Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat

Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat

Neuroscience Letters 258 (1998) 5–8 Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity ...

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Neuroscience Letters 258 (1998) 5–8

Effect of oral administration of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve in the rat Akira Niijima a ,*, Masayoshi Kubo b, Kazunori Hashimoto b, Yasuhiro Komatsu b, Masao Maruno b, Minoru Okada b a

Niigata University School of Medicine, c/o Department of Physiology, Niigata, 951-8151, Japan Central Research Laboratories, Tsumura and Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki, 300-1192, Japan

b

Received 21 January 1998; received in revised form 12 October 1998; accepted 12 October 1998

Abstract The effect of taste stimulation of Pinellia ternata, Zingiberis rhizoma and their mixture on the efferent activity of the gastric branch of the vagus nerve was observed in the anesthetized rat. Taste stimulation by Pinellia ternata (50 mg/ml, 10 min) resulted in a suppression in vagal gastric nerve activity. On the contrary, stimulation by Zingiberis rhizoma (50 mg/ml, 10 min) caused a facilitation in efferent activity. The mixture of Pinellia ternata and Zingiberis rhizoma (5:1, 50 mg/ml, 10 min stimulation) demonstrated no suppressive effect on gastric nerve activity. These observations indicate that it is reasonable to prescribe Pinellia ternata with Zingiberis rhizoma in traditional Japanese medicine to prevent suppressive effect of the taste of Pinellia ternata on gastric function.  1998 Elsevier Science Ireland Ltd. All rights reserved

Keywords: Pinellia ternata; Zingiberis rhizoma; Gastric branch; Vagus; Efferent activity

It is generally recognized that the reflex change in autonomic outflow modulates visceral functions. A reflex increase in salivary flow is observed by the sense of taste, especially acid or sweet taste [4]. Not only salivary secretion, but also modulation of autonomic outflow to visceral organs due to taste stimulation is also expected. In this context, it has been reported that oral stimulation by sweet taste solution elicits insulin secretion accompanied by enhancement of vagal pancreatic activity in the anesthetized rat [5,6] and that taste stimulation by 5% NaCl solution activates and by 10% sucrose solution suppresses vagal gastric nerve activity [3]. It is mentioned in a Japanese proverb that good medicine gives a bitter taste, suggesting the bitter taste or such kind of aversive taste originates a reflex change in autonomic outflow to the visceral organs. In this sense it is suggested that taste stimulation by Pinellia ternata (Hange in Japanese) and Zingiberis rhizoma (Syo* Corresponding author. Office and Laboratory, 31-32, Hamauracho, Niigata City, 951-8151 Japan. Fax: +81 25 2662450.

0304-3940/98/$ - see front matter PII S0304- 3940(98) 00830- 1

kyo in Japanese, ginger in English) may cause some reflex change in autonomic activity to the visceral organs because the former gives some astringent and aversive taste and the latter gives a hot taste with a strong odor. This paper mainly deals with the effect of taste stimulation by Pinellia ternata, Zingiberis Rhizoma and their mixture on the efferent activity of the vagus nerve in the anesthetized rat. Male Wistar rats weighing about 300 g were used. They were kept in a room at 24°C with illumination for 12 h/day (0700–1900 h). Food, but not water, was removed 12 h before the experiment. The animals were anesthetized by intraperitoneal injection of 1 g/kg urethane. A tracheal cannula was inserted. After the laparotomy, nerve filaments were dissected from the central cut end of the ventral gastric branch of the vagus nerve. The efferent nerve activity was recorded with a pair of silver wire electrodes. Nerve activity was amplified and displayed on an oscilloscope and stored on magnetic tape. All analysis of nerve activity was performed

 1998 Elsevier Science Ireland Ltd. All rights reserved

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after conversion of raw data to standard pulses using a window discriminator, which distinguished nerve activity from the background noise. A rate meter with a reset time of 5 s was used to observe the time course of the nerve activity that was recorded with a pen recorder. The effect of oral administration of homogeneous solution of Pinellia ternata, Zingiberis Rhizoma and their mixture on efferent nerve activity was investigated by comparing the mean number of impulses per 5 s over 50 s (i.e. mean value of 10 successive measured samples) before and after administrations. Significance was determined by ANOVA (P , 0.05). The post hoc test used was the t-test. Commercial tubers of Pinellia ternata and rhizomes of Zingiberis were pulverized and then extracted with water under reflux, respectively. The hot aqueous extracts were filtered and lyophilized. The extract was stored in a desiccator prior to use. For oral administration, 50 mg of the extract of Pinellia tuber, Zingiberis rhizoma and their mixture was dissolved in 1 ml distilled water and mixed using an ultrasonic cleaner for a few minutes to make a homogenized suspension. These solutions were applied to the tongue surface with a syringe by holding the tongue outside the buccal cavity. Each trial required 10 min to spread the solution slowly and continuously over the tongue, then the tongue was flushed with distilled water just after the stimulation. The efferent vagus responses to taste stimulation were examined and results are shown in Fig. 1A. The upper trace shows a typical example of the effect of Pinellia ternata solution. As shown in the trace, the vagal activity was suppressed almost immediately following the taste stimulation which lasted longer than 60 min. Discharge rate just before and 10, 30 and 60 min after taste stimulation was

68.7 ± 3.0, 26.5 ± 1.4*, 28.8 ± 2.2* and 47.6 ± 2.3* impulses/5 s ± SEM, respectively (* indicates significant suppression). The middle trace presents an example of the effect of Zingiberis solution. The taste stimulation by Zingiberis rhizoma solution provoked a gradual increase in efferent activity which lasted longer than 90 min. The discharge rate just before and that of 30, 60 and 90 min after stimulation was 75.2 ± 2.9, 132.0 ± 3.8**, 145.7 ± 3.7** and 140.8 ± 5.6**, respectively (** shows significant increase). The bottom trace shows the effect of a mixture of Pinellia ternata and Zingiberis rhizoma (5:1). As demonstrated in the trace, taste stimulation resulted in almost no effect on discharge rate although a slight suppressive effect was observed during and just after stimulation. The discharge rate just before, 30, 60 and 90 min after stimulation was 73.0 ± 2.3, 76.9 ± 3.2, 73.5 ± 2.2 and 75.0 ± 1.6, respectively. No significant difference was observed between the discharge rate before and those of after taste stimulation. Table 1 and Fig. 1B show the mean discharge rate before and after taste stimulation by Pinellia tuber, Zingiberis rhizoma and their mixture on efferent activity of the gastric vagus nerve. The mean discharge rate just before and 30, 60 and 90 min after taste stimulation by Pinellia ternata was 61.7 ± 3.2, 53.0 ± 3.2*, 50.5 ± 3.7* and 56.2 ± 6.7 impulses/5 s, respectively (n = 5, P , 0.05), and by Zingiberis rhizoma was 67.4 ± 3.9, 92.0 ± 10.3**, 92.7 ± 13.4** and 92.7 ± 12.2**, respectively (n = 5, P , 0.05), and by a mixture of Pinellia ternata and Zingiberis rhizoma (5:1) was 64.7 ± 2.9, 64.6 ± 4.0, 62.7 ± 3.8 and 63.0 ± 3.7, respectively (n = 5). No significant difference was recognized between the values before and after taste stimulation by the mixture.

Fig. 1. (A) Time courses of efferent activity of the gastric branch of the vagus nerve on effect of taste stimulation by Pinellia ternata, Zingiberis rhizoma and their mixture. (B) Effect of taste stimulation by Pinellia ternata, Zingiberis rhizoma and their mixture on the mean discharge rate of the gastric branch of the vagus nerve (n = 5).

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A. Niijima et al. / Neuroscience Letters 258 (1998) 5–8 Table 1

Effect of taste stimulation by Pinellia ternata, Zingiberis rhizoma and their mixture on the mean discharge rate of the gastric branch of the vagus nerve (n = 5) Impulses/5 s (mean ± SEM)

Pinellia (n = 5) Zingiberis (n = 5) Mixture (Hange5 + Syokyo1) (n = 5)

Control

30 min

60 min

90 min

61.7 ± 3.2 67.4 ± 3.9 64.7 ± 2.9

53.0 ± 3.2* 92.0 ± 10.3** 64.6 ± 4.0

50.5 ± 3.7* 92.7 ± 13.4** 62.7 ± 3.8

56.2 ± 6.7 92.7 ± 12.2** 63.0 ± 3.7

*Significant decrease compared with control; **significant increase to control; no letter, n.s.

On the contradictory taste reflex effects on vagal outflow due to different quality of taste stimulation have already been reported. For example, sweet taste stimulation accelerates, and salty taste stimulation suppresses vagal pancreatic nerve activity in anesthetized rats [6], and further, salty taste stimulation increases and sweet taste stimulation decreases efferent activity of the vagal gastric nerve [3]. The nerve signals originated by sweet or salty taste stimulation will be sent to the autonomic reflex center in the brain mainly through ligual nerve and chorda tympani, because the sensitive spots to sweet and salty taste exist on the tip of the tongue which is innervated by lingual nerves. It is also known that the spots sensitive to bitter taste exist on the basal portion on the tongue, and nerve signals evoked by bitter taste stimulation are mainly transmitted by the glossopharyngeal nerve to the brain. The pathway of the gustatory nerve signals by taste stimulation of Pinellia ternata and Zingiberis rhizoma solution can be suggested in this manner, because their taste seems to be in the category of bitter taste.

To study the pathway of gustatory signals due to the taste stimulation by emulsion of Pinellia ternata and Zingiberis rhizoma, denervation experiments were conducted. Six observations were made on two bilateral lingual nerve sectioned rats, and another six observations were made on bilateral glossopharyngeal nerve sectioned rats. Fig. 2 shows typical examples of the effects of taste stimulation of Pinellia ternata and Zingiberis rhizoma on efferent activity of the gastric branch of vagal nerve. The left traces demonstrate that taste stimulation by Zingiberis solution enhanced and by Pinellia solution suppressed vagal gastric nerve activity in lingual nerve denervated rats. However, in glossophsryngeal nerve sectioned rats taste stimulation of these solutions were without effect. Eight other observations in lingual nerve or glossopharyngeal nerve sectioned rats showed similar results to those mentioned above. Fig. 1B shows that in lingual nerve sectioned rats taste stimulation by Zingiberis solution resulted in a significant increase, and Pinellia solution caused a significant decrease in efferent discharge rates of gastric vagus nerve. However, in glosso-

Fig. 2. Effect of taste stimulation by Pinellia ternata and Zingiberis rhizoma on efferent activity of the gastric branch of the vagus nerve in bilateral lingual nerve sectioned and glossopharyngeal nerve sectioned rats.

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pharyngeal nerve sectioned rats there was no significant change in discharge rates after taste stimulation of these two solutions (Fig. 2B), suggesting that the afferent pathway seems to be the glossopharyngeal nerve. Results of these experiments reveal that the suppressive effect on vagal gastric nerve activity by taste stimulation with Pinellia terrnata was abolished by a mixture of Pinellia and small amount of Zingiberis. Further, it was found that the taste stimulation by Zingiberis itself resulted in an acceralation of vagal gastric nerve activity which may activate gastric function. It is generally known that in traditional Japanese medicine Zingiberis rhizoma has an antiemetic effect [1,2] and the effect is to increase appetite and ameriolate digestion. The effect of taste stimulation by Zingiberis may play a role in these effects. It is also known that the prescriptions containing Pinellia ternata show antiemetic [8] and sedative effects and that the intraduodenal administration of Pinellia ternata activates the efferent activity of the gastric branch of the vagus nerve [7]. Thus, it is reasonable to prescribe Zingiberis with Pinnelia for oral administration to remove the suppressive effect of Pinellia on vagal gastric activity by aversive taste, and to activate vagal gastric efferents through the duodenum and intestine [7]. In conclusion, it can be mentioned that aversive and astringent taste stimulation by Pinellia ternata suppressed vagal gastric activity and hot taste stimulation by Zingiberis rhizoma enhanced it, and the mixture of these substances

blocked the suppressive effect. It is suggested that the appropriate combination of different tastes can cause a reflex acceleration of vagal outflow and improve gastrointestinal function. Further studies will be expected in the future. [1] Frisch, C., Haseniohrl, R.U., Mattern, C.M., Hacker, R. and Huston, J.P., Blockade of lithium chloride-induced conditioned place aversion as a test for antiemetic agents: comparison of metoclopramide with combined extracts of Zingiber officiale and Ginkgo biloba, Pharmacol. Biochem. Behav., 52 (1995) 321– 327. [2] Kawai, T., Kinoshita, K., Koyama, K. and Takahashi, K., Antiemetic principles of Magnolia obovata bark and Zingiber officinale rhizome, Planta Med., 60 (1994) 17–20. [3] Jiang, Z.Y. and Niijima, A., Effects of taste stimulation on the efferent activity of the gastric vagus nerve in rats, Neurosci. Lett., 69 (1986) 42–46. [4] Lavelle, C.L.B., Applied Physiology of the Mouth, Lohn Wright, Bristol, 1975, p. 368. [5] Niijima, A., Togiyama, T. and Adchi, A., Cephalic phase insulin release induced by taste stimulus of monosodium glutamate (umami taste), Physiol. Behav., 48 (1990) 905–908. [6] Niijima, A., Effect of taste stimulation on the efferent activity of the panreatic vagus nerve in the rat, Brain Res. Bull., 26 (1991) 161–164. [7] Niijima, A., Okui, Y., Kubo, M., Higuchi, M., Taguchi, H., Mitsuhashi, H. and Maruno, M., Effect of Pinellia ternata tuber on the efferent activity of the gastric vagus nerve in the rat, Brain Res. Bull., 32 (1993) 103–106. [8] Takabe, N., On the antiemetic action of Pinellia, Acta Schol. Med. Uni. Gifu, 6 (1958) 243–250.