Goshajinkigan

Common Name(s): Goshajinkigan , Gosha-jinki-gan , GJG

Uses

The medical literature primarily documents the use of gosha-jinki-gan (GJG) in treating overactive bladder and diabetes; however, data from quality clinical trials are lacking to support these uses.

Dosing

Most clinical studies utilized a dosage range of 4.5 to 7.5 g/day.

Contraindications

GJG is composed of 10 crude traditional Japanese medicinal herbs; avoid use if hypersensitivity to any of the plant ingredients exists.

Pregnancy/Lactation

Avoid use during pregnancy and lactation.

Interactions

GJG interacts with dioxins, melatonin, oxaliplatin, and paclitaxel.

Adverse Reactions

In one study, patients reported mild adverse symptoms, including diarrhea, nausea, and urinary frequency. No abnormalities were recorded from hematology, biochemistry, and urinalysis results in another study.

Toxicology

A case report documented GJG causing interstitial pneumonia in an elderly patient.

GJG is composed of 10 crude drugs (see table) mixed with 19 parts lactose. 1

Botanical Latin Plant source Amount
Rehmanniae radix Rehmania glutinosa (Gaertn.) Li 5 g
Achyranthis radix Achyranthes fauriei H. Lév. & Vaniot 3 g
Corni fructus Cornus officinalis Siebold & Zucc. 3 g
Moutan cortex Paeonia moutan Sims 3 g
Alismatis rhizoma Alisma plantago-aquatica var. orientale Sam. 3 g
Dioscoreae rhizoma Dioscorea japonica Thunb. 3 g
Dioscorea opposita Thunb.
Plantaginis semen Plantago asiatica L. 3 g
Hoelen Poria cocos F.A. Wolf 3 g
processed Aconiti tuber Aconitum carmichaeli Debeaux 1 g
Cinnamomi cortex Cinnamomum cassia (L.) C. Presl. 1 g

History

Traditional Japanese Kampo medicines utilize aqueous extracts of plant material mixtures. 2 , 3 Various formulations have been used for thousands of years to treat diseases and promote good health. Treatment is based on symptoms rather than disease, and the herbal medicine GJG has been prescribed for fatigue, cold extremities, leg numbness and pain, copious urine with thirst, lumbago, and geriatric cloudy vision. 3

Chemistry

Review of the medical literature documents limited specific chemical studies on GJG.

Uses and Pharmacology

The medical literature primarily documents the use of GJG in treating overactive bladder and diabetes.

Bladder
Animal data

GJG inhibited rhythmic bladder contractions in anesthetized dogs at 100 mg/kg. 4 Intravenous administration of GJG at 10 and 100 mg/kg inhibited urinary bladder contraction induced by pelvic nerve stimulation, and GJG 100 mg/kg inhibited acetylcholine-induced bladder contraction. 5

In rats, GJG increased voiding bladder capacity, voiding interval, micturition volume, and threshold pressure, and pretreatment with GJG partially blocked detrusor muscle overactivity induced by intravesical administration of acetic acid. 6 C-fiber activation of transmitter proteins and sensory receptors induced by acetic acid was reduced in rats pretreated with GJG. 7 GJG may also inhibit bladder activity by interacting with the autonomic nervous system. 8 GJG did not inhibit the amplitude of bladder contractions in rats, and the effect on urinary frequency is not associated with anticholinergic activity. The mechanism of action involves decreased bladder sensation through spinal kappa-opioid receptors, which are associated with delayed full bladder sensation and increased bladder capacity. 1

Human data

Lower urinary tract symptoms (ie, flow and residual urine volume) improved 8 weeks after administration of GJG in 20 patients with prostatic disease. 9 Similar efficacy is documented in another study involving 25 patients treated with GJG, 10 with the mechanism of action involving activation of spinal kappa-opioid receptors leading to inhibition of the micturition reflex and inhibition of C-fiber activation of transmitter proteins and sensory receptors. In another clinical study of 30 patients, GJG improved similar lower urinary tract symptoms, as well as nocturia and urinary incontinence. 11 Although the details of the study could not be obtained, a clinical study of 704 patients treated with GJG 4.5 g/day for 1 year claimed improved symptoms of overactive bladder (ie, urge to urinate, daytime urinary frequency, nocturia, and urine leak) and quality of life. 12 A single treatment of GJG 7.5 g in 44 women documented improved symptoms of overactive bladder. 13

Diabetes
In vitro and animal data

A study on experimental diabetes found that GJG 417 mg/kg/day (5 times the daily dose in humans) inhibited the decrease in glucose tolerance by cyproheptadine. Induced peripheral neuropathy in rats was reduced by a dosage of GJG 209 mg/kg/day (2.5 times the daily dose in humans). 14 The vasodilating effects of GJG improved peripheral circulation in diabetic rats through increased production of nitric oxide. 15 The increased concentrations of nitric oxide may be associated with GJG antinociceptive effects in diabetic rats. 16 A single dose of GJG improved insulin resistance and glucose utilization in diabetic rats, potentially through a physiological link via the nitric oxide pathway. 17 GJG improved insulin sensitivity with or without exogenous insulin in diabetic rats, potentially by correcting abnormal insulin signaling in skeletal muscle. 18 Treatment with GJG in diabetic rats reduced nitroxidative stress and lipid peroxidation in the retina, and improved glucose metabolism within the cells. 19 Hypertriglyceridemia induced by consuming a sucrose-rich diet was reduced in rats administered GJG. 20

Human data

A 1-month clinical study examined the effects of GJG 7.5 g/day on insulin resistance in 71 patients with type 2 diabetes. At the end of the study, GJG reduced total cholesterol and triglyceride levels and improved insulin resistance. 21 , 22 A clinical study documents how GJG may improve ocular surface disorders, such as corneal sensitivity, superficial punctuate keratopathy (ie, irritation of cornea), and tear production in patients with insulin-dependent diabetes mellitus. 23 GJG may also improve visual disturbance due to cataracts. 24 A small study of 13 patients with diabetic neuropathy treated with GJG 7.5 g/day reported improved vibration sensation and relief from subjective symptoms, such as numbness and cold sensation. 25

Other pharmacologic uses
Bone

GJG reduced trabecular bone loss and improved bone microstructure as assessed by microcomputed tomography in ovariectomized rats. 26

Lower back pain

Three small clinical trials document the efficacy of GJG in treating lower back and lower leg pain, potentially by acting on opioid receptors. 27 , 28 , 29

Lymphedema

GJG may reduce lymphedema secondary to surgical procedures. 30

Male infertility

A small study of 30 infertile male patients administered a daily dosage of GJG 5 g/day for 3 months or more resulted in improved sperm motility and, in some patients, increased sperm count. 31 , 32

Muscle cramps

In a trial of 38 patients treated with GJG 30 mg/kg 3 times a day for 12 consecutive weeks, GJG reduced painful muscle cramps associated with hepatic cirrhosis. 33

Dosage

Most clinical studies utilized a dosage range of 4.5 to 7.5 g/day. 12 , 13 , 25

Contraindications

GJG is composed of 10 crude traditional Japanese medicinal herbs; therefore, avoid use if hypersensitivity to any of the plant ingredients exists.

Pregnancy/Lactation

Avoid use during pregnancy and lactation.

Interactions

Dioxins and related organochlorine compounds

A Kampo formula containing GJG significantly improved respiratory symptoms caused by dioxins. 34

Melatonin

Diurnal plasma melatonin was reduced in patients treated with GJG. 35

Oxaliplatin

Peripheral and sensory neurotoxicity are major adverse effects related to oxaliplatin therapy. The symptoms include paresthesia and dysestheia of the extremities induced by cold exposure. Three clinical studies document that coadministration of GJG with oxaliplatin reduced the neurotoxicity in patients with colorectal cancer. Two mechanisms have been proposed: GJG promotes release of dynorphin, which helps improve numbness and pallesthesia through the opiate system; GJG enhances nitric oxide production, improving circulation and blood supply to the nerves. 36 , 37 , 38

Paclitaxel

GJG may improve paclitaxel-induced peripheral neuropathy by increasing blood flow through production of nitric oxide and an analgesic effect by activating opioid receptors. 39 , 40

Adverse Reactions

In one study, patients reported mild adverse symptoms, including diarrhea, nausea, and urinary frequency. 11 In another study, no abnormalities were recorded from hematology, biochemistry, and urinalysis results. 28

Toxicology

A case report documents GJG as causing drug-induced interstitial pneumonia in an elderly patient. 41

Bibliography

1. Gotoh A, Goto K, Sengoku A, et al. Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats. J Pharmacol Sci . 2004;96(2):115-123.
2. Hu X, Sato J, Bajotto G, et al. Goshajinkigan (Chinese herbal medicine niu-che-sen-qi-wan) improves insulin resistance in diabetic rats via the nitric oxide pathway. Nagoya J Med Sci . 2010;72(1-2):35-42.
3. Nishizawa M, Sutherland WH, Nukada H. Gosha-jinki-gan (herbal medicine) in streptozocin-induced diabetic neuropathy. J Neurol Sci . 1995;132(2):177-181.
4. Suzuki T, Kurokawa K, Suzuki K, et al. Effects of Gosha-Jinki-Gan on the function of the urinary bladder in anesthetized dogs [in Japanese]. Hinyokika Kiyo . 1996;42(12):951-955.
5. Suzuki T, Higashi H, Saitoh K, Kurokawa K, Ohma C, Yamanaka H. Effects of gosha-jinki-gan on urinary bladder contraction in dogs [in Japanese]. Hinyokika Kiyo . 1997;43(4):271-274.
6. Zhang X, Ishizuka O, Tanabe T, et al. Effects of goshajinkigan (niu-che-sen-qi-wan) for resiniferatoxin-sensitive afferents on detrusor overactivity induced by acetic acid in conscious rats. Am J Chin Med . 2006;34(2):285-293.
7. Imamura T, Ishizuka O, Aizawa N, et al. Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder. Neurourol Urodyn . 2008;27(8):832-837.
8. Nishijima S, Sugaya K, Miyazato M, Ogawa Y. Effect of Gosha-jinki-gan, a blended herbal medicine, on bladder activity in rats. J Urol . 2007;177(2):762-765.
9. Watanabe A, Akashi T, Fujiuchi Y, Mizuno I, Nagakawa O, Fuse H. The efficacy of Gosyajinkigan for pollakisuria [in Japanese]. Hinyokika Kiyo . 2006;52(3):197-201.
10. Fujiuchi Y, Watanabe A, Fuse H. Effect of Goshajinkigan on storage symptoms in prostatic disease—fundamental researches of Chinese herbal medicine for voiding dysfunction and its future aspects [in Japanese]. Hinyokika Kiyo . 2008;54(6):463-466.
11. Ogushi T, Takahashi S. Effect of Chinese herbal medicine on overactive bladder. Hinyokika Kiyo . 2007;53(12):857-862.
12. Nishizawa Y, Yoshioka H et al. Efficacy and safety of Chinese traditional medicine, Niu-Che-Shwn-Qi-Wan (Japanese name: Goshajinki-gan) versus propiverine hydrochloride on health-related quality of life patients with overactive bladder in prospective randomized comparative study. Kampo to Saishin-chiryo (Kampo and the Newest Therapy) . 2007;16:131-142.
13. Kajiwara M, Mutaguchi K. Clinical efficacy and tolerability of gosha-jinki-gan, Japanese traditional herbal medicine, in females with overactive bladder. Hinyokika Kiyo . 2008;54(2):95-99.
14. Shoji M, Sato H, Hirai Y, et al. Pharmacological effects of Gosha-jinki-gan-ryo extract: effects on experimental diabetes [in Japanese]. Nippon Yakurigaku Zasshi . 1992;99(3):143-152.
15. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J. Effect of Gosha-jinki-gan, a Kampo medicine, on enhanced platelet aggregation in streptozotocin-induced diabetic rats. Jpn J Pharmacol . 1998;78(1):87-91.
16. Suzuki Y, Goto K, Ishige A, Komatsu Y, Kamei J. Antinociceptive mechanism of Gosha-jinki-gan in streptozotocin-induced diabetic animals: role of nitric oxide in the periphery. Jpn J Pharmacol . 1999;79(3):387-391.
17. Hu X, Sato J, Oshida Y, Xu M, Bajotto G, Sato Y. Effect of Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-Sen-Qi-Wan) on insulin resistance in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract . 2003;59(2):103-111.
18. Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Gosha-jinki-gan (a herbal complex) corrects abnormal insulin signaling. Evid Based Complement Alternat Med . 2004;1(3):269-276.
19. Cameron-Schaefer S, Kondo K, Ishige A, et al. Maintaining the redox-balance intact: gosha-jinki-gan but not insulin activates retinal soluble guanylate cyclase in diabetic rats. Ophthalmic Res . 2006;38(2):95-104.
20. Hirotani Y, Ikeda K, Myoutoku M. Effects of the herbal medicine goshajinkigan on sucrose-rich diet-induced hypertriglyceridemia in rats. J Trad Med . 2009;26(4):187-193.
21. Sato Y, Uno T, Oyun K, Koide T, Tamagawa T, Bolin Q. Role of herbal medicine (Kampo formulations) on the prevention and treatment of diabetes and diabetic complications. J Trad Med . 2006;23(6):185-195.
22. Uno T, Ohsawa I, Tokudome M, Sato Y. Effects of Goshajinkigan on insulin resistance in patients with type 2 diabetes. Diabetes Res Clin Pract . 2005;69(2):129-135.
23. Nagaki Y, Hayasaka S, Hayasaka Y, et al. Effects of goshajinkigan on corneal sensitivity, superficial punctate keratopathy and tear secretion in patients with insulin-dependent diabetes mellitus. Am J Chin Med . 2003;31(1):103-109.
24. Usuki Y, Usuki S, Hommura S. Successful treatment of a senile diabetic woman with cataract with goshajinkigan. Am J Chin Med . 1991;19(3-4):259-263.
25. Tawata M, Kurihara A, Nitta K, Iwase E, Gan N, Onaya T. The effects of goshajinkigan, a herbal medicine, on subjective symptoms and vibratory threshold in patients with diabetic neuropathy. Diabetes Res Clin Pract . 1994;26(2):121-128.
26. Yao X, Chen H, Emura S, Otake N, Shoumura S. Effects of hPTH (1-34) and Gosha-jinki-gan on the trabecular bone microarchitecture in ovariectomized rat tibia. Okajimas Folia Anat Jpn . 2007;83(4):107-113.
27. Ota H. Positioning of Kampo therapy and hormone replacement therapy in treatment of climacteric disorders [in Japanese]. Sanfujinka Kampo Kenkyu no Ayumi (Recent Progress of Kampo Medicine in Obstetrics and Gynecology) . 2001;18:21-29.
28. Sekine R, Watanabe H, Mimura M, et al. The effects of Gosha-jinki-gan on the low back pain and lower limb pain caused by the lumbar spine: A comparison of Gosha-jinki-gan with Benfotiamine [in Japanese with English abstract]. Itami to Kampo (Pain and Kampo Medicine) . 2003;13:84-87.
29. Maeshima S, Katayama Y. Spine and spinal cord diseases 1. Traditional Chinese medicines for the spinal disorders [in Japanese]. Kampo to Saishin-Chiryo (Kampo & the Newest Therapy) . 2004;13:232-236.
30. Abe Y. The efficacy of goshajinkigan against lymphedema [in Japanese]. Kampo Medicine . 2002;25:284-287.
31. Takayama H, Konishi T, Kounami T, et al. Clinical effects of goshajinkigan for male infertility [in Japanese]. Hinyokika Kiyo . 1984;30(11):1685-1689.
32. Amano T, Kunimi K, Ohkawa M. Analysis of fluorescence spectra from Chinese herbal medicine for male infertility. Am J Chin Med . 1995;23(3-4):213-221.
33. Nishizawa Y, Nishizawa Y, Amemori Y, et al. A randomized paralleled group comparison in multicenter cooperation: analgesic effect and safety with gosha- jinki-gan and shakuyaku-kanzo-to in the treatment of painful muscle cramps in patients with cirrhosis [in Japanese with English abstract]. Itami to Kampo (Pain and Kampo Medicine) . 2000;10:13-18.
34. Uchi H, Tokunaga S, Mitoma C, et al. A clinical trial of Kampo formulae for the treatment of symptoms of yusho, a poisoning caused by dioxins and related organochlorine compounds [published online ahead of print December 8, 2009]. Evid Based Complement Alternat Med . doi:10.1093/ecam/nep209.
35. Watanabe H, Kobayashi T, Tomii M, et al. Effects of Kampo herbal medicine on plasma melatonin concentration in patients. Am J Chin Med . 2002;30(1):65-71.
36. Mamiya N, Kono T, Mamiya K, Satomi M, Chisato N, Ebisawa Y. A case of neurotoxicity reduced with goshajinkigan in modified FOLFOX6 chemotherapy for advanced colon cancer [in Japanese]. Gan To Kagaku Ryoho . 2007;34(8):1295-1297.
37. Shindo Y, Tenma K, Imano H, Hibino M, Yoshino K, Nakamura M. Reduction of oxaliplatin-related neurotoxicity by Gosha-jinki-gan [in Japanese]. Gan To Kagaku Ryoho . 2008;35(5):863-865.
38. Kono T, Mamiya N, Chisato N, et al. Efficacy of goshajinkigan for peripheral neurotoxicity of oxaliplatin in patients with advanced or recurrent colorectal cancer [published online ahead of print December 1, 2009]. Evid Based Complement Alternat Med . doi:10.1093/ecam/nep200.
39. Hashimoto K, Sakuma Y, Kotani J. Histological study of a paclitaxel-induced peripheral neuropathy model treated with goshajinkigan. J Osaka Dent Univ . 2004;38(2):109-112.
40. Hashimoto K, Sakuma Y, Kotani J. Goshajinkigan improves paclitaxel-induced peripheral neuropathy in rats. J Osaka Dent Univ . 2006;40(1):47-52.
41. Katayama H, Hamada H, Yokoyama A, Kadowaki T, Ito R, Higaki J. A case of interstitial pneumonia caused by gosha-jinki-gan [in Japanese]. Nippon Ronen Igakkai Zasshi . 2004;41(6):675-678.

Copyright © 2009 Wolters Kluwer Health

Hide
(web3)