Antiarthritic, anti-inflammatory, and analgesic effects of Qingfu Guangjieshu ( 青附關節舒 )...
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Transcript of Antiarthritic, anti-inflammatory, and analgesic effects of Qingfu Guangjieshu ( 青附關節舒 )...
Antiarthritic, anti-inflammatory, and Antiarthritic, anti-inflammatory, and analgesic effects analgesic effects of of Qingfu GuangjieQingfu Guangjieshu (shu ( 青附關節舒青附關節舒 ) for the treatment of ) for the treatment of
rheumatoid arthritisrheumatoid arthritis
Antiarthritic, anti-inflammatory, and Antiarthritic, anti-inflammatory, and analgesic effects analgesic effects of of Qingfu GuangjieQingfu Guangjieshu (shu ( 青附關節舒青附關節舒 ) for the treatment of ) for the treatment of
rheumatoid arthritisrheumatoid arthritis
Hua ZhouHua Zhou11, Liang Liu, Liang Liu1, *1, *, Zhi Hong Jiang, Zhi Hong Jiang11, Xiong Cai, Xiong Cai11, Ivan Wong, Ivan Wong11, , Ying XieYing Xie11, Xiao Qing Yi, Xiao Qing Yi11, Hong Xi Xu, Hong Xi Xu22
1 The School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, P.R. China; 1 The School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, P.R. China;
2 Hong Kong Jockey Club Institute of Chinese Medicine, Hong Kong, China2 Hong Kong Jockey Club Institute of Chinese Medicine, Hong Kong, China
Nov. 2006Nov. 2006
Hua ZhouHua Zhou11, Liang Liu, Liang Liu1, *1, *, Zhi Hong Jiang, Zhi Hong Jiang11, Xiong Cai, Xiong Cai11, Ivan Wong, Ivan Wong11, , Ying XieYing Xie11, Xiao Qing Yi, Xiao Qing Yi11, Hong Xi Xu, Hong Xi Xu22
1 The School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, P.R. China; 1 The School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong, P.R. China;
2 Hong Kong Jockey Club Institute of Chinese Medicine, Hong Kong, China2 Hong Kong Jockey Club Institute of Chinese Medicine, Hong Kong, China
Nov. 2006Nov. 2006
2006 WCCM/ZH/Nov 2006 2
OutlineOutline
What is rheumatoid arthritis?What is rheumatoid arthritis? What is Qingfu Guanjieshu?What is Qingfu Guanjieshu? Antiarthritic, anti-inflammatory, and Antiarthritic, anti-inflammatory, and
analgesic effects of QFGJSanalgesic effects of QFGJS Mechanism of the action of QFGJSMechanism of the action of QFGJS SummariesSummaries Future research planFuture research plan
2006 WCCM/ZH/Nov 2006 3
1. What is rheumatoid arthritis1. What is rheumatoid arthritis??
2006 WCCM/ZH/Nov 2006 4
Rheumatoid arthritis may exist at least before the 17th century Rheumatoid arthritis may exist at least before the 17th century
2006 WCCM/ZH/Nov 2006 5
Afflicting 0.5~1.0% of the population Afflicting 0.5~1.0% of the population worldwideworldwide
Chronic inflammatory and destructive Chronic inflammatory and destructive joint disease, leading to disability and joint disease, leading to disability and reduction of quality of lifereduction of quality of life
Complicated pathogeneses, no ideal Complicated pathogeneses, no ideal therapy and medication availabletherapy and medication available
Long term treatment courseLong term treatment course
2006 WCCM/ZH/Nov 2006 6
Pathogenesis of RAPathogenesis of RA
Activation & proliferation
Activation & proliferation
Secretion of proinflammatory cytokines
Secretion of proinflammatory cytokines
Production of proinflammatory mediators
Production of proinflammatory mediators
Imbalance between MMPs and TIMPs
Imbalance between MMPs and TIMPs
T-lymphocytes
Macrophages
Synovial fibroblasts
Joint synovitis
Cartilage and bone destruction
Synovial hyperplasia
Joint pain
Functional disability
Ankylosis
Joint inflammation
MMPs: matrix metalloproteinasesTIMPs: tissue inhibitor of metalloproteinases
Animal model:Arthritic scorePaw volume
IL-1TNF-IL-6
COXs
2006 WCCM/ZH/Nov 2006 7
Therapeutic strategy and medication of RATherapeutic strategy and medication of RA
– Early therapeutic intervention with disease-modifyiEarly therapeutic intervention with disease-modifying anti-rheumatic drugs (DMARDs) and non-steroing anti-rheumatic drugs (DMARDs) and non-steroidal anti-inflammatory drugs (NSAIDs)dal anti-inflammatory drugs (NSAIDs)
– Combination therapies of multiple drugs including Combination therapies of multiple drugs including Chinese medicinesChinese medicines
Advantages of Chinese medicineAdvantages of Chinese medicine– Holistic approach and individualized therapyHolistic approach and individualized therapy– Regulatory or modulatory effects with mild side effRegulatory or modulatory effects with mild side eff
ectsects– Multiple chemicalsMultiple chemicalsmultiple effect pathwaysmultiple effect pathwaysmultmult
iple therapeutic targetsiple therapeutic targets
2006 WCCM/ZH/Nov 2006 8
2. What is 2. What is Qingfu GuangjieshuQingfu Guangjieshu ((青附關節舒青附關節舒 ))??
2006 WCCM/ZH/Nov 2006 9
A new Chinese proprietary drug under A new Chinese proprietary drug under development for the treatment of development for the treatment of rheumatoid arthritis (SFDA)rheumatoid arthritis (SFDA)
The formula of Qingfu Guangjieshu The formula of Qingfu Guangjieshu (QFGJS) is the core component of a (QFGJS) is the core component of a clinical herbal prescription that has been clinical herbal prescription that has been using in the treatment of RA and showing using in the treatment of RA and showing desirable therapeutic effectdesirable therapeutic effect
Consisting of five well documented Consisting of five well documented Chinese medicinesChinese medicines
2006 WCCM/ZH/Nov 2006 10
Sinomenium acutum, (family Menispermaceae)Caulis Sinomenii
青風藤 Qingfengteng
Plant Crude drug
Images courtesy of Qian X.Z. (plant) and Dr. Zhao Z.Z. (crude drug)
2006 WCCM/ZH/Nov 2006 11
Paeonia lactiflora Pall., (family Paeoniaceae)Radix Paeoniae Alba
白芍 BaiShao
Crude drug Decoction PiecesPlant
Images courtesy of Qian X.Z. (plant) and Dr. Zhao Z.Z. (crude drug and decoction pieces)
2006 WCCM/ZH/Nov 2006 12
Aconitum carmichaeli Debx., (family Ranunculaceae)Radix Aconiti Lateralis Preparata
附子 Fuzi
Crude drug
Plant
Images courtesy of Qian X.Z. (plant) and Dr. Zhao Z.Z. (crude drug)
Decoction Pieces
2006 WCCM/ZH/Nov 2006 13
Paeonia suffruticosa Andr., (family Paeoniaceae)Cortex Moutan
牡丹皮 Mudanpi
Crude drug Decoction PiecesPlant
Images courtesy of Qian X.Z. (plant) and Dr. Zhao Z.Z. (crude drug and decoction pieces)
2006 WCCM/ZH/Nov 2006 14
Curcuma Longa L., (family Zingiberaceae)Rhizoma Curcumae Longae
薑黃 Jianghuang
Crude drug Decoction PiecesPlant
Images courtesy of Qian X.Z. (plant) and Dr. Zhao Z.Z. (crude drug and decoction pieces)
2006 WCCM/ZH/Nov 2006 15
Development strategy of QFGJSDevelopment strategy of QFGJSPharmacognosy & chemical analyses
Capsulation
Pharmacodynamics
Pharmacokinetics
Safety evaluation
Clinical trial
Raw Materials (consistent
quality)
Bioactivity and chemical analyses
Quality control
standards
Pilot botanical drug product
Quality control standards
Drug substances (Extract)
Extraction (in-process control)
Optimized extraction methods
Chemical analyses
Quality control
standards
Chemical analyses
Qingfu Guangjieshu
SFDA’s approval
2006 WCCM/ZH/Nov 2006 16
Preparation and QC of QFGJS Preparation and QC of QFGJS
Selective extraction and purificationSelective extraction and purification– Water and ethanol extractionWater and ethanol extraction– Supercritical fluid extractionSupercritical fluid extraction– Purification by XAD-7HP polymeric resinPurification by XAD-7HP polymeric resin
QC with multiple components detectionQC with multiple components detection– TLC identification: all ingredient herbsTLC identification: all ingredient herbs– HPLC fingerprint: characterization of peaksHPLC fingerprint: characterization of peaks– Assay: at least one marker compound for Assay: at least one marker compound for
each herbeach herb
Xie, Y., Jiang, Z.H., Zhou, H., Liu, L. Xie, Y., Jiang, Z.H., Zhou, H., Liu, L. et al et al (2006) (2006) J Pharm Biomed AnalJ Pharm Biomed Anal, in press, in press
2006 WCCM/ZH/Nov 2006 17
Inter-batch quality consistency of QFGJS Inter-batch quality consistency of QFGJS was revealed by fingerprinting analysiswas revealed by fingerprinting analysis
Fig. HPLC fingerprints of QFGJS.
A. Batch No. 20040821; B. Batch No. 20040825; C. Batch No. 20040901.
Peaks 1-15 reflect the characteristic chemical constituents of QFGJS
The similarity of profiles A, B, and C implied a good consistency of QFGJS in chemical constituents
Sinomenine
PaeonolPaeoniflorin
TurmeroneBDC
DC
Curcumin
BDC: bisdemethoxycurcumin; DC: demethoxycurcumin
2006 WCCM/ZH/Nov 2006 18
3. Antiarthritic, anti-inflammatory, 3. Antiarthritic, anti-inflammatory, and analgesic effects of QFGJSand analgesic effects of QFGJS
Cai, X., Zhou, H., Liu, L. Cai, X., Zhou, H., Liu, L. et alet al (2005) (2005) Biochem. Bioph. Res. Co.Biochem. Bioph. Res. Co., 337:586-94., 337:586-94.Zhou, H., Wong, Y.F., Liu, L. Zhou, H., Wong, Y.F., Liu, L. et al et al (2006). (2006). Biol. Pharm. Bull.Biol. Pharm. Bull., 29(2). , 29(2).
2006 WCCM/ZH/Nov 2006 19
Anti-arthritic effect of QFJGS in adjuvant-Anti-arthritic effect of QFJGS in adjuvant-induced arthritisinduced arthritis (AIA) (AIA) model of rats model of rats
MeasurementsMeasurements– Incidence of arthritisIncidence of arthritis– Arthritic score and paw volumeArthritic score and paw volume– Erythrocyte sedimentation rate Erythrocyte sedimentation rate
(ESR)(ESR)– Radiological and Radiological and
histopathological scoreshistopathological scores– Serum level of proinflammatory Serum level of proinflammatory
cytokines: IL-1cytokines: IL-1, IL-6, and TNF-, IL-6, and TNF-
0 1 5 10 15 20 25 30
Drug admimistration:Drug admimistration: QFGJS was given to rats QFGJS was given to rats right after the injection of right after the injection of MT on day 0 until day 30MT on day 0 until day 30
Induction of arthritis by s.c. Induction of arthritis by s.c. injection of injection of Mycobacterium Mycobacterium tuberculosis (MT)tuberculosis (MT)
Normal pawNormal paw
Arthritic Arthritic pawspaws
TimeTime(Day)(Day)
TimeTime(Day)(Day)
The EThe Endnd
2006 WCCM/ZH/Nov 2006 20
(1) (1) Inhibitory effects of QFGJS on theInhibitory effects of QFGJS on the incidence of incidence of arthritisarthritis
Incidences of AIA on days 12 and 30 in different groups of rats treated with QFGJS, Indomethacin and vehicle.
* P<0.05 versus the vehicle-treated arthritic rats
0
25
50
75
100
Day 12 Day 30
Days after arthritis induction
VehicleIndo (1mg/kg)
QFGJS (0.97g/kg)GFGJS (1.94g/kg)
QFGJS (3.89g/kg)
Inci
denc
e (%
)
**
2006 WCCM/ZH/Nov 2006 21
Effects of QFGJS on disease progression of AIA
* P<0.05 versus the vehicle-treated arthritic rats
(2) (2) Inhibitory effects of QFGJS Inhibitory effects of QFGJS on arthritic scoreon arthritic score
0
3
6
9
12
0 6 12 18 24 30
Days after arthritis induction
Vehicle
Indo (1mg/kg)
QFGJS (3.89g/kg)
QFGJS (1.94g/kg)
QFGJS (0.97g/kg)
Art
hrit
ic s
core
0
*****
*********
** *
*
***
****
Treatment
2006 WCCM/ZH/Nov 2006 22
(3) (3) Inhibitory effects of QFGJS on hInhibitory effects of QFGJS on hind paw volumeind paw volume
Effects of QFGJS on disease progression of AIA
* P<0.05 versus the vehicle-treated arthritic rats
0.0
0.6
1.2
1.8
2.4
0 6 12 18 24 30
Days after arthritis induction
Vehicle
Indo (1mg/kg)
QFGJS (3.89g/kg)
QFGJS (1.94g/kg)
QFGJS (0.97g/kg)
Hin
d p
aw v
olu
me
(ml)
**
*
*
Treatment
** * * * * * *
********
* *
**
**
****
2006 WCCM/ZH/Nov 2006 23
(4) (4) Inhibitory effects of QFGJS on eInhibitory effects of QFGJS on erythrocyte sedirythrocyte sedimentation rate (ESR)mentation rate (ESR)
Effects of QFGJS on disease progression of AIA
* P<0.05; ** P<0.01; *** P<0.001 versus the vehicle-treated rats
0
15
30
45
60
0 10 20 30
Days after arthritis induction
Vehicle
Indo (1mg/kg)
QFGJS (3.89g/kg)
QFGJS (1.94g/kg)
QFGJS (0.97g/kg)
****
**
***
***
*
*
ES
R (
mm
/15m
in)
Treatment
2006 WCCM/ZH/Nov 2006 24
(5) (5) Protective effects of QFGJS on cartilage destruction Protective effects of QFGJS on cartilage destruction and bone erosionand bone erosion
(I) Representative radiographs of hind paw(I) Representative radiographs of hind paw
Normal rats Arthritic rats
Arthritic rats received QFGJS treatment
2006 WCCM/ZH/Nov 2006 25
(5) (5) Protective effects of QFGJS on cartilage destruction Protective effects of QFGJS on cartilage destruction and bone erosionand bone erosion
(II) Radiological score(II) Radiological score
Effects of QFGJS administered from day 0 after arthritis induction on radiological changes of AIA rats
* P<0.05; ** P<0.01 versus the vehicle-treated arthritic rats
0
1
2
3
4
5
6
Soft tissue swelling Bone erosion
VehicleIndo (1mg/kg)QFGJS (0.97g/kg)QFGJS (1.94g/kg)QFGJS (3.89g/kg)
Rad
olog
ical
sco
re
*
**
***
2006 WCCM/ZH/Nov 2006 26
(5) (5) Protective effects of QFGJS on cartilage destruction Protective effects of QFGJS on cartilage destruction and bone erosionand bone erosion
(III) Representative histopathological sections of tibiotarsal joints(III) Representative histopathological sections of tibiotarsal joints
Normal rats Arthritic rats
Arthritic rats received QFGJS treatment
2006 WCCM/ZH/Nov 2006 27
(5) (5) Protective effects of QFGJS on cartilage destruction Protective effects of QFGJS on cartilage destruction and bone erosionand bone erosion
(IV) Histopathological score of tibiotarsal joints(IV) Histopathological score of tibiotarsal joints
Effects of QFGJS administered from day 0 after arthritis induction on histopathological changes of AIA rats
* P<0.05 versus the vehicle-treated arthritic rats
0
1
2
3
4
5
6
Cellularinfiltration
Synovialhyperplasia
Pannusformation
Jiont spacenarrowing
Cartilagedestruction
Boneerosion
Vehicle
Indo (1mg/kg)
QFGJS (0.97g/kg)
QFGJS (1.94g/kg)
QFGJS (3.89g/kg)
*
His
tolo
gica
l sco
re
*
*
*
*
*
*
*
**
**
2006 WCCM/ZH/Nov 2006 28
Anti-inflammatory effect of QFJGSAnti-inflammatory effect of QFJGS Carrageenan-induced paw edemaCarrageenan-induced paw edema
0 1 2 3 4 5 6 7 8
0
20
40
60
80
***
******
**
*********
******
***
**
**
***
***
*** ***
***
******
****
% In
cre
ase
of p
aw
vo
lum
e
Time (h) after carageenan injection
CTL Indomethacin 10mg/kg Mixture D" (0.438 g/kg) Mixture D" (0.875 g/kg) Mixture D" (1.750 g/kg)
Inhibition of carrageenan-induced paw edema of rats by treatment of QFGJS at dosages of 0.438 (■), 0.875 (▲) and 1.750 (▼) g/kg, and by the reference drug indomethacin at dosage of 10mg/kg by p.o. (○). Drugs were orally administrated 1 h prior to carrageenan injection. Each point represents the mean S.E.M. (n=10). *P<0.05, **P<0.01, ***P<0.001 vs. control animals (●) at the corresponding time point.
QFGJSQFGJSQFGJS
2006 WCCM/ZH/Nov 2006 29
Analgesic effect of QFGJSAnalgesic effect of QFGJS Acetic acid-induced writhing responseAcetic acid-induced writhing response
0
2
4
6
8
10
12
14
16
18
20
Rotundine100mg/kg
Extract1.616g/kg
Extract0.808g/kg
Extract0.404g/kg
Control
***
**
*
Nu
mb
er
of w
rith
ing
ep
iso
de
s
Analgesic effect of QFGJS at dosages of 0.101, 0.404 and 1.616 g/kg and of the reference drug rotundine at dosage of 100mg/kg on acetic acid-induced writhing response of mice. Drugs were orally administered 2 h prior to the peritoneal injection of acetic acid. Each point represents the mean S.E.M. (n=11-14) *P<0.05, **P<0.01, ***P<0.001 vs. control animals.
QFGJS QFGJS QFGJS
2006 WCCM/ZH/Nov 2006 30
4. Mechanism of the action of QFGJS4. Mechanism of the action of QFGJS
2006 WCCM/ZH/Nov 2006 31
Central role of tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) in the pathogenesis of rheumatoid arthritis. Anti-TNF, anti TNF antibody; TNF R, TNF receptor; IL-1Ra, IL-1 receptor antagonist; VSM, vascular smooth muscle; MMPs, matrix metalloproteinases.
INFLAMMATION PAIN, FEVER
IMPAIRMENT OF REPAIR BONE RESORPTION JOINT DESTRUCTION
Anti-TNF
TNF R
IL-1Ra
IL-1
TNF-α
Cell migration Endothelial permeability
Chemokines Adhesion molecules
Prostanoids Neuropeptides
Kinins
Synergism with other cytokines
MMPs Aggrecanases (synoviocytes, chondrocytes)
Decreased synthesis of collagen and proteoglycan (chondrocytes)
Osteoclasts Extracellular matrix breakdown
VSM proliferation Angiogenesis
Infliximab Etanercept Anakinra
2006 WCCM/ZH/Nov 2006 32
Effects of QFGJS on serum levels of Effects of QFGJS on serum levels of proinflammatory cytokines in AIA modelproinflammatory cytokines in AIA model
Effects of QFGJS administered from day 0 after arthritis induction on cytokines levels in the serum collected on day 20
* P<0.05; ** P<0.05 versus the vehicle-treated arthritic rats
TNF-
IL-6IL-1
0
30
60
90
120
Vehicle Indo(1mg/kg)
QFGJS(0.97g/kg)
QFGJS(1.94g/kg)
QFGJS(3.89g/kg)
Treatment
* *
Seru
m I
L-1
(pg
/ml)
0
30
60
90
120
150
Vehicle Indo(1mg/kg)
QFGJS(0.97g/kg)
QFGJS(1.94g/kg)
QFGJS(3.89g/kg)
Treatment
C
*
Seru
m I
L-6
****
0
15
30
45
60
Vehicle Indo(1mg/kg)
QFGJS(0.97g/kg)
QFGJS(1.94g/kg)
QFGJS(3.89g/kg)
Seru
m T
NF
- (
pg/m
l)
Treatment
2006 WCCM/ZH/Nov 2006 33
Effects of QFGJS on COX-2 expressionEffects of QFGJS on COX-2 expression
Inhibition effect of QFGJS and indomethacin on COX-2 protein expression in inflamed paws induced by carrageenan injection. Data are expressed as mean SEM (n=10). ***p<0.001 versus SD control rats.
0.0
0.2
0.4
0.6
0.8
1.0
***
***
***
***
Mixture D"1.6 g/kg
Mixture D"0.8 g/kg
Mixture D"0.4 g/kg
Indomethacin 10mg/kg
Control
De
nsi
ty r
atio
of C
OX
-2
(no
rma
lize
d w
ith r
esp
ect
to c
on
tro
l)
COX-2
-actin
Con
trol
Indo
met
haci
n (1
0mg/
kg)
QF
GJS
(0
.4g/
kg)
QF
GJS
(0.
8g/k
g)
QF
GJS
(1
.6g/
kg)
QFGJS QFGJS QFGJS
2006 WCCM/ZH/Nov 2006 34
Effects of QFGJS on COX-1 expressionEffects of QFGJS on COX-1 expression
0.0
0.2
0.4
0.6
0.8
1.0
1.2
#
*
Mixture D"1.6 g/kg
Mixture D"0.8 g/kg
Mixture D"0.4 g/kg
Indomethacin 10mg/kg
ControlD
en
sity
ra
tio o
f C
OX
-1
(no
rma
lize
d w
ith r
esp
ect
to
co
ntr
ol)
COX-1
-actin
Con
trol
Indo
met
haci
n (1
0mg/
kg)
QF
GJS
(0
.4g/
kg)
QF
GJS
(0.
8g/k
g)
QF
GJS
(1
.6g/
kg)
QFGJS QFGJS QFGJS
Effect of QFGJS and indomethacin on COX-2 protein expression in inflamed paws induced by carrageenan injection. Data are expressed as mean SEM (n=9-10). *p<0.05 versus control rats, #p<0.05 versus rats administrated with indomethacin
2006 WCCM/ZH/Nov 2006 35
5. Summaries5. Summaries
2006 WCCM/ZH/Nov 2006 36
QFGJS significantly inhibited the QFGJS significantly inhibited the arthritis progression, markedly arthritis progression, markedly protected the affected joints against protected the affected joints against cartilage destruction and bone cartilage destruction and bone erosion in rats with adjuvant induced erosion in rats with adjuvant induced arthritisarthritis
The anti-arthritic effects of QFGJS The anti-arthritic effects of QFGJS may be related to its suppressive may be related to its suppressive action on the overproduced IL-1action on the overproduced IL-1, IL-, IL-6, and TNF-6, and TNF-
2006 WCCM/ZH/Nov 2006 37
QFGJS significantly inhibited acute QFGJS significantly inhibited acute inflammation induced by inflammation induced by carrageenan and pain induced by carrageenan and pain induced by acetic acidacetic acid
The anti-inflammatory effect of The anti-inflammatory effect of QFGJS may be related to its selective QFGJS may be related to its selective suppression on the protein suppression on the protein expression of COX-2 during expression of COX-2 during inflammationinflammation
2006 WCCM/ZH/Nov 2006 38
6. Future research plan6. Future research plan
2006 WCCM/ZH/Nov 2006 39
Cell populations in arthritic jointsCell populations in arthritic joints Cellular response of synoviocytesCellular response of synoviocytes Synthesis of proinflammatory mediatorsSynthesis of proinflammatory mediators IL-IL-11, IL-6, , IL-6, TNF-TNF- levels in paw tissues levels in paw tissues Matrix metalloproteinases (MMPs 1, 2, 3 Matrix metalloproteinases (MMPs 1, 2, 3
and 9) and tissue inhibitor of and 9) and tissue inhibitor of metalloproteinases (TIMPs 1, 2 and 4) in metalloproteinases (TIMPs 1, 2 and 4) in paw tissuespaw tissues
Signal transduction pathways: NF-Signal transduction pathways: NF-B B and MAPKand MAPK
2006 WCCM/ZH/Nov 2006 40
Related publicationsRelated publications1.1. Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and Mechanisms responsible for poor oral bioavailability of paeoniflorin: role of intestinal disposition and
interactions with sinomenine. interactions with sinomenine. Pharmaceutical ResearchPharmaceutical Research, 2006 Oct 25; [Epub ahead of print]. [IF 2005: 2.752], 2006 Oct 25; [Epub ahead of print]. [IF 2005: 2.752]2.2. Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats. Manipulation of the induction of adjuvant arthritis in Sprague-Dawley rats. Inflammation ResearchInflammation Research, 55(9):368-77. , 55(9):368-77.
[IF 2005: 1.210][IF 2005: 1.210]3.3. Suppression of the onset and progression of collagen-induced arthritis in rats by QFGJS, a preparation from an Suppression of the onset and progression of collagen-induced arthritis in rats by QFGJS, a preparation from an
anti-arthritic Chinese herbal formula. anti-arthritic Chinese herbal formula. . . J. EthnopharmJ. Ethnopharm.., 2006 Sep 16;[Epub ahead of print]. [IF 2005: 1.554], 2006 Sep 16;[Epub ahead of print]. [IF 2005: 1.554]4.4. Combinative method using HPLC quantitative and qualitative analyses for quality consistency assessment of a Combinative method using HPLC quantitative and qualitative analyses for quality consistency assessment of a
herbal medicinal preparation. herbal medicinal preparation. J Pharm Biomed AnalJ Pharm Biomed Anal, [Epub ahead of print]. [IF 2005: 1.889], [Epub ahead of print]. [IF 2005: 1.889]5.5. The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis. The comparative study of Sprague-Dawley and Lewis rats in adjuvant-induced arthritis. Naunyn-Schmiedeberg's Naunyn-Schmiedeberg's
Archives of PharmacologyArchives of Pharmacology, 373(2):140-7. [IF 2005: 2.098], 373(2):140-7. [IF 2005: 2.098]6.6. Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by HPLC. Simultaneous determination of six Aconitum alkaloids in proprietary Chinese medicines by HPLC. J. ChromatogJ. Chromatog
r. Ar. A, 1093(1-2):195-203. [I, 1093(1-2):195-203. [IF 2005: 3.096]F 2005: 3.096]7.7. Suppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-iSuppressive effects of QFGJS, a preparation from an anti-arthritic herbal formula, on rat experimental adjuvant-i
nduced arthritis. nduced arthritis. Biochem. Biophys. Res. Commun.Biochem. Biophys. Res. Commun., 337(2):586-94. [I, 337(2):586-94. [IF 2005: 3.000]F 2005: 3.000]8.8. The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro. The pharmacokinetics and tissue distribution of sinomenine in rats and its protein binding ability in vitro. Life SLife S
ci.ci., 77(25):3197-209. [, 77(25):3197-209. [IF 2005: 2.512]IF 2005: 2.512]9.9. Pharmacokinetic interaction of paeoniflorin and sinomenine: pharmacokinetic parameters and tissue distributioPharmacokinetic interaction of paeoniflorin and sinomenine: pharmacokinetic parameters and tissue distributio
n characteristics in rats and protein binding ability in vitro. n characteristics in rats and protein binding ability in vitro. The Journal of Pharmacological SciencesThe Journal of Pharmacological Sciences , in press. , in press. [SCI impact factor 200[SCI impact factor 2005: 1.792]5: 1.792]
10.10. The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model.The effects of sinomenine on intestinal absorption of paeoniflorin by the everted rat gut sac model. J. Ethnophar J. Ethnopharm.m., in press. [, in press. [IF 2005: 1.554]IF 2005: 1.554]
11.11. Influence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious ratInfluence of co-administrated sinomenine on pharmacokinetic fate of paeoniflorin in unrestrained conscious ratss. . J. Ethnopharm.J. Ethnopharm., 99(1):61-7. [, 99(1):61-7. [IF 2005: 1.554]IF 2005: 1.554]
12.12. Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory Suppressive effects of JCICM-6, the extract of an anti-arthritic herbal formula, on the experimental inflammatory and nociceptive models in rodents.and nociceptive models in rodents. Biol. Pharm. Bull. Biol. Pharm. Bull., in press. [, in press. [IF 2005: 1.317]IF 2005: 1.317]
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15.15. Review on the therapeutic strategies of traditional Chinese medicine in rheumatoid arthritis. Review on the therapeutic strategies of traditional Chinese medicine in rheumatoid arthritis. Chinese Journal of Chinese Journal of Traditional Chinese Medicine and PharmacyTraditional Chinese Medicine and Pharmacy , 20(5):309-11., 20(5):309-11.
2006 WCCM/ZH/Nov 2006 41
AcknowledgementsAcknowledgements
Team members: Team members: – Principal investigator: Prof. Liang LIUPrincipal investigator: Prof. Liang LIU
– Dr. Zhi Hong JIANG, Dr. Zhao Xiang BIAN, Prof. Kelvin Dr. Zhi Hong JIANG, Dr. Zhao Xiang BIAN, Prof. Kelvin CHAN, Dr. Zhong Zhen ZHAO, Yuen Fan WONG, Xiao CHAN, Dr. Zhong Zhen ZHAO, Yuen Fan WONG, Xiao Qing YIQing YI
– Ph.D. Students: Zhong Qiu LIU , Ying XIE, Xiong CAI Ph.D. Students: Zhong Qiu LIU , Ying XIE, Xiong CAI
Collaborations:Collaborations:– Hong Kong Jockey Club Institute of Chinese MedicineHong Kong Jockey Club Institute of Chinese Medicine
Dr. Edmund LEE, Dr. Hong Xi XU , Miss Margaret LI, Dr. Edmund LEE, Dr. Hong Xi XU , Miss Margaret LI, Mr. Andrew CHENG, Mr. Angus LAUMr. Andrew CHENG, Mr. Angus LAU
This project is funded the Hong KongThis project is funded the Hong KongJockey Club Charities TrustJockey Club Charities Trust
Team members: Team members: – Principal investigator: Prof. Liang LIUPrincipal investigator: Prof. Liang LIU
– Dr. Zhi Hong JIANG, Dr. Zhao Xiang BIAN, Prof. Kelvin Dr. Zhi Hong JIANG, Dr. Zhao Xiang BIAN, Prof. Kelvin CHAN, Dr. Zhong Zhen ZHAO, Yuen Fan WONG, Xiao CHAN, Dr. Zhong Zhen ZHAO, Yuen Fan WONG, Xiao Qing YIQing YI
– Ph.D. Students: Zhong Qiu LIU , Ying XIE, Xiong CAI Ph.D. Students: Zhong Qiu LIU , Ying XIE, Xiong CAI
Collaborations:Collaborations:– Hong Kong Jockey Club Institute of Chinese MedicineHong Kong Jockey Club Institute of Chinese Medicine
Dr. Edmund LEE, Dr. Hong Xi XU , Miss Margaret LI, Dr. Edmund LEE, Dr. Hong Xi XU , Miss Margaret LI, Mr. Andrew CHENG, Mr. Angus LAUMr. Andrew CHENG, Mr. Angus LAU
This project is funded the Hong KongThis project is funded the Hong KongJockey Club Charities TrustJockey Club Charities Trust
2006 WCCM/ZH/Nov 2006 42
Thank you!Thank you!Thank you!Thank you!