|Ahead of print publication
Anti-inflammatory effect of Śirīṣāvaleha prepared by two liquid media on carrageenan induced rat paw oedema model
Harmeet Kaur1, Galib Ruknuddin2, Mukesh Nariya3, Biswajyoti Patgiri4, Prashant Bedarkar4, Pradeep Kumar Prajapati2
1 Department of Rasashastra and Bhaishajya Kalpana, Desh Bhagat Ayurvedic College and Hospital, Mandi Gobindgarh, Punjab, India
2 Department of Rasashastra and Bhaishajya Kalpana, All India Institute of Ayurveda, New Delhi, India
3 Department of Pharmacology, Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India
4 Department of Rasashastra and Bhaishajya Kalpana Including Drug Research, Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India
Department of Rasashastra and Bhaishajya Kalpana, Desh Bhagat Ayurvedic College and Hospital, Mandi Gobindgarh - 147301, Punjab
Source of Support: None, Conflict of Interest: None
Background: Steroidal and non-steroidal anti-inflammatory agents have several limitations, due to which people are moving towards use of traditional medicines. Considering this, the current attempt is aimed to evaluate in vivo anti-inflammatory effect of a poly-herbal formulation Śirīṣāvaleha prepared in presence of water and Kanji (sour gruel). Kanji is anticipated to bring extraction of more principles from the raw drugs and may improve therapeutic attributes of the drug. Considering this, Kanji was used as a liquid medium for preparation of Śirīṣāvaleha and was evaluated for anti-inflammatory activity in comparison to Śirīṣāvaleha prepared with water. Materials and Methods: The activity was screened in carrageenan induced rat paw oedema model in albino rats. The raw materials were collected; authenticated and trial formulations were prepared by following standard classical guidelines. Randomly selected animals were divided into four groups of six animals each. The test drugs were administered orally at a dose of 1.8 g/kg for five days. Phenylbutazone was used as standard anti-inflammatory drug for comparison. Results: Results showed the presence of pronounced anti-inflammatory activity in Śirīṣāvaleha prepared with water (SW) followed by Śirīṣāvaleha prepared with Kanji (SK). Conclusion: Study shows that both samples of Śirīṣāvaleha have anti-inflammatory effect.
Keywords: Avaleha, carageenan, inflammation, Kanji, Śirīṣāvaleha
|How to cite this URL:|
Kaur H, Ruknuddin G, Nariya M, Patgiri B, Bedarkar P, Prajapati PK. Anti-inflammatory effect of Śirīṣāvaleha prepared by two liquid media on carrageenan induced rat paw oedema model. Ancient Sci Life [Epub ahead of print] [cited 2019 Mar 22]. Available from: http://www.ancientscienceoflife.org/preprintarticle.asp?id=252114
| Introduction|| |
Inflammation is involved in disorders in a number of body systems as seen in asthma, uveitis, atherosclerosis and this makes it as an important concern to clinicians and scientists., Treatment of inflammation with steroidal and non steroidal drugs (NSAIDs) have serious adverse effects such as delayed wound healing, osteoporosis, immunosupression, cataract formation, increased intraocular pressure, gastric ulceration, induction of asthma, renal effects, reducing life span in some individuals.,, Śirīṣāvaleha is a compound Ayurvedic formulation which comprises powders of nine drugs in equal proportion, jaggery as sweetening substance and Śirīṣa (Albizia lebbeck Benth.) as a main ingredient. Bark of Śirīṣa has been used traditionally in various inflammatory conditions such as toothache and gum diseases. Śirīṣa has been recommended in Ayurvedic system of medicine for a variety of diseases including Bronchial Asthma. Albizzia lebbeck Benth. contains alkaloids, tannins, phenols, glycosides, flavanoids, steroids and saponins abundantly in its bark., The other ingredients of formulation i.e. Pippalī (Piper longum Linn.), Haridrā (Curcuma longa Linn.), Kuṣṭha (Saussurea lappa C. B. Clarke), Śuṇṭhi (Zingiber officinalis Roscoe) and Nāgakesara (Mesua ferrea Linn.) are also known to have anti-inflammatory activities. Few initial studies on Śirīṣāvaleha have reported that it has significant anti-inflammatory, immunomodulatory, anti-tussive and anti-asthmatic activities. Based on the above information, the present study was undertaken on different samples of Śirīṣāvaleha prepared by using Śirīṣa tvak (bark) in presence of two liquid media viz. water and Kanji. Ayurveda ācāryas have used various liquids in the preparation of formulations according to the need and suitability. Such liquids may have synergistic action and may enhance therapeutic efficacy of a formulation. Śirīṣāvaleha is well proven drug for bronchial asthma. Kanji (gruel) possess Vātakaphahara (palliating exacerbated Vāta and Kapha) and Vātānulomana (causing Vāta to move in right path) qualities that are beneficial in Tamaka Śvāsa (bronchial asthma)., In addition, Kanji is expected to enhance extraction of principles from the raw drugs and thus may improve therapeutic attributes of the drug. Hence, it was planned to evaluate anti-inflammatory activities of both the samples of Śirīṣāvaleha prepared with water and Kanji as liquid media.
| Materials and Methods|| |
Collection and preparation of Śirīṣāvaleha
Śirīṣāvaleha is a compound Ayurvedic formulation [Table 1], which comprises powders of nine drugs in equal proportion and jaggery as sweetening substance. Stem bark of Śirīṣa (Albizia lebbeck Benth.) was freshly collected from the botanical garden, Sasoi, Jamnagar. All prakṣepa dravya (adjuvants) such as Pippalī (Piper longum Linn.), Haridrā (Curcuma longa Linn.), Priyaṅgu (Callicarpa macrophylla Vahl.), Śuṇṭhi (Zingiber officinale Roscoe.), Kuṣṭha (Saussurea lappa C. B. Clarke), Dāruharidrā (Berberis aristata DC.) and Elā (Elettaria cardamomum Maton.) were procured from the Pharmacy, Gujarat Ayurved University, Jamnagar, Gujarat. Nīlinī (Indigofera tinctoria Linn.) was collected from local area of Jamnagar and Nāgakesara (Mesua ferrea Linn.) from Udupi, Karnataka. Jaggery was purchased from a local market of Jamnagar. All the herbal drugs were authenticated at Pharmacognosy Laboratory, Institute for Post Graduate Teaching and Research in Ayurveda (IPGT and RA), Gujarat Ayurved University, Jamnagar. These drugs were cleaned and shade dried. As Kanji may help in extracting more principles into the finished product, Śirīṣāvaleha was prepared in presence of water (SW) and Kanji (SK). Kanji was prepared by following classical guidelines.
Both the test formulations were prepared in the department of Rasashastra and Bhaishajya Kalpana, IPGT and RA. Śirīṣa kvātha (decoction) was prepared in the presence of water and Kanji, then jaggery was added to it and treacle was prepared. After obtaining Avaleha Siddhi Lakṣaṇa (chief desired characteristics for preparation of linctus), Prakṣepa dravya (adjuvants) were added and packed in air tight containers.
Wistar strain albino rats of either sex weighing 200 ± 20g were used for in vivo evaluation of this experimental study. Animals were obtained from the Animal house attached to the Pharmacology laboratory of I. P. G. T. & R. A. Animals were exposed to 12 hour light and dark cycle with ideal laboratory condition in terms of ambient temperature (22 ± 2°C) and humidity (50-60%). They were fed with Amrut brand rat pellet feed supplied by Pranav Agro Industries and tap water given ad libitum. Experiment was carried out in conformity with the Institutional Animal Ethics Committee (IAEC) after obtaining its permission (Approval number-IAEC/16/2014/03).
Animal grouping and dose
The selected animals were divided into four groups each consisting of six animals. Group I was treated orally with distilled water (5 ml/kg) and served as Control group. While Group II and III were administered with test drugs i. e. Śirīṣāvaleha (1.8 g/kg, po) prepared with water (SW) and Kanji (SK) respectively. The dose was calculated by extrapolating human dose to animals based on the body surface area ratio by referring to the standard table of Pagets and Barnes (1969). The test formulation was suspended in distilled water and administered orally at a volume of 5 ml/kg body weight with the help of oral catheter. Group IV served as a standard and received Phenylbutazone (100 mg/kg, po).
In vivo anti-inflammatory activity was evaluated against Carrageenan-induced paw oedema model. Carrageenan injection produces marked swelling of the paw and anti-inflammatory drugs are used to suppress this swelling. The test drugs and vehicle were administered daily for consecutive five days. Phenylbutazone was administered one hour before the carrageenan injection in a single dose. On the fifth day, prior to carrageenan injection, the initial paw volume of left hind paw up to the tibia-tarsal articulation was measured using a Plethysmometer (model 520, IITC Life Science Inc.). The paw was immersed into special water cell containing plain water exactly up to the tibio-tarsal articulation, where the pressure is changed due to the immersion. This pressure change is calibrated in mH and shown on a special electronic monitor digitally and noted down. One hour after drug administration, oedema was produced by injecting 0.1 ml freshly prepared 1% w/v carrageenan (Sigma type 1) in sterile saline solution to the sub-plantar aponeurosis of the left hind limb. The rats were administered with distilled water in the dose of 2 ml per 100 g body weight to ensure uniform hydration and hence, to minimize variations in oedema formation. Paw volume was recorded at one, three and five hours after carrageenan injection. Results were expressed as an increase in paw volume in comparison to the initial paw volumes and also in comparison with control group.
The data have been represented as Mean ± SEM. Student's t test for unpaired data has been used for analyzing the data generated during the study. P < 0.05 was considered as statistically significant. For applying these statistical tests and analyzing, Sigma Stat software 3.5 was used.
| Results|| |
Data pertaining to the effect of different samples of Śirīṣāvaleha on carrageenan-induced left hind paw oedema has been given in [Table 2]. Statistically significant decrease in paw odema was observed in SW and SK treated groups after one hour of carrageenan injection in comparison to control groups. Although both SW and SK treated group showed decrease in paw oedema after three hours but result was statistically significant only in SW treated group. Whereas, SW treated group showed statistically highly significant (P < 0.001) decrease and SK treated group showed statistically significant (P < 0.02) decrease in paw oedema after 5 hour in comparison to control group. Standard drug Phenylbutazone produced significant decrease in paw oedema at all-time intervals in comparison to control group.
|Table 2: Effect of Śirīṣāvaleha on carrageenan- induced paw edema in albino rats|
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| Discussion|| |
Inflammation is the physiological response to tissue damage and is accompanied by characteristic series of local changes. It is a body defense reaction in order to eliminate or limit the spread of injurious agent as well as to remove the consequent necrosis cells and tissues. Some of many tissue products that cause these reactions are histamine, bradykinin, serotonin, prostaglandins, several different reaction products of the complement system, reaction products of the blood clotting system and multiple substances called lymphokines that are released by sensitized T cells.
In the normal course any test drug used for the treatment of asthma, ideally should be evaluated against air-way inflammation. Carrageenan induced paw edema is considered to represent the phases of the inflammatory reaction which is characterized by fluid and cell exudation. A number of phlogistic mediators such as histamine, serotonin, bradykinin and prostaglandins have been implicated in the development of carrageenan edema.
Śirīṣāvaleha with water produced significant decrease in carrageenan induced paw oedema in early phase (1 hr) as well as late phase (3 hrs & 5 hrs). Śirīṣāvaleha with Kanji produced significant decrease in carrageenan induced paw oedema in early phase (1 hr) as well as late phase (5 hrs). This shows the presence of pronounced anti-inflammatory activity in Śirīṣāvaleha prepared with water followed by Śirīṣāvaleha prepared with Kanji using Śirīṣa tvak in both samples and their contribution to the therapeutic efficacy in asthma. The anti-inflammatory activity may be because it inhibits the release of histamine and serotonin from mast and basophil cells and thus lead to decrease in vascular permeability in early phase while inhibit subsequent release of acute inflammatory mediators in late phase and thus inhibit the fluid exudation in acute inflammation in rats.,,
The anti-inflammatory activity is one of the multidimensional attributes of the compound formulation Śirīṣāvaleha. This may be due to the presence of phytochemicals like flavonoids, saponins, tannins and alkaloids. Flavonoids are efficient free radical scavengers and are pro-inflammatory mediators in the pathogenesis of inflammation.,,, Consumption of flavonoids is reported to be associated with better lung function in asthmatic patients, and also reduce asthma inflammation through antioxidant, anti-allergic and anti-inflammatory properties. Flavonoids can inhibit both cyclooxygenase and lioxygenase pathways of arachidonic metabolism., Alkaloids in asserted skeletal type based on pyridine ring system have been reported to have striking anti-inflammatory activity. Saponins and tannins are the core chemical classes of anti-inflammatory agents from natural sources.,,
The observed anti-inflammatory activity of test drugs may be due to inhibition of formation or activity of one or more of the phlogistic mediators, or it may be due to a general mechanism like increasing the membrane stability in the cell.
Active component of Haridrā and Śuṇṭhi are Curcumin, Gingerol and Shogaol. These modulate the inflammatory response by down-regulating the activity of cyclooxygenase-2 (COX-2) and NF-κB (nuclear factor-kappa B), inhibition of arachidonic acid metabolism via lipoxygenase and scavenging of free radicals generated in this pathway. They inhibit prostaglandin and leukotriene biosynthesis through suppression of 5-lipoxygenase or prostaglandin synthetase and decreased expression of pro-inflammatory cytokines and down-regulation of enzymes, such as protein kinase C, that mediate inflammation. These possible mechanisms may be responsible for anti-inflammatory activity of drug to much extent.
| Conclusion|| |
From the present study it is concluded that, Śirīṣāvaleha has significant anti-inflammatory activity. Śirīṣāvaleha prepared with water (SW) has pronounced activity followed by Śirīṣāvaleha prepared with Kanji (SK) using Śirīṣa tvak (bark) in both samples. Hence, may have their contribution towards the therapeutic efficacy in conditions associated with inflammation.
Financial support and sponsorship
IPGT & RA.
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]