|Year : 2014 | Volume
| Issue : 4 | Page : 458-461
Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark: A tribal claim
Anurag Gupta1, K Nishteswar2, Vinay J Shukla3, BK Ashok4
1 Department of Ayurveda, Shri Ram Singh Hospital and Heart Institute, Krishnanagar, Delhi, India
2 Department of Dravyaguna, Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India
3 Pharmaceutical Chemistry Laboratory, Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India
4 Drug Discovery Group, Research and Development, The Himalaya Drug Company, Bangaluru, Karnataka, India
|Date of Web Publication||18-Jun-2015|
Head, Dept. of Dravyaguna, I.P.G.T. and R.A., Gujarat Ayurved University, Jamnagar - 361 008, Gujarat
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Plants occupy an important place in folk medicine all over the world for centuries and indigenous communities have developed their own specific knowledge on plant resources, uses, management, and conservation. Research interest and activities in the area of ethno medicine have increased tremendously in the last decade. Currently, scientists are evincing keen interest in the scientific evaluation of ethno medical claims. Bark powder of Arjuna (Terminalia arjuna [Roxb.] Wight and Arn) is used by tribals for the management of some painful conditions. Aim: To evaluate analgesic activity of T. arjuna bark in rodents. Materials and Methods: For evaluation of analgesic activity, different experimental models, that is, the acetic acid-induced writhing syndrome in mice, formaldehyde-induced paw licking response and tail flick test in rats were designed. Experiments were carried out at two-dose levels, that is, therapeutically equivalent dose (TED) and TED × 2. Animals were divided into three groups (six animals in each group), first group serving as a control group, second and third group labeled as test drug group. Results: Test drug at both the doses significantly decreased the writhing syndrome in comparison to control the group. In comparison to control the group, incidences of formalin-induced paw licking were reduced in test drug groups in both early and late phases of pain. In tail flick response, threshold was significantly increased in both test drug groups at every time intervals. Conclusion: Study showed that stem bark of T. arjuna possesses analgesic activity in all experimental models.
Keywords: Arjuna bark, pain, reverse pharmacology
|How to cite this article:|
Gupta A, Nishteswar K, Shukla VJ, Ashok B K. Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark: A tribal claim. AYU 2014;35:458-61
|How to cite this URL:|
Gupta A, Nishteswar K, Shukla VJ, Ashok B K. Evaluation of analgesic activity of Terminalia arjuna (Roxb.) Wight and Arn bark: A tribal claim. AYU [serial online] 2014 [cited 2020 Oct 30];35:458-61. Available from: https://www.ayujournal.org/text.asp?2014/35/4/458/159041
| Introduction|| |
Terminalia arjuna (Roxb.) W. A. (Family: Combretaceae), is a source plant of Ayurvedic classical drug namely Arjuna. Charaka Samhita included Arjuna among the groups indicated for the management of Udarda (urticaria).  Vrindamadhava (9 th AD), a medieval compendium recommended it in the management of Hridroga (heart disease).  The drug is attributed with wound healing property by most popular Nighantus like Dhanvantari, Kaiyadeva, Raja, and Bhavaprakash.  Hridya (cardiotonic) activity was described by Bhavamishra.  Arjuna is frequently employed by tribals in the management various diseased conditions.
Tribal claims include
Five gram powder, made of equal quantities of stem bark of T. arjuna, Pterocarpus marsupium, and flowers of Cassia occidentalis are mixed in 100 ml of hot milk and given once a day for a month or two, to save the patient from tuberculosis.  Leaf paste of T. arjuna is used like soap nut to get rid of dandruff.  Twenty gram of stem bark of T. arjuna in 50 ml of water is boiled to half, filtered, mixed in 50 ml of goat milk and given internally, once a day for a week, to control palpitation and high-blood pressure.  Five gram of finely powdered stem bark of T. arjuna is administered twice a day for 3 days to relive pain in lower limbs. 
Terminalia arjuna is a large deciduous tree, commonly found throughout the greater parts of the country. Bark available in pieces, flat, curved, recurved, channeled to half quilled, 0.2-1.5 cm thick, market samples up to 10 cm in length and up to 7 cm in width, the outer surface somewhat smooth and grey, the inner surface somewhat fibrous and pinkish, transversely cut smoothened bark shows pinkish surface; fracture - short in inner and laminated in the outer part; taste is bitter and astringent. 
Certain experimental studies provided evidence for its hypotensive activity in dogs,  protection against isoproterenol induced myocardial ischemic injury in Wistar albino mice and hypolipidemic activity in hyperlipidemic rabbits.  Some of the studies confirmed antibacterial, antiviral, and wound healing activities. ,, Clinical studies documented beneficial activity in patients suffering from congestive cardiac failure.  A critical review of research studies so far carried out on Arjuna clearly indicates that the bark of it was not studied for its analgesic activity. Keeping this in view, the present study was planned and carried out based on tribal claim for assessing analgesic activity in Swiss albino mice by tail flick method, acetic acid-induced writhing reflex and formaldehyde-induced paw licking method.
| Materials and Methods|| |
Collection of plant materials
The bark of T. arjuna was collected from outskirts of Jamnagar, Gujarat and was authenticated by expert, Pharmacognosy Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar. Sample was deposited in the herbarium of Pharmacognosy Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar. The flat thick bark was made into pieces, and shade dried for 15 days and then pulverized. Powder was stored in air tight glass container to carry out further evaluation.
Charles foster strain albino rats of either sex; weighing 200 ± 20 g for formaldehyde-induced paw licking response and Swiss albino mice of either sex, weighing 30 ± 6 g for the acetic acid-induced writhing syndrome and tail flick test were used for the study. Animals were obtained from the animal house attached to the Pharmacology Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar. The animals were maintained on "Amrut" brand animal pellet feed of Pranav Agro Industries and tap water was given ad libitum. The temperature and humidity were kept at optimum level and animals were exposed to natural day-night cycles. The experiments were carried out in conformity with the guidelines of the Institutional Animal Ethics Committee (IAEC) after obtaining its permission (approval no. IAEC/10/12/21) and care of animals was taken as per the Committee's guidelines for the Purpose of Control and Supervision on Experiments on Animals (CPCSEA) guidelines.
Dose fixation and grouping
The dose fixation for the experimental animals was done on the basis of body surface area ratio by referring to the standard table of Paget and Barnes.  The adult human dose (3 g/day) was converted to animal dose. On this basis, the rat dose and mice dose were found to be 270 mg/kg and 400 mg/kg, respectively. All experiments were carried out at two-dose levels, viz., therapeutically equivalent dose (TED) and TED × 2. For each study, 18 animals were selected and divided into three groups containing equal animals wherein first group serving as a control group receiving distilled water only and second and third group labeled as TED and TED × 2 groups. The test drug was suspended in deionized water and administered orally with the help of gastric catheter sleeved to syringe.
Acetic acid-induced writhing syndrome
Acetic acid (1% v/v) was administered intraperitoneally to all the groups at a dose of 1 ml/kg body weight 60 min after the administration of test compounds.  The analgesic effect was recorded by counting the number of writhes after the injection of acetic acid for a period of 30 min. A writhe is indicated by abdominal constriction and full extension of the hind limbs.
Formaldehyde-induced paw licking response in rats
The effect of test drug on the formaldehyde-induced paw licking response was evaluated by adopting the method used in previous research work.  After the injection of formaldehyde, the animals were kept under observation for half an hour. The time taken for the onset of paw licking, and its frequency was measured in two phases as 0-10 min and 20-30 min.
Tail flick test
The basal reaction time of animals to radiant heat was recorded by placing the tip (last 1-2 cm) of the tail on the radiant heat source. The tail withdrawal from the heat (flicking response) is taken as the end point. The animals that showed a flicking response within 3-5 s were selected for the study. A cut-off period of 15 s is observed to avoid damage to the tail. After the administration of the drug, the tail flick response was taken at 30 min, 60 min, 90 min, 120 min, 180 min, and 240 min. 
Student's t-test for unpaired data has been used for analyzing the data generated during the study.
| Observations and Results|| |
Study on acetic acid-induced writhing syndrome in mice showed that pretreatment with test drug at both the dose levels apparently decreased the latency of onset of writhing. However, only the decrease observed in onset of writhing in TED treated group is found to be statistically significant. Test drug at both the doses significantly decreased the writhing syndrome in comparison to control group [Table 1].
In comparison to control group, incidences of formalin-induced paw licking were reduced in test drug groups at both the dose levels in both early and late phases of pain. However, only the inhibition of pain observed in late phase nociception is found to be statistically significant in both test drug groups [Table 2].
In tail flick response, threshold for tail flick response was significantly increased in both test drug-treated groups at every time intervals in comparison to control group. The observed increase for tail flick response in TED dosed group is found to be better than that of high dose treated group [Table 3].
| Discussion|| |
Intraperitoneal administration of acetic acid releases prostaglandins and phlogistic mediators like PGE2 and PGE2a, and their levels were increase in the peritoneal fluid of the acetic acid-induced mice.  The drug in the therapeutic dose and in the double dose group significantly (P < 0.001) reduced the number of abdominal constrictions and stretching of the hind limbs induced by the injection of acetic acid in a dose-dependent manner. The abdominal constrictions produced after the administration of acetic acid are related to sensitization of the analgesic receptors to prostaglandins. It is, therefore, possible that the drug is effective due to its analgesic effect, probably by inhibiting the synthesis or action of prostaglandins.
When formalin is injected subcutaneously into the paw, it produces intense pain reaction. The effect is seen in two phases. The initial phase lasts for 0-10 min of the formaldehyde injection, it is supposed to be mediated through modulation of neuropeptides.  The second phase, which is observed 20-30 min of the formaldehyde injection, is supposed to be mediated through release of inflammatory mediators like prostaglandin. Centrally acting drugs inhibit both phases, while peripherally acting drugs only inhibit the second phase. Test drug at both dose levels insignificantly decreased the paw licking episodes at first phase while significantly decreased at later phase which indicates analgesic activity of test drug seems to be through central mechanism.
Tail flick model, which is thermal-induced nociception indicates narcotic involvement which is sensitive to opioid m receptors.  The study shows prolonged analgesic effect of the test drug. The presence of analgesic activity in this model indicates that the mechanism of action is central. The mechanism through which this effect is brought about may be due to modulation of opioid receptors or by release of endogenous analgesic factors such as encephalin and endorphin.
| Conclusion|| |
A tribal claim about powdered stem bark of Arjuna (T. arjuna) indicated in the management of pain was evaluated in animals (rats and mice) for its analgesic activity against acetic acid-induced writhing syndrome, formaldehyde-induced paw licking response and tail flick test. The study was carried in three groups, that is, control, TED, and TED × 2 groups. Statistically significant analgesic activity was observed in acetic acid-induced writhing syndrome and formaldehyde-induced paw licking response with both TED and TED × 2 groups. In tail flick test, TED group has shown statistically significant response in comparison to TED × 2 groups. The present study has produced scientific validation of the tribal claim which may promote to explore its value by well-planned clinical trials.
| References|| |
Agnivesha, Charaka, Dridhabala, Charaka Samhita, Sutra Sthana, 5/17, edited by Vaidya Jadavji Trikamji Aacharya, reprint ed. Chaukhamba Orientalia, Varanasi, 2011; 34.
Srimad Vrinda, Vindramadhavaparanam Siddhayoga, edited by Vaidya Ganesh Apate, 2 nd
ed. Anandashrama Mudranalaya, Pune, 1943; 274.
Sastry JLN. Dravyaguna Vijnana. 3 rd
ed., Vol. II. Varanasi: Chaukhambha Orientalia; 2008. p. 498.
Sri Bhavamisra, Bhavaprakasha Nighantu, edited by Brahmashankar Mishra. Part - I, Vatadi Varga. 11 th
ed. Chaukhambha Bharati Academy, Varanasi, 2007. p. 26-27.
Hemadri K. A Treatise on Tribal Medicine. 1 st
ed. Vijayawada: Dr. Koppula Hemadri′s House of Tribal Medicine; 2011. p. 31.
Ibidem. A Treatise on Tribal Medicine. p. 37.
Ibidem. A Treatise on Tribal Medicine. p. 39.
Ibidem. A Treatise on Tribal Medicine. p. 41.
Anonymous. Ayurvedic Pharmacopeia of India. 1 st
ed., Vol. II, Part I. New Delhi: CCRAS, Department of AYUSH, Ministry of H and FW, Govt. of India; 2002. p. 17.
Nammi S, Gudavalli R, Babu BS, Lodagala DS, Boini KM. Possible mechanisms of hypotension produced 70% alcoholic extract of Terminalia arjuna
(L.) in anaesthetized dogs. BMC Complement Altern Med 2003;3:5.
Dev S. A selection of prime Ayurvedic plant drugs-Ancient-modern concordance. New Delhi: Anamaya Publishers; 2006. p. 403-4.
Perumal Samy R, Ignacimuthu S, Sen A. Screening of 34 Indian medicinal plants for antibacterial properties. J Ethnopharmacol 1998;62:173-82.
Cheng HY, Lin CC, Lin TC. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna
Linn. Antiviral Res 2002;55:447-55.
Rane MM, Mengi SA. Comparative effect of oral administration and topical application of alcoholic extract of Terminalia arjuna
bark on incision and excision wounds in rats. Fitoterapia 2003;74:553-8.
Bharani A, Ganguly A, Bhargava KD. Salutary effect of Terminalia arjuna
in patients with severe refractory heart failure. Int J Cardiol 1995;49:191-9.
Paget GE, Barnes JM. In: Laurence DR, Bacharacha AL, editors. Evaluation of Drug Activity: Pharmacometrics. New York: Academic Press; 1969.
Koster R, Anderson M, De Beer EJ. Acetic acid for analgesic screening. Fed Proc 1959;18:412-5.
Bittar M, de Souza MM, Yunes RA, Lento R, Delle Monache F, Cechinel Filho V. Antinociceptive activity of I3, II8-binaringenin, a biflavonoid present in plants of the guttiferae. Planta Med 2000;66:84-6.
D′Amour E, Smith DL. A method for determination of pain sensation. J Pharmacol Exp Ther 1941;72:74-9.
Witkin LB, Heubner CF, Galdi F, O′Keefe E, Spitaletta P, Plummer AJ. Pharmacology of 2-amino-indane hydrochloride (Su-8629): a potent non-narcotic analgesic. J Pharmacol Exp Ther 1961;133:400-8.
Fernando TR, Ratnasooriya WD, Deraniyagala SA. Antinociceptive activity of aqueous leaf extract of Tetracera sarmentosa
L. in rats. Pharmacogn Mag 2009;1:381-6.
Abbott FV, Young SN. Effect of 5-hydroxytryptamine precursors on morphine analgesia in the formalin test. Pharmacol Biochem Behav 1988;31:855-60.
[Table 1], [Table 2], [Table 3]