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Research Article
Anti-Inflammatory and Antiosteoarthritis
Effects of Saposhnikovia divaricata ethanol Extract:
In Vitro and In Vivo Studies
Jin Mi Chun,1Hyo Seon Kim,1A Yeong Lee,1Seung-Hyung Kim,2andHoKyoungKim
3
1K-herb Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea
2Institute of Traditional Medicine and Bioscience, Daejeon University, Daejeon 34520, Republic of Korea
3Mibyeong Research Center, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea
Correspondence should be addressed to Ho Kyoung Kim; hkkim@kiom.re.kr
Received November ; Revised January ; Accepted January
Academic Editor: Ken Yasukawa
Copyright © Jin Mi Chun et al. is is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Saposhnikovia divaricata Schischkin has been used in traditional medicine to treat pain, inammation, and arthritis. e aim of
this study was to investigate the anti-inammatory and antiosteoarthritis activities of Saposhnikovia divaricata extract (SDE). e
anti-inammator y eect of SDE was evaluated in vitro in lipopolysaccharide- (LPS-) treated RAW . cells. e antiosteoarthritic
eect of SDE was investigated in an in vivo rat model of monosodium iodoacetate- (MIA-) induced osteoarthritis (OA) in which
rats were treated orally with SDE ( mg/kg) for days. e eects of SDE were assessed in vivo by histopathological analysis
and by measuring weight-bearing distribution, cytokine serum levels, and joint tissue inammation-related gene expression. SDE
showed anti-inammatory activity by inhibiting the production of nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis
factor-𝛼(TNF-𝛼), and interleukin- (IL-) in LPS-induced RAW . cells. In addition, SDE promoted recovery of hind limb
weight-bearing, inhibited the production of proinammatory cytokines and mediators, and protected cartilage and subchondral
bone tissue in the OA rat model. erefore, SDE is a potential therapeutic agent for OA and/or associated symptoms.
1. Introduction
Osteoarthritis (OA) is the most frequent musculoskeletal
disorder and the most common degenerative joint disease in
the elderly []. OA is a condition caused in part by injury,
loss of cartilage structure and function, and dysregulation of
proinammatory and anti-inammatory pathways [, ]. It
primarily aects the articular cartilage and subchondral bone
of synovial joints and results in joint failure, leading to pain
upon weight-bearing including walking and standing [].
ere is no cure for OA, as it is very dicult to restore the
cartilage once it is destroyed []. e goals of treatment are
to relieve pain, maintain or improve joint mobility, increase
the strength of the joints, and minimize the disabling eects
of the disease. Pharmacological treatments of OA aim to
reduce pain in order to increase the patient’s joint function
and quality of life. Although cartilage destruction is the main
event in OA, the degradation of collagen is the fundamental
incident that determines the irreversible progression of OA
in association with inammation [, ]. Treatments with anti-
inammatory and chondroprotective activity are expected to
relieve pain and maintain matrix integrity in OA patients.
erefore, decreasing inammation will likely be bene-
cial in OA management. Recent studies suggest protective
roles for herbal resources on the progression of OA, in
terms of mitigating chondrocyte inammation and further
cartilage destruction, through their ability to interact with
joint-associated tissues, resulting in the mitigation of joint
pain [].
e root of Saposhnikovia divaricata Schischkin (Umbel-
liferae) has been widely used in traditional medicine for
the treatment of headache, pain, inammation, and arthritis
in Korea and China [, ]. e diverse pharmacologi-
cal eects of Saposhnikovia divaricata (SD) also include
anti-inammatory, analgesic, antipyretic, and antiarthritic
properties [, ]. A recent study demonstrated that SD
Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2016, Article ID 1984238, 8 pages
http://dx.doi.org/10.1155/2016/1984238
Evidence-Based Complementary and Alternative Medicine
chromone extract possesses potential antirheumatoid arthri-
tis eects in a mouse model of collagen-induced arthritis [];
however, few studies have been conducted to support the
anti-inammatory and antiarthritis activity of Saposhnikovia
divaricata extract (SDE).
erefore, the present study investigated the anti-inam-
matory and antiosteoarthritis activities of a % ethanol
extract of SD. First, the anti-inammatory eect of SDE
was evaluated in vitro in LPS-induced RAW . cells.
Next, the antiosteoarthritis eect of SDE was measured by
assessing weight-bearing distribution, degradation of artic-
ular cartilage, and inammatory responses in a rat model of
monosodium iodoacetate- (MIA-) induced OA.
2. Materials and Methods
2.1. Preparation of SDE. e rhizomes of SD were purchased
as a dried herb from Hanherb Co. (Guri, Korea). e
plant materials were conrmed taxonomically by Dr. Go-Ya
Choi of the Korea Institute of Oriental Medicine (KIOM).
A voucher specimen (number SDE-) was deposited
in the Korean Herbarium of Standard Herbal Resources.
Dried rhizomes of SD (g) were extracted twice with
% ethanol (with a h reux) and the extract was then
concentrated under reduced pressure. e decoction was
ltered, lyophilized, and stored at ∘C. e yield of dried
extract from crude starting materials was .% (w/w).
2.2. Quantitative High-Performance Liquid Chromatography
(HPLC) Analysis. Chromatographic analysis was performed
with a HPLC system (Waters Co., Milford, MA, USA) and a
photodiode array detector. For the HPLC analysis of SDE, the
prim-O-glucosylcimifugin standard was purchased from the
Korea Promotion Institute for Traditional Medicine Industry
(Gyeongsan, Korea), and sec-O-glucosylhamaudol and -O-
𝛽-D-glucosyl--O-methylvisamminol were isolated within
our laboratory and identied by spectral analyses, primarily
by NMR and MS.
SDE samples (. mg) were dissolved in % ethanol
( mL). Chromatographic separation was performed with an
XSelect HSS T C column (. × mm, 𝜇m, Waters
Co., Milford, MA, USA). e mobile phase consisted of
acetonitrile (A) and .% acetic acid in water (B) at a ow-rate
of . mL/min. A multistep gradient program was used as fol-
lows: % A ( min), –% A (– min), % A (– min),
and –% A (– min). e detection wavelength was
scannedat–nmandrecordedatnm.einjection
volume was . 𝜇L. Standard solutions for the determination
of three chromones were prepared at a nal concentration of
. mg/mL (prim-O-glucosylcimifugin), . mg/mL (-
O-𝛽-D-glucosyl--O-methylvisamminol), and . mg/mL
(sec-O-glucosylhamaudol) in methanol and kept at ∘C.
2.3. Evaluation of Anti-Inammatory Activity In Vitro
2.3.1. Cell Culture and Sample Treatment. RAW . cells
were obtained from the American Type Culture Collec-
tion (ATCC, Manassas, VA, USA) and grown in DMEM
medium containing % antibiotics and .% FBS. Cells
were incubated in a humidied atmosphere of % CO2at
∘C. To stimulate the cells, the medium was replaced with
fresh DMEM medium, and lipopolysaccharide (LPS, Sigma-
Aldrich Chemical Co., St. Louis, MO, USA) at 𝜇g/mL was
added in the presence or absence of SDE ( or 𝜇g/mL)
for an additional h.
2.3.2. Determination of Nitric Oxide (NO), Prostaglandin E2
(PGE2), Tumor Necrosis Factor-𝛼(TNF-𝛼), and Interleukin-
6(IL-6)Production. Cells were treated with SDE and stim-
ulated with LPS for h. NO production was analyzed by
measuring nitrite using the Griess reagent according to a
previous study []. Secretion of the inammatory cytokines
PGE2,TNF-𝛼, and IL- was determined using an ELISA
kit (R&D systems) according to manufacturer instructions.
e eects of SDE on NO and cytokine production were
determined at nm or nm using a Wallac EnVision™
microplate reader (PerkinElmer).
2.4. Evaluation of Antiosteoarthritis Activity In Vivo
2.4.1. Animals. Male Sprague-Dawley rats ( weeks old) were
purchased from Samtako Inc. (Osan, Korea) and housed
under controlled conditions with a -h light/dark cycle at
22 ± 2∘Cand55 ± 15% humidity. Rats were provided with
a laboratory diet and water ad libitum. All experimental
procedures were performed in compliance with the National
Institutes of Health (NIH) guidelines and approved by the
AnimalCareandUseCommitteeoftheDaejeonuniversity
(Daejeon, republic of Korea).
2.4.2. Induction of OA with MIA in Rats. e animals were
randomized and assigned to treatment groups before the
initiation of the study (𝑛=6per group). MIA solution
( mg/ 𝜇L of .% saline) was directly injected into the
intra-articular space of the right knee under anesthesia
induced with a mixture of ketamine and xylazine. Rats were
divided randomly into four groups: () the saline group with
no MIA injection, () the MIA group with MIA injection, ()
the SDE-treated group ( mg/kg) with MIA injection, and
() the indomethacin- (IM-) treated group (mg/kg) with
MIA injection. Rats were administered orally with SDE and
IM week before MIA injection for weeks. e dosage of
SDEandIMusedinthisstudywasbasedonthoseemployed
in previous studies [, , ].
2.4.3. Measurements of Hindpaw Weight-Bearing Distribution.
Aer OA induction, the original balance in weight-bearing
capability of hindpaws was disrupted. An incapacitance tester
(Linton instrumentation, Norfolk, UK) was used to evaluate
changes in the weight-bearing tolerance. Rats were carefully
placed into the measuring chamber. e weight-bearing force
exerted by the hind limb was averaged over a s period.
e weight distribution ratio was calculated by the following
equation: [weight on right hind limb/(weight on right hind
limb + weight on le hind limb)] × [].
2.4.4. Measurements of Serum Cytokine Levels. e blood
samples were centrifuged at , g for min at ∘C; then
Evidence-Based Complementary and Alternative Medicine
T : Real-time PCR primer sequences.
Gene Primer sequence
IL-𝛽Forward -CCCTGCAGCTGGAGAGTGTGG-
Reverse -TGTGCTCTGCTTGAGAGGTGCT-
IL- Forward -TTCCTACCCCAACTTCCAATG-
Reverse -ATGAGTTGGATGGTCTTGGTC-
TNF-𝛼Forward -GACCCTCACACTCAGATCATCTTCT-
Reverse -TGCTACGACGTGGGCTACG-
NOS-II Forward -CTTTACGCCACTAACAGTGGCA-
Reverse -AGTCATGCTTCCCATCGCTC-
COX- Forward -TGGTGCCGGGTCTGATGATG-
Reverse -GCAATGCGGTTCTGATACTG-
GAPDH Probe Applied Biosystems® Rat GAPD (GAPDH) Endogenous Control (VIC®/MGB Probe, E)
theserumwascollectedandstoredat−∘Cuntiluse.e
levels of IL-𝛽,IL-,TNF-𝛼,andPGE
2in the serum were
measured using ELISA kits from R&D Systems (Minneapolis,
MN, USA) according to manufacturer instructions.
2.4.5. Real-Time Quantitative RT-PCR Analysis. Tot al RNA
was extracted from knee joint tissue using the TRI reagent®
(Sigma-Aldrich, St. Louis, MO, USA), reverse-transcribed
into cDNA and PCR-amplied using a TM One Step RT PCR
kit with SYBR green (Applied Biosystems, Grand Island, NY,
USA). Real-time quantitative PCR was performed using the
Applied Biosystems Real-Time PCR system (Applied
Biosystems, Grand Island, NY, USA). e primer sequences
and the probe-sequence are shown in Table . Aliquots of
sample cDNAs and an equal amount of GAPDH cDNA were
amplied with the TaqMan® Universal PCR master mixture
containing DNA polymerase according to manufacturer
instructions (Applied Biosystems, Foster, CA, USA). PCR
conditions were min at ∘C, min at ∘C, s at ∘C,
and min at ∘C for cycles. e concentration of target
gene was determined using the comparative Ct (threshold
cycle number at cross-point between amplication plot and
threshold) method, according to manufacturer instructions.
2.4.6. Histopathological Analysis. Tissue specimens from the
kneejointofratswereremoved,xedin%formalin,
embedded in paran, and serially sectioned at 𝜇m. Tissue
sections were then stained with hematoxylin and eosin
(H&E) or Safranin O-fast green. Histological changes were
examined by light microscopy (Olympus CX/BX, Olym-
pus Optical Co., Tokyo, Japan) and photographed (Olympus
DP).
2.5. Statistical Analysis. All results are presented as the
mean ±standard deviation (SD). e statistical analysis was
performed using one-way analysis of variance (ANOVA),
Duncan’s multiple range test was performed to identify
signicant dierences between groups, and 𝑝values of <.
were considered to be statistically signicant.
3. Results
3.1. Chemical Prole of SDE. To identify and quantify the
levels of marker components in SDE, HPLC analysis was
performed. e chromatogram of the main components is
shown in Figure . e three components of SDE, prim-O-
glucosylcimifugin, -O-𝛽-D-glucosyl--O-methylvisammi-
nol, and sec-O-glucosylhamaudol, were detected at approx-
imately ., ., and .min, respectively. e prim-O-
glucosylcimifugin content was the highest (.%), followed
by -O-𝛽-D-glucosyl--O-methylvisamminol (.%) and
sec-O-glucosylhamaudol (.%).
3.2. Eect of SDE on NO, PGE2, TNF-𝛼,andIL-6Production
In Vitro. We examined the eects of SDE on the levels of
NO, PGE2,TNF-𝛼, and IL- in LPS-stimulated RAW .
cells. Cells were treated with SDE plus LPS or LPS alone for
h. SDE signicantly inhibited the production of NO, PGE2,
TNF-𝛼,andIL-atarangeofor𝜇g/mL (Figure ).
In addition, SDE did not aect cell viability and was not toxic
to RAW . cells (data not shown).
3.3. Eect of SDE on Changes in Hindpaw Weight-Bearing
Distribution. Weight distribution was measured between
sensitized and contralateral hind limbs and used as an
index of joint discomfort in the arthritic knee. erefore,
we evaluated hindpaw weight-bearing using an incapacitance
tester for days. e ratio of hindpaw weight distribution
between the right and le limbs was used to assess the
progression of OA []. e weight-bearing distribution of
the MIA group reduced rapidly and became signicantly
dierent from that of the saline group by day post-MIA
injection and was maintained for at least days. By contrast,
in the SDE- and IM-treated groups, these values were only
slightlydecreasedatdaycomparedwiththoseoftheMIA
group. Beyond that, there was full recovery and the balance
between both hind legs returned to normal in the SDE-
and IM-treated groups. ese results demonstrate signicant
recovery of hind limb weight-bearing in the SDE-treated
group (Figure ).
Evidence-Based Complementary and Alternative Medicine
(AU)
(min)
0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80 1
2
3
(a)
(min)
0.00 5.00 10.00 15.00 20.00 25.00 30.00 35.00 40.00
1
2
3
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
0.45
(AU)
(b)
F : HPLC chromatograms of standard compounds (a) and SDE (b). () Prim-O-glucosylcimifugin, () -O-𝛽-D-glucosyl--O-
methylvisamminol, and () sec-O-glucosylhamaudol.
Nitric oxide (𝜇M)
### ∗∗
∗∗∗
SDE (𝜇g/mL) −−
LPS (1 𝜇g/mL) −+++
200 400
0.0
10.0
20.0
30.0
40.0
(a)
###
∗∗
∗∗∗
SDE (𝜇g/mL) −−
LPS (1𝜇g/mL) −++ +
200 400
0
200
400
600
800
1000
PGE2(pg/mL)
(b)
###
∗
∗∗
SDE (𝜇g/mL) −−
LPS (1𝜇g/mL) −++ +
200 400
0
20000
40000
60000
80000
TNF-𝛼(pg/mL)
(c)
###
∗∗ ∗∗∗
SDE (𝜇g/mL) −−
LPS (1𝜇g/mL) −++ +
200 400
0
5000
10000
15000
20000
25000
IL-6(pg/mL)
(d)
F : Eects of SDE on the production of cytokines and inammatory mediators in LPS-stimulated RAW . macrophages. Cells were
treatedwithSDE(,,or𝜇g/mL) plus LPS ( 𝜇g/mL) or LPS alone for h. (a) NO production was measured using the Griess reagent.
(b–d)ProductionofPGE
2,TNF-𝛼, and IL- was measured by ELISA. Values are expressed as the means ±SD (𝑛=3). ###𝑝< 0.001 versus
untreatedLPSandSDE;∗𝑝< 0.05,∗∗𝑝< 0.01,and∗∗∗ 𝑝< 0.001 versus LPS alone.
3.4. Eect of SDE on Inammatory Cytokine Serum Levels.
Proinammatory cytokines have important roles in the main-
tenance of chronic inammation and tissue damage during
the progression of OA. erefore, we investigated the eects
of SDE on the serum levels of IL-𝛽,IL-,TNF-𝛼,andPGE
2
in the MIA-induced OA model. e serum levels of IL-𝛽,IL-
, TNF-𝛼,andPGE
2increased in the MIA group compared
with those in the saline group but were suppressed in the
SDE-andIM-treatedgroupscomparedwiththoseintheMIA
group (Figure ). ese results indicate that SDE might have
cartilage protection eects in the MIA model by regulating
inammatory cytokines.
3.5. Expression of Cytokine and Inammatory Mediator mRNA
in Knee Joint Tissues. We investigated the eects of SDE on
themRNAlevelsofCOX-,iNOS,IL-𝛽,IL-,andTNF-𝛼in
thekneejointtissuesofrats.Wealsoinvestigatedtheeects
of SDE on the mRNA levels of cytokines in the knee joint
tissues of rats. e expression of cytokine and inammatory
mediator mRNAs increased following MIA injection, but the
expression of the cytokine was attenuated in the SDE- and
IM-treated groups (Figure ). us, our results indicate that
SDE suppresses the expression of inammatory cytokines in
MIA-treated rats.
3.6.EectsofSDEonHistopathology. Following sacrice of
the rats, the knee joints were evaluated histologically for
severity of inammation, synovial hyperplasia, and bone
damage by H&E and Safranin O staining. e MIA group
exhibited histological changes indicative of severe arthritis,
with extensive inltration of inammatory cells into articular
tissues, exudation into the synovial space, synovial hyper-
plasia,andcartilageerosion;however,treatmentwithSDE
andIMinhibitedthedamageandsynovialhyperplasiain
Evidence-Based Complementary and Alternative Medicine
IM
SDE
MIA
Saline
###
### ###
∗
∗∗
∗∗
∗∗∗
∗∗∗
0.0
20.0
40.0
60.0
Weight-bearing distribution (%)
714210
Days aer MIA induction
F : Eects of SDE on changes in hindpaw weight-bearing
distribution in MIA-induced OA in rats. e weight-bearing distri-
bution ratio was measured once a week for days aer the injection
of MIA using an incapacitance tester, compared to that of the MIA-
induced group. ### 𝑝< 0.001 versus saline; ∗𝑝< 0.05,∗∗𝑝< 0.01,
and ∗∗∗𝑝< 0.001 versus MIA.
joints (Figure ). ese histological features show that SDE
attenuates the severity of MIA-induced OA in rats.
4. Discussion
e current available treatments for OA focus on target
symptom reduction, maintenance of joint mobility, and limi-
tation of the loss of functional capacity. Many studies suggest
that traditional herbal resources benet the management of
inammatory arthritis and may therefore benet OA [–
]. SD shows several medicinal therapeutic eects; however,
to date, no studies have been conducted to evaluate the
ecacy of SD for the treatment of OA. erefore, the present
study was conducted to evaluate the anti-inammatory
and antiosteoarthritic activities of SDE using LPS-induced
macrophages and a MIA-induced OA model.
Inammatory mediators play key roles in the progression
of cartilage destruction in OA []. e proinammatory
cytokines are deemed to display catabolic properties that
inuence the pathophysiological processes of OA []. Our
results show that SDE inhibits the production of NO, PGE2,
TNF-𝛼, and IL- in LPS-stimulated RAW . cells.
e antiosteoarthritic eect of SDE in MIA-induced
rats was evaluated by measuring weight-bearing distribu-
tion, inammatory cytokines, and mediators in serum,
inammation-relatedgeneexpressioninkneejoints,and
histopathological parameters. In this study, we also provide
evidence for an OA-related pain-relieving eect of SDE in the
MIAOAmodel.OApaincanbetriggeredbyjointmovement
and typically results in diminished use and reduced joint
mobility[].OurresultsshowthatSDEsignicantlyprotects
weight-bearing in MIA-induced OA in rats, suggesting that
SDEcouldbeusefulfortreatingOApain.
Saline MIA SDE IM
###
∗∗
∗∗∗
0
100
200
300
400
500
IL-1𝛽 (pg/mL)
(a)
Saline MIA SDE IM
##
∗∗
0
20
40
60
80
100
IL-6(pg/mL)
(b)
Saline MIA SDE IM
##
∗
∗
0
20
40
60
80
TNF-𝛼(pg/mL)
(c)
Saline MIA SDE IM
###
∗
∗∗
0
500
1,000
1,500
PGE2(pg/mL)
(d)
F : Eects of SDE on serum levels of cytokines and inam-
matory mediators in MIA-induced OA in rats. (a) Serum IL-𝛽,
(b) IL-, (c) TNF-𝛼,and(d)PGE
2levels were measured by ELISA.
##𝑝< 0.01 and ###𝑝< 0.001 versus saline; ∗𝑝< 0.05,∗∗𝑝< 0.01,
and ∗∗∗𝑝< 0.001 versus MIA.
e chondroprotective eects of SDE, via reduction of
inammation, have been established in rheumatoid arthritis
animal models []. Consistent with published work, the
present study demonstrated that SDE exerts chondropro-
tective eects in MIA-induced OA in rats by suppressing
the expression of inammatory cytokines and mediators in
serum and inammation-related genes in knee joints.
OA is a condition caused in part by injury loss of cartilage
structure and function and dysregulation of proinammator y
and anti-inammatory pathways [, ]. Inammation is an
important factor associated with the development and pro-
gression of OA. Catabolic and proinammatory mediators,
for example, cytokines, NO, and PGE2,areproducedby
inamed synovium and alter the balance of cartilage matrix
Evidence-Based Complementary and Alternative Medicine
Saline MIA SDE IM
##
∗∗
0.0
0.5
1.0
1.5
iNOS expression (fold)
(a)
Saline MIA SDE IM
#
∗∗
0.0
0.5
1.0
1.5
COX-2expression (fold)
(b)
Saline MIA SDE IM
#
∗∗
0.0
0.5
1.0
1.5
IL-1𝛽 expression (fold)
(c)
Saline MIA SDE IM
##
∗∗ ∗∗
0.0
0.5
1.0
1.5
IL-6expression (fold)
(d)
Saline MIA SDE IM
#
∗∗
0.0
0.5
1.0
1.5
TNF-𝛼expression (fold)
(e)
F : Eects of SDE on the expression of cytokines and inammatory mediators in the knee joint of rats with MIA-induced OA.
Expression of (a) iNOS, (b) COX-,(c) IL-𝛽, (d) IL-, and (e) TNF-𝛼mRNA was determined by real-time RT-PCR. #𝑝< 0.05 and ##𝑝< 0.01
versus saline; ∗𝑝< 0.05 and ∗∗𝑝< 0.01,versusMIA.
Saline MIA SDE (200 mg/kg) IM (2mg/kg)
(a)
Saline MIA SDE (200 mg/kg) IM (2mg/kg)
(b)
F : Histopathological features of the knee joint tissues of rats with MIA-induced OA. Representative photographs of knee joint tissues
stained with (a) H&E or (b) Safranin O-fast green (magnication, x).
Evidence-Based Complementary and Alternative Medicine
degradation and repair. ese processes will then exacer-
bate clinical symptoms and joint degradation in OA [].
erefore, inhibiting proinammatory cytokines could be an
important approach to managing OA. In this study, SDE may
inhibit inammatory reactions and partially prevent and slow
the progression of OA. In addition, we demonstrated that
SDE attenuates histological damage and synovial hyperplasia
in joints, compared with MIA group. ese results suggest
that SDE prevents the degradation of cartilage and cartilage
inammation, resulting in the prevention of OA progression.
SD contains major bioactive constituents, including
chromones such as prim-O-glucosylcimifugin, -O-𝛽-D-
glucosyl--O-methylvisamminol, cimifugin, and sec-O-glu-
cosylhamaudol, which are usually obtained from the roots
of the plant [, , ]. Prim-O-glucosylcimifugin, the
chromone with the highest content in the roots of SD,
showed signicant anti-inammatory eects on LPS-
inducedinammatoryresponsesinRAW.cellsand
signicantly protected mice against LPS-induced acute lung
injury []. SD ethanol extract and chromones isolated
from SD showed potential anti-inammatory and protective
eects in LPS-activated RAW . cells [, ]. In the
present study, we conrmed the presence of the chromones,
which were prim-O-glucosylcimifugin, -O-𝛽-D-glucosyl-
-O-methylvisamminol, and sec-O-glucosylhamaudol in
SDE, and this partially explains the anti-inammatory
activity of SDE.
5. Conclusions
In conclusion, SDE showed anti-inammatory activity by
inhibiting the production of NO, PGE2,TNF-𝛼,andIL-
in LPS-induced RAW . cells. SDE also attenuated joint
pain and stiness, inhibited the production of proinamma-
tory cytokines and mediators, and protected cartilage and
subchondral bone tissue in an OA rat model. erefore,
our results suggest that SDE may be a potentially suitable
therapeutic agent for OA and/or its associated symptoms.
Conflict of Interests
e authors declare that there is no conict of interests
regarding the publication of this paper.
Acknowledgments
is work was supported by Evaluation of Eectiveness
of Alternative Herbal Medicine Resources (K, K)
and Characteristic Analysis of Alternative Herbal Medicine
Resources (K) from the Korea Institute of Oriental
Medicine (KIOM). We thank Dr. Go-Ya Choi of KIOM for
thecriticalauthenticationofplantmaterialandforthehelpful
discussions.
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