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 Table of Contents  
REVIEW ARTICLE
Year : 2022  |  Volume : 9  |  Issue : 1  |  Page : 19-26

A Review on Potential Anti-Inflammatory Activity of Some Medicinal Plants in Animal Model


Department of Dravyaguna Vijnana, Pt. Khushilal Sharma Government Ayurveda College and Institute, Bhopal, Madhya Pradesh, India

Date of Submission22-Feb-2022
Date of Decision15-Jun-2022
Date of Acceptance07-Jul-2022
Date of Web Publication15-Sep-2022

Correspondence Address:
Nitin Ujjaliya
Department of Dravyaguna Vijnana, Pt. Khushilal Sharma Government Ayurveda College and Institute, Bhopal, Madhya Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AYUHOM.AYUHOM_14_22

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  Abstract 


Inflammation is a protective response that develops against tissue injury and infection. Chronic inflammation, on the other hand, is the root cause of the pathogenesis of many inflammatory disorders, including cancer. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Therefore, the search for anti-inflammatory drugs without side effects has become a dream and ongoing effort of the Pharma companies. The concept and treatment of inflammation are described under Shotha and Shwayathu Chikitsa in Ayurveda. The concept of ama explains the pathogenesis of chronic inflammation. This review includes the anti-inflammatory activity of some medicinal plants in acute and chronic inflammatory animal models. Data were collected from existing articles on anti-inflammatory studies from various search engines. Here, a brief overview of some medicinal plants having anti-inflammatory activity along with their doses, used part extract, used animal model, and the result is provided. In this review, it was found that the majority of the selected plants have more or similar effects in comparison to standard drugs, indicating that medicinal plants have significant anti-inflammatory potential. This overview will attract the interest of investigators aiming at the design of novel therapeutic approaches for the treatment of various inflammatory conditions.

Keywords: Acute inflammation, anti-inflammatory activity, chronic inflammation, experimental model, medicinal plants


How to cite this article:
Jain PV, Ujjaliya N, Mandloi S. A Review on Potential Anti-Inflammatory Activity of Some Medicinal Plants in Animal Model. AYUHOM 2022;9:19-26

How to cite this URL:
Jain PV, Ujjaliya N, Mandloi S. A Review on Potential Anti-Inflammatory Activity of Some Medicinal Plants in Animal Model. AYUHOM [serial online] 2022 [cited 2022 Oct 7];9:19-26. Available from: http://www.ayuhom.com/text.asp?2022/9/1/19/356166




  Introduction Top


Inflammation is a complex biological response of vascular tissues to harmful stimuli, including pathogens, irritants, or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue.[1] Inflammation is generally divided into two types: acute inflammation and chronic inflammation. Inflammatory reactions arbitrate by different mechanisms and occur in phases like:[2]

Acute phase: Temporary local vasodilation and increased capillary permeability.

Sub-acute phase: Infiltration of leukocytes and phagocytic cells.

Chronic proliferative phase: Tissue deterioration and fibrosis.

Acute inflammation is the initial response of the body to risk factors like an infection or trauma, etc.; this is nonspecific and the first line of defense of the body against danger.[3] The main features of acute inflammation include: (a) Accumulation of fluid and plasma at the affected site, (b) Intravascular activation of platelets, and (c) Polymorphonuclear neutrophils as inflammatory cells.[4] When the risk factors lengthen and are not removed, acute inflammation will then turn and extend to chronic inflammation. It occurs for a longer duration and is associated with the presence of macrophages, lymphocytes, blood cell proliferation, fibrosis, and tissue necrosis. The macrophages produce a wide number of biologically active products, which leads to tissue destruction and fibrosis characteristics of chronic inflammation.[5],[6]

The inflammatory process is a combination of many pathways like a synthesis of prostaglandin, interleukin (IL) or other chemo toxins, adhesive protein receptor action, and platelet-activating factors. Inflammation initiates with any stress on the membrane or by other trigger or stimuli, and these activate hydrolysis of membrane phospholipid by phospholipase A into arachidonic acid, which further substrate for cyclooxygenase and lipoxygenase enzyme and the byproduct of these are prostaglandins PGE2, PGH2 and leukotrienes such as LTC4 and LTB4. Several cytokines also play essential roles in orchestrating the inflammatory process, especially IL-1 and tumor necrosis factor-a (TNF-a). IL-1 and TNF are considered principal mediators of the biological responses to bacterial (lipopolysaccharide, also called endotoxin). They are secreted by monocytes, macrophages, adipocytes, and other cells. Working in concert with each other and various cytokines and growth factors, including IL-8 and granulocyte-macrophage colony-stimulating factor, they induce gene expression and protein synthesis in a variety of cells to mediate and promote inflammation. Prostaglandin (PGE2) or prostacyclin (PGI2) release, increases blood flow as well as increases blood vessel permeability by assisting the release of nitric oxide from endothelium-derived releasing factor, which causes again vasodilation and helps in sticking platelets and other chemo toxins (bradykinin, histamine), while LTs generally are pro-inflammatory. LTB4 is a potent chemotactic agent for polymorphonuclear leukocytes, eosinophils, and monocytes. In higher concentrations, LTB4 stimulates the aggregation of polymorphonuclear leukocytes and promotes degranulation and the generation of superoxide. LTB4 promotes the adhesion of neutrophils to vascular endothelial cells and their transendothelial migration and stimulates the synthesis of pro-inflammatory cytokines from macrophages and lymphocytes.[7],[8],[9]

The process of inflammation is necessary for the healing of wound. If it remains unchecked, it may cause the manifestation of various diseases. Inflammatory diseases are identified as a major cause of morbidity across the population.[1] It has been demonstrated already in the first phases of the COVID-19 pandemic that the augmented inflammatory response, leading to the fulminant “cytokine storm,” may result in severe multisystemic end-organ damage. The amplitude of the cytokine storm is considered the main factor associated with systemic organ failure and death.[10] Inflammation cascades can lead to the development of diseases such as arthritis, chronic asthma, diabetes, inflammatory bowel disease, and cancer.[11] Rheumatoid arthritis is the major inflammatory disease affecting people. An increase in life expectancy and aging populations are expected to make osteoarthritis the fourth-leading cause of disability by the year 2020.[12] Inflammatory diseases are becoming common in our aging society. These diseases decrease the quality of life, thus imposing a huge economic burden on individuals and consequently on society.[13]

Anti-inflammatory drugs like nonsteroidal anti-inflammatory drugs (NSAIDs) are generally used to reduce inflammation, but they are effective for only temporary relief of symptoms, and most of these treatments are inadequate for chronic use. Long-term uses of NSAIDs cause damage to the human biological system and important organs such as the liver and gastrointestinal tract.[14] Thus, there is a worldwide interest in searching for new phytochemical compound drugs. Recent studies on Zingiber officinale Rosc. suggest that it might be as effective as NSAIDs in the treatment of inflammation and related pain.[15],[16] The Indian Spice turmeric (Curcuma longa L.), possessing curcumin and synthetic analogs, have established reputation as an anti-inflammatory by inhibiting COX-1 and COX-2.[17] These examples of the anti-inflammatory activity of plants have drawn attention to further research in the development of medicinal plants as anti-inflammatory agents.

Many medicinal plants have exhibited potent anti-inflammatory effects in various animal experimental models.[18] In this review, some of the medicinal plants which were proven anti-inflammatory activity in animal models are discussed.


  Materials and Methods Top


Search strategy for the identification of studies:

In this study, all the data were gathered from search engines such as PubMed, Google Scholar, and Elsevier. The literature has been collected from the online open-access database and Ayurvedic texts. All the references which were used to publish this review article were written in English. Research articles reported on animals investigating the anti-inflammatory activity of medicinal plants published from years 2001 to 2021 were reviewed for this paper, and anti-inflammatory clinical studies on medicinal plants were excluded.

Free text searches were performed across each database to combine the terms or key words: “anti-inflammatory agents,” “in vivo study,” “anti-inflammatory medicinal plants.” The general structure of the search strategy was “anti-inflammatory agents” with the following MeSH terms or synonyms: (anti-inflammatory agents) OR (agents, anti-inflammatory) OR (anti-inflammatories) OR (anti-inflammatory); OR (anti-inflammatory herb) OR (anti-inflammatory plant) OR (anti-inflammatory medicinal plants). Higher dose results are included in the present review as they found more effective in accessed anti-inframammary studies.

This review is focused on the animal models of inflammation that researchers have used. Hence, the aim of this review is to summarize the investigation and findings in animal model studies on the anti-inflammatory activity of plants [Table 1].
Table 1: List of some medicinal plants having anti-inflammatory potential in vivo (rat and mice)

Click here to view



  Results Top


In the literature review, it was found that research involves a number of experimental models to study anti-inflammatory activity. Out of these models, carrageenan-induced paw edema model is widely used for acute inflammation, while the cotton pellet-induced granuloma model is widely used for chronic inflammation.

Animal models not only enable us to have a more comprehensive understanding of the inflammation at a molecular level in a controlled manner but also fulfill the need for drug screening tools. This allows a faster and more convenient screening. Based on the mechanistic studies, drugs targeting different molecules in the cascade are being developed. To evaluate the effect of the drug properly, reliable and appropriate animal models are required.[34] According to Lewis, models are of two types: acute inflammatory models and chronic inflammatory models.[35] Some potential anti-inflammatory drugs studied by different scholars in both models are mentioned here [Table 1].

Acute models are designed to test drugs that modulate erythema, changes in vascular permeability, leukocyte migration and chemotaxis, phagocytosis-polymorphonuclear leucocytes, and other phagocytic cells, measurement of local pain, antipyretic activity, local analgesic action, and rat paw edema.[36]

Chronic models are designed to find drugs that may modulate the disease process and these include sponge and pellet implants and granuloma pouches which deposit granulation tissue, adjuvant induced arthritis and rabbit monoarticular arthritis which have an immune etiology.[35]


  Discussion Top


The number of medicinal plants has been studied in anti-inflammatory animal models. Some of these medicinal plants proven with anti-inflammatory activity are discussed here. The anti-inflammatory activity of these plants was evaluated in acute and chronic inflammatory experimental models. All these studies were performed by using various extracts (e.g., methanol, ethanol, aqueous, chloroform, petroleum ether, etc.) at various doses. Aspirin, diclofenac sodium, dexamethasone, and acetylsalicylic acid were used as standard drugs in control groups. The inflammation is either acute or chronic and mainly occurs in three distinct phases.[37] Therefore, it is necessary to evaluate the activities of the test substance in different phases of inflammation while evaluating the anti-inflammatory effect. It is evident that carrageenan is commonly used to induce acute inflammation and is believed to be biphasic. Based on this, it could be argued that the suppression of the first phase may be due to inhibition of the release of early mediators, such as histamine and serotonin, and the action in the second phase may be explained by an inhibition of cyclooxygenase.[38] These mediators take part in the inflammatory response. Bauhinia variegate, Pterospermum acerifolium, Ficus relisiosa, Wrightia tinctoria, Grewia asiatica, Aegle marmelos, Cissus quadrangularis, Terminalia arjuna, and Pongamia pinnata were studied for their anti-inflammatory activity in carrageenan-induced paw edema model. Therefore, it can be inferred that the inhibitory effect on inflammation in these plants may be due to cycloxygenage inhibition, which is involved in prostaglandin synthesis.[29] It has been reported that the second phase of edema is sensitive to the most clinically effective anti-inflammatory drugs, which have been frequently used to access the anti-edematous effect of natural products.[38],[39] Histamine and dextran-induced paw inflammation models are also applied for screening of acute inflammation. Anti-inflammatory activity of Eclipta prostrata was assessed in histamine-induced pow edema. Thus, the effect of this plant may be due to its anti-histaminic effect. Dextran-induced edema model includes both histamine and serotonin for the induction of edema.[40],[41],[42] T. arjuna leaves extract was also assessed in dextran-induced paw edema model. Its anti-inflammatory effect may be due to its anti-histaminic and anti-serotonin effects. Chronic inflammation is the reaction arising when the acute response is insufficient to eliminate the pro-inflammatory agents. Chronic inflammation includes the proliferation of fibroblasts and infiltration of neutrophils with exudation of fluid. It occurs by means of the development of proliferative cells, which can either spread or form granuloma.[43] The cotton pellet granuloma model represents the pathological events in chronic inflammation. It is a widely used model for the assessment of chronic anti-inflammatory activity of newer compounds.[44] The transudate and proliferative elements of chronic inflammation are evaluated through this model.[45] The moist and dry weight of cotton pallets is linked with the transudate and granulomatous tissue formation, respectively.[46] Bauhinia variegata, W. tinctoria, Euphorbia hirta, A. marmelos, P. pinnata, Solanum nigrum, and E. prostrata were assessed in cotton pallet model. Thus, the anti-inflammatory effect of these medicinal plants may be due to the inhibition of transudative or proliferative phase. The xylene-induced ear edema model is useful for the evaluation of the topical anti-inflammatory activity of drugs.[25] E. hirta and Oroxylum indicum were investigated for their anti-inflammatory activity in Xylene-induced ear edema. E. hirta inhibited ear edema formation due to the hindrance of phospholipase A2, which is the precursor of the inflammatory effect. O. indicum may be inhibited by ear edema due to Cycloxygenage inhibition which is involved in prostaglandin synthesis. Formalin-induced paw edema model has a close resemblance with arthritis.[47] It is biphasic. The early neurogenic phase is conciliated by bradykinin and substance P, whereas the later inflammatory phase involves histamine, 5 HT, Prostaglandins, and bradykinin.[48] Anti-inflammatory activity of Sesbania grandiflora was evaluated in formalin-induced edema model. Thus, the anti-inflammatory effect of this plant in this model may be due to the effect on any of these mediators.

Plant containing important phytoconstituent like phenolic compounds, tennin, flavonoids, and terpenoids are known to possess antioxidant properties. Free radicals are implicated in inflammatory conditions. The high content of phenolic compound exhibit DPPH radical scavenges activity. O. indicum ethanol extract contains flavonoid and phenolic compounds.[19] O. indicum has been found to scavenge DPPH, Fe3+, NO and superoxide gene, which are major players in eliciting inflammation.[19] B. variegata leaf possesses protein, triterpenoid, and flavonoids.[20] P. acerifolium extract was found to be a rich source of polyphenol compounds.[21] Polyphenol compound inactivates NF-Kb, arachidonic pathway, and protein kinases.[49] Ficus religiosa possesses phenolic compound triterpenoid, tannin, beta-sitosterol phytoconstituents.[22] A preliminary phytoconstituent investigation indicated the presence of steroid, triterpenoid, and flavonoid in W. tinctoria extract.[23] S. grandiflora leaves extract possesses alkaloids, carbohydrates, steroids, glycosides, saponins, and tannins. Anti-inflammatory effects of several plants have been attributed to the presence of triterpenoids, alkaloids, glycosides, flavonoids, tannins, saponins, and sterols. Phytochemical screening of E. hirta revealed the presence of flavonoids, phenolic compounds, tannins, triterpenoid, sterol, proteins, amino acid, and glycosides. The phytochemical study revealed the presence of most of the above-mentioned phytoconstituents. Therefore, it is possible that the anti-inflammatory effect may be due to the presence of these phytochemical constituents.[25] A. marmelos root bark extract has the presence of glycosides and alkaloids.[27] C. quadrangularis extract possesses flavonoids, coumarin, and steroid as phytoconstituents.[28] T. arjuna leaf methanol extract has alkaloids, triterpenoids, tannins, and flavonoids phytoconstituents.[29] T. arjuna bark ethanol extract contains tannins, flavonoids, gums, carbohydrates, steroids, and alkaloids. Antioxidants can also exert an anti-inflammatory effect. Flavonoids and other phenolic compounds of the plant are reported as antioxidant.[30] P. pinnata leaves ethanol extract showed the presence of flavonoids, glycoside, proteins, tannins, terpenoids, and carbohydrate. Many investigations have proven that a variety of flavonoid possesses anti-inflammatory activity in various animal models of inflammation.[31] Anti-inflammatory effect of S. nigrum may be by virtue of active constituents mainly flavonoids.[32]

Experimental studies which are reviewed in present article were performed by using various doses of medicinal plants. Higher dose was found more effective in all studies. Hence, in present review effective dose is mentioned. O. indicum, F. religiosa, W. tinctoria, C. quadrangularis, T. arjuna; extract of these plants showed better anti-inflammatory effect than the standard drug in experimental studies, while other plants had possessed significantly effective results compared to standard drugs.

In Ayurveda, the terms Shotha, Shopha, and Shwayathu are used to describe inflammation. The vitiated Vata dosha displaces the vitiated (morbid) Rakta (blood), Pitta and Kapha and pushes them into the channels of circulation. The Vayu is further obstructed by these morbid elements and causes an accumulation of Pitta, Kapha, and Rakta in between Twak (skin) and Mamsa (muscle). This swelling occurred between twaka and mamsa is called Shotha. The presence of Pitta and Rakta in between the skin and muscle is responsible for the development of inflammation and the presence of Kapha is responsible for fluid accumulation.[50]

Anti-inflammatory experimental studies of 14 herbal plants were chosen for review. Majority of these drugs were found having Tikta, Kashaya, Madhura Rasa; Laghu, Ruksha Guna; Katu Vipaka. O. indicum (Shyonaka), P. acerifolium (Muchukunda), W. tinctoria (Shweta kutaja), S. grandiflora (Agastya), E. hirta (Dugdhika), A. marmelos (Bilwa), P. pinnata (Karanja), S. nigrum (Kakamachi) and E. prostrata (Bhrungaraja) possess Tikta Rasa.[51] Tikta Rasa posseses Vishaghna (Antipoisonous), Kledalasika Upashoshana (dries up moisture, lymph tissue), Shodhana (purification property), Pittashleshmahara Properties.[52] O. indicum, B. variegate (Kanchanara), F. religiosa (Ashwaththa), A. marmelos and P. pinnata possess Kashaya rasa.[51] Kashaya Rasa exhibits Sanshamana (mitigation), shoshan (dries up), Shleshma-Rakta-Pitta prasadana activities.[52] P. aceriflolium, E. hirta, P. pinnata and E. prostrata possess Katu Rasa.[51] Katu Rasa has Shwayathuhara (cures inflammation), Shophhara, Shoshana and Kaphahara Actions.[52] O. indicum, F. religiosa, E. hirta, G. asiatica (Alpasthi), C. quadrangularis (Asthisamharaka) have Madhura Rasa.[51] Madhura Rasa has Pittahara and Vishahara (Reduced potency of poison) Properties.[52] O. indicum, B. variegata, W. tinctoria, S. grandiflora, Eagle marmelos, C. quadrangularis, P. pinnata and E. prostrata possess Laghu, Ruksha Guna. F. religiosa and E. hirta have Ruksha Guna. G. asiatica and S. nigrum contain Laghu guna.[51] Laghu Guna dravyas have Kaphaghna and Anupalepa properties. Ruksha dravyas possess Atikledahara, Rukshana and Kaphahara properties.[52] All medicinal plants except G. asiatica and C. quadrangularis exhibit Katu Vipaka.[51] Vagbhata considers that the effect of Vipaka is similar to its Rasa.[52] Therefore, Katu Vipaka also has Swayathuhara, Shophhara, Shoshana, and Kaphahara properties. Hence, the anti-inflammatory action of herbal plants mentioned in this review can be attributed to the above properties (Tikta, Kashaya, Madhura Rasa; Laghu, Ruksha Guna; Katu Vipaka) mentioned in Ayurveda texts.

Further research should be done on medicinal plants having Kashaya, Tikta Rasa; Laghu, Ruksha Guna; Katu Vipaka to evaluate their anti-inflammatory potential and for better therapeutic approach.

Limitations

In the present article, medicinal plants, which were published from the year 2001 to 2021, were selected for review. Further, a systematic review should be done for herbal plants having Kashaya, Tikta Rasa; Laghu, Ruksha Guna, and Katu Vipaka to explore the anti-inflammatory potency of these properties.


  Conclusion Top


In this review, the majority of plants were found to have more or similar effects in comparison to the standard drug, while only a few plants were found to be less effective than the standard drug. The result of these studies is an indicative that these plants can be used in various acute and chronic inflammatory disorders. Thus, it can be concluded there is great potential for developing anti-inflammatory agents through herbal plants. Therefore, there is a need for further studies by using other specific inflammatory disease models like the Murine model of asthma, Helicobacter pylori-induced gastritis, etc., and clinical studies to evaluate the exact mechanism of action so that new anti-inflammatory agents can be developed from these plants.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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