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The Anti-Nociceptive and Anti-Inflammatory Effect of Achyranthes Japonica Nakai

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The Anti-Nociceptive and Anti-Inflammatory Effect of Achyranthes Japonica Nakai 2004. Vol. 25. No. 4. 8-14 Korean Journal of Oriental Medicine Original Articles The Anti-nociceptive and Anti-inflammatory Effect of Achyranthes Japonica Nakai Hi-Joon Park, Ji-Suk Lee, Mi-Sook Hong, Chang-Ju Kim, Jin-Woo Kim, Hye-Jung Lee, Sabina Lim Research Group of Pain and Neuroscience, East-West Medical Research Institute, WHO Collaboration Center, Kyung Hee University, Seoul, Korea Objective : Achyranthes japonica Nakai (AJ) has been classified as a herb that activates blood flow and clears the stagnated blood. In this study, we evaluated its anti-nociceptive and anti-inflammatory activity in animals to clarify the effect of AJ on pain or inflammation. Methods : ICR mice and Sprague-Dawley rats were pretreated with an ethanolic extract of AJ with two dosages of 200 mg/kg (p.o.) and 400 mg/kg (p.o.). Nociceptive responses of acute pain were determined by hotplate and tail-flick tests. The effects of AJ on inflammation were evaluated by flexion/extention test and mechanical hyperalgesia test in models induced by both carrageenan and Complete Freund's Adjuvant (CFA). Results : AJ showed significant analgesic effects in both hotplate and tail-flick tests at the dose of 400 mg/kg. It also produced a significant inhibition of carrageenan-induced paw edema and CFA induced arthritis in rats at the dose of 400 mg/kg. Conclusion : We have demonstrated the analgesic and anti-inflammatory properties of an 80% ethanolic extract of AJ in animals. This suggests the application of AJ in relief of pain or inflammatory disease. Key Words: Analgesia; Inflammation; Achyranthes japonica Nakai Introduction stagnated blood. Although it has been used for the treatment of inflammatory diseases, including arthritis The root of Achyranthes japonica Nakai (AJ) has in clinics, experimental studies have not yet clarified the been used in traditional medicine in Korea for the effect of AJ on pain or inflammation. Recently, there treatment of various diseases of joint and blood has been an increase of interest in herbal medicines as circulation. Achyranthes japonica Nakai is classified as the treatment for intractable diseases such as rheumatoid a herb that activates our blood flow and clears the arthritis1,2). Based on its use in traditional medicine, we evaluated the possible anti-nociceptive and anti- inflammatory properties of the extract of AJ. Received 28 February 2004; received in revised from 15 October 2004; accepted 20 October 2004 Correspondent to : Sabina Lim Research Group of Pain and Neuroscience, East-West Medical Research Institute. Kyung Hee University, 1 Hoegi-dong, Dongdaemoon-gu, Seoul, 130-701, Korea Tel: 82-2-961-0338, Fax: 82-2-961-7831, E-mail: [email protected] 8 The Anti-nociceptive and Anti-inflammatory Effect of Achyranthes Japonica Nakai (661) guidelines of NIH and the Korean Academy of Medical Materials and Methods Sciences. 1. Plant Material 5. Anti-nociceptive effect The root of AJ was obtained from the department of Nociceptive responses to acute pain were determined herbal pharmacy in Kyung Hee Medical Center, and by hotplate and tail-flick tests at 1, 3 and 5 hr after the was identified and authenticated by Dr. N.J. Kim administration of extract (200 and 400 mg/kg, p.o.) in (Research Institute of East-West Medicine, Kyung Hee mice. Saline was given to control group (p.o.). University). 1) Hot plate test 2. Chemicals For hotplate nociceptive test, mice were placed on 53 The following components were used: -carrageenan ±0.5℃ hotplate apparatus (Ugo Basile, Italy). A glass and indomethacine were purchased from Sigma. cylinder (18 cm height and 20 cm diameter) was used to Complete Freund's Adjuvant (CFA) was purchased maintain the mice on the hotplate. Animals were placed from Difco Labs. on the heated surface and removed immediately after they licked the footpad of any paw. The time spent on 3. Extraction of AJ the hotplate was recorded3,4) The contents of 300 g Acyranthes japonica Nakai (root) was placed into 3 liter-round bottomed flask fitted 2) Tail-flick test with condenser and a heated mantle. The content was Nociceptive responses to acute pain were determined refluxed with 80% v/v ethanol (200 ml distilled by tail-flick test3,4). Mice were retained in specially water+800 ml ethanol) for 3 hrs. The resulting slurry designed holders with the hind limbs protruding out and was filtered through Whatman No. 1 filter paper and the the tail hanging freely5). The tail-flick responses were residue was again refluxed with fresh solvent as above. determined by immersing the distal 1/3 of the tail in The two volumes of the combined filtrate was reduced heated water (51±0.5℃) which was used as the using an evaporator (Buchi, Switzerland) under reduced nociceptive stimulus, and the time elapsed till the tail pressure. Then, the concentrated extract was dried at the flicking was measured. freezing vacuumed drier (EYELA, Japan), and then, it was stored in a vacuumed dessicator until use. The final 6. Anti-inflammatory effect weight from natural product was 53.85 g (17.95%). We used two kinds of inflammatory models, carrageenan- and CFA-induced inflammation, in rats. 4. Animal Adult male ICR mice (25-30 g, n = 60) and Sprague- 1) Acute Inflammation (carrageenan induced paw Dawley rats (180-200 g, n = 40) were conditioned at edema) standard temperature (22±3C) and under the standard Acute inflammation was induced in rats by injection 12 hr light/dark cycle (lights on at 07:00 hr) with free 50㎕ of carrageenan (1% w/v) solution in distilled water access to food and water. The experimental procedures into the subplantar region of right hind paw. The were carried out in accordance with the animal care volume of paws was measured using a water 9 (662) Korean J of Oriental Med 2004;25(4) displacement plethysmometer (UGO BASIL, Italy) at vocalizations emitted during both the flexion and the time point of 0, 1, 3, and 5 hr after inoculation6). AJ extension periods was then quantified. A flexion and an extract (200 and 400 mg/kg, p.o.) was given to extension stimulus was repeated every 5 s until a total experimental group 1 hr before testing. Saline or of five stimuli each had been delivered to each hind indomethacine (10 mg/kg) was also administered to the limb. Vocalization rating of 0 (no vocalization) or 1 control groups. (vocalization) was given in response to each flexion or extension stimulus, depending on whether or not the 2) Chronic inflammation (CFA induced chronic animal vocalized. Thus, for each animal the arthritis) vocalization rating ranged from 0 to 5 at each hind limb (1) CFA induced arthritis and drug administration both in extension or flexion test. To induce arthritis using CFA, the right foot of the rat (4) Mechanical hyperalgesia test was held and the fossa of the lateral malleolus of the The Randall-Selitto test was applied to evaluate fibula was located. A 26 1/2-gauge needle was mechanical hyperalgesia in arthritic animals. A graded vertically penetrated through the skin, and turned mechanical force was delivered through an analgesia distally to insert into the articular cavity from the gap meter (Dae Jong, Korea) onto the convex surface of the between the tibiofibular and tarsus bone until a distinct paw. Rats showed withdrawal of their hind paw or loss of resistance was felt. A volume of 50 ㎕ CFA was vocalization, when the applied force reached the then injected7,8). Animals receiving CFA injection were nociceptive threshold10). then randomly divided into 2 groups: the control (saline, p.o.) group and AJ (400 mg/kg, p.o.), 7. Statistical procedure respectively. These treatments were continued for 25 Continuous data were expressed as mean±SEM, and days from the day 0 to 24, after the injection. tested for statistical significance with two way repeated (2) Evaluation of ankle joint edema measures ANOVA, taking the treatment as the between The ankle circumference was measured 30 min after groups measure and times as the repeated measure, the rats were retained in specially designed holders with followed by Dunn's multiple comparison test. Discrete the hind limbs protruding and tail hanging freely. The data were expressed as median±median-derived circumferences of the ankles were measured around the absolute deviation (MAD). The Mann-Whitney U test lower edge of lateral and medial malleolus with a scaled was used for comparison between the groups. soft ruler without elasticity to a precision of 1 mm. The circumferential difference in mm (CD) between the Results arthritic (ipsilateral) and the normal (contralateral) leg was calculated (CD = ipsilateral - contralateral)9). 1. Analgesic activity of AJ (3) Flexion and extension test 1) Hot plate test Arthritis-induced hyperalgesia was evaluated by In the hotplate test, the extract of AJ (400 mg/kg, quantifying the total number of vocalization evoked by p.o.) showed significant analgesic effect at all the time ankle flexion or extension. The rat was held points. Extract at the dose of 200 mg/kg displayed comfortably and gentle extension was applied to the increased analgesic activity, but the significance only ankle joint of each hind limb. The number of appeared at 3 hr after the administration (Fig. 1). 10 The Anti-nociceptive and Anti-inflammatory Effect of Achyranthes Japonica Nakai (663) Control 200 mg/kg 400 mg/kg Control 200 mg/kg 400 mg/kg Increase of TFLs(%) Time(hr) Fig. 1. The analgesic effect of the root of Achyranthes Fig. 2. The analgesic effect of the root of Achyranthes japonicain Nakai in hotplate test of mice. 400 mg/kg japonicain Nakai tail-flick test of mice. The 400 ethanol extract of Achyrantes japonica Nakai (p.o.) mg/kg (p.o.) ethanol extract of Achyrantes japonica showed significant anti-nociceptive effects at 1, 3 Nakai displayed significantly increased latencies at and 5 hr after administration.
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