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 Cheongpa-jun(CP) is an herbal formula containing aqueous extract of Ledebouriella seseloides, Achyranthes japonica, Acanthopanax sessiliflorum and Rhynchosia molubilis, all of which are reputed for their beneficial effects in the treatment of osteoarthritis. The study on the anti-inflammatory effects of the agent using carrageen and adjuvant induced paw edema , pain , cytokine and WBC in rats. Inflammation was induced by injecting complete Freund's adjuvant (CFA, 0.05ml 1:1 oil/saline suspension) into the hindpaw of the male Sprague-Dawley rat 30min, 7h and 24h after CP injection. CP showed a marked inhibitory effect on edema in two models of inflammation in rats, at the dose of 200, 400 and 800 mg/kg. Unilateral joint swelling was accompanied by significant unilateral mechanical allodynia(p<0.05) and thermal hyperalgesia(p<0.05). CP attenuate thermal allodynia, at 400mg/kg did attenuate mechanical allodynia compared with vehicle treated arthritic animal. The anti-hyperalgesic effect on mechanical hyperalesia was at 200 mg/kg or 400mg/kg CP. In the groups of Freund’s adjuvant arthritis, the counts of WBC showed high in control group compared with CP treated group.. Rat Cytokine Antibody Array 1.1 (Ray Biotech) coated with 19 specific cytokine antibodies were probed with protein samples and the relative cytokine levels were compared. Compared to saline-injected rats, there were significant increases (p<0.05-0.01) in the levels of four cytokines in the sera after inflammation, including interleukin (IL)-1beta (7h), IL-6 (7h), tumor necrosis factor-alpha (7h), tissue inhibitor of metalloproteinase-1(TIMP-1) (7h, 24h). Although different cytokines exist in the blood, their levels did not same, nor did not appear to depend on, the local cytokine levels. The findings provide specific targets for further studying the involvement of cytokines in inflammation.
| Cheongpa-Jun |
[Composition] Cibotium barometz, Acantho panax, Achyranthes japonica, Ledebouriella divaricata, Eucommia ulmoides etc.
[Function and clinical use] Strengthens the sinews and bones and benefits the joints: used for pain and soreness affecting the lower back and knees from deficiency, because it tonifies and nourishes the Liver and Kidneys.
Clears Damp Heat in the Lower Burner. Used in cases of Damp Heat pouring downwards manifesting as knee pain or lower back Damp Painful Obstruction.
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| Anti-inflammatory activity |
[Carrageenan-induced hind paw edema (acute inflammation)]
The first phase (1-3h) : serotonin, PG
The second phase (3-5h) : PMNs
| 1. |
Carrageenan-evoked hyperalgesia was quantified in separate groups of animals as a measure of the nociceptive response to a thermal stimulus using the Hargreaves Test test with the temperature adjusted to 51 ± 1ºC. |
| 2. |
Anti-inflammatory activity was determined in vivo using the carrageenan-induced rat paw edema test. |
| 3. |
The CP was administered orally at doses of 10, 50, 100, 200, and 500 mg/kg (0.1 ml/20 g) as a suspension in EtOH/Tween 80/H2O (2:2:20, v/v/v; vehicle) 1 h before carrageenan. |
| 4. |
Control animals received an equal volume of vehicle. |
| 5. |
Animals were then injected subplantarly with either 0.1 ml of 1% carrageenan solution in saline (0.1 mg/paw) or sterile saline (0.9% NaCl) into one of the hind paws |
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| Chronic arthritis |
Chronic monoarthritis ;(duration 9 weeks)
Complete Freund's adjuvant(CFA) was prepared by mixing incomplete adjuvant and a suspension of killed mucobacterium tuberculosis in equal volume until a thick water –oil in emulsion was formed.
Under light anesthesia by 2% chlorohydrate(i.p.) rats was single injected subcutaneously into the plantar surface of hindpaw at a volume of 50ul.
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 ▣ Control saline
▣ Original product water Ex. (100, 300 mg/kg)
▣ 30% EtOH Ex. (100, 300 mg/kg)
▣ Positive control : phenylbutazone (50 mg/kg) |
 Acetic acid-induced writhing syndrome
(peripheral : pain substances)
The withdrawal latency of each hind paw was determined and hyperalgesia defined as a decrease in the latency (s) calculated as the difference between carrageenan and saline paw latency times.
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| 1. |
Paw volumes were measured every hour up to 4 h after subplantar injection using a glass plethysmometer. |
| 2. |
The edema was considered to be the difference in volume between the carrageenan- and saline-treated paws. |
| 3. |
Anti-inflammatory activity was reported as percent inhibition of the edema compared with the vehicle control group. | |
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Summary of densitometric quantification of relative cytokine protein levels.
Compared to saline-injected rats, there were significant increases in the levels of five proinflammatory cytokines in the serum, |
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The relative expression levels of five cytokines were determined by densitometry. The array membranes were scanned with Bio-Rad densitometry. The densities of signals were normalized with background and positive control. | | |
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| Standard of research |
Patients among the above 76 cases
⇒ whose hospitalization is within 30 days
or ⇒ whose hospitalization is just the 30th day
Treatment group : 55 cases of the above patients who took only CPJ as medication from the first day to the last day of hospitalization.
Control group : 21 cases pf the above patients who took medication other than CPJ from the first day to the last day of hospitalization.
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| Treatment methods |
1) By Medication treatment
① CPJ Treatment group
Took total 2 packs of CPJ(Cheongpa-jeon) (牛膝, 五加皮, 杜仲, 防風 etc.) daily, three times a day from the 1st duration of hospitalization through to the last day.
② Control group
Took total 2 packs of medication apart from CPJ, three times a day from the first day of hospitalization to the last day.
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2) VAS assessment : Basic assessment using Visual analogue scale
Table 1. Change of VAS score
| |
VAS
1-5 |
VAS
6-10 |
Total |
| CPJ |
52 (94.54%) |
3 (5.46%) |
55 |
| No-CPJ |
13 (61.9%) |
8 (38.1%) |
21 |
Self-perceptional degree of the symptoms. Measured “10” in the first medical examination. Measured “0” when the symptoms have faded away.
Table 2. Change of SLR
| |
VAS
1-5 |
VAS
6-10 |
One leg
20-40
41-60
61-80 |
17 (89.4%)
2 (10.6%)
0 (0%) |
7 (77.8%)
1 (11.1%)
1 (11.1%) |
Both legs
20-40
41-60
61-80 |
12 (48%)
5 (20%)
8 (32%) |
7 (100%)
0 (0%)
0 (0%) |
The figure measured on the 30th day after hospitalization. The angle change shown less than 20 degree in raising leg. Classified into a disorder in one leg and a disorder in both legs. When judged the disorder was appeared in both sides, took the lower figure from the SLR test. | 
Graph. Duration of hospitalization
Analyzed by VAS assessment, SLR test, and Duration of hospitalization
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VAS assessment |
SLR test |
Duration of hospitalization |
| Result |
CPJ > No-CPJ |
CPJ > No-CPJ |
CPJ > No-CPJ |
⇒ The clinical effect of herbal supplement CPJ on patients with HIVD turns out to be higher than No-CPJ medication. | | |
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