated with many diseases. Recent studies suggest the brain is involved in maintaining gut barrier function. Since tofogliflozin, a sodium/glucose cotransporter 2 (SGLT2) inhibitor acts centrally to increase food intake, and feeding and gut functions are deeply associated, this study aimed to clarify the hypothesis that gut barrier function is influenced by centrally administered SGLT2 inhibitors in rats using Evans blue method. Intracisternal SGLT2 inhibitor blocked colonic hyperpermeability in response to lipopolysaccharide dose-dependently (15 μg-). The blockade was cancelled by atropine, vagotomy, intracisternal orexin receptor antagonist, intracisternal compound C, an adenosine monophosphate-activated protein kinase (AMPK) inhibitor, or subcutaneously injected sulpiride, a dopamine D2 receptor antagonist. Subcutaneous SGLT2 inhibitor at much higher doses of 5 mg or more could improve colonic hyperpermeability, and the improvement was also blocked by atropine or intracisternal orexin receptor antagonist or compound C. These results indicate SGLT2 inhibitor administered centrally or peripherally reduces colonic hyperpermeability through the vagal pathway although we could not exclude the possibility that peripherally administered SGLT2 inhibitor might act first in periphery. Brain orexin, AMPK and dopamine D2 signaling are involved in this process. SGLT2 inhibitors may be useful to treat leaky gut-related diseases.