PlayOn Ingredient Spotlight: Arnica

PlayOn Ingredient Spotlight: Arnica


  • Clinical data demonstrates arnica application aids in the recovery process by reducing swelling, bruising, pain, and inflammation in several controlled and placebo-tested trials.
  • The DuraCool technology in PlayOn creates an unnoticeable film on the skin combining active arnica compounds with other key anti-inflammatory, pro-recovery factors.
  • The film serves as a medication reservoir with more powerful and longer-lasting delivery than other brands due to DuraCool technology.


Arnica montana (arnica) has been used for hundreds of years, notably given its name in 1533 and documented successful use as a treatment for vision loss in amaurosis as early as 1785. Years of anecdotal evidence corroborate the efficacy of arnica as a treatment for contusions, wounds, and inflammation, and the era of peer review seeks to prove its ability to aid recovery. The uses of Arnica are becoming increasingly studied, with many significantly successful uses documented, as well as some insignificant effects [1-5]. The aim of PlayOn is to help your body recover from pain, inflammation, bruising, and swelling; this article documents the evidence of how one of PlayOn’s key ingredients, arnica, helps achieve this goal.


The sesquiterpene lactones, phenolic acids, and flavonoid compounds of the arnica flower are largely responsible for the plant’s anti-inflammatory and antioxidant properties. A specific sesquiterpene lactone, helenin, has been intricately studied and promotes anti-inflammatory properties through inhibition of NF-κB [2, 6-8]. Arnica treatment has been shown to significantly decrease concentrations of TNFα, IL-6, MCP-1, COX2, ICAM1, and reactive oxygen species (ROS) in human and murine cell models [5] (Table 1). Helenin inhibits NF-κB by stabilizing the NF-κB /IκB complex (IκB is the inhibitor protein) in T cells, B cells, macrophages, and epithelial cells [8, 9]. NF-κB activation drives the inflammatory process, as it is a transcription factor for the genes of the proinflammatory proteins COX2, IL1, IL2, IL-6,  IL8, TNFα, ICAM-1, ELAM-1, and VCAM-1 (Table 1, Figure 1) [8, 10, 11]. Quantification of arnica treatment in vivo documented a 3x reduction in COX2, a 3x reduction of TNFα, a 2.8x reduction of IL-12, a 4.9x reduction of Nitric Oxide (an ROS), as well as significant reductions in NF-κB and Nitric Oxide Synthase [9, 12]. The reduction of these markers indicates a lowered inflammatory response, revealing insights into the mechanism of arnica as a recovery agent.

Table 1: Inflammatory Markers Inhibited by Arnica

NF-κβNuclear factor kappa-light-chain-enhancer of activated B cellsCell survival, DNA transcription, and cytokine production are all mediated by NF-κβ, which is a heterodimer protein. NF-κβ is a rapid-acting transcription factors (for genes involved in inflammatory pathways) that remains present in the cell in an inactive state, only needing cleavage from the inhibitory protein IκBα to become active. NF-κβ becomes activated in response to stress stimuli such as cellular debris, damaged tissue, cytokines, free radicals, and microbes.
TNFαTumor Necrosis FactorA type of pro-inflammatory cytokine that promotes the expression of adhesion molecules on endothelial cells to direct leukocytes to the site of inflammation. TNFα is produced largely by macrophages, but also other cell types such as mast cells and endothelial cells.
IL-6Interleukin 6A type of pro-inflammatory cytokine released by macrophages that detect microbial molecules. IL-6 also has an opposing role as an anti-inflammatory myokine (a cytokine released by muscle cells).
MCP-1Monocyte Chemoattractant Protein 1A type of cytokine that attracts monocytes (hence the name), T cells, and dendritic cells to inflamed tissue. Production of MCP-1 is controlled by NF-κβ.
COX2Cyclooxygenase 2COX2 is the main target inhibited by common NSAIDs such as ibuprofen or Advil (COX2 inhibitors). COX2 is an enzyme that synthesizes prostaglandins, which are responsible for vasodilation and the inhibition of blood platelet aggregation, and significant mediators of the inflammatory response.
ICAM1Intercellular Adhesion Molecule 1Cytokine release (from mast cells) increases the production of ICAM1, as do IL-1, TNF, macrophages, and lymphocytes. ICAM1 binds integrin (a receptor on the surface of leukocytes), which then adheres leukocytes to endothelial walls, prompting release from the blood to the extracellular matrix.
ROSReactive Oxygen Species                            Reactive oxygen species are involved in cell signaling and maintaining homeostasis and low levels but can induce DNA damage and modify other biologically active compounds from inappropriately controlled levels of ROS.

Clinical Evidence

Many studies elect to administer arnica orally; while this medication route documents positive results, the mechanistic effects of arnica are body-wide, whereas PlayOn offers site-specific application to target specific tissues without altering broader cellular function. Brinkhaus et al. observed a significant effect of orally administered arnica on the swelling of cruciate ligament reconstructions with only trends toward lowered swelling for arthroscopy and knee replacements, finding insignificant effects for the latter surgery types [1]. Topical application of arnica has been demonstrated to inhibit the inflammatory process through a multitude of mechanisms, contributing to its ability to reduce swelling and bruising [5-8]. Literature reviews detailing significant positive effects of arnica treatment include reduced pain and swelling, improved blood flow and platelet aggregation, muscle soreness, arthritis relief, bruising, and determined that active arnica compounds possess similar activity to diclofenac and ibuprofen. With positive results documented, it is important to note a dosage-dependent effect such that sufficiently high concentrations of arnica are required to elicit the response. [2, 3, 13, 14].

Swelling, bruising, and the associated tenderness are major focal areas in the process of injury and repair. In human bruising studies, Leu et al. showed a 20 % Arnica gel applied topically significantly improves bruising more effectively than control, petroleum, and low percentage vitamin K formulation conditions [3]. Seeley et al. conducted a randomized, double-blind, and placebo controlled study in a clinical setting evaluating ecchymosis and skin discoloration, finding significant reductions in the area of ecchymosis 1 and 7 days after facial surgeries [15]. Kawakami et al. investigated the effect of Arnica on two subgroups of mice based on kinetics of inflammation: early edema onset and late edema onset. The distinction between these groups arises from individual variation in the inflammatory response, classified and measured by when the swelling of the test subject peaked. Relative to control, arnica treatment significantly lowered edema and degranulation of mast cells, while increasing the lymphatic vessel diameter in the late edema onset group [6]. Direct reduction of swelling is potentially further understood by the lymphatic vessel diameter increase. Lymphatic vessels transport macrophages towards and cellular debris away from injury. Therefore, an increase in vessel size can either act to accelerate macrophage delivery (and thereby the duration of the inflammatory response) or increase the rate at which cellular debris and fluids are removed from an injury site (and thereby reduce swelling and promote healing). Mast cells release pro-inflammatory chemical signals; hence, lowered mast cell degranulation signifies a reduction in the signals promoting inflammatory behavior.


While arnica is actively studied to gain further insights into its mechanism of action, current literature highlight its ability to reduce swelling, bruising, and a multitude of inflammatory signals. The DuraCool technology in PlayOn creates an unnoticeable film on the skin combining active arnica compounds with other key anti-inflammatory, pro-recovery factors. The film serves as a medication reservoir with more powerful and longer-lasting delivery than other brands due to DuraCool technology. Click Here (Page coming soon) to learn more about the efficacy of DuraCool’s mechanism and what makes Trifecta Therapeutics’ products effective.



1.            Brinkhaus, B., et al., Homeopathic arnica therapy in patients receiving knee surgery: results of three randomised double-blind trials. Complement Ther Med, 2006. 14(4): p. 237-46.

2.            Kriplani, P., K. Guarve, and U.S. Baghael, <i>Arnica montana L</i>. – a plant of healing: review. Journal of Pharmacy and Pharmacology, 2017. 69(8): p. 925-945.

3.            Leu, S., et al., Accelerated resolution of laser‐induced bruising with topical 20% arnica: a rater‐blinded randomized controlled trial. British Journal of Dermatology, 2010. 163(3): p. 557-563.

4.            Stevinson, C., et al., Homeopathic arnica for prevention of pain and bruising: randomized placebo-controlled trial in hand surgery. JRSM, 2003. 96(2): p. 60-65.

5.            Verre, J., et al., Anti-inflammatory effects of Arnica montana (mother tincture and homeopathic dilutions) in various cell models. J Ethnopharmacol, 2024. 318(Pt B): p. 117064.

6.            Kawakami, A.P., et al., Inflammatory Process Modulation by HomeopathicArnica montana6CH: The Role of Individual Variation. Evidence-Based Complementary and Alternative Medicine, 2011. 2011: p. 1-12.

7.            Lyss, G., et al., The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65. J Biol Chem, 1998. 273(50): p. 33508-16.

8.            Lyss, G., et al., Helenalin, an anti-inflammatory sesquiterpene lactone from Arnica, selectively inhibits transcription factor NF-kappaB. Biol Chem, 1997. 378(9): p. 951-61.

9.            Iannitti, T., et al., Effectiveness and Safety of Arnica montana in Post-Surgical Setting, Pain and Inflammation. Am J Ther, 2016. 23(1): p. e184-97.

10.         Baeuerle, P.A. and T. Henkel, Function and activation of NF-kappa B in the immune system. Annu Rev Immunol, 1994. 12: p. 141-79.

11.         Yamamoto, K., et al., Transcriptional Roles of Nuclear Factor κB and Nuclear Factor-Interleukin-6 in the Tumor Necrosis Factor α-Dependent Induction of Cyclooxygenase-2 in MC3T3-E1 Cells (∗). Journal of Biological Chemistry, 1995. 270(52): p. 31315-31320.

12.         Verma, N., et al., Evaluation of inhibitory activities of plant extracts on production of LPS-stimulated pro-inflammatory mediators in J774 murine macrophages. Mol Cell Biochem, 2010. 336(1-2): p. 127-35.

13.         Smith, A.G., et al., Clinical Trials, Potential Mechanisms, and Adverse Effects of Arnica as an Adjunct Medication for Pain Management. Medicines, 2021. 8(10): p. 58.

14.         Brito, N., P. Knipschild, and J. Doreste-Alonso, Systematic Review on the Efficacy of Topical Arnica montana for the Treatment of Pain, Swelling and Bruises. Journal of Musculoskeletal Pain, 2014. 22(2): p. 216-223.

15.         Seeley, B.M., et al., Effect of Homeopathic <i>Arnica montana</i> on Bruising in Face-lifts. Archives of Facial Plastic Surgery, 2006. 8(1): p. 54-59.

One thought on “PlayOn Ingredient Spotlight: Arnica”
  1. Justin Estrada Justin Estrada

    Love it very informative

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