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Arnica (Arnica montana) and Inflammation (general): evidence and sources
inferred from anti-inflammatory action
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Background: Homeopathic Arnica montana is used in surgery as prevention or treatment for the reduction of pain and other sequelae of surgery. Our aim was to perform a metaanalysis of clinical trials to assess efficacy of Arnica montana to reduce the inflammatory response after surgery. Method: We conducted a systematic review and metaanalysis, following a predefined protocol, of all studies on the use of homeopathic Arnica montana in surgery. We included all randomized and nonrandomized studies comparing homeopathic Arnica to a placebo or to another active comparator and calculated two quantitative metaanalyses and appropriate sensitivity analyses. We used "Hegde's g," an effect size estimator which is equivalent to a standardized mean difference corrected for small sample bias. The PROSPERO registration number is CRD42020131300. Results: Twenty-three publications reported on 29 different comparisons. One study had to be excluded because no data could be extracted, leaving 28 comparisons. Eighteen comparisons used placebo, nine comparisons an active control, and in one case Arnica was compared to no treatment. The metaanalysis of the placebo-controlled trials yielded an overall effect size of Hedge's g = 0.18 (95% confidence interval -0.007/0.373; p = 0.059). Active comparator trials yielded a highly heterogeneous significant effect size of g = 0.26. This is mainly due to the large effect size of nonrandomized studies, which converges against zero in the randomized trials. Conclusion: Homeopathic Arnica has a small effect size over and against placebo in preventing excessive hematoma and other sequelae of surgeries. The effect is comparable to that of anti-inflammatory substances.
Objectives Arnica montana is a widely used therapeutic plant used traditionally to treat various ailments. The objective of this study was to evaluate the botany, phytochemistry and ethnopharmacology along with special emphasis given on pharmacological activity of plant A. montana. Key findings The plant extracts have been reported to possess antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal and immunomodulatory activity. A wide range of chemical compounds including sesquiterpene lactones and their short-chain carbonic acid esters, flavonoids, carotenoids, essential oils, diterpenes, arnidiol, pyrrolizidine alkaloids, coumarins, phenolic acids, lignans and oligosaccharides, etc., are found in different parts of the plant. Summary It has been scrutinized that extensive research has been carried out to explore the therapeutic potential of flowers of the plant. Therefore, investigations should be carried out to explore the therapeutic potential of other parts of the plant for better therapeutic utilization.
2 sources supporting Arnica for Inflammation (general). Includes scientific publications, books, monographs and traditional-use references.
Mechanistic basis
This use is associated with the plant's anti-inflammatory action. Further evidence for that pharmacology:
Arnica montana L. (Asteraceae) has a long and successful tradition in Europe as herbal medicine. Arnica flowers (i.e., the flowerheads of Arnica montana ) are monographed in the European Pharmacopoeia (Ph. Eur.), and a European Union herbal monograph exists, in which its use as traditional herbal medicine is recommended. According to this monograph, Arnica flowers (Arnicae flos Ph. Eur.) and preparations thereof may be used topically to treat blunt injuries and traumas, inflammations and rheumatic muscle and joint complaints. The main bioactive constituents are sesquiterpene lactones (STLs) of the helenanolide type. Among these, a variety of esters of helenalin and 11α,13-dihydrohelenalin with low-molecular-weight carboxylic acids, namely, acetic, isobutyric, methacrylic, methylbutyric as well as tiglic acid, represent the main constituents, in addition to small amounts of the unesterified parent STLs. A plethora of reports exist on the pharmacological activities of these STLs, and it appears unquestioned that they represent the main active principles responsible for the herbal drug's efficacy. It has been known for a long time, however, that considerable differences in the STL pattern occur between A. montana flowers from plants growing in middle or Eastern Europe with some originating from the Iberic peninsula. In the former, Helenalin esters usually predominate, whereas the latter contains almost exclusively 11α,13-Dihydrohelenalin derivatives. Differences in pharmacological potency, on the other hand, have been reported for the two subtypes of Arnica-STLs in various instances. At the same time, it has been previously proposed that one should distinguish between two subspecies of A. montana , subsp. montana occurring mainly in Central and Eastern Europe and subsp. atlantica in the southwestern range of the species distribution, i.e., on the Iberian Peninsula. The question hence arises whether or not the geographic origin of Arnica montana flowers is of any relevance for the medicinal use of the herbal drug and the pharmaceutical quality, efficacy and safety of its products and whether the chemical/pharmacological differences should not be recognized in pharmacopoeia monographs. The present review attempts to answer these questions based on a summary of the current state of botanical, phytochemical and pharmacological evidence.
Arnica montana has been widely used as a homeopathic remedy for the treatment of several inflammatory conditions in pain management and postoperative settings. This review gives an overview of the therapeutic use of Arnica montana in the above-mentioned fields also focusing on its mechanisms of action learned from animal models and in vitro studies. Arnica montana is more effective than placebo when used for the treatment of several conditions including post-traumatic and postoperative pain, edema, and ecchymosis. However, its dosages and preparations used have produced substantial differences in the clinical outcome. Cumulative evidence suggests that Arnica montana may represent a valid alternative to non-steroidal anti-inflammatory drugs, at least when treating some specific conditions.
Ethnopharmacological relevance The plant Arnica montana L. has been shown to alleviate inflammation, pain and swelling associated with trauma, and post-operative clinical conditions, yet the mechanism of action is not well understood. Aim of the study The study was designed to investigate the effect of Arnica montana (A. montana) mother tincture and homeopathic dilutions on inflammation markers, oxidative stress and cell migration in diverse cell culture models. Materials and methods We tested A. montana mother tincture and a range of homeopathic dilutions in different human and murine cell culture models to demonstrate their anti-inflammatory properties by measuring the inflammatory markers: tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule (ICAM-1), reactive oxygen species (ROS) and cell migration. The inflammatory markers were measured by ELISA assays. The intracellular oxidative stress (ROS) in microglial cells was measured using Deep Red CellROX probe. The cell migration was examined by wound healing using the Oris Cell migration assay. Results These data showed the ability of A. montana (mother tincture and mainly 1C dilution) to significantly reduce TNFα production in inflamed macrophages compared with vehicle (control). They significantly reduced both IL-6 and MCP-1 in inflamed human microglial cells and significantly decreased COX-2 expression in inflamed murine fibroblasts. Moreover, A. montana mother tincture reduced the cell migration whereas 9C dilution significantly enhanced the migration of fibroblast cells compared with vehicle. The expression of ICAM-1 was significantly reduced with A. montana mother tincture and 1C, 3C, 5C, and 9C dilutions in inflamed human endothelial cells compared with vehicle. A. montana mother tincture and 1C, 3C, 5C and 9C dilutions induced a significant and consistent effect on ROS production in inflamed murine microglial cells. A. montana 1C had the largest impact on ROS production. Conclusions Mother tincture and 1C dilution of A. montana showed anti-inflammatory properties assessed by measurement of several markers (pro-inflammatory cytokines, adhesion molecule, ROS) in various human and murine cell models. In addition, A. montana 3C, 5C, 9C dilutions have anti-inflammatory and antioxidant effects as highlighted on both primary endothelial cells and murine microglial cells.
Arnica montana is well known for its anti-inflammatory properties. While the anti-inflammatory activity of Arnica flowers (Arnicae flos) has been extensively studied, that of the whole plant (Arnicae planta tota) is less characterized. We compared the ability of Arnicae planta tota and Arnicae flos extracts to inhibit the pro-inflammatory NF-κB-eicosanoid pathway, using several in vitro and in vivo assays. We showed that Arnicae planta tota inhibited NF-κB reporter activation, with an IC 50 of 15.4 μg/mL (vs. 52.5 μg/mL for Arnicae flos). Arnicae planta tota also inhibited LPS-induced expression of ALOX5 and PTGS2 genes in human differentiated macrophages. ALOX5 and PTGS2 encode the 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) enzymes that initialize the conversion of arachidonic acid into leukotrienes and prostaglandins, respectively. Arnicae planta tota inhibited 5-LO and COX-2 enzymatic activity in vitro and in human primary peripheral blood cells, with lower IC 50 compared to Arnicae flos. Finally, Arnicae planta tota applied topically reduced carrageenan-induced mouse paw oedema more efficiently than Arnicae flos. Altogether, Arnicae planta tota displayed a superior anti-inflammatory activity compared to Arnicae flos, suggesting that Arnicae-planta-tota-containing products might be more effective in alleviating the manifestations of acute inflammation than those based on Arnicae flos alone.
Background: ultraviolet radiation types A and B (UV) (400-315nm and 315-280nm respectively) are the main components present in sunlight known to cause skin injuries. Arnica montana is a plant that has been widely studied for containing anti-inflammatory, healing and analgesic properties capable of preventing or ameliorating lesions. Here, we investigated the therapeutic effect of topical application of Arnica montana after UVB-induced cutaneous injuries in mice. Methods: mice were exposed to UVB radiation (Philips TL40W/12 RS lamp) in a period of 3 hours. After one hour of radiation exposure, the animals were treated with topical application of Arnica montana ointment (250 mg/g) in the ear. At the time of 16 hours after treatment, the parameters of edema, oxidative stress and inflammatory reaction were measured in the ear of mice. Results: our results demonstrated that topical treatment with Arnica montana reduced the UVB-induced inflammatory response as demonstrated by the reduction of ear edema, inhibition of myeloperoxidase activation, decrease of nuclear factor kappa B levels and reduction of proinflammatory cytokines levels, such as interleukin-1beta, interleukin-6, tumour necrosis factor-alpha and interferon-gamma. In addition, Arnica montana ameliorated oxidative damage mediated by UVB radiation, as demonstrated by the reduction of lipid peroxidation, protein oxidation and increase of tissue antioxidant capacity and glutathione levels in the ear. Conclusion: we concluded that Arnica montana ointment is effective in alleviating the auricular inflammatory process and oxidative damage induced by acute UVB radiation, sustaining the traditional use of Arnica montana for the treatment of skin disorders.
A dark brown polymeric complex was isolated from flowering parts of medicinal plant Arnica montana L. by hot alkaline extraction followed by neutralization and multi-step extractions with organic solvents. It was recovered in 5.7% yield, on GPC showed two peaks of molecular mass of 9 and 3.5kDa. The compositional analyses of Arnica complex revealed the presence of carbohydrates (26%), uronic acids (12%), phenolics (1.25mM or 213mg of GAE/1g), and low protein content (∼1%). The carbohydrate moiety was rich mainly in rhamnogalacturonan and arabinogalactan. The antitussive tests showed the reduction of the cough efforts by Arnica complex, however, its total antitussive effect was lower compared with that of codeine, the strongest antitussive agent. The bronchodilatory activity of Arnica complex was similar to salbutamol, a classic antiasthmatic drug, and was confirmed by significantly decreased values of specific airways resistance in vivo and by considerably attenuated the amplitude of acetylcholine and histamine-induced contractions in vitro. Arnica complex did not show any cytotoxic effect on mouse fibroblast cultures and human lung cells, up to the dose of 500μg/mL.