The Anti-emetic Effect of Banhasasim-tang Intravenous Herbal Acupuncture in MTX-induced Rat-Pica Model

Young-Kwon Cho; Chan Lee; Hyun-Jin Lee; Yun-Kyoung Yim; Cho, Young-Kwon; Lee, Chan; Lee, Hyun-Jin; Yim, Yun-Kyoung

doi:10.13048/jkm.17004

JKM > Volume 38(1); 2017 > Article

Cho, Lee, Lee, and Yim: The Anti-emetic Effect of Banhasasim-tang Intravenous Herbal Acupuncture in MTX-induced Rat-Pica Model

Original Article

The Journal of Korean Medicine 2017; 38(1): 34-45.

Published online: March 31, 2017

DOI: https://doi.org/10.13048/jkm.17004

The Anti-emetic Effect of Banhasasim-tang Intravenous Herbal Acupuncture in MTX-induced Rat-Pica Model

Young-Kwon Cho¹, Chan Lee¹, Hyun-Jin Lee¹

, Yun-Kyoung Yim¹^{, *}

¹Department of Meridian & Acupoints, College of Korean Medicine, Daejeon University

Correspondence to: 임윤경(Yun-Kyoung Yim), Department of Meridian & Acupoints, College of Korean Medicine, Daejeon University, #12407, 62, Daehak-ro, Dong-gu, Daejeon, 34520, Republic of Korea., Tel: +82-42-280-2610, E-mail: docwindy@dju.kr

Received February 1, 2017 Revised March 17, 2017 Accepted March 17, 2017

Abstract

Objectives

This study aimed to investigate the effect of banhasasim-tang intravenous herbal acupuncture (BST-IVHA) on emesis induced by chemotherapy in rats.

Methods

This study used methotrexate(MTX)-induced Rat-Pica model. The rats were randomly allocated into seven groups; normal group, two saline groups, four Banhasasim-tang(BST) groups (groups treated with BST-IVHA). All the experimental animals except those in the normal group were injected with MTX. Those in the pre-treatment groups were treated with saline injection (saline group) or BST-IVHA (BST group) before MTX injection. Those in the post-treatment groups were treated with saline injection or BST-IVHA after MTX injection. Two different dosages of BST-IVHA solution (low dose; BST-1 group, high dose; BST-2 group) were used. The changes in body weight, food intake, and kaolin consumption at 24h, 48h, and 60h were monitored and analyzed.

Results

1. No significant change was found in body weight. 2. The food intake at 48h was increased significantly in the BST-1 pre-treatment group(19.89±0.01g) compared to the pre-saline group(18.68±0.26g). 3. The kaolin consumption was significantly decreased in the BST-1 pre-treatment group at 24h(0.24±0.02g) and 60h(0.36±0.14g), in the BST-2 pre-treatment group at 48h(0.02±0.01g) and 60h(0.80±0.31g) compared to the pre-saline group(24h:0.81±0.37g, 48h:0.76±0.43g, 60h:1.56±0.03g). The kaolin consumption was also significantly decreased in the in the BST-1 post-treatment group at 24h(0.05±0.02g), 48h(0.64±0.06g) and 60h(0.14±0.05g), in the BST-2 post-treatment group at 48h(0.01±0.01g) and 60h(0.01±0.01g) compared to the post-saline group(24h:0.51±0.4g, 48h:3.58±0.33g, 60h:2.5±0.2g).

Conclusions

BST-IVHA showed an anti-emetic effect in MTX-induced rat-pica model. This result suggests that BST-IVHA could be an effective treatment for chemotherapy-induced emesis.

Keywords: Anti-emesis, Banhasasim-tang, Intravenous herbal acupuncture, Chemotherapy, MTX

Fig. 1

Body weight change after MTX injection in pre-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) 24h before and right before MTX injection. Body weight change was monitored every 24 hours after MTX injection.

Normal : No treatment

Pre-Saline : treated with saline (0.4ml) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h before MTX (20mg/kg) injection

Fig. 2

Body weight change after MTX injection in post-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) right after and 24h after MTX injection. Body weight change was monitored every 24 hours after MTX injection.

Normal : No treatment

Post-Saline : treated with saline (0.4ml) 0h and 24h after MTX (20mg/kg) injection

Post-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h after MTX (20mg/kg) injection

Post-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h after MTX (20mg/kg) injection

Fig. 3

Food intake after MTX injection in pre-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) 24h before and right before MTX injection. Food intake was monitored 24h, 48h, and 60h after MTX injection. Each value and vertical bar represent mean±S.D. (n=5)

Normal : No treatment

Pre-Saline : treated with saline (0.4ml) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h before MTX (20mg/kg) injection

** : P<0.01, vs normal group by Mann-Whitney U Test

† : P<0.05 vs saline group by Mann-Whitney U Test

Fig. 4

Food intake after MTX injection in post-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) right after and 24h after MTX injection. Food intake was monitored 24h, 48h, and 60h after MTX injection. Each value and vertical bar represent mean±S.D. (n=5)

Normal : No treatment

Post-Saline : treated with saline (0.4ml) 0h and 24h after MTX (20mg/kg) injection

Post-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h after MTX (20mg/kg) injection

Post-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h after MTX (20mg/kg) injection

** : P<0.01, * : P<0.05 vs normal group by Mann-Whitney U Test

Fig. 5

Kaolin consumption after MTX injection in pre-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) 24h before and right before MTX injection. Kaolin intake was monitored 24h, 48h, and 60h after MTX injection. Each value and vertical bar represent mean±S.D. (n=5)

Normal : No treatment

Pre-Saline : treated with saline (0.4ml) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h before MTX (20mg/kg) injection

Pre-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h before MTX (20mg/kg) injection

*** : P<0.001, * : P<0.05 vs normal group by Mann-Whitney U Test

† : P<0.05 vs saline group by Mann-Whitney U Test

Fig. 6

Kaolin consumption after MTX injection in post-treatment groups

Rats were treated with Banhasasim-tang intravenous herbal acupuncture (BST-IVHA) right after and 24h after MTX injection. Kaolin intake was monitored 24h, 48h, and 60h after MTX injection. Each value and vertical bar represent mean±S.D. (n=5)

Normal : No treatment

Post-Saline : treated with saline (0.4ml) 0h and 24h after MTX (20mg/kg) injection

Post-BST-1 : treated with BST-IVHA (0.4ml, 0.028g/kg) 0h and 24h after MTX (20mg/kg) injection

Post-BST-2 : treated with BST-IVHA (0.4ml, 0.138g/kg) 0h and 24h after MTX (20mg/kg) injection

*** : P<0.001 vs normal group by Mann-Whitney U Test

† : P<0.05 vs saline group by Mann-Whitney U Test

Table 1

The Compositions of Banhasasim-tang(BST)

Herbs	Pharmacognostic name	Dose(g)
半夏	Pinellia ternate Breitenbach	8
黃芩	Scutellaria baicalensis Georgi	6
人蔘	Panax ginseng C. A. Meyer	6
甘草	Glycyrrhiza uralensis Fischer	6
乾薑	Zingiber officinale Roscoe	4
黃連	Coptis japonica Makino	2
生薑	Zingiber officinale Roscoe	4
大棗	Zizyphus jujuba Miller var. inermis Rehder	4
Total amount		40

Table 2

Group Assignment

Group		Treatment
Normal		No treatment

pre-treatment groups	Pre-Saline	Saline injection + MTX

	Pre-BST-1	BST-IVHA (0.028g/kg) + MTX

	Pre-BST-2	BST-IVHA (0.138g/kg) + MTX

post-treatment groups	Post-Saline	MTX + Saline injection

	Post-BST-1	MTX + BST-IVHA (0.028g/kg)

	Post-BST-2	MTX + BST-IVHA (0.138g/kg)

BST-IVHA : Banhasasim-tang intravenous herbal acupuncture

참고문헌

1. Park JG, Park CI, Kim NK. Oncology. 1st ed. Seoul: Ilchokak;2009. 3:p. 128

2. Graham KM, Pecoraro DA, Ventura M, Meyer CC. Reducing the incidence of stomatitis using a quality assessment and improvement approach. Cancer Nurs. 1993; 16:2. 117–22.

3. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004; 100:9. 1995–2025.

4. Hockenberry-eaton M, Benner A. Patterns of nausea and vomiting in children: nursing assessment and intervention. Oncol Nurs Forum. 1990; 17:4. 575–84.

5. Kim HJ, Kim HS. Nausea/Vomiting and Self-care in patients with Cancer on Chemotherapy. J Korean Acad Funda Nurs. 2005; 12:2. 180–5.

6. Ackland SP, Schilsky RL. High-dose methotrexate: a critical reappraisal. J Clin Oncol. 1987; 5:12. 2017–31.

7. Jacobs SA, Stoller RG, Chabner BA, Jones DG. 7-Hydroxy methotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high-dose methotrexate. J Clin Incest. 1976; 57:2. 534–8.

8. Kim SH, Kim DH. Traditional oriental medicine’s therapy on anticancer agent’s side effect. Daejeon University Journal of the institute of Oriental Medicine. 1993; 2:1. 32–51.

9. Bae BC. PyoJunImSangBangJeHak. Clinical Basic of Herb Prescription. Seoul: SeongBoSa;1995. p. 123–5.

10. Meridians & Acupoints Compliation Committe of Korean Medical Colleges. Principles of Meridians & Acupoints; A Guidebook for College Students. 7th ed. Daejeon: JongRyeoNaMu Publishing;2015. 101:p. 106

11. Yamamoto K, Takeda N, Yamatodani A. Establishment of an Animal Model for Radiation-induced Vomiting in Rats Using Pica. J Radiat Res. 2002; 43:2. 135–41.

12. Lohr L. Chemotherapy-induced nausea and vomiting. Cancer J. 2008; 14:2. 85–93.

13. Kim W. Chemotherapy-induced nausea and vomiting. KSCO News&Education. 2008; 4:24–9.

14. de Boer-Dennert M, de Wit R, Schmitz PI, Djontono J, v Beurden V, Stoter G, et al. Patient perceptions of the side-effects of chemotherapy: the influence of 5HT3 antagonists. Br J Cancer. 1997; 76:8. 1055–61.

15. Kim SG. Managements of Chemotherpay Induced Nausea and Vomiting. Korean J Clin Oncol. 2012; 8:1. 23–9.

16. Hornby PJ. Central neurocircuitry associated with emesis. Am J Med. 2001; 111:Suppl 8A. 106S–12S.

17. Kris MG, Radford JE, Pizzo BA, Inabinet R, Hesketh A, Hesketh PJ. Use of an NK1 receptor antagonist to prevent delayed emesis after cisplatin. J Natl Cancer Inst. 1997; 89:11. 817–8.

18. Jordan K, Gralla R, Jahn F, Molassiotis A. International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): Content and implementation in daily routine practice. Eur J Pharmacol. 2014; 722:197–202.

19. Schwartzberg L. Chemotherapy-induced nausea and vomiting: state of the art in 2006. J Support Oncol. 2006; 4:2 Suppl 1. 3–8.

20. Takahashi T, Hoshi E, Takagi M, Katsumata N, Kawahara M, Eguchi K. Multicenter, phase II, placebo controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin. Cancer Sci. 2010; 101:11. 2455–61.

21. Botrel TE, Clark OA, Clark L, Paladini L, Faleiros E, Pegoretti B. Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT(3)R) in preventing chemotherapy induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis. Support Care Cancer. 2010; 19:6. 823–32.

22. Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, et al. Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol. 2009; 10:2. 115–24.

23. Shin HS, Lee SB, Ryu KH. Effect of Nei-Guan Acupressure on Nausea, Vomiting and Anorexia in Gynecological Cancer Patients Receiving Chemotherapy. J East-West Nurs Res. 2009; 15:1. 26–33.

24. Park YK, Park KI, Park KS, Hwang DS, Lee CH, Jang JB, et al. A Clinical Study on Two Cases of Chemotherapy Induced Nausea and Vomiting (CINV) and Radiotherapy Induced Nausea and Vomiting (RINV) Patients Treated by Gamihachul-Tang-Gagam-bang. The Journal of Oriental Obstetrics & Gynecology. 2015; 28:3. 97–106.

25. Raghavendran HR, Rekha S, Shin JW, Kim HG, Wang JH, Park HJ, et al. Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model. Food and Chemical Toxicology. 2011; 49:1. 215–221.

26. Garcia MK, McQuade J, Haddad R, Patel S, Lee R, Yang PY, et al. Systematic Review of Acupuncture in Cancer Care: A Synthesis of the Evidence. JCO. 2013; 31:7. 952–60.

27. Cheon SY, Zhang XY, Lee IS, Cho SH, Chae YB, Lee HS. Pharmacopuncture for cancer care: a systematic review. Evidence-Based Complementary and Alternative Medicine. 2014; 2014:804746

28. Internal Medicine Professors of Korean Medical Colleges. Digestive system in Internal Medicine. Seoul: HanSeong Planning;2000. p. 84–8.

29. Mun JJ, Ahn KS, Kim SH, Uhm HS, Ji GY, Kim SB. SangHanRonJeongHae. Interpretation of Treatise on Febrile Diseases. Seoul: Han UiMunHwaSa;2003. p. 317–20.

30. Lee JS, Kim JS, Ryu BH, Yun SH. Effect of Banhasasimtang Granule on Gastric Emptying in Rats. Korean J Orient Int Med. 2006; 27:2. 471–9.

31. Ryu BH, Ryu KW, Kim JS, Yun SH. Evaluation for Therapeutic Effectiveness of Banwhasashim-tang in Functional Dyspepsia. Korean J Orient Int Med. 2003; 24:2. 329–36.

32. Jang MU, Im SU. Experimental Study for Effect of Banhasasim-tang on Mice with Reflux Esophagitis. Korean J Orient Int Med. 2013; 34:4. 362–74.

33. Lee JH. DongUiImSangNaeGwaHak I. Clinical Internal Medicine of Oriental Medicine I. Seoul: BubIn Books;1999. p. 271–8.

34. Takeda N, Hasegawa S, Morita M, Matsunaga T. Pica in rats is analogous to emesis: an animal model in emesis research. Pharmacol Biochem Behav. 1993; 45:4. 817–21.

35. Raghavendran HR, Rekha S, Cho HK, Jang SS, Son CG. Ginsenoside rich fraction of Panax ginseng C.A. Meyer improve feeding behavior following radiation-induced pica in rats. Fitoterapia. 2012; 83:6. 1144–50.

36. Kim SG. Managements of chemotherapy induced nausea and vomiting. Korean Journal of Clinical Oncology. 2012; 6:23–9.