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CMI JOURNAL 415 

 

 
 

Clinical Medicine Insights 
 

DOI:https://doi.org/10.52845/CMI/2023-4-3-3 

CMI 04 (03), 415-429 (2023)                                                                                                                                                               
ISSN (O) 2694-4626

 

ORIGINAL ARTICLE                                                   

Efficacy of High- and Low-Dose, Highly Bioavailable Curcumin 

(Curcurouge
®
) for Treating Knee Osteoarthritis: A Randomized, Double-

Blind, Placebo-Controlled Prospective Study 

Yasuaki Nakagawa M.D.
1,2 

, Shigeru Yamada M.D.
3
 ,Shogo Mukai M.D.

3 
,Kaori 

Akiyoshi
4
,Yasuhiro Katsuura

5 
,Tadashi Hashimoto

5
 

1
Clinical Research Center, National Hospital Organization Kyoto Medical Center, JAPAN 

2
Department of Orthopaedic Surgery, Japan Baptist Medical Foundation, JAPAN 

3
Department of Orthopaedic Surgery, National Hospital Organization  

4
Department of Medical Infomatics, National Hospital Organization  

5
Therabiopharma Incorporation, JAPAN 

*Corresponding Author: Yasuaki Nakagawa, MD 

  

 

 

 

 

Abstract:  

Purposes : To evaluate the clinical effects of orally administered CurcuRouge○R in patients with knee 

osteoarthritis (OA) after 12 weeks of treatment.  

Methods: In this randomized, double-blind, placebo-controlled, prospective clinical study. 90 patients 

over the age 40 with knee OA of Kellgren-Lawrence (KL) Grade II or III were enrolled.  A placebo or 

CurcuRouge○R 
containing 60 mg or 180 mg/day of curcumin was administered orally every day for 12 

weeks.  To monitor adverse events, blood biochemical analyses were performed before and after 12 weeks 

of each intervention.  The patients’ knee symptoms were evaluated for 12 weeks using the Japanese Knee 

Osteoarthritis Measure (JKOM) criteria, a knee pain visual analog scale (VAS), the Japanese Orthopedic 

Association (JOA) knee scoring system, the need for nonsteroidal anti-inflammatory drugs (NSAIDs) and 

a timed up-and-go test (TUG). 

Results: The declining trend in NSAIDs needs was significantly greater in high-dose CurcuRouge
○R
 group 

than in placebo group.  The decrease of highly sensitive CRP was significantly greater in high-dose of 

CurcuRouge
®
 than placebo group.  In patients with KL Grade II, JOA and VAS scores improved 

significantly more in the high-dose CurcuRouge
○R 

group than in the placebo group. We didn’t find 

CurcuRouge
® 

related adverse event during the study period. 

Conclusion: CurcuRouge○R has succeeded in proofing a potential for treating human knee OA, 

particularly at an early stage. 

Trial Registration: jRCTs 051200058 

Keywords: Knee osteoarthritis, treatment, safety, highly bioavailable curcumin, CurcuRouge○R 

Level of Evidence: Level I, a randomized, double-blind, placebo-controlled prospective study 

Copyright : © 2021 The Authors. Published by Medical Editor and Educational Research Publishers Ltd. 

This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/lic enses/by-

nc-nd/4.0/). 

https://creativecommons.org/lic%20enses/by-nc-nd/4.0/
https://creativecommons.org/lic%20enses/by-nc-nd/4.0/


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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

Introduction

Osteoarthritis (OA) is a common degenerative 

disease that causes disability and poor quality of 

life.  It affects approximately 240 million people 

worldwide, with 10% of men and 18% of women 

affected [1].  Hip or knee OA is a chronic condition 

mostly treated with analgesics and nonsteroidal 

anti-inflammatory drugs (NSAIDs), but these 

medications can cause serious gastrointestinal and 

cardiovascular adverse events, especially with long-

term use [2,3].  Thus, disease-modifying agents that 

not only alleviate joint pain but also slow the 

progression of the condition are required. 

Curcumin is a polyphenol extracted from turmeric, 

that has long been used safely in foods like curry 

[4].  Curcumin, a promising therapeutic food 

material with anti-inflammatory and anti-oxidative 

properties; has long been used as an anti-

inflammatory treatment in traditional Chinese and 

Ayurvedic medicine [4].  It regulates various 

biochemical and molecular pathways by modulating 

several molecular targets, including transcription 

factors, cytokines, enzymes, and genes, that 

regulate cell proliferation or apoptosis [5].  It 

appears to have anti-inflammatory effects 

comparable to steroidal drugs and NSAIDs such as 

indomethacin and phenylbutazone [6].  Some 

studies have linked curcumin’s anti-inflammatory 

properties to the suppression of prostaglandin 

synthesis by its effect on cyclooxygenase [7], a key 

enzyme responsible for the conversion of 

arachidonic acid to prostaglandins.  It has also been 

shown to inhibit proteasome activity and induce 

apoptosis in human colon cancer cells, both in vitro 

and in vivo [8].  Furthermore, it inhibits nuclear 

factor-kappa B (NF-kB) activation [9],  which is a 

key event in the chronic inflammatory process.  

Based on these findings, curcumin is expected to be 

effective for a wide range of diseases related to 

chronic inflammation, including cancer, 

cardiovascular disease, metabolic syndrome, 

Alzheimer’s disease, OA, and other common 

diseases and aging conditions [4,5,10,11].  

Furthermore, it has been shown to be a potent 

inhibitor of the chondrocyte production of 

inflammatory and catabolic mediators [10].   

However, curcumin has a very low bioavailability.  

Theracurmin○R , which is a submicron-particle 

colloidal dispersion of curcumin [12], has better 

oral bioavailability in humans [13]. In a 

randomized, double-blind, placebo-controlled, 

prospective clinical trial in patients with OA to 

evaluate the efficacy of Theracurmin ○R,
, Nakagawa 

showed that Theracurmin○R 
improved the knee pain 

visual analog scale (VAS) scores [14]. To further 

improve bioavailability, Sunagawa developed 

CurcuRouge○R(Therabiopharma, Kanagawa, Japan), 

a novel amorphous formulation of curcumin.  They 

confirmed that CurcuRouge○R  was 3.4-fold higher 

bioavailable than Theacurmin○R in a single-dose, 

double-blind, two-way crossover study in 12 

volunteers [15].   

The purpose of the current study was to determine 

the clinical efficacy of orally administered 

CurcuRouge○R  in patients with knee OA after 12 

weeks of treatment.  We hypothesized that 

consuming CurcuRouge○R  ingestion for 12 weeks 

would improve the symptoms and functional 

abilities of patients with knee OA. 

Materials and Methods 

To test our hypothesis, we conducted a randomized, 

double-blind, placebo-controlled, prospective 

clinical study with three treatment groups: high 

dose (180 mg/day curcumin) and low dose (60 

mg/day curcumin) CurcuRouge○R  and placebo.  At 

the start of the treatment period, randomization was 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

performed after baseline tests and using a 

computer-generated numbers table without 

stratification.  Based on randomization, the 

allocation was performed by someone who was not 

involved in the current project.  From September 

2020 to October 2022, 90 patients over the age of 

40 with knee OA confirmed by the radiographic 

analysis were selected and enrolled in the study.  

They were divided into three groups of 30 patients 

each.  Before participating, all subjects provided 

written informed consent.  All procedures were 

reviewed and approved by the Nara Medical 

University Certified Review Board (nara0017), and 

this study was performed in accordance with the 

World Medical Association’s Declaration of 

Helsinki.  This study was registered at Japan 

Registry for Clinical Trials (jRCTs051200058). 

In this study, patients over the age of 40 with 

primary medial knee OA and KL Grades of II or III 

with radiographic classification were eligible.  

However, patients with severe renal dysfunction or 

on dialysis, severe liver dysfunction or cirrhosis, 

severe cardiovascular diseases, severe 

cerebrovascular dysfunction, severe diabetes 

mellitus, curcumin abuse, or pregnancy were 

excluded from this study.  Furthermore, those who 

had received more than two types of anticoagulants, 

previous knee surgeries, knee injection treatment 

including hyaluronic acid during the study, knee 

steroid injections two months before the study, or 

other steroids four weeks before the study were 

excluded.  If patients required NSAIDs during the 

study, oral celecoxib two pills per day (100 mg per 

pill) were prescribed.  The other combined therapy 

we allowed was pain relief patches. 

A high or low-dose of CurcuRouge○R or placebo 

was administered orally twice a day, for 12 weeks.  

Patients in the high-dose CurcuRouge○R  group took 

two capsules containing 90 mg of curcumin per 

capsule, while those in the low-dose CurcuRouge○R  

group took two capsules containing 30 mg of 

curcumin per capsule per day.  Similarly, patients in 

the placebo group took two placebo capsules per 

day that were similar in shape and color to those of 

CurcuRouge○R . The placebo was primarily made of 

crystalline cellulose, silicon dioxide, calcium 

stearate and food colorings.  For the compliance 

check, the patients were asked to report the number 

of remaining capsules and the prescribed celecoxib 

pills at their 2, 4, 6, 8, 10 and 12-week visits at our 

outpatient clinic. 

The study’s flow chart is depicted in Figure 1.  The 

high- and low-dose CurcuRouge○R and placebo 

groups included 30 patients.  The drop-out cases 

due to adverse events were two in the high-dose 

group (due to severe lumbago and buttock pain in 

one case and vertigo and nausea in one case), four 

in the low-dose group (due to dermatitis in one 

case, consent withdrawal in one case, severe knee 

pain in one case and un-wellness in one case), and 

none in the placebo group.  The study’s safety 

committee decided that all of the aforementioned 

adverse events were unrelated to CurcuRouge○R .  

One case in the high-dose group was excluded due 

to poor drug intake compliance.  Finally, 83 

patients (27 in the high-dose CurcuRouge○R  group, 

26 in the low-dose CurcuRouge○R group, and 30 in 

the placebo group) were included for further 

analysis.   

Blood biochemical analyses were performed before 

the study and after 12 weeks of each intervention, 

and blood curcumin concentrations were analyzed 

after 12 weeks using a previously described 

analytical method [15].  The patients’ knee 

symptoms were assessed at 0, 2, 4, 6, 8, 10 and 12 

weeks according to the Japanese Knee 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

Osteoarthritis Measure (JKOM) criteria [16], the 

JKOM knee pain VAS, and the knee scoring system 

of the Japanese Orthopedic Association (JOA) knee 

scoring system [17].  The JKOM consists of 25 

questions divided into four subcategories for patient 

self-assessment (pain and stiffness, condition in 

daily life, general activities, and health conditions) 

and is based on the World Health Organization’s 

International Classification of Functioning, 

Disability, and Health, validated in the same way as 

the Western Ontario and McMaster Universities’ 

Arthritis Index.  The JOA scale assesses four 

functions: the ability to walk (30 points), the ability 

to climb up and down stairs (25 points), the range 

of motion (ROM; 35 points), and joint swelling (10 

points).  Each knee joint can achieve a maximum 

score of 100 points on the JOA scale.  The 

improved JKOM, VAS, and JOA scores (the 

differences between the scores at each time point 

and before the study) were calculated.  

Furthermore, adverse events and the number of 

celecoxib pills taken during the 12-week period 

were recorded.  We also calculated NSAIDS 

necessity in 3 groups. 

A timed up-and-go test (TUG) and the ROM of 

their knee joints were measured before the study 

and after 12 weeks of each intervention.  These 

performance-based measures are recommended as 

validated outcome measures by the Osteoarthritis 

Research Society International to assess physical 

function in adults with knee OA [18,19].  In TUG, 

participants were asked to stand up, walk around a 

cone three meters away, and then return to their 

chairs at their regular pace.  The chair had no arms, 

and a height of 50 cm from the seated position.  The 

time and number of gaits required to complete this 

task were recorded.  The primary endpoints were 

JKOM, VAS, and JOA knee score, as well as 

NSAID necessities.  The secondary endpoints were 

TUG, knee ROM, blood biochemistry analyses, and 

adverse events. 

The primary analysis was performed following the 

full-analysis-set principal.  Data were expressed as 

mean and standard deviation (SD) and compared 

among groups using a three-factor analysis of 

variance for parametric variables or the Kruskal-

Wallis test for non-parametric variables.  A paired 

student’s t-test was used to compare data at 0 and 

12 weeks of treatment in each group.  Categorical 

data were compared using the chi-squared test.  The 

level of statistical significance was set to a p value 

of less than 0.05.  All statistical analyses were 

performed using EZR, a modified version of the R 

commander designed to include statistical functions 

frequently used in biostatistics. 

Results 

The baseline characteristics of the study patients in 

each of the three groups are summarized in Table 1.  

The majority of patients were female, accounting 

for 77.8% in the high-dose of CurcuRouge○R group, 

88.5% in the low-dose of CurcuRouge○R group, and 

70.0% in the placebo group.  The patient ages were 

also comparable across the three groups.  The KL 

grading system was used to quantify disease 

severity in order to effectively randomize disease 

status upon study entry between groups.  For KL 

Grade II, there were nine cases in the high-dose 

CurcuRouge○R  group, eight cases in the low-dose 

CurcuRouge○R  group, and 10 cases in the placebo 

group.  For KL Grade III, there were 18 cases in the 

high-dose group, 18 cases in the low-dose group, 

and 20 cases in the placebo group.  There were no 

statistical differences in the baseline characteristics, 

as well as compliance, among the three groups.

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

 

Figure1. Patient flowchart for the study 

 

Table 1. Baseline characteristics of the studied groups. 

 curcuRouge® 

90 mg 

curcuRouge® 

30 mg 

Placebo P-value 

Number of patients 27 26 30  

Male/female 6/21 3/23 9/21 0.251 

Age (mean ± SD) 71.1 ± 6.5 71.4 ± 10.3 70.1 ± 9.5 0.837 

Kellgren-Lawrence 

Classification (Ⅱ/Ⅲ) 

9/18 8/18 10/20 

 
0.999 

Osteoarthritis lesion (one 

knee/both) 

19/8 18/8 19/11 0.875 

JOA score (mean ± SD) 72.3 ± 11.1 73.4 ± 9.2 73.2 ± 12.1 0.933 

JKOM score (mean ± SD) 30.2 ± 19.0 31.3 ± 19.8 32.3 ± 16.6 0.911 

VAS score (mean ± SD) 0.46 ± 0.24 0.39 ± 0.24 0.49 ± 0.23 0.283 

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

JOA, the Japanese Orthopedic Association knee 

scoring system; JKOM, the Japanese Knee 

Osteoarthritis Measure; VAS, the knee pain Visual 

Analogue Scale. 

Figure 2 depicts the blood curcumin concentrations, 

with mean curcumin concentration in the high-dose 

and low-dose CurcuRouge
○R
 groups, as well as the 

placebo group,
 

at 12 weeks of treatment being 

199.6, 79.1, and 0 ng/mL respectively.  The high-

dose CurcuRouge
○R
 group had significantly higher 

blood curcumin concentrations than the low-dose 

group.

  

 

Figure 2. Blood curcumin concentrations 12 weeks after treatment. 

 

In each group, the JOA knee OA scores at 12 weeks 

were significantly higher than those at 0 weeks.  

The changes in JOA knee OA scores from 0 to 12 

weeks are depicted in Figure 3a.  At 8 weeks, the 

JOA score was significantly higher in the high-dose 

CurcuRouge
○R
 group than in the placebo group, with 

no significant differences among the three groups at 

12 weeks.  In addition, JKOM scores at 12 weeks 

were significantly lower than those at 0 weeks in 

the high-dose CurcuRouge
○R 

and placebo groups, 

with no significant differences among the three 

groups.  Furthermore, VAS scores at 12 weeks were 

significantly lower than those at 0 weeks in all 

groups (Fig. 3b), with no significant differences 

among the three groups.  The NSAID need ratio in 

the three groups is depicted in Figure 3c.  The 

declining trend in the high-dose CurcuRouge
○R
 

group was significantly greater than that in the 

placebo group (p<0.05), with respect to the 

approximate regression line slope.  

 

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

Points 

 

Figure 3a. Improvement of Japanese Orthopedic Association (JOA) scores in the studied groups over 

weeks. 

Points 

 

Figure. 3b Improvement of Visual Analogue Scale (VAS) scores in the studied groups over weeks. 

 

 

 

-0.2

0

0.2

0.4

0.6

0.8

0 week 2 weeks 4 weeks 6 weeks 8 weeks 10 weeks 12 weeks

Improved VAS Scores 

90mg 30mg placebo



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

% 

 

Figure. 3c Nonsteroidal anti-inflammatory drug (NSAID) need ratio changes in the studied groups 

over weeks. 

 

The number of gaits in TUG in the three groups is 

depicted in Figure 4.  The number of gaits at 12 

weeks of treatment was significantly lower than that 

at 0 weeks in the high-dose CurcuRouge
○R
 group, 

with no significant differences among the three 

groups.  In terms of knee ROM and gait time 

changes in TUG, there were no significant 

differences among three groups. 

 

Figure 4. The number of gaits in the timed up-and-go test (TUG) in the studied groups.   

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

In patients with KL Grade II, JOA score 

significantly improved from 0 to 12 weeks in the 

high-dose CurcuRouge
○R 

group (19.2±14.7 points) 

more than in the placebo group (4.5±8.9 points) 

(Fig. 5a), while VAS score was significantly 

reduced (high-dose -0.36±0.18, placebo -0.01±0.22) 

(Fig. 5b).  In terms of JKOM scores, ROM of knee 

joints, and TUG gait time, there were no significant 

differences among three groups.  The number of 

gaits at 12 weeks of treatment was significantly 

lower than that at 0 weeks in the high-dose 

CurcuRouge
○R 

group, with no significant differences 

in the other two groups (Fig. 5c). 

 

Figure 5a. Improvement of Japanese Orthopedic Association (JOA) scores in patients with Kellgren-

Lawrence (KL) Grade II in the studied groups. 

 

Figure 5b. Improvement of Visual Analogue Scale (VAS) scores in patients with Kellgren-Lawrence 

(KL) Grade II in the studied groups. 

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

 

 

Figure 5c. Timed up-and-go test (TUG) gait number in patients with Kellgren-Lawrence (KL) Grade 

II in the studied groups. 

 

In patients with KL grade III, there were no 

significant differences in JOA, JKOM, or VAS 

scores, as well as ROM of knee joints, and TUG 

gait time and number, among the three groups. 

At 12 weeks of treatment, all laboratory results 

were comparable to baseline values in each groups, 

except in some patients in each group for slight 

increases in triglyceride (four cases in the high-dose 

group, three in the low-dose group, and three in the 

placebo group), blood urea nitrogen (two cases in 

the high-dose group, seven in the low-dose group, 

and four in the placebo group), uric acid (three 

cases in the low-dose group and one in the placebo 

group), and slight decreases in hematocrit (three 

cases in the high-dose group, two in the low-dose 

group, and three in the placebo group), and albumin 

(five cases in the high-dose group, two in the low-

dose group, and four in the placebo group) levels.  

These were all minor changes.  On comparing the 

laboratory results at 12 weeks of treatment to those 

at 0 weeks, only highly sensitive C-reactive protein 

(hs-CRP) levels significantly differed, with a 

greater reduction in the high-dose group than in the 

placebo group (P=0.0432) (Fig. 6).  Table 2 

summarizes the adverse events that occurred in all 

groups during this study.  According to the study’s 

safety committee, all of the aforementioned adverse 

events were unrelated to CurcuRouge○R or the 

placebo. 

 

 

 

 

 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

 

Figure 6. Reduction of highly sensitive C-reactive protein levels at three months in the studied groups. 

 

Table 2. Adverse events in the studied groups occuring during the study period. 

 curcuRouge® 90 mg curcuRouge® 30 mg Placebo 

Gastrointestinal disorders 1 case 2 cases 1 case 

Vertigo 2 cases 1 case 0 cases 

Diarrhea 2 cases 0 cases 1 case 

Lower limb edema 2 cases 1 case 1 case 

Itching 1 case 1 case 1 case 

Radial nerve palsy 0 cases 0 cases 1 case 

 

Discussion 

In this study, we revealed that blood curcumin 

concentrations were significantly higher in the 

high-dose CurcuRouge
○R
 than in the low-dose 

CurcuRouge
○R
 group.  In each group, JOA knee OA 

scores 12 weeks after treatment were significantly 

higher and VAS scores were significantly lower 

than at 0 weeks.  The declining trend of NSAID 

needs in the high-dose group was significantly 

greater than that in the placebo group (P<0.05), 

with respect to the approximate regression line-

slope.    Only in the high-dose group, TUG gait 

number at 12 weeks decreased significantly 

compared with 0 weeks.  In patients with KL Grade 

II, JOA and VAS scores significantly improved 

from 0 to 12 weeks in the high-dose group more 

than in the placebo group.  The reduction of hs-

CRP levels was significantly greater in the high-

dose group than in the placebo group (P=0.0432).  

Several adverse events occurred in all groups 

during this study, but the study’s safety committee 

determined that all of them were unrelated to 

CurcuRouge○R  or the placebo.  These results 

indicate that CurcuRouge
®
 can be an effective and 

safe treatment for patients with OA, especially 

those with KL Grade II. 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

Curcumin has anti-inflammatory as well as anti-

oxidative activities and is expected as a treatment of 

osteoarticular diseases. A high dose of standardized 

curcumin extract (500 mg twice daily) was reported 

to associate with the improvements on the TUG, 

six-minute walk test, and JOA total score in OA 

patients [20].
  
But the doubts have been raised about 

the ability of oral curcumin to reach 

pharmacologically active concentrations in synovial 

fluid or joint tissues [21] because its oral 

bioavailability is only 1% [22].  In the present 

study, we were able to prove that super-absorbable 

curcumin formulation, CurcuRouge
®
, improved 

symptoms including pain in patients with KL Grade 

II.   

According to the basic research or animal models 

for the relationship between curcumin and OA, 

Zeng reported that curcumin could reduce synovial 

cell viability, inhibit cell proliferation, increase cell 

apoptosis, and eventually alleviate OA-related 

inflammation by inhibiting matrix 

metalloproteinase (MMP)-3 expression [23].  

Nicoliche demonstrated that curcumin treatment has 

a protective effect on cartilage by increasing IHH, 

Col2, and SOX-5 expressions and the number of 

chondrocytes, without affecting cartilage thickness 

or MMP-8 and MMP-13 expressions [24].  In 

addition, curcuminoid delivery via hyaluronic 

acids/chitosan nanoparticles suppressed 

chondrocyte apoptosis by inactivating the nuclear 

factor-kappa B (NF-Kb) pathway [25].  Curcumin 

might have the potential to inhibit OA development 

via suppressing NF-kB/hypoxia-inducible factor 2α 

pathway activation [26].  Moreover, in the OA rats 

model, Nakahata demonstrated that curcumin 

monoglucuronide sodium salt (TBP1901) injections 

significantly reduced synovial inflammation at 

weeks 1 and 2 as well as tumor necrosis factor-α 

expression in the articular cartilage at week 6.  

TBP1901 injections also suppressed articular 

cartilage damage, subchondral bone plate 

thickening, subchondral bone plate perforation, and 

osteophyte formation at week 10 [27].  TBP1901 

intra-articular injections suppressed synovial 

inflammation in the acute phase of posttraumatic 

OA in destabilized medial meniscus rats.  In the 

chronic phase, TBP1901 suppressed articular 

cartilage damage and regulated subchondral bone 

plate changes [27]. Therefore, curcumin is thought 

to have anti-inflammatory and chondroprotective 

effects in the OA model.   

In clinical study using CurcuRouge
® 

in elderly 

volunteers,
 

Kishimoto demonstrated that 

CurcuRouge
®
 administration significantly reduces 

the neutrophil-to-lymphocyte ratio, an indicator of 

prognosis in cardiovascular disease, cancer, 

infectious diseases, and aging [28].  Curcumin's 

safety has been reported in several studies. In this 

regard, Bannuru found no differences between 

patients receiving curcuminoids and those receiving 

placebo in the incidence of treatment withdrawal 

due to adverse events [29].  According to Hsiao's 

meta-analysis, low-dose (daily dose <1,000mg) and 

high-dose (daily dose ≧1,000mg) curcuminoids had 

less adverse event rate than NSAIDs in knee OA 

[30].  

The limitations of our study were the small number 

of patients (n=90) and the short treatment duration 

(12 weeks) for knee OA.  This was a pilot study to 

determine the effect of CurcuRouge○R  on knee OA, 

but we were able to observe significant 

improvements in JOA and VAS scores, NSAID 

(celecoxib) needs, and TUG.  Future studies may on 

a larger number of patients with knee OA over a 

longer duration are required to validate our 

findings. 



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CMI JOURNAL                                                                                       Yasuaki Nakagawa, MD 

 
 

In conclusion, CurcuRouge○R  has succeeded in 

proofing a potential for treating human knee OA, 

particularly at an early stage. 

Acknowledgments  

We thank Mr. Atsushi Imaizumi and Mr. Atsuhiro 

Kishimoto for technical assistance.   

Conflict of Interests  

Financial Support and Potential Conflicts of Interest 

of our article is in the following: This research was 

financially supported by Therabiopharma 

Corporation (Kanagawa, Japan).  The authors 

declare that there is no conflict of interest except 

the above. 

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