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 v.6(4); 2017 Dec 

 

 PMC5741390
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Integr Med Res. 2017 Dec; 6(4): 344–353.

Published online 2017 Sep 19. doi: 10.1016/j.imr.2017.09.001
PMCID: PMC5741390
PMID: 29296561
An analysis of the combination frequencies of constituent
medicinal herbs in prescriptions for the treatment of bone
and joint disorder in Korean medicine: determination of a
group of candidate prescriptions for universal use
Yoo Kyoung Han, Seo Yul Kim, Jae Young Ahn, and Jin Ung Baek⁎

Author information Article notes Copyright and License information Disclaimer

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Abstract
Background

This study aimed to select prescriptions (mixtures of medicinal herbs)

used in the treatment of bone and joint disorders in Korean medicine,
and through the analysis of medicinal herb combination frequencies,
select a high-frequency medicinal herb combination group for further
experimental and clinical research.

Methods

We systematically searched for terms related to bone and joint disorder

in the “Dongeuibogam (Dong yibaojian)”, a seminal Korean medicine
book. We reviewed the results of published papers regarding the effects
in bone and joint disorders (especially in osteoporosis, osteomalacia,
osteopenia, rheumatoid arthritis, and degenerative arthritis).

Results

In total, 34 candidates of a medicinal herb combination for the treatment

of bone and joint disorders(CMHCTBJDs) and nine candidates of a
medicinal herb for the treatment of bone and joint disorders(CMHTBJDs)
were selected.

Conclusion

: The candidates of a medicinal herb combination for the treatment of

bone and joint disorders (CMHCTBJDs) and candidates of a medicinal
herb for the treatment of bone and joint disorders(CMHTBJDs) proposed
in this study can be useful material for text mining to develop natural
products with the effects in BJDs and also it has the potential to reduce
the experimental and developmental time period.
Keywords: Dongeuibogam (Dong yi bao gian), Text mining, Bone
disorder
Go to:

1. Introduction

Natural products and their derivatives have historically been invaluable

as a source of therapeutic agents.1 Although their application is often
viewed with skepticism by the Western medical establishment, they are
used in ancient medical traditions such as Ayurveda and traditional
Chinese medicine (TCM) which are a rich source of therapeutic leads for
the pharmaceutical industry.2 However, it is very difficult to get a
‘discovery’ from traditional medicine.2

This study is a kind of ‘discovery’, namely ‘mining’ from Korean

medicine(KM) that is one of traditional medicine.

We aimed to sort candidates of medicinal herb combinations which have

a high probability of treatment effect for more than one disorder among
high morbidity rate disorders such as osteoporosis, osteomalacia,
osteopenia, rheumatoid arthritis, and degenerative arthritis by analyzing
constituent herbs from prescriptions (mixtures of medicinal herbs)
which are widely used for various kinds of bone and joint disorders
(BJD) in KM.

Furthermore, in this study, the frequency of medicinal herb

combinations comprising each prescription for the treatment of bone
and joint disorder (PTBJD) was analyzed after selecting all of the
prescriptions recorded in “Dongeuibogam (Dong yi bao gian)”, a principal
piece of Korean medicine literature, for the treatment of BJDs.

Although commonly used prescriptions for specific symptoms are fixed

in Western medicine, the prescription could be different for individuals
in KM since the prescriptions are customized based on patient’s age,
gender, etc. Therefore, many prescriptions exist for specific symptoms in
KM, and that is why we combined all individual medicinal herbs from
PTBJDs when analyzing the frequency of individual medicinal herbs and
combinations of medicinal herbs from PTBJD.
Go to:

2. Methods

This methodology assumed that the higher the dose within a PTBJD, the
stronger the effect, and that the more frequently used medicinal herbs
are in PTBJDs, the more important it is.3

In this paper, we found frequency of individual medicinal herbs and

combinations of less than seven medicinal herbs from PTBJD in
“Dongeuibogam” and made a list of high-ranked combinations.
By assessing the efficacy of the medicinal herbs of the combinations via
analysis of previous studies, we would like to suggest preliminary data
for experimental and clinical researchers to develop new herbal
formulae for osteoporosis, osteomalacia, osteopenia, rheumatoid
arthritis, and degenerative arthritis.

Since it is practically hard to develop herbal formulae using more than

six medicinal herbs, the number of medicinal herbs is limited from one to
six.

This study is comprised of three steps. Each step was performed as

described in the following section.

2.1. Establishing a list of PTBJDs and constituents of each item in

“Dongeuibogam”

According to the medical information website produced by the National

Library of Medicine
(MedlinePlus; https://www.nlm.nih.gov/medlineplus/), definitions of
osteoporosis, osteomalacia, osteopenia, rheumatoid arthritis, and
degenerative arthritis are “a condition that affects especially older
women and is characterized by decrease in bone mass with decreased
density and enlargement of bone spaces producing porosity and
brittleness”, “a disease of adults that is characterized by softening of the
bones and is analogous to rickets in the young”, “reduction in bone
volume to below normal levels especially due to inadequate replacement
of bone lost to normal lysis”, “a usually chronic disease that is considered
an autoimmune disease and is characterized especially by pain, stiffness,
inflammation, swelling, and sometimes destruction of joints”, and
“arthritis typically with onset during middle or old age that is
characterized by degenerative and sometimes hypertrophic changes in
the bone and cartilage of one or more joints and a progressive wearing
down of apposing joint surfaces with consequent distortion of joint
position and is marked symptomatically especially by pain, swelling, and
stiffness” respectively.

However, as there is no correspondent definition in “Dongeuibogam”, we

tried to select specific indications which are the most similar to
symptoms of Western medicine by analyzing terms describing effects
and selected all prescriptions which have one of the specific indications.

To sum up, in the first step, after selecting all of the prescriptions
recorded in “Dongeuibogam”, their indications were analyzed and the
medicinal herbs constituting each of the PTBJD were selected (Fig. 1).
Data of “Dongeuibogam” was obtained from a state-run website, “Korean
traditional knowledge portal” (http://www.koreantk.com/ktkp2014/).

Fig. 1
First research step; establishing a list of PTBJDs and constituents of each item in
“Dongeuibogam”.

PTBJD, prescription for the treatment of bone and joint disorder.

2.2. Selection of medicinal herb combinations from 64 PTBJDs in

order of frequency
In the second step, the combinations with the highest repeat frequencies
were selected as candidates of a medicinal herb combination for the
treatment of bone and joint disorders (CMHCTBJD), and all medicinal
herbs which comprise these combinations were selected as candidates of
a medicinal herb for the treatment of bone and joint disorders
(CMHTBJD). Only the medicinal herbs with doses in the upper 80%
cumulative proportion per prescription were included in the CMHCTBJD
(Fig. 2). This ensured that only main therapeutic medicinal herbs were
selected.

Fig. 2
Second research step; selection of medicinal herb combinations from 64 PTBJDs in the
order of frequency.

PTBJD, prescription for the treatment of bone and joint disorder.

2.3. Preliminary evaluation of the effects of CMHTBJDs via analysis of

previous studies
2.3.1. Selection and analysis of previous studies regarding effects in BJDs 
We searched for CMHTBJDs in the previous studies, and identified
relevant studies.
2.3.2. Searching the database 

In addition to commonly used scientific databases (such as PubMed,

Cochrane, and Scopus), Korean databases (Ndsl, Oasis, and Riss) were
used since we were searching specifically for studies related to KM. The
starting period for these study searches was not defined; however, June
30, 2015, was set as the final time point.
2.3.3. Searching keywords 

The final goal of this study was selecting CMHTBJDs which have
treatment effects on at least one of BJDs, especially osteoporosis,
osteomalacia, osteopenia, rheumatoid arthritis, or degenerative arthritis
among various BJDs (Fig. 3). We used the following terms for the
searches: “scientific names of CMHTBJD (and names of herbal medicine
of CMHTBJD) + osteoporosis, osteomalacia, osteopenia, rheumatoid
arthritis, degenerative arthritis”.

Fig. 3
Third research step; preliminary evaluation of the effects of CMHTBJDs via analysis of
previous studies.

BJD, bone and joint disorder; CMHTBJD, candidates of a medicinal herb for the treatment of
bone and joint disorder.

Go to:

3. Results
3.1. Sixty-four PTBJDs in “Dongeuibogam”

In total, 64 PTBJDs were selected in “Dongeuibogam” and each PTBJD

comprised an average of 7.9 medicinal herbs (Table 1).

Table 1
Sixty-four PTBJDs from “Dongeuibogam”

Name of PTBJDs (No. of constituents)

Baifuzisan (8)/Baihuguizhitang (5)/Baozhentang (20)/Busundangguisan (7)/Butianwan
(1)/Cangzhufujiandang (9)/Cangzhugao (2)/Chaijianmeiliansan (4)/Dafangfengtang
(13)/Dajupitang (4)/Dancangzhuwan (1)/Dangguigao (18)/Digupisan (9)/Dingtongsan
(12)/Dixiansan (5)/Duhuojishengtang (15)/Ermiaocangbaisan (2)/Ermiaosan (2)/Ershenggao
(3)/Fuzitang (8)/Guntanwan (4)/Hugusan (12)/Huoxuesan (1)/Jiangusan (2)/Jiaweilonghusan
(5)/Jiaweiqianghuotang (9)/Jiegudan (10)/Jiegusan (7)/Jieguzijindan (9)/Liuweidihuangyuan
(6)/Lurongsijinwan (9)/Maidousan (6)/Maijiansan (11)/Manjingsan (9)/Meiyaojiangshengdan
(9)/Qianghuoxuduantang (15)/Qianghuoyufengtang (27)/Qianjinzhimiwan (4)/Qinggusan
(9)/Qingshenganluwan (8)/Qizhixiangfuwan (1)/Quanshenghugusan (7)/Renshenqingjisan
(9)/Ruxiangdingtongwan (7)/Ruxiangheihudan (9)/Shengxisan (6)/Shenxianjijidan
(22)/Tianmawan (10)/Tietanyuan (5)/Tuanyusan (6)/Weishengtianhuayuan
(12)/Wubishanyaoyuan (12)/Wuwutang (3)/Wuzhengtang (9)/Wuzhengwan (7)/Wuzhuwan
(5)/Xialingwanshoudan (5)/Xianyiliangtang (8)/Yiziqingjinsan (10)/Yuhangao (4)/Yuzhenwan
(4)/Zirantongsan (12)/Ziyindabuwan (13)
Open in a separate window

PTBJD, prescription for the treatment of bone and joint disorder.

3.2. Selection of medicinal herb combinations from 64 PTBJDs by
frequency order

The following medicinal herb combinations were selected: 53

combinations of one medicinal herb; 141 combinations of two medicinal
herbs; 209 combinations of three medicinal herbs; 246 combinations of
four medicinal herbs; 232 combinations of five medicinal herbs; and 169
and combinations of six medicinal herbs. By focusing on the top five of
each of these (plus ties) selection of the following occurred: five
combinations comprising one medicinal herb, 13 combinations of two
medicinal herbs, 10 combinations of three medicinal herbs, five
combinations of four medicinal herbs, and one combination of five
medicinal herbs. These comprise the CMHCTBJD with a highest
probability of efficacy in the treatment of BJD. Also, it is noted that all
CMHCTBJDs comprised only nine medicinal herbs (Table 2).

Table 2
Medicinal herb combinations from 64 PTBJDs in the order of frequency (80%) *

No of constituents in each combination; name of constituents (frequency)

1; E(13)/A(6)/D(4)/F(4)/G(4)
2; A, D(4)/A, E(4)/C, D(3)/A, B(3)/A, C(3)/B, C(3)/B, D(3)/E, I (3)/B, E(3)/C, E(3)/E, G(3)/E,
H(3)/D, E(3)
3; A, D, E(3)/A, B, C(3)/A, B, D(3)/A, B, E(3)/B, C, D(3)/A, C, D(3)/B, D, E(3)/E, D, C(3)/A,
C, E(3)/B, C, E(3)
4; A, B, D, E(3)/A, B, C, D(3)/B, C, D, E(3)/A, C, D, E(3)/A, B, C, E(3)
5; A, B, C, D, E(3)
9 CMHTBJDs: Angelica gigas Nakai., root (A), Atractylodes japonica Koidz. ex Kitam.,
rhizome (B), Poria cocos (Schw.) Wolf., sclerotium (C), Paeonia lactiflora Pall., root
(D), Rehmannia glutinosa (Gaertn.) DC., root (E), Dioscorea polystachya Turcz., rhizome (F),
Gypsum(G), Panax ginseng C.A.Mey., root (H), Saposhnikovia divaricata (Turcz.) Schischk.,
root (I)
Open in a separate window
*
Selecting CMHCTBJDs as the top five on the basis of frequency, only including frequencies
>3, and including ties for 5th place.
CMHTBJD, candidates of a medicinal herb for the treatment of bone and joint disorder;
PTBJD, prescription for the treatment of bone and joint disorder.

3.3. Preliminary evaluation of the effects of nine CMHTBJDs via

analysis of previous studies

A total of 496 studies of nine CMHTSs were found; of these, 80 studies

were concerned with effects in at least one of osteoporosis, osteomalacia,
osteopenia, rheumatoid arthritis, and degenerative arthritis, resulting in
an average of 8.9 publications per candidate herb (Fig. 4).

Fig. 4
Number of previous studies on nine CMHTBJDs.

CMHTBJD, candidates of a medicinal herb for the treatment of bone and joint disorder.

Studies were specifically divided into in vitro studies (VT), in vivo studies

(VV), clinical studies (C), and reviews (R). A number of previous studies
on each medicinal herbs are 13 for Angelica gigas Nakai., root (VT:6,
VV:‘4, R:3), five for Atractylodes japonica Koidz. ex Kitam., rhizome (VT:1,
VV:3, R:1), two for Poria cocos (Schw.) Wolf., sclerotium (VV:1, R:1), 10
for Paeonia lactiflora Pall., root (VT:3, VV:6, R:1), nine for Rehmannia
glutinosa (Gaertn.) DC., root (VT:5, VV:4), 10 for Dioscorea polystachya
Turcz., rhizome (VT:4, VV:6), one for Gypsum (VV:1), 28 for Panax
ginseng Mey., root (VT:13, VV:13, R:1, C:1), and two for Saposhnikovia
divaricata (Turcz.) Schischk., root (VT:2). According to these, nine
CMHTBJDs have been subjects of research studies on osteoporosis,
osteomalacia, osteopenia, rheumatoid arthritis, and degenerative
arthritis (Table 3).

Table 3
Preliminary evaluation of the effects of nine CMHTBJDs in bone and joint disorder via
analysis of the previous studies

Name of CMHTBJD/classification of the study (No.)/source database/main outcome

Angelica gigas Nakai., (1) P/Prevents cartilage destruction in osteoarthritis &
VT (6)
root favor cartilage repair4
(2) P, S/Demonstrates inhibitory effects on RANKL-
mediated osteoclast differentiation in bone marrow
macrophages in vitro5
(3) P/Inhibits IL-1β-induced rheumatoid synovial
fibroblast proliferation & COX-2, PGE2, & MMPs
production6
(4) P/Stimulates UDP-sugar synthase genes through
promoting gene expression of IGF-1 & IGF1R in
chondrocytes7
(5) P/Decreases the hydrogen peroxide-induced IL-1beta,
TNF-alpha, MMP-1 & MMP-13 & increases SOX9 gene
expression8
(6) R/Shows inhibitory effect on osteoclast differentiation
& function9
(1) P/Less trabecular bone loss & thick cortical areas were
VV (4)
observed10
(2) P/Prevents the OVX-induced bone loss in rats via
Name of CMHTBJD/classification of the study (No.)/source database/main outcome
estrogen-independent mechanism11
(3) P/APS-3c can improve the proteoglycans synthesis of
chondrocytes in vivo & IL-1 β-stimulated chondrocytes in
vitro12
(4) R, O/Has a suppressing inflammation effect on
Freund‘s adjuvant arthritis in rats13
RW
(1) P, S/Has potent binding affinity with IL6R protein14
(3)
(2) P, S/Has strong antiinflammatory & antiarthritic
effects15
(3) R/Turns out to be the most frequently used herb for the
treatment of osteoporosis since 200016
Atractylodes (1) N, O, R/Has beneficial effect on osteoporosis by
japonica Koidz. ex VT (1) inhibition of osteoclast differentiation & by inhibition of
Kitam., rhizome functioning osteoclast17
(1) S/Increases the growth & differentiation of osteoblastic
VV (3)
MC3T3-E1 cells18
(2) S/Inhibits osteoclast differentiation from its precursors19
(3) N, R/Decreases the arthritic scores & inhibits
pathological changes of knee joint tissues in CIA mice20
RW (1) P/Consists one of the most used herbal drugs
(1) prescription cluster for osteoporosis treatment21
Poria cocos (Schw.) (1) N, R/Inhibits RANKL-induced osteoclast
VV (1)
Wolf., sclerotium differentiation in bone marrow-derived macrophages22
RW (1) P, S, N/Triterpenoids are known to have a pivotal
(1) influence on rheumatoid arthritis23
Paeonia lactiflora Pall., (1) N, S/Reduces or prevents osteoblast degeneration in
VT (3)
root osteoporosis24
(2) S/Contributes to the prevention for osteoporosis25
(3) R/May be useful as potential sources of therapeutic
agents against postmenop- ausal osteoporosis26
(1) P, N, S/Inhibits RANKL-induced osteoclastogenesis by
VV (6)
inhibiting ERK, p38 & NF-κB pathway27
(2) N/Negatively regulates osteoclast differentiation &
formation28
(3) N, S/Suppresses inflammatory process by reducing the
production of prostaglandin E2, leukotriene B4, nitric
oxide, reactive oxygen species, proinflammatory cytokines
& chemokines29
Name of CMHTBJD/classification of the study (No.)/source database/main outcome
(4) N, R/Relieves arthrocele & arthralgia & elevates the
contents of L-ENK, beta-END, IL-2 & degrades the
contents of SP, IgG, IL-1beta, IL-6 & inhibits abnormal
secretion accentuation of synovial cell like fiber30
(5) S/Inhibits abnormal proliferation of synoviocytes &
treats the rheumatoid arthritis31
(6) S/Total glucosides of paeony treats rheumatoid
arthritis32
(1) P/The beneficial effects of total glucosides of peony in
RW(1) treating rheumatoid arthritis were verified by randomized
controlled trials33
Rehmannia (1) N, R, S/Has potential as a therapeutic material to
glutinosa (Gaertn.) DC., VT (5) attenuate the inflammatory disease such as rheumatoid
root arthritis34
(2) N/Contains active ingredients involved in bone tissue
metabolism & may be effective in improving osteoporosis35
(3) N, S/Improves the osteoporosis resulted from
augmentation of osteoblast proliferation36
(4) R/Shows remarkable inhibitive effect on RANKL-
treated osteoclast differentiation without cytotoxicity37
(5) P, N/Enhances the bone metabolism in osteoporosis38
(1) N, R/Can be used for prevention & curing the
VV (4)
postmenopausal obese39
(2) N, C, S/Controls rapid reduction of bone turnover in
postmenopausal women40
(3) P, S/Prevention of bone loss41
(4) N, R/Decreases the serum level of cholesterol &
increases the serum level of ALP42
Dioscorea polystachya (1) P/Inhibits the IL-1β-induced expression of
VT (4)
Turcz., rhizome inflammatory mediators43
(2) P, N, R/Reduces the proliferation of human fibroblast-
like synovial cells44
(3) P/Potents inhibitory activities on bone resorption45
(4) P/Potents inhibition against bone resorption46
(1) P/Might prevent bone loss during aging & provide
VV (6)
beneficial effects in osteoporosis in elderly people47
(2) P/Lies in the synchronous inhibitory effects on both the
bone formation & the bone resorption48
Name of CMHTBJD/classification of the study (No.)/source database/main outcome
(3) N/Counteracts the progression of osteoporosis &
augments bone mineral density49
(4) P/Inhibits bone loss in bone mineral content50
(5) P/Inhibits the decrease in cancellous bone mineral
content, cancellous bone mineral density, & cortical bone
mineral content51
(6) N, O, R/Shows inhibitory effect on bone loss in
osteoporetic condition, & reduces the increase of ALP
activity & osteocalcin level in serum52
(1) P/Improves amount, density & biomechanical
Gypsum VV (1)
performance of bone trabeculae in osteoporotic vertebra53
(1) P/Promotes the differentiation of bone marrow
Panax VT
mesenchymal stem cells & mononuclear cells into
ginseng C.A.Mey., root (13)
osteoblasts & osteoclast54
(2) P, S/Reduces receptor activator of nuclear factor kappa
B ligand-induced tartrate-resistant acid phosphatase
activity, pit formation (actin rings), & TRAP-positive
multinucleated cells development in RAW264.7 cells55
(3) P/Inhibits osteoclastogenesis by suppressing MAPK in
LPS-activated RAW264.7 cells56
(4) P, S/Plays an important therapeutic role in osteoporosis
patients by improving osteogenic differentiation of Bone
marrow stromal cells57
(5) P/Has therapeutic potential for preventing cartilage
collagen matrix breakdown in diseased tissues such as
those found in patients with arthritic disorders58
(6) P/Protects the cell against the development of
chondrocyte senescence in osteoarthritis59
(7) P/Exerts a protective effect against the cartilage
degradation of osteoarthritis60
(8) P/Can be a potential alternative to the current antiTNF-
alpha therapeutics for rheumatoid arthritis61
(9) P, S/Reduces cell infiltration & cartilage destruction in
the arthritic joint62
(10) N, R/Has osteogenic & antiosteoclastogenesis
properties & regards as potential therapeutic agents for
management of osteoporosis63
(11) N, R/Has beneficial effects against arthritis without
any adverse effects64
Name of CMHTBJD/classification of the study (No.)/source database/main outcome
(12) S/Inhibits dexamethasone-induced apoptosis through
promotion of GPR120 induction in bone marrow-derived
mesenchymal stem cells65
(13) R/Can be applicable for the improvement of arthritic
symptoms as a new diet-supplement66
VV (1) P/Prevents loss of cell viability caused by Dex-induced
(13) apoptosis in MC3T3E1 cells67
(2) P, S/The serum levels of TNF—a, IL—1β, & IL—6
were increased68
(3) P/The bone-modulating effects of PNS may be due to
the increased bone formation & decreased bone resorption69
(4) P/Protects against bone loss in rat model by increasing
the serum levels of TNF—α, IL—1β, & IL—668
(5) P/Enhances bone mineral density, bone strength, &
prevents the deterioration of trabecular microarchitecture
without hyperplastic effect on uterus70
(6) P, S/Can ameliorate arthritis in mice with CIA by
targeting pathogenic Th17 & osteoclast differentiation71
(7) P/Alleviates autoimmune arthritis by suppressing T cell
activation72
(8) N, R/Alternative medicine for the relief & prevention
of rheumatoid arthritis symptoms73
(9) S/Prevents postmenopausal bone loss by inhibiting
osteoclast differentiation, a process controlled by estrogen74
(10) S/Inhibits osteoclastogenesis by modulating NF-κB &
MAPKs pathways75
(11) S/Inhibits differentiation & maturation of osteoclasts76
(12) S/Reduces the carrageenan-induced paw edema &
suppresses the production of serum IL-677
(13) P/The expression levels of chondrogenic genes, such
as type II collagen & SOX9, were increased in the
presence of ginsenoside Rb178
RW (1) P, N, R, S/Most important therapeutic agent for the
(1) treatment of osteoporosis79
(1) P/Enhances the therapeutic effect in treating
CS (1)
rheumatoid arthritis80
Saposhnikovia
(1) P/Reduces the inflammatory responses in the joints of
divaricata (Turcz.) VT (2)
collagen-induced arthritis rats81
Schischk., root
 Name of CMHTBJD/classification of the study (No.)/source database/main outcome
(2) N, R/Reduce osteoblast activity82
Open in a separate window

CMHTBJD, candidates of a medicinal herb for the treatment of bone and joint disorder; CS,
Clinical study; C, Cochrane; N, Ndsl; O, Oasis; P, PubMed(); (), RW, Review; R, Riss; S,
Scopus, VT, in vitro study, VV, in vivo study.

Go to:

4. Discussion

In this paper, medicinal herbs which have high probability of treatment

effect for more than one disorder among five BJDs in KM were selected
from “Dongeuibogam” by analyzing frequency and effectiveness. Then,
analysis of the previous studies was done.

According to Table 3, an average of 8.9 studies per CMHTS that described

their effects in at least one of five BJDs was obtained. We found that more
than 10 researches on four items such as Angelica gigas Nakai.
(root), Paeonia lactiflora Pall. (root), Dioscorea polystachya Turcz .
(rhizome), and Panax ginseng Mey. (root) have already been performed,
although one or two studies on two CMHTS including gypsum and Poria
cocos (Schw.) Wolf. (sclerotium) were done.

Looking at the possible mechanisms of nine CMHTSs in Table 3 the final

results found were: (1) Angelica gigas Nakai, root: Angelica gigas Nakai
prevents cartilage destruction and bone loss via inhibitory effect on
osteoclast differentiation, also beneficial effect on inflammatory and
arthritic diseases; (2) Atractylodes japonica Koidz. ex Kitam.,
rhizome: Atractylodes japonica Koidz is effective on osteoporosis by
inhibiting differentiation and function of osteoclast; (3) Poria
cocos (Schw.) Wolf., sclerotiu: Poria cocos (Schw.) Wolf. inhibits
osteoclast differentiation, and triterpenoids, which are obtained
from Poria cocos, are known to have crucial influence on rheumatoid
arthritis; (4) Paeonia lactiflora Pall, root: Paeonia lactiflora Pall regulates
osteoclast differentiation and formation, and suppresses inflammatory
process, as its effect in curing rheumatoid arthritis is shown in other
previous studies; (5) Rehmannia glutinosa (Gaertn.) DC.,
root: Rehmannia glutinosa (Gaertn.) DC. is capable of moderating
inflammatory disease and ameliorating osteoporosis via osteoblast
proliferation, as well as preventing obese and bone loss on
postmenopausal women; (6) Dioscorea polystachya
Turcz., rhizome: Dioscorea polystachya Turcz. inhibits bone resorption
and functions as an efficient treatment for osteoporosis; (7) gypsum
(VV:1): gypsum improves amount, density, and biomechanical
performance of bone trabeculae in osteoporotic vertebra; (8) Panax
ginseng Mey., root: Panax ginseng Mey. promotes bone differentiation
through improving osteogenic abilities and inhibiting osteoclastic
functions, prevents bone loss and enhances bone density and strength,
and protects the cell against cartilage degradation, consequently
showing potential as highly effective therapeutic agent for osteoarthritis,
osteoporosis, and rheumatoid arthritis; and (9) Saposhnikovia
divaricata (Turcz.) Schischk., root: Saposhnikovia divaricate (Turcz.)
Scischk. reduces inflammatory responses and osteoblast activity.

However, in spite of the explanations so far, there could be a few

fundamental questions regarding methodology and results of this study
since the research method we used was not general.

First of all, one may wonder if it is possible to match today’s BJDs and
BJDs written in the classical literature. Of course, the definition of BJDs in
KM and Western medicine is different, nevertheless we tried to select
specific indications which are the most similar to symptoms of today’s
BJDs by analyzing terms describing effects and selected all prescriptions
which have one more of specific indications. As shown above, we tried to
select information from classical literature that is the closest to today’s
theory but inconsistency of definition still remained. This has inevitable
consequences because we select information from the classical literature
which has a different theoretical system compared with today’s system.
Although carrying out follow up experiments or clinical research, we
think we should solve problems that are derived from inconsistency of
definition such as “the different terminology between ancient and
modern disease” and “inclusion and exclusion criteria”. Therefore, even
though inconsistency of definition is existed, it is worthwhile to try to
select CMHCTBJDs and CMHTBJDs by matching today’s BJDs and BJDs
written in the classical literature.

Second of all, one may wonder why 80% of medicinal herbs in PTBJD are
only included in CMHCTBJD in the second step of method. In Korean
traditional prescription, a little amount of herbs, such as Zingiber
officinale Roscoe so-called “Guide herb (shǐyà o)” are added for balance of
medicinal herbs or to improve digestive functions. These “Guide herb
(shǐyà o)” do not have major treatment effects but frequently added in
prescriptions; which means just frequently used medicinal herbs in
prescriptions does not mean that the herbs are principle ingredients.
Therefore, the minor herbs were excluded from CMHCTBJD and only
80% of medicinal herbs in PTBJD were included in CMHCTBJD. The other
doubt in the second step of the method is that instead of selecting the
most frequently used medicinal herbs in 64 PTBJD as CMHTBJD, why
CMHTBJD is selected after sorting CMHCTBJD out. The reason is that
prescriptions are not simply a quantitative addition of the individual
medicinal herbs, instead they produce a superior efficacy to single
medicines.83, 84 Therefore, proposing medicinal herbs of possible
combinations instead of single medicines to a clinical researcher could
be more useful for follow-up experiments.
Third, since definitions are different as shown above, main clinical signs
are different; and therefore you might want to know which steps of
which disease among five BJDs medicinal herbs or medicinal herb
combinations can be used, and how to distinguish five BJDs from similar
other diseases and use medicinal herbs or medicinal herb combinations.
Also one might wonder how optimum component ratio of medicinal
herbs of the combination can be decided after selecting medicinal herb
combinations. As the purpose of this study is a selection of information
from classical literature, it seems that these kinds of problems are
beyond research range and thus it is hard to answer in this paper. These
problems should be solved during follow-up experiments or clinical
research.

Fourth, because previous research is not done for all of nine CMHTBJDs
and type and result of the previous research is a little different, you may
think that there are some different results between ancient and modern
literature analysis. But, the reason for doing modern literature analysis
in this study is not to compare to ancient literature analysis. Instead it is
because proposing candidates of medicinal herb to experimental and
clinical researchers by discovering from the classical literature is also the
final purpose of this study. By summarizing previous studies for
experimental and clinical researchers, it is expected to motivate
researchers to conduct follow-up study and help to establish research
direction using candidates of medicinal herb selected from this research.
Therefore, instead of comparing previous research and ancient literature
analysis and discussing the difference, we think that it is a more
productive way to refer to previous research and find a direction of
follow up study of 34 CMHCTBJDs and nine CMHTBJDs.

The fundamental questions discussed above are not only key points but
also characters of this paper. Therefore, if you do not agree with the
authors’ answers, you may criticize this paper as the paper lacks
methodological structure. The answer regarding the criticism is as
below. We have done “text mining and literature review” regarding
“cognitive-enhancing herbal formulae” and “medicinal herbs in
prescriptions for the treatment of stroke” using similar methodology that
this research used.85, 86 Subsequently, we have done experimental
research on efficacy of medicinal herbs using the result we
gotobtained.87, 88 As a result, although it is hard to conclude since there
are only two cases, we provisionally conclude that the methodology (text
mining and literature review) is very useful for selection of medicinal
herbs which had the specific efficacy we were looking for.

In the present study, we finally selected 34 CMHCTBJDs and 9 CMHTBJDs

from “Dongeuibogam” and reviewed the results of previous studies
regarding the effects in BJDs (especially in osteoporosis, osteomalacia,
osteopenia, rheumatoid arthritis, and degenerative arthritis). In order to
develop universally applicable PTBJDs, it will be necessary to conduct
longer and more complex experiments and clinical trials. However, the
methodology used in this study is regarded as a meaningful challenge to
discover “a hidden treasure” for BJDs from classical literature. The result
of this study, 34 CMHCTBJDs and 9 CMHTBJDs, will be certainly valuable
as fundamental data for experiment and clinical research.
Go to:

Conflicts of interest

The authors declare that there are no conflicts of interest regarding the
publication of this paper.
Go to:

Acknowledgment
This work was supported by the AntiAging Research Center Dong-eui
University.
Go to:

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