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Anti-Inflammatory Properties of Plants
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This entry is adapted from the peer-reviewed paper 10.3390/life13040874

Inflammation is a natural protective response of the human body to a variety of hostile agents and noxious stimuli. Standard anti-inflammatory therapy includes drugs whose usage is associated with a number of side effects. Since ancient times, natural compounds have been used for the treatment of inflammation. Traditionally, the use of medicinal plants is considered safe, inexpensive, and widely acceptable. In Serbia, traditional medicine, based on the strong belief in the power of medicinal herbs, is the widespread form of treatment.

traditional medicine anti-inflammatory properties ethnopharmacology

1. Introduction

Inflammation is the body’s automatic protective defence reaction to tissue injury or the invasion of foreign factors (toxins and pathogens) [1]. A controlled inflammatory response is an important beneficial process that is part of the maintained normal homeostasis of tissue [2]. The duration and extent of the inflammatory response are of key importance for its outcome and consequences. The process of acute inflammation includes phagocytosis, apoptosis, or activations of pro-inflammatory mediators that leads to the clearance of injurious stimuli and restore normal physiology [3]. However, chronic inflammation is not a useful process and it causes various pathological disorders including Alzheimer’s disease, cancer, rheumatoid arthritis, type 2 diabetes, and obesity, as well as a cardiovascular and pulmonary disease [4]. Chronic disorders are regarded as a leading cause of death globally, with 60% of these deaths due to chronic inflammatory diseases [5]. These inflammatory changes are induced by cytokines and other inflammatory mediators. Cytokines are classified into two major categories: pro-inflammatory and anti-inflammatory cytokines. Several cytokines including interleukin (IL)-1, tumour necrosis factor-alpha (TNF-a), IL-6 and IL-8, and chemokines such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macro-phage colony-stimulating factor (GM-CSF) play a key role in acute inflammatory reactions [6].
A conventional therapeutic option for the treatment of inflammation and associated pain is nonsteroidal anti-inflammatory drugs, but their use is associated with a multitude of unwanted effects. For this reason, new research is focused on the search for safe natural substitutes for conventional anti-inflammatory drugs. The latest research has determined numerous pharmacological targets including cytokines, chemokines, transcription factors, complement activation pathways, eicosanoids, reactive oxygen species (ROS), and reactive nitrogen species (RNS) [4][7].
Since ancient times, people have relied on medicinal plants in the treatment of various health disorders, including inflammation and its complications. These actions are attributed to the complex chemical composition and the presence of secondary biomolecules in plants such as phenolic compounds, flavonoids, saponins, and sesquiterpenes [8]. The challenge of science is to find the exact chemical compound responsible for the observed pharmacological effects [9]. Moreover, it is important to recognize the side effects and potential interactions between medicinal plants and other synthetic drugs [10].

2. Anti-Inflammatory Plants from Serbian Traditional Medicine

The use of medicinal plants in Serbia for the treatment of diseases related to inflammatory processes has a long history. The most frequent, in Serbia, inflammation treated with plants, is located at the mucous membrane, the upper respiratory tract, the gastrointestinal tract, and the skin [11][12]. There are several studies dealing with the ethnopharmacology approach of medicinal plant application among Serbian people, mainly in rural areas [13][14][15]. However, plants used as anti-inflammatories in Serbian traditional medicine belong to different families: Asteraceae (Achillea millefolium, Calendula officinalis, Matricaria chamomilla), Rosaceae (Agrimonia eupatoria), Poaceae (Agropyrum repens), Liliaceae (Allium cepa, A. sativum), Malvaceae (Althaea officinilas), Betulaceae (Betula pendula), Fabaceae (Glycyrrhiza glabra), Juglandaceae (Juglans regia), Hypericaceae (Hypericum perforatum), Lamiaceae (Mentha piperita, Salvia officinalis), and Salicaceae (Salix alba) (Figure 1).
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Figure 1. Plants used as anti-inflammatory in Serbian traditional medicine: (a) Achillea millefolium; (b) Agrimonia eupatoria; (c) Agropyrum repens; (d) Allium cepa; (e) Allium sativum; (f) Althaea officinilas; (g) Betula pendula; (h) Calendula officinalis; (i) Glycyrrhiza glabra; (j) Juglans regia; (k) Hypericum perforatum; (l) Matricaria chamomilla; (m) Mentha piperita; (n) Salix alba; (o) Salvia officinalis.

2.1. Achillea millefolium L., Asteraceae (Eng. Yarrow, Srb. Hajdučka Trava)

Yarrow is one of the most famous and most commonly used plants in traditional Serbian medicine. The internal and external use of this plant in which people have great confidence is widespread. In the form of poultices and ointments, it is used by people to treat various inflammatory and injured skin conditions. This action was confirmed by in vitro and in vivo studies in which extracts of yarrow showed a significant anti-inflammatory effect as well as a healing effect. In addition to independent use, it is also used as part of complex herbal mixtures for various medicinal purposes [16][17][18]. The data obtained in one in vivo study showed that the oil yarrow extracts had a significant anti-inflammatory property. The application of tested oil extracts on the artificially irritated skin of volunteers demonstrated the ability to re-establish their optimal skin parameters to the values measured prior to the irritation. The topical anti-inflammatory activity is attributed to the sesquiterpenes being caused by their inhibition of the arachidonic acid metabolism [19]. Internally, yarrow is part of tea mixtures intended for the treatment of asthma as chronic inflammation of the respiratory tract [17]. One study aimed to evaluate the ethanolic extract of A. millefolium flower for antitussive and anti-asthmatic potential through animal experimental models. The results of the study revealed the potent antitussive and antiasthmatic activities of A. millefolium flower extract [20].

2.2. Agrimonia eupatoria L., Rosaceae (Eng. Common Agrimony, Srb. Petrovac)

Common agrimony, church steeples, or sticklewort is another important herb of traditional medicine with numerous uses. Aerial parts of this plant are used internally in the form of tea or externally in the form of baths. It is known to be used for painful joints and inflammatory diseases of the mouth and throat [16][17]. Anti-inflammatory effects are well studied and confirmed in a lot of in vitro and in vivo studies. Experiments showed that A. eupatoria exerts an immunoprotective effect and decreases the levels of pro-inflammatory cytokines while increasing those of anti-inflammatory cytokines [21][22]. Antioxidant, anti-inflammatory, and peripheral analgesic activities were observed for A. eupatoria infusion and polyphenol-enriched fraction. Based on the results of this study, it was concluded that the traditional use of the A. eupatoria infusion as an antioxidant and anti-inflammatory is justified and suggests that its polyphenols (isoquercetin, tiliroside, and kaempferol O-acetyl-hexosyl-O-rhamnoside) contribute to this activity and should be considered as lead molecules for designing new pharmacophores [23][24].

2.3. Agropyrum repens L., Poaceae (Eng. Couch Grass, Srb. Pirevina)

Couch grass is a very common perennial species of grass native to most parts of Europe. For medicinal purposes, the rhizome is used to make tea for the treatment of various inflammatory conditions. Traditional use has been recorded for inflammation of the bladder, bronchitis, arthritis, and rheumatism [16][17]. One study showed that oral administration of ethanol extract of rhizomes of A. repens induced moderate inhibition of carrageenan foot oedema of the rat hind-paw compared to indomethacin. In the other study, the cream containing dry couch grass extract was tested for allergic contact dermatitis in rats. The results showed that the anti-inflammatory effects of the couch grass cream were comparable to the standard glucocorticoid cream activity [25].

2.4. Allium cepa L., Liliaceae (Eng. Onion, Srb. Crni Luk)

Onion is widely used in Serbia both for therapeutic purposes and as a spice and part of traditional cuisine. The whole plant is edible, but the bulbs that grow underground are most commonly used. It is used in fresh and dried form as a spice in food and in the form of teas or poultices for the treatment of various diseases, including inflammatory conditions such as headache, common cold, arthritis, and asthma. Externally, onion juice or juice is used in the treatment of skin inflammation, purulent wounds, burns, frostbite, and insect bites [16][17]. Numerous modern research has confirmed the justification of the use of onion as an anti-inflammatory agent. It was reported that the anti-inflammatory properties of Allium species are due to the presence of effective compounds such as tannin, flavonoids, anthocyanin, saponin, etc. Thiosulfinates and cepaenes from onion showed anti-inflammatory properties mediated through the inhibition of chemotaxis of human polymorphonuclear leukocytes. Furthermore, it has been established that cepaenes inhibit cyclooxygenase (COX) and lipoxygenase (LOX) enzymes. Quercetin, a well-known constituent of onion decreased the production of inflammatory cytokines such as IL-1a, IL-4, and TNF-a and inhibited the proliferation and activity of lymphocytes. These effects have been confirmed through several studies on animals and humans [26][27][28].

2.5. Allium sativum L., Liliaceae (Eng. Garlic, Srb. Beli Luk)

Garlic is another valuable plant from the genus Allium which is very widespread. Among people, garlic is a medicine for all ailments, in which there is a great and unshakable trust. This belief often goes so far that garlic is still used today in some households in the countryside not only as a preventative but also as a protective agent against “evil spirits” and other dangerous “invisibles”, for fortune-telling, recovery, spells, and magic. The primordial belief in the medicinal, protective, and magical power of garlic left a deep mark on the material and spiritual life of the people. Garlic is eaten almost regularly and is added as an ingredient to various dishes. During epidemics of typhus, cholera, plague, dysentery, flu, and in general, whenever there was a great plague of infectious diseases, garlic was always recommended and used daily as a preventive and curative tool [16][17]. Garlic extracts and their related phytochemicals have been reported to possess anti-inflammatory activity in numerous studies [29]. Allicin, the main constituent of garlic, demonstrated a defensive mechanism against pathogens by its ability to enhance the activity of immune cells and influence signaling pathways associated with these immune cells. Moreover, allicin works on T-cell lymphocytes by inhibiting the SDF1α chemokine which is associated with the weakness of the dynamic structure of the actin cytoskeleton in addition to this, it leads to inhibit the transendothelial migration of neutrophils [30]. Another report indicated that thiacremonone (a sulfur compound isolated from garlic) prevents neuroinflammation and amyloidogenesis by blocking the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity, and for that reason can be used to treat neurodegenerative disorders related to inflammation [31].

2.6. Althaea officinilas L., Malvaceae (Eng. Marshmallow, Srb. Beli Slez)

Marshmallow is a widespread plant in Serbia. All parts of the plant can be used for treatment, but the root, which is the richest in active principle, is used most often. Macerate of white marshmallow is used as an auxiliary mucus agent for inflammation of the respiratory tract and gastroenteritis, and as compresses for inflammation of the skin. Cultivated plants are generally used to obtain plant raw materials because they are of better quality with a higher content of active principles [16][17]. The in vitro experiments on human monocytic cell line THP-1 showed a significant anti-oxidant and anti-inflammatory activity of root extracts of A. officinalis. The investigated preparation showed the ability to ameliorate the migratory capacity of macrophages. These anti-inflammatory effects were comparable to or even better than diclofenac [32].

2.7. Betula pendula Roth., Betulaceae (Eng. Common Birch, Srb. Bela Breza)

Common birch is widely distributed in temperate and northern climate zones. It is used in the traditional medicine of numerous countries, and its positive effects on human health have been known since ancient times. It belongs to the group of medicinal plants. Numerous studies on the chemical composition and activities of birch isolates aim to confirm their biological effects and use in traditional medicine. Birch leaf is one of the main ingredients of tea mixtures for the treatment of inflammation of the urinary tract acting as a diuretic and does not irritate the renal parenchyma. Birch tar is also used in folk medicine, a substance derived from the dry distillation of the wood, bark, and roots of the birch tree. It is used in dermatology, especially in eczema as a condition of chronic inflammation of the skin. In addition to tea and tar, birch sap is also used, a colorless liquid that oozes in the spring from cut birch trees [16][17]. One study investigates the influence of the aqueous extract of Betula pendula on primary human lymphocytes in comparison to the synthetic anti-arthritis drug methotrexate in vitro on human peripheral blood mononuclear cells (PBMC). These results provide a strong rational base for the widespread use of the leaf extract of Betula pendula in the treatment of immune disorders such as rheumatoid arthritis, through the reduction of proliferating inflammatory lymphocytes [33].

2.8. Calendula officinalis L. Asteraceae (Eng. Calendula, Srb. Neven)

Calendula is native to the Mediterranean region but it is widely cultivated all over Serbia. It has a very wide application in traditional medicine. It is used in the form of tea, as an addition to salads and other dishes, and externally in the form of oils, ointments, compresses, or rinsing teas. For curative purposes, inflorescences are used and rarely is the above-ground part of the plant in bloom. Traditionally, many beneficial effects are attributed to this plant. It is used as an anti-inflammatory and a remedy for healing wounds and skin disorders. Calendula ointments, suspensions, or tinctures are used topically for treating acne, reducing inflammation, controlling bleeding, and soothing irritated tissue [16][17]. Numerous studies confirm the anti-inflammatory effect of this plant applied topically. One in vitro study assessed the anti-inflammatory potential of calendula oil using lipopolysaccharide (LPS)-stimulated macrophages, as an in vitro model of inflammation. Scientists investigated the ability of a commercial calendula flower extract to inhibit NO production on macrophages exposed to LPS. The obtained results showed a dose-dependent NO inhibition of up to 50%, presenting a safety profile, thus, reinforcing the anti-inflammatory activity of calendula flower extract. In conclusion, the results of this study support the usefulness of Calendula oil in the treatment of injured skin and for conditions or diseases for which NOS contributes to the pathophysiology, such as contact dermatitis, vitiligo, rosacea, melasma, and psoriasis [34]. A study on rats provided evidence that Calendula officinalis presented anti-inflammatory and antibacterial activities as well as the capability of stimulating fibroplasia and angiogenesis. Calendula extracts showed a positive effect on the inflammatory and proliferative phases of the healing process of cutaneous wounds in rats [35]. In addition, the topical application of C. officinalis ointment has helped to prevent dermatitis and pain, thus, reducing the incidence rate of skipped radiation treatments in randomized trials [36].

2.9. Glycyrrhiza glabra L., Fabaceae (Eng. Liquorice, Srb. Sladić)

Liquorice is a famous medicinal plant worldwide. The root is the most used part of this plant with an extremely sweet flavor and pleasant odor. Liquorice has had an important place in traditional Serbian medicine since ancient times. In monastery hospitals, tea made from a mixture of liquorice root, rhizomes, and barley was used as a universal remedy for reconvalescence. Modern research has also confirmed its beneficial effect on the liver, so licorice root is a common ingredient in detox tea mixes. The active ingredients show anti-inflammatory action and have a beneficial effect on spasms and pain relief. Liquorice is part of several tea mixtures with therapeutic usages, namely Species pectorales, Species diureticae, and Species urologicae) and it is also part of a tea mix for the pediatric population. Black sugar is a product of liquorice made from the aqueous extract by steaming to dryness, which contains around 25% glycyrrhizin [16][17]. Many studies have investigated the anti-inflammatory effect of this plant and the results have confirmed the justification of its use in tradition. Some studies concluded that glycyrrhetinic acid and aqueous extract of liquorice possess strong anti-inflammatory activity, which was comparable with diclofenac [37][38]. Additionally, it was further recommended that the activity of anti-inflammatory formulations such as famotidine or diclofenac can be further enhanced through the addition of liquorice aqueous extract [38]. A lot of studies evaluated the impact of G. glabra and its bioactive components on different mechanisms of inflammation. Results showed inhibition of proinflammatory cytokine through inhibition of LPS-induced IL-1β, IL-6, IL-8, and TNF-α responses of macrophages. Furthermore, one study showed that extract of this plant inhibits serum levels of TNF-α and reduces antigen induce arthritis symptoms in mice [39].

2.10. Juglans regia L. Juglandaceae (Eng. Walnut, Srb. Orah)

Walnut is an ancient plant that is cultivated and grows wild in Serbia. In addition to the nutritional value of the fruit, the leaf and pericarp of the young fruit are traditionally used in healing. Externally, walnut-leaf tea is used to rinse the skin and mucous membranes in various inflammatory processes. Walnut tea is drunk orally for inflammation of the mucous membrane of the digestive organs. Furthermore, walnut leaves are added to tea mixtures for improving the resistance of the body’s immunity [16][17]. The justification of traditional use has been confirmed by research. One study evaluated the antitussive, antioxidant, and anti-inflammatory effects of a walnut extract rich in bioactive compounds, using a citric acid-induced cough model in rats. Walnut septum showed significant antitussive and anti-inflammatory activities [40]. The ethanolic extracts of J. regia leaves exhibited potent anti-inflammatory activity comparable with indomethacin against carrageenan-induced hind paw edema model in mice without inducing any gastric side effects [41].

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