Effects of bakumondoto on neuropeptide levels in human saliva and plasma
Bakumondoto is empirically used to treat to dry mouth (xerostomia) associated with salivary gland dysfunction. Salivary glands are supplied with nerve fibers that contain neruopeptides, such as substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). These ne...
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| Published in | Journal of Traditional Medicines Vol. 26; no. 3; pp. 122 - 130 |
|---|---|
| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
Medical and Pharmaceutical Society for WAKAN-YAKU
2009
和漢医薬学会 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1880-1447 1881-3747 |
| DOI | 10.11339/jtm.26.122 |
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| Abstract | Bakumondoto is empirically used to treat to dry mouth (xerostomia) associated with salivary gland dysfunction. Salivary glands are supplied with nerve fibers that contain neruopeptides, such as substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). These neuropeptides are important modulators of salivation. We studied the effect of bakumondoto on substance P-, CGRP-, VIP-like immunoreactive substances (IS) in saliva and plasma taken from healthy subjects. Bakumondoto (18.0 g) or placebo was orally administered to five healthy males. Saliva and blood samples were taken before, and at 20-240 min after administration, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for neuropeptides. A single oral administration of bakumondoto caused significant increases in saliva substance P- and CGRP-IS levels compared with placebo. And this medicine tended to raise saliva volume. In this study, we concluded bakumondoto might affect substance P and CGRP locally in the salivary gland and the elevated levels of these neuropeptides might stimulate production of saliva. Also, the monitoring of saliva and plasma neuropeptide levels might be able to predict the pharmacologic effects of bakumondoto. |
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| AbstractList | 麦門冬湯は, 唾液腺機能異常に関連するドライマウスなどの口腔内乾燥症状に対して経験的に使用される. 唾液腺にはsubstance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP)などの神経ペプチドが局在している. 我々は, 健常人の唾液及び血漿中のsubstance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP)濃度に与える麦門冬湯の効果を検討した. 麦門冬湯(18.0g)あるいは対照薬を5人の健常人へ経口投与し, 唾液ならびに血液を, 投与前及び投与後20～240分に採取し, 高感度酵素免疫測定法により各種神経ペプチド濃度を測定した. その結果, 本剤投与後のsubstance P, CGRPの唾液中濃度は, 対照群に比較して有意に上昇した. また本剤投与後の唾液分泌量は増大傾向であった. 以上の結果から, 麦門冬湯は唾液腺におけるsubstance PとCGRPに作用し, これらの効果が唾液分泌を刺激している可能性が示された. また, 唾液と血漿中神経ペプチド濃度をモニターすることは, 麦門冬湯の効果を予測することが可能であると考えられた. Bakumondoto is empirically used to treat to dry mouth (xerostomia) associated with salivary gland dysfunction. Salivary glands are supplied with nerve fibers that contain neruopeptides, such as substance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide (VIP). These neuropeptides are important modulators of salivation. We studied the effect of bakumondoto on substance P-, CGRP-, VIP-like immunoreactive substances (IS) in saliva and plasma taken from healthy subjects. Bakumondoto (18.0 g) or placebo was orally administered to five healthy males. Saliva and blood samples were taken before, and at 20-240 min after administration, followed by the extracting procedure, and submitted to a highly sensitive enzyme immunoassay system for neuropeptides. A single oral administration of bakumondoto caused significant increases in saliva substance P- and CGRP-IS levels compared with placebo. And this medicine tended to raise saliva volume. In this study, we concluded bakumondoto might affect substance P and CGRP locally in the salivary gland and the elevated levels of these neuropeptides might stimulate production of saliva. Also, the monitoring of saliva and plasma neuropeptide levels might be able to predict the pharmacologic effects of bakumondoto. |
| Author | ITOH, Hiroki TAKEYAMA, Masaharu SATOH, Yuhki |
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| References | 2)Mandel, I. D.: The role of saliva in maintaining oral homeostasis. J. Am. Den.t Assoc., 119, 298-304, 1989. 11)Gibbns, I. L.: Target-related patterns of co-existence of neuropeptide Y, vasoactive intestinal peptide, enkephalin and substance P in cranial parasympathetic neurons innervating the facial skin and exocrine glands of guinea-pigs. Neuroscience, 38, 541-560, 1990. 25)Kagami, H., Horie, K., Nishiguchi, H., Shigetomi, T., Ueda, M.: Effect of 'bakumondoto', a Chinese-Japanese herbal medicine, on cultured and dispersed salivary gland cells. J. Ethnopharmacol., 53, 89-95, 1996. 26)Ma, Q. P., Hill, M., Sirinathsinghiji, D.: Colocalization of CGRP with 5-HT1B/1C receptors and substance P in trigeminal ganglion neurons in rats. Eur. J. Neurosci., 13, 2099-2104, 2001. 12)Pikula, D. L., Harris, E. F., Desiderio, D. M., Fridland, G. H., Lovelace, J. L.: Methionine enkepharlin-like, substance P-like, and beta-endorphin-like immunoreactivity in human parotid saliva. Arch. Ora.l Biol., 37, 705-709, 1992. 17)Nagano, T., Takeyama, M., Ikawa, K.: Anethole trithione raises levels of calcitonin gene-related peptide in saliva of healthy subjects. Pharm. Pharmacol. Commun., 4, 459-463, 1998. 22)Kitagawa, T., Shimozono, T., Aikawa, T., Yoshida, T., Nishimura, H.: Preparation and characterization of hetero-bifunctional cross-linking reagents for protein modifications. Chem. Pharm. Bull., 29, 1130-1135, 1981. 29)Naito, T., Itoh, H., Takeyama, M.: Effects of Hange-koboku-to (Banxia-houpo-tang) on neuropeptide levels in human plasma and saliva. Biol. Pharm. Bull., 26, 1609-1613, 2003. 13)Ekström, J.: Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. J. Dent. Res., 66, 524-530, 1987. 6)Ohno, S., Suzuki, T., Dohi, Y.: The effect of bakumondoto on salivary secretion in Sjogren syndrome. Ryumachi, 30, 10-16, 1990. 24)Santavirta, N., Konttinen, Y. T., Segerberg, T. M., Konttinen, Y. T., Santavitra, S., Matucci-Cerinic, M.: Neuropeptides of the autonomic nervous system in Sjogren's syndrome. Ann. Reum. Dis., 56, 737-740, 2006. 20)Takeyama, M., Wakayama, K., Alabama, F., Kondo K., Fujii, N., Yajima, H.: Micro-enzyme immunoassay of vasoactive intestinal polypeptide (VIP)-like immunoreactive substance in bovine milk. Chem. Pharm. Bull., 38, 960-962, 1990. 1)Fox, P. C., van deer Ven P. F., Sonies, B. C.: Xerostomia: evaluation of a symptom with increasing significance. J. Am. Dent. Assoc., 110, 519-525, 1985. 27)Nagano, T., Itoh, H., Hayashi, T., Takeyama, M.: Pilocarpine raises the levels of substance P and α-calcitonin gene-related peptide in human saliva. Pharm. Pharmacol. Commun. 5, 571-574, 1999. 23)Aalto, Y., Forsgren, S., Körell, U., Franzén, L., Gustafsson, H., Henriksson, R.: Time-and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation. Int. J. Radiat. Oncol. Biol. Phys., 33, 297-305, 1995. 10)Ekström, J., Ekman, R., Håkanson, R., Luts, A. F.: Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. Neuroscience, 26, 933-949, 1994. 8)Hauser-Kronberger, C., Albegger, K., Saria, A., Hacker, G. W.: Neuropeptides in human salivary (submandibular and parotid) glands. Acta. Otolaryngol., 112, 343-348, 1992. 5)Sugano, S., Takeyama, I., Ogino, S., Kenmochi. M., Kaneko, T.: Effectiveness of formula ophiopogoins in the treatment of xerostomia and pharyngoxerosis. Act. Otolaryngol. Suppl., 522, 124-129, 1996. 7)Lundberg, J. M., Änggard, A., Fahrenkrug, J., Hökfelt, T., Mutt, V.: Vasoactive intestinal polypeptide in cholinergic neurons of exocrine glands: functional significance of coexisting transmitters for vasodilation and secretion. Proc. Natl. Acad. Sci., 77, 1651-1655, 1980. 16)Navazesh, M., Christensen, C. M.: A comparison of whole mouth resting and stimulated salivary measurement procedures. J. Dent. Res., 61, 1158-1162, 1982. 4)Goto, M.: Long-term effect of Japanese herb medicine, bakumondoto (mai-men-dong-tang), for the treatment of sicca syndrome. Int. J. Immunother., 10, 173-178, 1994. 15)Kohler, P. F., Winter, M. E.: A quantitative test for xerostomia. Arthritis. Rheum., 28, 1128-1132, 1985. 21)Takeyama, M., Kondo, K., Hayashi, Y., Yajima, H.: Enzyme immunoassay of gastrin releasing peptide (GRP)-like immunoreactivity in milk. Int. J. Pept. Protein. Res., 34, 70-74, 1989. 9)Kusakabe, T., Matsuda, H., Kawakami, T., Syoui, N., Kurihara, K., Tsukuda, M., Takenaka, T.: Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini. Cell Tissue Res., 288, 25-31, 1997. 14)Bobyock, E., Chernick, W. S.: Vasoactive intestinal polypeptide interacts with alph-adrenergic-, cholinergic-, and substance P mediated responses in rat parotid and submandibular glands. J. Dent. Res., 68, 1489-1494, 1989. 18)Takeyama, M., Mori, K., Takayama, F., Kondo, K., Kitagawa, K., Fujii, N.: Enzyme immunoassay of a substance P-like immunoreactive substance in human plasma and saliva. Chem. Pharm. Bull., 38, 3494-3496, 1990. 28)Nishizawa, Y., Nishizawa, K., Yoshioka, F., Nosaka, S., Amakata, Y., Goto, H., Hushiki, S.: Long-term effect of traditional Chinese herbal medicine, Mai-Men-Dong-Tang on sicca syndrome, especially, salivary secretion in patients with primary Sjogren's syndrome: A multicenter, randomized well controlled group-parallel double-blind study. Jpn. J. Saliva, 43, 62-66, 2002. 19)Nagano, T., Ikawa, K., Takeyama, M.: Enzyme immunoassay of calcitonin gene-related peptide in human plasma and saliva. Jpn. J. Hosp. Pharm., 24, 363-369, 1998. 3)Chang, H. M., But, P. P. M.: Pharmacology and Appplications of Chinese Materia Medica, Vol. 1 and 2. World Science Publications, Singapore, 1987. |
| References_xml | – reference: 21)Takeyama, M., Kondo, K., Hayashi, Y., Yajima, H.: Enzyme immunoassay of gastrin releasing peptide (GRP)-like immunoreactivity in milk. Int. J. Pept. Protein. Res., 34, 70-74, 1989. – reference: 12)Pikula, D. L., Harris, E. F., Desiderio, D. M., Fridland, G. H., Lovelace, J. L.: Methionine enkepharlin-like, substance P-like, and beta-endorphin-like immunoreactivity in human parotid saliva. Arch. Ora.l Biol., 37, 705-709, 1992. – reference: 25)Kagami, H., Horie, K., Nishiguchi, H., Shigetomi, T., Ueda, M.: Effect of 'bakumondoto', a Chinese-Japanese herbal medicine, on cultured and dispersed salivary gland cells. J. Ethnopharmacol., 53, 89-95, 1996. – reference: 14)Bobyock, E., Chernick, W. S.: Vasoactive intestinal polypeptide interacts with alph-adrenergic-, cholinergic-, and substance P mediated responses in rat parotid and submandibular glands. J. Dent. Res., 68, 1489-1494, 1989. – reference: 29)Naito, T., Itoh, H., Takeyama, M.: Effects of Hange-koboku-to (Banxia-houpo-tang) on neuropeptide levels in human plasma and saliva. Biol. Pharm. Bull., 26, 1609-1613, 2003. – reference: 1)Fox, P. C., van deer Ven P. F., Sonies, B. C.: Xerostomia: evaluation of a symptom with increasing significance. J. Am. Dent. Assoc., 110, 519-525, 1985. – reference: 19)Nagano, T., Ikawa, K., Takeyama, M.: Enzyme immunoassay of calcitonin gene-related peptide in human plasma and saliva. Jpn. J. Hosp. Pharm., 24, 363-369, 1998. – reference: 11)Gibbns, I. L.: Target-related patterns of co-existence of neuropeptide Y, vasoactive intestinal peptide, enkephalin and substance P in cranial parasympathetic neurons innervating the facial skin and exocrine glands of guinea-pigs. Neuroscience, 38, 541-560, 1990. – reference: 20)Takeyama, M., Wakayama, K., Alabama, F., Kondo K., Fujii, N., Yajima, H.: Micro-enzyme immunoassay of vasoactive intestinal polypeptide (VIP)-like immunoreactive substance in bovine milk. Chem. Pharm. Bull., 38, 960-962, 1990. – reference: 6)Ohno, S., Suzuki, T., Dohi, Y.: The effect of bakumondoto on salivary secretion in Sjogren syndrome. Ryumachi, 30, 10-16, 1990. – reference: 4)Goto, M.: Long-term effect of Japanese herb medicine, bakumondoto (mai-men-dong-tang), for the treatment of sicca syndrome. Int. J. Immunother., 10, 173-178, 1994. – reference: 15)Kohler, P. F., Winter, M. E.: A quantitative test for xerostomia. Arthritis. Rheum., 28, 1128-1132, 1985. – reference: 17)Nagano, T., Takeyama, M., Ikawa, K.: Anethole trithione raises levels of calcitonin gene-related peptide in saliva of healthy subjects. Pharm. Pharmacol. Commun., 4, 459-463, 1998. – reference: 23)Aalto, Y., Forsgren, S., Körell, U., Franzén, L., Gustafsson, H., Henriksson, R.: Time-and dose-related changes in the expression of substance P in salivary glands in response to fractionated irradiation. Int. J. Radiat. Oncol. Biol. Phys., 33, 297-305, 1995. – reference: 5)Sugano, S., Takeyama, I., Ogino, S., Kenmochi. M., Kaneko, T.: Effectiveness of formula ophiopogoins in the treatment of xerostomia and pharyngoxerosis. Act. Otolaryngol. Suppl., 522, 124-129, 1996. – reference: 22)Kitagawa, T., Shimozono, T., Aikawa, T., Yoshida, T., Nishimura, H.: Preparation and characterization of hetero-bifunctional cross-linking reagents for protein modifications. Chem. Pharm. Bull., 29, 1130-1135, 1981. – reference: 2)Mandel, I. D.: The role of saliva in maintaining oral homeostasis. J. Am. Den.t Assoc., 119, 298-304, 1989. – reference: 27)Nagano, T., Itoh, H., Hayashi, T., Takeyama, M.: Pilocarpine raises the levels of substance P and α-calcitonin gene-related peptide in human saliva. Pharm. Pharmacol. Commun. 5, 571-574, 1999. – reference: 9)Kusakabe, T., Matsuda, H., Kawakami, T., Syoui, N., Kurihara, K., Tsukuda, M., Takenaka, T.: Distribution of neuropeptide-containing nerve fibers in the human submandibular gland, with special reference to the difference between serous and mucous acini. Cell Tissue Res., 288, 25-31, 1997. – reference: 10)Ekström, J., Ekman, R., Håkanson, R., Luts, A. F.: Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. Neuroscience, 26, 933-949, 1994. – reference: 28)Nishizawa, Y., Nishizawa, K., Yoshioka, F., Nosaka, S., Amakata, Y., Goto, H., Hushiki, S.: Long-term effect of traditional Chinese herbal medicine, Mai-Men-Dong-Tang on sicca syndrome, especially, salivary secretion in patients with primary Sjogren's syndrome: A multicenter, randomized well controlled group-parallel double-blind study. Jpn. J. Saliva, 43, 62-66, 2002. – reference: 7)Lundberg, J. M., Änggard, A., Fahrenkrug, J., Hökfelt, T., Mutt, V.: Vasoactive intestinal polypeptide in cholinergic neurons of exocrine glands: functional significance of coexisting transmitters for vasodilation and secretion. Proc. Natl. Acad. Sci., 77, 1651-1655, 1980. – reference: 18)Takeyama, M., Mori, K., Takayama, F., Kondo, K., Kitagawa, K., Fujii, N.: Enzyme immunoassay of a substance P-like immunoreactive substance in human plasma and saliva. Chem. Pharm. Bull., 38, 3494-3496, 1990. – reference: 8)Hauser-Kronberger, C., Albegger, K., Saria, A., Hacker, G. W.: Neuropeptides in human salivary (submandibular and parotid) glands. Acta. Otolaryngol., 112, 343-348, 1992. – reference: 3)Chang, H. M., But, P. P. M.: Pharmacology and Appplications of Chinese Materia Medica, Vol. 1 and 2. World Science Publications, Singapore, 1987. – reference: 26)Ma, Q. P., Hill, M., Sirinathsinghiji, D.: Colocalization of CGRP with 5-HT1B/1C receptors and substance P in trigeminal ganglion neurons in rats. Eur. J. Neurosci., 13, 2099-2104, 2001. – reference: 13)Ekström, J.: Calcitonin gene-related peptide in rat salivary glands: neuronal localization, depletion upon nerve stimulation, and effects on salivation in relation to substance P. J. Dent. Res., 66, 524-530, 1987. – reference: 24)Santavirta, N., Konttinen, Y. T., Segerberg, T. M., Konttinen, Y. T., Santavitra, S., Matucci-Cerinic, M.: Neuropeptides of the autonomic nervous system in Sjogren's syndrome. Ann. Reum. Dis., 56, 737-740, 2006. – reference: 16)Navazesh, M., Christensen, C. M.: A comparison of whole mouth resting and stimulated salivary measurement procedures. J. Dent. Res., 61, 1158-1162, 1982. |
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| Snippet | Bakumondoto is empirically used to treat to dry mouth (xerostomia) associated with salivary gland dysfunction. Salivary glands are supplied with nerve fibers... 麦門冬湯は, 唾液腺機能異常に関連するドライマウスなどの口腔内乾燥症状に対して経験的に使用される. 唾液腺にはsubstance P, calcitonin gene-related peptide (CGRP), and vasoactive intestinal polypeptide... |
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| Title | Effects of bakumondoto on neuropeptide levels in human saliva and plasma |
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