Influence of Intragastric Administration of Traditional Japanese Medicine, Ninjin’Yoeito, on Cerebral Blood Flow via Muscarinic Acetylcholine Receptors

Abstract

Ninjin’yoeito (NYT) is a traditional medicine that has been used for mitigating physical frailty, such as fatigue and anorexia, as well as for cognitive dysfunction. Maintenance of adequate cerebral blood flow (CBF) is important for preventing cognitive dysfunction. The present study aimed to examine the effect of NYT on CBF. Male C57BL/6 J mice were anesthetized with urethane and were artificially ventilated. We measured CBF in the neocortex with laser-speckle contrast imaging for 10 min before administration and 60 min after administration. We administered NYT solution (0.25, 0.5, 1, and 2 g/kg) or vehicle (distilled water; DW) over 5 min via an intragastric catheter. We surgically transected the vagus nerve to investigate its contribution as a neural pathway and intraperitoneally injected atropine to block muscarinic acetylcholine receptors. Finally, we tested the CBF response to cutaneous brushing stimulation applied to the left hind paw (30 sec). CBF decreased after DW administration, starting from 30 min onward, whereas CBF did not change after NYT. The averaged CBF change following DW administration differed from that following NYT (1 g/kg) but not from those following the other doses of NYT. Arterial pressure was not affected by either solution. CBF after NYT (1 g/kg) was not affected by vagotomy but was lower following additional atropine. In response to brushing stimulation, CBF in the right (contralateral) parietal cortex increased. The magnitude of CBF increase following NYT was greater than that following DW. These results suggest that NYT prevents CBF decrease via cholinergic activation independent of vagal activity and enhances the CBF response to somatosensory stimulation.

Review of frequently used Kampo prescriptions: Part 4, Ninjin'yoeito

“…Previous studies indicated that NYT ameliorated dementia or depression/anxiety [94][95][96] by increasing the levels of neurotrophic factors [94,97], attenuating the inhibition of neurogenesis [95,98], suppressing microglial overactivity [99], increasing cerebral blood flow [100], and enhancing cerebral glucose metabolism [92]. Furthermore, NYT improved diminished motivation [86,87,101,102] and suppressed the hypothalamic-pituitary-adrenal (HPA) axis by downregulating the sympathetic-adrenal-medullary (SAM) axis and GABA neurons to improve sociability [103].…”