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



2006 WCCM/ZH/Nov 2006 14

Curcuma Longa L., (family Zingiberaceae)Rhizoma Curcumae Longae

薑黃 Jianghuang



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


(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


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



0.0

0.6

1.2

1.8

2.4

0 6 12 18 24 30


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)


* P<0.05; ** P<0.01; *** P<0.001 versus the vehicle-treated rats

0

15

30

45

60

0 10 20 30


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


(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


(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


(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


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


QFGJS(0.97g/kg)

QFGJS(1.94g/kg)

QFGJS(3.89g/kg)

Treatment

C

*

Seru

m I

L-6

****

0

15

30

45

60


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]

13.13. Quantification of sinomenine in Caulis Sinomenii collected from different growing regions and wholesale herbal Quantification of sinomenine in Caulis Sinomenii collected from different growing regions and wholesale herbal markets by a modified HPLC method. markets by a modified HPLC method. Biol. Pharm. Bull.Biol. Pharm. Bull., 28(1):105-9. [, 28(1):105-9. [IF 2005: 1.317]IF 2005: 1.317]

14.14. Quantification of aconitum alkaloids in aconite roots by a modified RP-HPLC method. Quantification of aconitum alkaloids in aconite roots by a modified RP-HPLC method. Phytochem. Anal.Phytochem. Anal., 16(6):4, 16(6):415-21. [15-21. [IF 2005: 1.398]IF 2005: 1.398]

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!

antiarthritic, anti-inflammatory, and analgesic effects of qingfu guangjieshu ( 青附關節舒 )...

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