Anti-Inflammatory and Barrier-Stabilising Effects of Myrrh, Coffee Charcoal and Chamomile Flower Extract in a Co-Culture Cell Model of the Intestinal Mucosa

Abstract

Recent clinical evidence suggests the efficacy of a traditional herbal medicinal product containing myrrh (Commiphora molmol Engl.), coffee charcoal (Coffea arabica L.) and chamomile flower dry extract (Matricaria chamomilla L.) in the therapy of inflammatory bowel diseases (IBD). However, the mechanisms of action in this context have not been entirely elucidated. The present study aimed to evaluate the effects of myrrh, coffee charcoal and chamomile flower extract on the inflammatory cross talk between immune and intestinal epithelial cells together with the resulting intestinal barrier disorders. A complex co-culture cell model consisting of intestinal epithelial cell (IEC) monolayers (Caco-2, HT29-MTX-E12) and macrophages (THP-1) was established for the simultaneous investigation of these two IBD characteristics. The lipopolysaccharide (LPS) activation of the macrophages led to a pro-inflammatory mediator release and thereby an inflammatory stimulation of IECs with chemokine release and reduced barrier function. The effects of the individual plant extracts and a ternary combination on inflammatory mediator release (IL-6, TNF, IL-8, MCP-1, PGE2) was quantified by ELISA. The transepithelial electrical resistance (TEER) of IEC monolayers was measured to evaluate the effects on the barrier function. Budesonide served as a positive control. All three plant extracts exhibited anti-inflammatory properties via the inhibition of the inflammatory mediator release to a varying extent. An intestinal barrier stabilising effect was observed for myrrh and coffee charcoal. Myrrh exerted the most distinct pharmacological activity. Dose reducing and synergistic interactions emerged within the threefold combination. Thus, our results provide a mechanistic basis for the use of the herbal combination of myrrh, coffee charcoal and chamomile flower extract in IBD treatment and underline the potential benefits of the phytotherapeutic multi-component/multi-target approach in this complex pathogenesis.

Effects of Coffee and Its Components on the Gastrointestinal Tract and the Brain–Gut Axis

“…Similarly, the anti-inflammatory properties have been investigated in coffee preparations such as coffee “charcoal”, a herbal preparation produced by roasting green dried coffee and milling to powder. In this case, the intestinal cells increased their barrier function, and inflammatory mediators such as interleukin (IL) IL-6, IL-8, tumor necrosis factor (TNF), methyl-accepting chemotaxis protein-1 (MCP-1), and prostaglandin (PG) E2 were inhibited [ 76 ]. However, this preparation also preserves most of the compounds in coffee and it is difficult to identify a specific molecule responsible for these effects.…”

Sesquiterpenes from Myrrh and Their ICAM-1 Inhibitory Activity In Vitro

“…Compounds 1–6 are described here for the first time and four substances ( 7, 10, 12, 13 ) were previously unknown for the genus Commiphora . The isolation of compounds 9 and 14 was published before [ 6 ] as part of a characterization of a myrrh extract. Now these two substances together with recently obtained compounds and two reference substances, namely, furanoeudesma-1,3-diene (FUR) and curzerenone (CUR), are examined in an ICAM-1 in vitro assay.…”

“…UC aetiology is not fully understood but the current understanding is that different factors lead to an inadequate immune response and intestinal barrier impairment [ 11 , 12 , 13 ]. Myrrh extracts have already shown activity in in vitro and in vivo tests aiming towards this inadequate immune response and intestinal barrier impairment [ 5 , 6 , 8 , 50 ]. This study hints towards a new possible mechanism for myrrh or myrrh constituents in IBD emphasizing a multimodal activity of myrrh.…”

“…The essential oil of myrrh can, for example, inhibit the production of IL-1b-stimulated IL-6 and IL-8 in human gingival fibroblasts [ 4 ]. Further, ethanolic extracts were able to reduce CXCL13 and TNFα levels in activated human macrophages [ 5 ] or IL-6, IL-8, PGE 2 , MCP-1 and TNFα in a co-culture cell model of the intestinal mucosa [ 6 ], whereas an aqueous extract inhibited LPS-induced production of NO in peritoneal macrophages [ 7 ]. These effects seem to be not limited to cell culture models and have also been confirmed in vivo.…”

Topical Collection “Pharmacology of Medicinal Plants”

“…), coffee charcoal ( Coffea arabica L.) and chamomile flower dry extract ( Matricaria chamomilla L.) on the inflammatory crosstalk between immune and intestinal epithelial cells. The results provide a mechanistic basis for the use of the herbal combination of myrrh, coffee charcoal and chamomile flower extract in inflammatory bowel disease treatment and underline the potential benefits of the phytotherapeutic multi-component/multi-target approach in this complex pathogenesis [ 16 ]. Baldim et al argued about the safety aspects of using some natural products and their several pharmacological properties that are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects, in particular for the treatment of glaucoma and the use of nanoparticles to improve the residence time of the particles in the eye, although further research is needed [ 17 ].…”