Traditional Chinese medicine for atopic eczema: PentaHerbs formula suppresses inflammatory mediators release from mast cells
Introduction
Atopic eczema (AE) is a common chronic relapsing disease with high prevalence in children (Leung et al., 2007). It has been estimated that 15% of school children aged 13–14 years have a history of AE in Hong Kong (Leung et al., 1997). Inasmuch as the etiology of AE is only partially understood, treatment is empirical and is based on the use of topical or systemic corticosteroids aimed at reducing skin inflammation (Leung, 2000). As there is no definitive cure for the condition among Western medicines, there has been considerable interest in the use of traditional Chinese medicine (TCM) as a potential adjunct therapy for AE. This prompted us to investigate the effect of TCM intervention for the treatment of AE. PentaHerbs formula (PHF) is an ancient Chinese concoction which contains Cortex Moutan, the dried root bark of Paeonia suffruticosa Andr. (Ranunculaceae), Cortex Phellodendri, the dried bark of Phellodendron chinensis Schneid. (Rutaceae), Flos Lonicerae, the dried flower of Lonicera japonica Thunb. (Capri-foliaceae), Herba Menthae, the dried aerial part of Mentha haplocalyx Briq. (Labiatae) and Rhizoma Atractylodis, the dried rhizome of Atractylodes lancea (Thunb.) DC. (Compositae) at the proportion of 2:2:2:1:2. In our previous randomized, double-blind, placebo-controlled studies in 85 children with AE (Hon et al., 2004, Hon et al., 2007b), it was found that PHF is efficacious in improving quality of life and reducing topical corticosteroid use in children with moderate-to-severe AE. The PHF was proposed to work according to the following TCM principles: (i) Flos Lonicerae and Herba Menthae clear damp-heat from the exterior, (ii) Cortex Moutan clears heat from blood, and (iii) Rhizoma Atractylodis and Cortex Phellodendri clear damp-heat from the interior. These herbs possess anti-allergic, anti-inflammatory, anti-pruritic and sedative properties and have been extensively used in China for the treatment of allergic diseases including AE, asthma and allergic rhinitis (Hon et al., 2006). We have so far demonstrated that the PHF could dose dependently inhibit peripheral blood mononuclear cells proliferation and brain-derived neurotrophic factor secretion upon staphylococcal enterotoxin B stimulation (Leung et al., 2008) and these in vitro immunomodulatory properties might account for the clinical benefits in AE patients.
Mast cells are well known for their critical roles in allergic diseases which are attributable to their potent capability to produce multiple proinflammatory mediators including preformed granular contents such as histamine, newly synthesized lipid mediators such as prostaglandin D2 (PGD2) and cytokines (GM-CSF, IL-6 and TNFα) after activation (Wang and Lau, 2006). Subsequent to activation by antigens, cytokines, growth factors or hormones, chemical mediators released from skin mast cells cause immediate skin inflammatory reactions including local vasodilation, T-cell recruitment and itching (Theoharides et al., 2007). In addition to the progression of the immediate inflammatory response, the release of these mediators also initiates the onset of the late-phase inflammatory responses. Inhibition of mast cell activation in skin is thus a potential therapeutic strategy in AE treatment.
Although our recent randomized study showed PHF could reduce the use of topical corticosteroid and improve the quality of life in patients with AE, this treatment did not result in significant decrease in their AE severity (Hon et al., 2007b). We hypothesize that the dosage of PHF in the clinical trial might be sub-therapeutic, or the ratio of the herbal materials had not been optimized. We hence proposed to further investigate the modulating effects of PHF on inflammatory mediator release and cytokine production from mast cells for the better understanding of the underlying mechanisms of the observed clinical efficacy on AE treatment. The rat peritoneal mast cell (RPMC) is a good model for investigating the contribution of inflammatory mediators released by mast cell degranulation in skin related diseases as it is functionally comparable to human skin mast cells in their responses to substance P and compound 48/80 (Mousli et al., 1994, Emadi-Khiav et al., 1995) while the human mast cell line (HMC-1) is appropriate for investigating the release of cytokines from mast cells.
Section snippets
Sources and authentication of herbal materials
The PentaHerbs formula consists of five herbal components: Cortex Moutan (the dried root bark of Paeonia suffruticosa Andr. in the family of Ranunculaceae), Cortex Phellodendri (the dried bark of Phellodendron chinensis Schneid. in the family of Rutaceae), Flos Lonicerae (the dried flower of Lonicera japonica Thunb. in the family of Capri-foliaceae), Herba Menthae (the dried aerial part of Mentha haplocalyx Briq. in the family of Labiatae), and Rhizoma Atractylodis (the dried rhizome of
Effects of PHF on anti-IgE and compound 48/80 activated RPMC
Rat peritoneal mast cells spontaneously released undetectable level of PGD2 and less than 15% of total cellular histamine when incubated in buffer alone and none of the tested herbal extracts affected these levels of spontaneous mediator release. Anti-IgE and compound 48/80 alone induced 44.2 ± 4.1% and 58.9 ± 2.3% of histamine release and 2598 ± 280 pg/106 cells and 2642 ± 536 pg/106 cells of PGD2 production, respectively. As shown in Fig. 1, Fig. 2, PHF significantly inhibited both histamine release
Discussion
Mast cells are located in tissues that interface with the external environment including the skin and the number of mast cells is increased during the early phase of AE (Theoharides et al., 2007). The mediators released from activated mast cells, including histamine, prostaglandins and cytokines contribute to prutitus and inflammation in AE (Alenius et al., 2002). Besides immunological trigger, which involves the aggregation of cell surface high-affinity receptors for IgE (FcɛRI) by their
Acknowledgments
We would like to thank Ms. Cheng L. and Mr. Lau C.P. for the herbal authentication works and Ms. Fong Y.S.C., manger of Centre for Clinical Trial on Chinese Medicine for her assistance towards the study as well as the supports of the Ming Lai Foundation and the International Association of Lions Clubs District 303- Hong Kong and Macau Tam Wah Ching Chinese Medicine Resource Centre.
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2023, Journal of EthnopharmacologyEffects of topical application of a tri-herb formula on inflammatory dry-skin condition in mice with oxazolone-induced atopic dermatitis
2021, PhytomedicineCitation Excerpt :They were then treated with or without individual herbal extracts or three-herbs formula (0–2 mg/ml) for 24 h. Relative number of viable cells were determined according to the procedures described previously (Wu et al., 2018). HMC-1 cells (1 × 105/ml) were pre-incubated for 30 min with Herba Menthae, Cortex Moutan or tri-herb formula (0-2 mg/ml) or dexamethasone (1 μM), followed by a 24 h incubation with a mixture of calcium ionophore A23187 (1 μM) and phorbol-12 myristate 13-acetate (50 nM) (A23187 + PMA, Sigma-Aldrich, St. Louis, Missouri, USA) as previously described (Chan et al., 2008). Then, cell free supernatants were assayed for IL-6, IL-10 and TNF-α production by commercially available human cytokine ELISA kits (BD OptEIA, San Diego, CA, USA).