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Japanese Kampo Medicines for Diabetes Mellitus
CHAPTE R 8
Japanese Kampo Medicines for Diabetes Mellitus Hiroshi Suzuki1,2, Hirohito Sone2, Kenichi Watanabe1 1Niigata
University of Pharmacy and Applied Life Sciences, Niigata, Japan; 2Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Introduction There is a long history of the use of Japanese Kampo medicines for the treatment of diabetes mellitus and these medicines are now gaining favorable attention. Despite better blood glucose level control offered by Western medicine, Japanese Kampo medicines can be adopted for the treatment of diabetes mellitus because of their favorable safety profile over Western medicine. Here we illustrate the disease state of diabetes mellitus and the use of Kampo medicines for the treatment of diabetes mellitus.
The Disease State of Diabetes Mellitus “Syo-katsu,” a term that originated in China and has been used since 50 BCE, refers to symptoms that resemble diabetes mellitus. The symptoms of syo-katsu consist of thirst and polyuria, which are very similar to the symptoms of diabetes mellitus. Diabetes mellitus can be divided into three states of medical conditions: “jou-syou,” “chu-syou,” and “ka-shou.” The disease states of jou-syou are thirst, polyuria, and body weight loss, which are initial symptoms of diabetes mellitus of the nonobese type. Similarly, the disease states of chu-syou are hunger, bulimia, and severe body weight loss, which belong to the obesity type. Finally, the disease states of ka-shou are polyuria, red tongue, and darkish face, which are the advanced symptoms of diabetes mellitus. In general practice, we can use byakkokaninjinto to treat the patients with jou-syou, tyouijoukito to treat the patients with chu-syou, and rokumigan to treat the patients with ka-shou.
Treatment of Diabetes Mellitus Using Japanese Kampo Medicines We can divide the treatment of diabetes mellitus using Kampo medicines into three patterns: (1) hyperglycemia, (2) subjective symptoms, and (3) complications of diabetes mellitus. Japanese Kampo Medicines for the Treatment of Common Diseases: Focus on Inflammation. http://dx.doi.org/10.1016/B978-0-12-809398-6.00008-1 Copyright © 2017 Elsevier Inc. All rights reserved.
69
70 Chapter 8
Hyperglycemia Byakkokaninjinto, made from sekkou, chimo, ninjin, kyoumai, and kanzo, is used to treat patients with the main symptoms, such as thirst and polydipsia, belonging to the jou-syou category. Sekkou and chimo are known for their effect of decreasing blood glucose levels (Suzuki et al., 1984). It is reported that byakkokaninjinto improved the blood glucose levels of diabetes mellitus model mice (Nagayoshi et al., 1966). In addition, it is reported that bofutsusyosan and gosyajinkigan have the effect of improving insulin resistance (Uno et al., 2005).
Subjective Symptoms Thirst, Polydipsia, and Polyuria Byakkokaninjinto is used to treat patients having thirst, polydipsia, and polyuria. Goreisan is used to treat patients having thirst, polydipsia, edema, and oliguria. Hachimijiougan is used to treat patients having weakness of the lower limbs, chills, numbness, and nocturnal incontinence. Gosyajinkigan, which is made from goshitsu, syazenshi, and hachimijiougan, is used to treat patients having prominent chills of the lower limbs and edema. Seishinrenshiin is used to treat patients with gastrointestinal weakness, chills, residual urine, frequent urination, oversensitivity, and insomnia (Fukuzawa, 2015). Fatigue Juzentaihoto is used to treat patients having fatigue, tendency toward anemia, chillness of the limbs, and drying of the skin and mucosa. Hochuekkito is used to treat patients with fatigue of the limbs, gastrointestinal weakness, appetite loss, and postprandial sleepiness (Fukuzawa, 2015). Obesity Daisaikoto is used to treat patients with obesity, shoulder stiffness, and constipation. It is also used to treat patients having hypertension and dyslipidemia. Bofutsusyosan is used to treat patients with obesity, pot belly, rush of blood to the head, and constipation. Bouiougito is used to treat patients having fatigue, flabby skin, edema, excessive sweating, and arthralgia (Shimada et al., 2011). Yokukansan is reported to significantly decrease the body weight loss of the patients with obesity. It is reported that daisaikoto, bofutsusyosan, and bouiougito decrease body weight by improving lipid metabolism and decreasing fat tissue (Yoshida et al., 1995a,b,c; Li et al., 2009; Akagiri et al., 2008; Ohira et al., 2015). Bofutsusyosan is reported to have the effect of decreasing body weight (Iwasaki et al., 2007; Itoh et al., 2005). In addition, bofutsusyosan also has the effects of decreasing visceral fat, blood glucose levels, and blood cholesterol levels (Hiroki et al., 2004).
Japanese Kampo Medicines for Diabetes Mellitus 71
Complications of Diabetes Mellitus Diabetic Neuropathy The patients with diabetes mellitus also have frequent muscle cramps. Shakuyakukanzoto has been reported to have rapid effects on muscle cramps so that it can be used for the treatment of diabetes-associated muscle cramps (Yoshida et al., 1995a,b,c). Similarly, hachimijiougan has the effect of relieving numbness. There is a report suggesting that gosyajinkigan significantly relieved numbness and was superior to mecobalamin (Sato et al., 2006). Dysautonomia Orthostatic Hypotension Hangebyakujutsutenmato is used to treat patients with gastrointestinal weakness, dizziness, and headache. Similarly, reikeijuchukanto is used to treat patients having dizziness due to bad metabolism, palpitation, rush of blood to the head, headache, and decreased urine volume (Fukuzawa, 2015). Symptoms of Upper Digestive Tract, Stool Abnormalities
Hangesyakushinto, rikkunshito, and ninjinto are used to treat patients having gastric atony (such as dull feeling in the stomach). Hangesyakushinto, shinbuto, and keishikasyakuyakuto are used to treat patients having diarrhea. Keishikasyakuyakudaioto and mashijingan are used to treat the patients having constipation (Fukuzawa, 2015). Neogenic Bladder Dysfunction, Impotence
Hachimijiougan, gosyajinkigan, and seishinrennshiin are used to treat patients with neogenic bladder dysfunction. Similarly, hachimijiougan is used to treat patients having impotence and sexual debility (Fukuzawa, 2015). Diabetic Nephropathy Saireito, which includes syousaikoto and goreisan, has beneficial effects on the treatment of nephrotic syndrome, and it is reported that saireito treatment has improved the clinical condition of microalbuminuria (Aiso et al., 2011). Saireito is also used to treat patients with thirst, edema, and dizziness. Tokishakuyakusan is used to treat patients with cold hands and feet, edema, and dizziness. Seishinrennshiin is used to treat patients with gastrointestinal weakness, pollakiuria, residual urine, urodynia, and dysuria (Fukuzawa, 2015). Diabetic Retinopathy Keishibukuryogan is used to treat patients experiencing chills and rush of blood to the head. Unseiin, which includes shimotsuto and orengedokuto, is used to treat patients with chills, rush of blood to the head, irritation, dry skin and eyes, and cerebral hemorrhage (Fukuzawa, 2015).
72 Chapter 8 Table 8.1: List of Japanese Kampo Medicines for Diabetes Mellitus Kampo Medicine
Symptoms Treated
Byakkokaninjinto Daisaikoto Bofutsushosan Goreisan Hachimijiougan Gosyajinkigan Rokumigan Seishinrenshiin Syakuyakukanzoto
Thirst, polydipsia, polyuria Obesity, constipation, chest side painfulness Weight gain, pot belly, rush of blood to the head, constipation Thirst, edema, polydipsia without polyuria Pollakiuria, thirst, coldness and numbness of lower half of body, edema Pollakiuria, thirst, prominent coldness and edema of lower limbs Pollakiuria, thirst, numbness of lower half of body without coldness Chills, pollakiuria, gastrointestinal weakness, oversensitivity Dehydration, leg cramps
Revised edition Fukuzawa, M., Diabetes mellitus and Kampo medicine. J. Jpn. Soc. Med. Func. Foods 2015. 9 (3), 128–130.
Conclusion The clinical use of Japanese Kampo medicines for the treatment of patients with diabetes mellitus is increasing. There are several reports of the beneficial effects of Kampo medicines in treating patients with diabetes mellitus. We have given a list of a few important Kampo medicines used in the treatment of diabetes mellitus and its symptoms in Table 8.1. The identification of the possible mechanisms of action of these Kampo medicines would further improve their potential usage for the treatment of various disease conditions.
References Aiso, Y., Ito, K., Sugawara, M., 2011. The examination of clinical usefulness of Saireito to early diabetic Nephropathy. Jpn. J. Med. Pharm. Sci. 65 (6), 751–755. Akagiri, S., Naito, Y., Ichikawa, H., et al., 2008. Bofutsushosan, an oriental herbal medicine, attenuates the weight gain of white Adipose tissue and the increased size of Adipocytes associated with the increase in their expression of uncoupling protein 1 in high-fat diet-fed male KK/Ta mice. J. Clin. Biochem. Nutr. 42, 158–166. Fukuzawa, M., 2015. Diabetes mellitus and Kampo medicine. J. Jpn. Soc. Med. Func. Foods 9 (3), 128–130. Hiroki, C., Yoshimoto, K., Yoshida, T., 2004. Efficacy of Bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin. Exp. Pharmacol. Physiol. 31, 614–619. Itoh, T., Senda, S., Inoue, H., et al., 2005. The effect of Bofutsusyosan on weight reduction in humans. Kampo Med. 56, 933–939. Iwasaki, M., Yagi, T., Shichiri, M., 2007. The effect of Bofutsusyosan on the patients have obesity. J. Jpn. Soc. Study Obes. 13, 137–142. Li, Y., Koikeda, T., Ueda, T., et al., 2009. The effect of general-purpose Daisaikoto on obesity. Jpn. J. Med. Pharm. Sci. 61, 499–509. Nagayoshi, S., Nishiura, T., Hagiwara, Y., 1966. The effect of Hachimijiogan on alloxan-induced diabetes mellitus. Kampo Med. 17 (1), 236–239. Ohira, M., Saiki, A., Yamaguchi, T., Imamura, H., Sato, Y., Ban, N., Kawana, H., Nagumo, A., Tatsuno, I., Kosuge, T., Akiba, T., 2015. The efficacy of Yokukansan in obesity patients on overeating due to anger (a retrospective study). Kampo Med. 66 (3), 191–196. Sato, Y., Uno, T., Oyun, K., Koide, T., Tamagawa, T., Bolin, Q., 2006. Role of herbal medicine (Kampo formulations) on the prevention and treatment of diabetes and diabetic complications. J. Tradit. Med. 23, 185–195.
Japanese Kampo Medicines for Diabetes Mellitus 73 Shimada, T., Akase, T., Kosugi, M., et al., 2011. Preventive effect of Boiogito on metabolic disorders in the TSOD mouse, a model of spontaneous obese type II diabetes mellitus. Evid. Based Complement. Alternat. Med. 931073. Suzuki, J., et al., 1984. Folia Pharmacol. Jpn. 83 (1), 1. Uno, T., Ohsawa, I., Tokudome, M., Sato, Y., 2005. Effects of Gosyajinkigan on insulin resistance in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 69, 129–135. Yoshida, A., et al., 1995a. Neurolog. Therap. 12, 534–592. Yoshida, T., et al., 1995b. J. Jpn. Soc. Study Obes. 1 (2), 122–155. Yoshida, T., et al., 1995c. Int. J. Obes. 19, 717–722.
Japanese Kampo Medicines for Diabetes Mellitus Hiroshi Suzuki1,2, Hirohito Sone2, Kenichi Watanabe1 1Niigata
University of Pharmacy and Applied Life Sciences, Niigata, Japan; 2Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
Introduction There is a long history of the use of Japanese Kampo medicines for the treatment of diabetes mellitus and these medicines are now gaining favorable attention. Despite better blood glucose level control offered by Western medicine, Japanese Kampo medicines can be adopted for the treatment of diabetes mellitus because of their favorable safety profile over Western medicine. Here we illustrate the disease state of diabetes mellitus and the use of Kampo medicines for the treatment of diabetes mellitus.
The Disease State of Diabetes Mellitus “Syo-katsu,” a term that originated in China and has been used since 50 BCE, refers to symptoms that resemble diabetes mellitus. The symptoms of syo-katsu consist of thirst and polyuria, which are very similar to the symptoms of diabetes mellitus. Diabetes mellitus can be divided into three states of medical conditions: “jou-syou,” “chu-syou,” and “ka-shou.” The disease states of jou-syou are thirst, polyuria, and body weight loss, which are initial symptoms of diabetes mellitus of the nonobese type. Similarly, the disease states of chu-syou are hunger, bulimia, and severe body weight loss, which belong to the obesity type. Finally, the disease states of ka-shou are polyuria, red tongue, and darkish face, which are the advanced symptoms of diabetes mellitus. In general practice, we can use byakkokaninjinto to treat the patients with jou-syou, tyouijoukito to treat the patients with chu-syou, and rokumigan to treat the patients with ka-shou.
Treatment of Diabetes Mellitus Using Japanese Kampo Medicines We can divide the treatment of diabetes mellitus using Kampo medicines into three patterns: (1) hyperglycemia, (2) subjective symptoms, and (3) complications of diabetes mellitus. Japanese Kampo Medicines for the Treatment of Common Diseases: Focus on Inflammation. http://dx.doi.org/10.1016/B978-0-12-809398-6.00008-1 Copyright © 2017 Elsevier Inc. All rights reserved.
69
70 Chapter 8
Hyperglycemia Byakkokaninjinto, made from sekkou, chimo, ninjin, kyoumai, and kanzo, is used to treat patients with the main symptoms, such as thirst and polydipsia, belonging to the jou-syou category. Sekkou and chimo are known for their effect of decreasing blood glucose levels (Suzuki et al., 1984). It is reported that byakkokaninjinto improved the blood glucose levels of diabetes mellitus model mice (Nagayoshi et al., 1966). In addition, it is reported that bofutsusyosan and gosyajinkigan have the effect of improving insulin resistance (Uno et al., 2005).
Subjective Symptoms Thirst, Polydipsia, and Polyuria Byakkokaninjinto is used to treat patients having thirst, polydipsia, and polyuria. Goreisan is used to treat patients having thirst, polydipsia, edema, and oliguria. Hachimijiougan is used to treat patients having weakness of the lower limbs, chills, numbness, and nocturnal incontinence. Gosyajinkigan, which is made from goshitsu, syazenshi, and hachimijiougan, is used to treat patients having prominent chills of the lower limbs and edema. Seishinrenshiin is used to treat patients with gastrointestinal weakness, chills, residual urine, frequent urination, oversensitivity, and insomnia (Fukuzawa, 2015). Fatigue Juzentaihoto is used to treat patients having fatigue, tendency toward anemia, chillness of the limbs, and drying of the skin and mucosa. Hochuekkito is used to treat patients with fatigue of the limbs, gastrointestinal weakness, appetite loss, and postprandial sleepiness (Fukuzawa, 2015). Obesity Daisaikoto is used to treat patients with obesity, shoulder stiffness, and constipation. It is also used to treat patients having hypertension and dyslipidemia. Bofutsusyosan is used to treat patients with obesity, pot belly, rush of blood to the head, and constipation. Bouiougito is used to treat patients having fatigue, flabby skin, edema, excessive sweating, and arthralgia (Shimada et al., 2011). Yokukansan is reported to significantly decrease the body weight loss of the patients with obesity. It is reported that daisaikoto, bofutsusyosan, and bouiougito decrease body weight by improving lipid metabolism and decreasing fat tissue (Yoshida et al., 1995a,b,c; Li et al., 2009; Akagiri et al., 2008; Ohira et al., 2015). Bofutsusyosan is reported to have the effect of decreasing body weight (Iwasaki et al., 2007; Itoh et al., 2005). In addition, bofutsusyosan also has the effects of decreasing visceral fat, blood glucose levels, and blood cholesterol levels (Hiroki et al., 2004).
Japanese Kampo Medicines for Diabetes Mellitus 71
Complications of Diabetes Mellitus Diabetic Neuropathy The patients with diabetes mellitus also have frequent muscle cramps. Shakuyakukanzoto has been reported to have rapid effects on muscle cramps so that it can be used for the treatment of diabetes-associated muscle cramps (Yoshida et al., 1995a,b,c). Similarly, hachimijiougan has the effect of relieving numbness. There is a report suggesting that gosyajinkigan significantly relieved numbness and was superior to mecobalamin (Sato et al., 2006). Dysautonomia Orthostatic Hypotension Hangebyakujutsutenmato is used to treat patients with gastrointestinal weakness, dizziness, and headache. Similarly, reikeijuchukanto is used to treat patients having dizziness due to bad metabolism, palpitation, rush of blood to the head, headache, and decreased urine volume (Fukuzawa, 2015). Symptoms of Upper Digestive Tract, Stool Abnormalities
Hangesyakushinto, rikkunshito, and ninjinto are used to treat patients having gastric atony (such as dull feeling in the stomach). Hangesyakushinto, shinbuto, and keishikasyakuyakuto are used to treat patients having diarrhea. Keishikasyakuyakudaioto and mashijingan are used to treat the patients having constipation (Fukuzawa, 2015). Neogenic Bladder Dysfunction, Impotence
Hachimijiougan, gosyajinkigan, and seishinrennshiin are used to treat patients with neogenic bladder dysfunction. Similarly, hachimijiougan is used to treat patients having impotence and sexual debility (Fukuzawa, 2015). Diabetic Nephropathy Saireito, which includes syousaikoto and goreisan, has beneficial effects on the treatment of nephrotic syndrome, and it is reported that saireito treatment has improved the clinical condition of microalbuminuria (Aiso et al., 2011). Saireito is also used to treat patients with thirst, edema, and dizziness. Tokishakuyakusan is used to treat patients with cold hands and feet, edema, and dizziness. Seishinrennshiin is used to treat patients with gastrointestinal weakness, pollakiuria, residual urine, urodynia, and dysuria (Fukuzawa, 2015). Diabetic Retinopathy Keishibukuryogan is used to treat patients experiencing chills and rush of blood to the head. Unseiin, which includes shimotsuto and orengedokuto, is used to treat patients with chills, rush of blood to the head, irritation, dry skin and eyes, and cerebral hemorrhage (Fukuzawa, 2015).
72 Chapter 8 Table 8.1: List of Japanese Kampo Medicines for Diabetes Mellitus Kampo Medicine
Symptoms Treated
Byakkokaninjinto Daisaikoto Bofutsushosan Goreisan Hachimijiougan Gosyajinkigan Rokumigan Seishinrenshiin Syakuyakukanzoto
Thirst, polydipsia, polyuria Obesity, constipation, chest side painfulness Weight gain, pot belly, rush of blood to the head, constipation Thirst, edema, polydipsia without polyuria Pollakiuria, thirst, coldness and numbness of lower half of body, edema Pollakiuria, thirst, prominent coldness and edema of lower limbs Pollakiuria, thirst, numbness of lower half of body without coldness Chills, pollakiuria, gastrointestinal weakness, oversensitivity Dehydration, leg cramps
Revised edition Fukuzawa, M., Diabetes mellitus and Kampo medicine. J. Jpn. Soc. Med. Func. Foods 2015. 9 (3), 128–130.
Conclusion The clinical use of Japanese Kampo medicines for the treatment of patients with diabetes mellitus is increasing. There are several reports of the beneficial effects of Kampo medicines in treating patients with diabetes mellitus. We have given a list of a few important Kampo medicines used in the treatment of diabetes mellitus and its symptoms in Table 8.1. The identification of the possible mechanisms of action of these Kampo medicines would further improve their potential usage for the treatment of various disease conditions.
References Aiso, Y., Ito, K., Sugawara, M., 2011. The examination of clinical usefulness of Saireito to early diabetic Nephropathy. Jpn. J. Med. Pharm. Sci. 65 (6), 751–755. Akagiri, S., Naito, Y., Ichikawa, H., et al., 2008. Bofutsushosan, an oriental herbal medicine, attenuates the weight gain of white Adipose tissue and the increased size of Adipocytes associated with the increase in their expression of uncoupling protein 1 in high-fat diet-fed male KK/Ta mice. J. Clin. Biochem. Nutr. 42, 158–166. Fukuzawa, M., 2015. Diabetes mellitus and Kampo medicine. J. Jpn. Soc. Med. Func. Foods 9 (3), 128–130. Hiroki, C., Yoshimoto, K., Yoshida, T., 2004. Efficacy of Bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance. Clin. Exp. Pharmacol. Physiol. 31, 614–619. Itoh, T., Senda, S., Inoue, H., et al., 2005. The effect of Bofutsusyosan on weight reduction in humans. Kampo Med. 56, 933–939. Iwasaki, M., Yagi, T., Shichiri, M., 2007. The effect of Bofutsusyosan on the patients have obesity. J. Jpn. Soc. Study Obes. 13, 137–142. Li, Y., Koikeda, T., Ueda, T., et al., 2009. The effect of general-purpose Daisaikoto on obesity. Jpn. J. Med. Pharm. Sci. 61, 499–509. Nagayoshi, S., Nishiura, T., Hagiwara, Y., 1966. The effect of Hachimijiogan on alloxan-induced diabetes mellitus. Kampo Med. 17 (1), 236–239. Ohira, M., Saiki, A., Yamaguchi, T., Imamura, H., Sato, Y., Ban, N., Kawana, H., Nagumo, A., Tatsuno, I., Kosuge, T., Akiba, T., 2015. The efficacy of Yokukansan in obesity patients on overeating due to anger (a retrospective study). Kampo Med. 66 (3), 191–196. Sato, Y., Uno, T., Oyun, K., Koide, T., Tamagawa, T., Bolin, Q., 2006. Role of herbal medicine (Kampo formulations) on the prevention and treatment of diabetes and diabetic complications. J. Tradit. Med. 23, 185–195.
Japanese Kampo Medicines for Diabetes Mellitus 73 Shimada, T., Akase, T., Kosugi, M., et al., 2011. Preventive effect of Boiogito on metabolic disorders in the TSOD mouse, a model of spontaneous obese type II diabetes mellitus. Evid. Based Complement. Alternat. Med. 931073. Suzuki, J., et al., 1984. Folia Pharmacol. Jpn. 83 (1), 1. Uno, T., Ohsawa, I., Tokudome, M., Sato, Y., 2005. Effects of Gosyajinkigan on insulin resistance in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 69, 129–135. Yoshida, A., et al., 1995a. Neurolog. Therap. 12, 534–592. Yoshida, T., et al., 1995b. J. Jpn. Soc. Study Obes. 1 (2), 122–155. Yoshida, T., et al., 1995c. Int. J. Obes. 19, 717–722.