Volume 13, Number 1 | Spring 2018

Kampo Medicine – Current Research
The Traditional Herbal Medicine Boiogito (FangYi-Huang-Qi-Tang) Slows Postprandial Oxidationof Ingested Glucose Only in Women

Koichiro Tanaka1), Hiroshi Uchino3), Kazuhiko Nara1),
Yoshifumi Irie1), Takahisa Hirose3) and Yoshihisa Urita1,2)

1) Department of Traditional Japanese Medicine, Departmentof General Medicine and Emergency Care, School ofMedicine, Faculty of Medicine, Toho University
2) Division of General Medicine, Department of General
Medicine and Emergency Care, School of Medicine,Faculty of Medicine, Toho University
3) Division of Diabetes, Metabolism and Endocrinology,
Departement of Internal Medicine, Toho University
School of Medicine, Tokyo, JAPAN

Corresponding Author: Hiroshi Uchino M.D, Ph.D.3)(h.uchino@med.toho-u.ac.jp)

postprandial glucose and lipid metabolism withincretin axis.
Research Design and Methods: Age and BMI
matched subjects (6 men and 5 women) wereevaluatedfor2weeks

BOT

treatmentonpostprandial glucose, lipid metabolism and incretin
axis on meal tolerance test with 13C-glucose breath
testing to measure glucose oxidation rate.
Results:BOT

significantly

decreasedglucoseoxidation rate only in women. Postprandial glucose,triglyceride, NEFA, RLP-c and active-GLP1 were notaffected by BOT administration in either sex.
Conclusions: Traditional herb, BOT appears todecreased postprandial glucose oxidation only inwomen. The gender difference in the effect of glucose
oxidation may not be mediated by neither insulin nor
incretion dependent pathway.

Main Messages
1. Highlights the gender specific effect of ingested
glucose oxidation of traditional herbal medicine,Boiogito (BOT), which has been used to treat
various metabolic diseases.
2. BOT decreased postprandial glucose oxidation
only in women.
3. The gender difference in the effect of glucose
oxidation may not be mediated by neither insulin
nor incretion dependent pathway.

(JapaneseClinicalTrials

Registry,No.

UMIN000016493)
KEYWORDS: Boiogito, glucose metabolism, glucose
oxidation, women
Introduction
Metabolic syndrome (MetS) is a cluster ofdiseases and disorders that increase the risk ofdeveloping cardiovascular diseases and diabetes
mellitus. The prevalence of MetS is increasing in theAreas of Uncertainty
1. Patients with metabolic syndrome and diabetes areneeded to determine the precise effects of BOT onenergy metabolisms and substrate oxidation rate.
2. The mechanism for gender difference should beidentify precisely.
3. Substantial number of the patients and long term
effect should be done in the double blind fashion,
to confirm the further benefit of the BOT.

populations of not only in obese Caucasian, but alsoinnon-obese

Asian,

whichhas

resultedin

considerable medical and social problems. Obesity1）

is not a sole problems forMetS, while the bodymass index (BMI) cut point for screening AsianAmericans for prediabetes and diabetes likely to belower than Caucasians.

Boiogito (BOT, Fang-Yi-Huang-Qi-Tang) is acommon formulation in traditional herbal medicine
in east Asian countries 5,8) and has been used to treat

ABSTRACT
Objective: Boiogito (BOT, Fang-Yi-Huang-Qi-Tang)
is a traditional herbal medicine and used to treat
metabolic diseases in Asia, especially in women. We
evaluated the gender specific effect of BOT on

obesity, fatigue, hyperhidrosis, edema of lower
extremities, oliguria, and arthralgia.8) Shimada, etal. reported that BOT had a preventive effect on
metabolic disorders in the Tsumura, Suzuki Obese

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

9Volume 13, Number 1 | Spring 2018

Diabetes (TSOD) mouse, a model of spontaneousLaboratory testingobese type 2 diabetes. In addition to these, BOT is

Venous blood was sampled from each participant

more often used in women than in man.11) However,using a conventional method every 30 min from 9:00

if any, few reports have examined how BOT improves

AM to 12:00 PM (7 times in total). Plasma

whole body energy substrate metabolism in suchconcentrations of glucose, insulin, triglyceride, freeconditions. Thus, we initially investigated the effects

fatty acid (FFA), active glucagon-like peptide-1(GLP-of BOT, particularly its effects on postprandial

1) and remnant-like particle cholesterol (RLP-C)

glucose and lipid metabolism to clarify the difference

were measured.

of gender
13C-glucose breath test

Methods

13C-glucose

Subjects

methodEleven healthy volunteers, sex (6 menbreath testing is non-invasive, simpletodetect

dynamicalterationofand 5

metabolism.2,7) Based on the previous researches,women), age (36± 11.3 years) and BMI (21.5 ± 2.4)

this test had been performed as done with othermatched, were enrolled in the single center parallel

herbal medicine.9) Briefly, on the day of the test, each

designedparticipant took the last dose of BOT at 8:00 AM andtreatment,trial.

No

participant

had

medicalincluding

diabetes

mellitusandate the test meal between 8:30 and 8:45 AM, along

hyperlipidemia in the 6 months before the start ofwith 200 ml of tap water containing 100mg of [1-13C]-

this study. The protocol of the study was approved byglucose (Otsuka Pharmaceutical Co. Ltd. Tokyo,

the Ethical Committee of Toho University School ofJapan). Breath samples were collected every 10 min

Medicine (No. 21038), University Hospital Medicalfor 180 min, starting at 9:00 AM. Baseline (i.e.,

Information Network; UMIN Clinical Trials Registry,

without 13C) breath samples were collected before

Number UMIN000016493.

8:30 AM. Stable isotope 13C enrichment in eachsample was measured, and the glucose oxidation

Boiogito
BOT is a powdered, freeze-dried water extract andrate of each participant was calculated as previously

was purchased from Tsumura Co. Ltd. (Tokyo,tracer to tracee ratio and was expressed as Δ overJapan).

manufacturer’s

baseline per mil (‰) using a non-dispersive infrared

instructions, the standard daily dose of BOT forisotope spectrometry device (UBiT-IR 300; Otsuka

adults is 7.5g of powder, which comprises a mixture

Electronics Co.,Ltd., Osaka, Japan).

of 6 decocted medicinal herbs (g): Sinomenium stem

The results were converted to percentage 13CO2(5.0), Astragali radix (5.0), Atractylodis rhizoma

recovery in breath per hour (% dose/h) based on body(3.0), Glycyrrhizae radix (1.5), Zingiberis rhizoma

surface area (BSA) and the assumed CO2 production(1.0) and Zizyphi fructus (3.0). Participants were

(VCO2) as follows:

Accordingtothedescribed.4)

13C enrichment

was measured as thegiven BOT 3 times a day (2.5 g per dose) for 2 weeks.
% dose/ hour =Δ‰×VCO2 ×0.01123×10/dose(mg) ×
Test meal (cookie test)

atom% excess(APE)/molecular weight(MW) where

A test meal consisted of 30 pieces of solid test cookies,

MW is 46, VCO2 is 300 (BSA mmol/hour, BSA(m2) iswhich in total consisted of 75g carbohydrate (85%0.024265×weight(kg)0.5378×height0.3964 (cm), A (dose)flour starch, 15% maltose), 28.5g butterfat, 1.6g fiber,

is 80mg and APE is 99.5 atom%. Maximum

and 8.0g protein and contained 592 kcal (Neocookie;

concentration (Cmax; %dose/ hour), time to maximum

SARAYA Co.Ltd., Osaka, Japan).3)

concentration (Tmax; min), and area under the curve

10The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 13, Number 1 | Spring 2018(AUC) at each time point (%dose/ hour･min) wereResults

calculated. Cmax and AUC reflect absorption of theEleven healthy volunteers (5 women and 6 men)labeled substrate.

participated in this study. The results of 13C-glucose
breath tests are shown in Fig. 1. The two way layout

Statistical analysis

ANOVA was revealed the significant difference of theThe two way layout analysis of variance (ANOVA)

paired-data between baseline and after two weeks

was used to analyze the difference of the paired-dataadministration of BOT by sexes. BOT significantly

by sex and each time. After that, we calculate thedecreased glucose oxidation from 20 to 170 min

Wilcoxon signed-rank test, to examine the statistical(p<0.05) only in women. No characteristic other thansignificance of any difference in measurements. All

sex was associated with a significant difference invalues are expressed as mean standard deviation

measurements.

(SD). A p value less than 0.05 was considered toGlucose,indicate statistical significance.

triglyceride (TG), RLP-C concentration were notInsulin,

serum

activeGLP-1,FFA,

statistically significant by BOT in either sex (Fig.2).

Figure legends
Postprandial 13C-glucose breath test as measured by 13C-glucose oxidation rate (% dose / hour), in male(A) and female (B). Dotted line and solid line indicate pre- and post- Boiogito (BOT) values, respectively.

BOT significantly decrease glucose oxidation in female, but not in male from 20 to 170 min (p<0.05). Values
are mean ± SD.

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

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Volume 13, Number 1 | Spring 2018

Discussionformulation BOT decreased postprandial glucose

This is the first report to study the effect of herbal

oxidation rate, which is independent on neither

medicine, BOT, on postprandial dynamic alternation

insulin nor GLP-1-incretin pathways, in healthyon energy substrate metabolism. We evaluatedwomen. Further studies of patients with metabolic

13C-glucose breath testing

syndrome and diabetes are needed to determine thewhich is non-invasive method. In the present study,

precise effects of BOT on energy metabolisms andglucose oxidation withtwoweeks'

postprandialBOTingestion13C-glucose

inducedoxidationindecrease

substrate oxidation rate.

women.

However, postprandial blood glucose, insulin andFunding Statement

active GLP-1 concentration was not altered by BOTThisin both men and women.

funding agency in the public, commercial or not-for-

BOT has been used to treat a number of conditions

profit sectors.

research received no specific grant from any

in obese people for more than two millenniums andtraditionally suggested that it improves obesity

Competing Interests Statement

among women. If BOT delays glycolysis without

All authors have no competing financial interests tochanging total energy expenditure, the body woulddeclare.

instead obtain energy by lipid oxidation. Such lipid
consumption decreases fat stores, thus reducing

Contributorship Statement

obesity, albeit serum TG, FFA and RLP-c level did

K.T, H.U, K.N., T.N., K.S., T.H., and Y.U. contributed

not significantly change in this trial. This might beto the research and reviewed and edited theconsidered either by enhanced rates of lipid turnover

manuscript. K.T. contributed to the research, dataor reduced glucose absorption by intestine.

analysis and interpretation, discussion, and writing

Hoo et al. isolated the effective fraction fromof the manuscript. H.U. contributed research, data

Astragali radix, a principal ingredient of BOT, andanalysis and interpretation , discussion, and writing

reported that it alleviates glucose intolerance,

the manuscript. K.N. contributed research, data

insulin resistance and hypertriglyceridemia in db/db

analysis and interpretation , discussion, and writing

diabetic mice4).

the manuscript. T.N. contributed to the protocol,

It is widely believed that BOT is an effective

datatreatment for obesity in middle-aged women, which

manuscript. K.S contributed to the protocol, data

slows postprandial glucose oxidation rate somewhat

generation, discussion and writing the manuscript.

observed in the present study. Sex differences in lipid

T.H. contributed to the research, data analysis andandbeeninterpretation, and writing and editing of theinvestigated. Lipid oxidation tends to be suppressed

manuscript. Y.U. contributed to the research, data

lower in female than in male with oral fructose

analysis and interpretation, and writing and editing

ingestion7). Besides, it is known that female has sex-of the manuscript. K.T. and H.U. are guarantor ofspecific mechanism relevant in nutritional change,

this work, had full access to all the data and takes

might be the effect of fibroblast growth factor 21

responsibility for the accuracy of the data and the(FGF 21)6). BOT may also share the sex-specificanalysis.

glucosemetabolism

hasrecentlygeneration,discussionandwriting

thedifference in fuel energy metabolism.
Although the present findings were preliminary

Data sharing statement No additional data aredata,available.

12

thisstudy

suggeststhattheherbal

The Journal of Kampo, Acupuncture and Integrative Medicine (KAIM)

Volume 13, Number 1 | Spring 2018

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