Onjisaponins, from the root of Polygala tenuifolia Willdenow, as effective adjuvants for nasal influenza and diphtheria-pertussis-tetanus vaccines.

Active substances from hot water extracts from 267 different Chinese and Japanese medicinal herbs were screened for mucosal adjuvant activity with influenza HA vaccine in mice. The extract from the root of Polygala tenuifolia was found to contain potent mucosal adjuvant activity. The active substances were purified and identified as onjisaponins A, E, F, and G. When each onjisaponin (10 microg) was intranasally (i.n.) inoculated with influenza vaccine (10 microg) in mice, serum hemagglutination-inhibiting (HI) antibody titers increased 3-14 times over control mice administered vaccine alone after 4 weeks. When each onjisaponin (10 microg) was i.n. inoculated with the vaccine (10 microg) followed by i.n. vaccination of the vaccine alone after 3 weeks, serum HI antibody titers increased 27-50 fold over those mice given i.n. vaccinations without onjisaponins. These same conditions also significantly increased nasal anti-influenza virus IgA antibody titers. Two inoculations with onjisaponin F (1 microg) and influenza HA vaccine (1 microg) at 3 weeks intervals, significantly increased serum HI antibody and nasal anti-influenza virus IgA and IgG antibody titers after only 1 week over mice given HA vaccine alone after the secondary vaccination. Intranasal vaccination with onjisaponin F inhibited proliferation of mouse adapted influenza virus A/PR/8/34 in bronchoalveolar lavages of infected mice. Separate intranasal vaccinations with onjisaponins A, E, F, and G (10 microg) each and diphtheria-pertussis-tetanus (DPT) vaccine (10 microg) of mice followed by i.n. vaccination with DPT vaccine alone after 4 weeks showed significant increases in serum IgG and nasal IgA antibody titers after 2 weeks following secondary vaccination over mice vaccinated with DPT vaccine alone. All onjisaponins showed little hemolytic activity at concentrations up to 100 microg/ml. The results of this study suggest that onjisaponins may provide safe and potent adjuvants for intranasal inoculation of influenza HA and DPT vaccines.

Cholinergic inputs to rostral ventrolateral medulla pressor neurons from hypothalamus.

The rostral ventrolateral medulla (RVLM) has cholinergic mechanisms responsible for pressor responses. Stimulation of the hypothalamic paraventricular nucleus (PVN) causes an increase of arterial pressure via activation of neurons in the RVLM. In this study, we examined whether PVN stimulation causes a pressor response via activation of cholinergic mechanisms in the RVLM. Male Wistar rats were used and they were anesthetized, paralyzed and artificially ventilated. Electrical stimulation of the PVN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine into the RVLM inhibited and potentiated, respectively, the pressor response induced by PVN stimulation. PVN stimulation also increased the firing rate of RVLM barosensitive neurons and the increase in the firing rate was inhibited and potentiated by scopolamine and physostigmine, respectively, iontophoretically applied on neurons. Microinjection of L-glutamate into the PVN produced a release of ACh in the RVLM. The inhibitory amino acid gamma-aminobutyric acid injected into the lateral parabrachial nucleus (LPBN) inhibited the pressor response induced by PVN stimulation. These results suggest that PVN stimulation causes an increase in arterial pressure via activation of cholinergic inputs in the RVLM. It appears that the pressor response is mediated, at least in part, via cholinergic inputs from the LPBN.

[Pharmacological studies of Houttuyniae herba: the anti-inflammatory effect of quercitrin].

Anti-inflammatory activities of quercitrin (Qu) were studied using various experimental models in mice, rats and guinea pigs. Qu (50, 100 and 200 mg/kg, p.o.) inhibited the rat hind paw edema induced by various phlogistics (carrageenin, dextran, histamine, serotonin and bradykinin) in a dose-dependent manner, and 200 mg/kg of this compound also inhibited the scald edema induced by hot water (54 degrees C). Qu did not show any significant inhibition of the ultraviolet light-induced erythema in guinea-pigs and of the increase of vascular permeability induced by acetic acid in mice. Qu did not affect the granuloma formation in a cotton pellet and the development of adjuvant arthritis in rats. These results indicate that Qu might have an inhibitory effect on acute inflammation.

[Pharmacological studies on Zingiber mioga (ZM) (1). General pharmacological effects of water extracts (author's transl)].

In the central nervous system, ZM decreased locomotor activity and potentiated hypnosis of hexobarbital-Na in mice. ZM had little hypothermic action and there were no anticonvulsive effects on chemoconvulsion and electroconvulsion shock. ZM, 3 mg/kg i.v. produced a sleep-like pattern in the spontaneous EEG activity of cat; from 20 to 30 min. after injection, spindle burst-like waves (12-13 Hz) appeared in the cortex and subcortex. These EEG activities were antagonized by atropine sulfate. In the respiratory and cardiovascular system, ZM, 1 mg/kg or over produced a fall in blood pressure and stimulated respiration in dogs. This hypotensive action was antagonized by atropine sulfate and diphenhydramine hydrochloride, and tachyphylaxis was observed in blood pressure. This compound inhibited cardiomotility in isolated toad heart, had little effect on peripheral blood flow, and produced contractions of isolated guinea pig ileum which were inhibited by atropine by sulfate. Regarding inflammatory response, ZM showed inhibitory effects on the acute edema induced serotonin and dextran. These results indicate that water extracts of ZM have cholinergic actions and in peripheral tissues, histaminergic-like actions.

[Pharmacological studies on Zingiber Mioga (2). Effects of water extracts on the central nervous system (author's transl)].

Effects on the cat central nervous system of water extracts of Zingiber Mioga (ZM) were studied by electroencephalography (EEG). ZM had little effect on the EEG arousal response to electrical stimulation of mid-brain reticular formation. ZM (3 approximately 5 mg/kg, i.v.) suppressed the recruiting response and the augmenting response recorded from the posterior sigmoid gyrus, respectively. ZM (1 approximately 3 mg/kg, i.v.) decreased the photic driving response, while 5 mg/kg, i.v., tended to enhance the response. In the chronic experiments, ZM(1 approximately 3 mg/kg, i.v.) induced a drowsy pattern in the cortex and subcortex, and shortened the lasting time of the EEG arousal response to sonic stimulation. After 5 to 10 minutes, behavior showed a drowsy to light sleeping state, and electromyogram recorded from the platysma showed a decreased amplitude and frequency, but, did not have an inhibitory effect on the motor system, (ataxia). ZM (5 mg/kg, i.v.) induced desynchronization in the cortex and subcortex, arousal wave appeared in hippocampus, midbrain reticular formation, nucl. ventralis postero-lateralis and amygdala, and behavior tended toward the awake stage. After 10 minutes, EEG transferred to a drowsy pattern and behavior showed a drowsy to light sleeping state. The animal could be readily awakened by sonic stimulation, at every time. ZM appears to have an inhibitory effect on the central nervous system.