In vitro studies on the anti-inflammatory potential of chamomile, myrrh and coffee charcoal – components of a traditional herbal medicinal product (Myrrhinil-Intest®)
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In the past decades, phytoconstituents have appeared as critical mediators for immune regulations among various diseases, both in eukaryotes and prokaryotes. These bioactive molecules, showing a broad range of biological functions, would hold tremendous promise for developing new therapeutics. The discovery of phytoconstituents’ capability of functionally regulating immune cells and associating cytokines, suppressing systemic inflammation, and remodeling immunity have rapidly promoted the idea of their employment as anti-inflammatory agents. In this review, we discuss various roles of phyto-derived medicines in the field of inflammatory diseases, including chronic inflammation, autoimmune diseases, and acute inflammatory disease such as COVID-19.
Nevertheless, traditional phyto-derived medicines often concurred with their clinical administration limitations, such as their lack of cell specificity, inefficient cytoplasmic delivery, and rapid clearance by the immune system. As alternatives, phyto-derived nano-approaches may provide significant benefits. Both unmodified and engineered nanocarriers present the potential to serve as phytoconstituent delivery systems to improve therapeutic physio-chemical properties and pharmacokinetic profiles. Thus, the development of phytoconstituents’ nano-delivery designs, their new and perspective approaches for therapeutical applications are elaborated herein.
Introduction:
Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.
Methods:
This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-alpha), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.
Results:
Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P = 0.017), IL-6 G allele at position -174 (P = 0.002), and TNF-alpha G allele at position -238 (P < 0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (-174) and TNF-alpha GG genotype (-238) in the patient group were also significantly overrepresented (P < 0.001), while IL-6 CG genotype (-174) and TNF-alpha GA genotype (-238) were significantly decreased in the patients with IBS (P < 0.001). The frequencies of IL-6 (-174, nt565) GG haplotype and TNF-alpha (-308, -238) GG haplotype were also significantly higher in the patient group (P < 0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-alpha GA were significantly decreased in the patients with IBS (P < 0.001).
Conclusion:
IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.
Das größte Immunsystem des Menschen, der Darm, wird in seinen vielschichtigen Regelkreisen beschrieben. Die Bedeutung verschiedenster Laborparameter, auch im Stuhl, wird hervorgehoben. Aus einem internistischen Krankengut werden diese bei 431 Patienten in den Stuhl-Erstuntersuchungen (u.a. sekretorisches IgA, α1-Antitrypsin, Lysozym) ausgewertet. An exemplarischen Langzeitverläufen (M. Crohn, Colitis ulcerosa, Divertikulitis/-ose, Zöliakie, Asthma bronchiale) wird auch die Bedeutung der Tumor-M2-PK-Bildung im Blut und Stuhl dargestellt. Die therapeutische Wirkung eines Kombinations-Phytotherapeutikum (Myrrhe, Kaffeekohle, Kamille) auf die klinischen Verläufe sowie auf die Blut- und Stuhlparameter wird aufgezeigt.
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The herbal treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard treatment for maintaining remission in ulcerative colitis (UC).
To compare the efficacy of the two treatments in maintaining remission in patients with ulcerative colitis.
We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers.
A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine treatment group and 25/47 patients (53%) in the herbal treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers.
The herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.
Aqueous extracts of 10 plants, used in Somalian traditional medicine for treatment of diarrhoeal diseases, have been screened for effects against cholera toxin-induced intestinal hypersecretion in mice. Two extracts inhibited the hypersecretion more than 50% (compared to a control group, receiving saline). For two extracts the effect did not differ significantly from the controls. The rest of the extracts showed inhibiting activities ranging from 25% to 43%.
The resinous exudates of the Commiphora species, known as 'myrrh', are used in traditional Chinese medicine for the treatment of trauma, arthritis, fractures and diseases caused by blood stagnation. Myrrh has also been used in the Ayurvedic medical system because of its therapeutic effects against inflammatory diseases, coronary artery diseases, gynecological disease, obesity, etc.
Based on a comprehensive review of traditional uses, phytochemistry, pharmacological and toxicological data on the genus Commiphora, opportunities for the future research and development as well as the genus' therapeutic potential are analyzed.
Information on the Commiphora species was collected via electronic search (using Pubmed, SciFinder, Scirus, Google Scholar and Web of Science) and a library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 2000 to the end of December 2011.
The resinous exudates from the bark of plants of the genus Commiphora are important indigenous medicines, and have a long medicinal application for arthritis, hyperlipidemia, pain, wounds, fractures, blood stagnation, in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. Phytochemical investigation of this genus has resulted in identification of more than 300 secondary metabolites. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effects, including antiproliferative, antioxidant, anti-inflammatory and antimicrobial. The bioactive steroids guggulsterones have attracted most attention for their potent hypolipidemic effect targeting farnesoid X receptor, as well as their potent inhibitory effects on tumor cells and anti-inflammatory efficiency.
The resins of Commiphora species have emerged as a good source of the traditional medicines for the treatment of inflammation, arthritis, obesity, microbial infection, wound, pain, fractures, tumor and gastrointestinal diseases. The resin of C. mukul in India and that of C. molmol in Egypt have been developed as anti-hyperlipidemia and antischistosomal agents. Pharmacological results have validated the use of this genus in the traditional medicines. Some bioassays are difficult to reproduce because the plant materials used have not been well identified, therefore analytical protocol and standardization of extracts should be established prior to biological evaluation. Stem, bark and leaf of this genus should receive more attention. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from the genus Commiphora.
Background & aims:
Circular smooth muscle phasic contractions and tone are suppressed during colonic inflammation, but the contributing factors are poorly understood. This study investigated if the expression level of voltage-gated long-lasting (L-type) Ca(2+) channel protein and functional Ca(2+) channel current are down-regulated in the circular muscle cells of the inflamed canine colon.
Methods:
L-type Ca(2+) channel expression was compared between normal and inflamed smooth muscle cells by Western immunoblots using an antibody directed against the pore-forming alpha 1C-subunit, and patch-clamp methods were used to evaluate Ca(2+) channel current density.
Results:
The expression of the L-type Ca(2+) channel protein was significantly reduced in inflamed compared with normal circular smooth muscle cell membranes, and this finding was associated with suppressed levels of Ca(2+) channel current in patch-clamped cells. The L-type Ca(2+) channel current in normal and inflamed cells increased proportionately in response to Bay K 8644, but the maximal current density was still lower in the inflamed cells. Acetylcholine increased the L-type Ca(2+) channel current in normal but not in inflamed cells.
Conclusions:
The expression level of L-type Ca(2+) channels is down-regulated in the circular smooth muscle cell membranes of the inflamed colon, which may result in reduced Ca(2+) influx. The functional and pharmacologic properties of the channels seem normal. Although some Ca(2+) channels are still present in the inflamed cells, acetylcholine does not activate these channels, which may be caused by additional upstream defects in the receptor signaling cascade. The down-regulation of L-type Ca(2+) channel expression may suppress circular smooth muscle contractions in the inflamed colon and contribute to the abnormalities in motility and digestion observed during inflammatory disorders.
Several calcium-channel blockers currently in use for the treatment of cardiovascular disorders have recently been tested for their effects on gastrointestinal motility. The rationale for this approach centers on the concept that calcium-channel blockers are at least as potent in inhibiting intestinal smooth muscle as in relaxing vascular smooth muscle. This review will give outline of the most recent findings on the role of calcium and calcium channels in smooth muscle and neuronal function in the digestive system. It will also consider the mechanisms by which calcium-channel blockers may affect gastrointestinal motility and assess potential clinical applications in gastroenterology. The main goal for researchers in this field will be the development of gut-selective agents, with no cardiovascular side effects.
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder, which presents with one or more gastrointestinal symptoms without any structural or organic abnormality. The etiology and pathophysiological mechanisms of IBS remain uncertain. Residual or reactivated inflammation at the molecular level is considered the underlying mechanism of post-infectious IBS. On the other hand, genetic variations in the immunological components of the body, including cytokine gene polymorphisms, are proposed as a potential mechanism of IBS even in patients without previous gastrointestinal infection. Several studies have suggested imbalanced cytokine signaling as an etiology for IBS. In this review, recent findings on cytokine profiles and cytokine gene polymorphisms in patients with IBS are described and the role of cytokines in animal models of IBS is discussed.
STW 5 (Iberogast®), an established herbal combination, was effective in randomized, double blind clinical studies in functional dyspepsia and irritable bowel syndrome. Since STW 5 was found to influence intestinal motility and has anti-inflammatory properties, this study investigated the expression of adenosine receptors and characterized their role in the control of the anti-inflammatory action of STW 5 and its fresh plant component STW 6 in inflammation-disturbed rat small intestinal preparations. The inflammation was induced by intraluminal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS, 0.01 M). The effects of coincubation with selective receptor agonists and antagonists, STW 5, STW 6, or combinations of these compounds on acetylcholine (ACh)-evoked contraction of ileum/jejunum preparations were tested. Adenosine receptor mRNA expression was examined by reverse transcription-polymerase chain reaction (RT-PCR). In untreated preparations, RT-PCR revealed the presence of all adenosine receptor subtypes. Suppressed expression was detected for all subtypes in inflamed tissues, except for A(2B)R mRNA, which was unaffected. STW 5 reversed these effects and enhanced A(2A)R expression above control levels. Radioligand binding assays confirm the affinity of STW 5 to the A(2A)R, and the A(2A)R antagonist was able to prevent the effect of STW 5 on TNBS-induced attenuation of the ACh contraction. Our findings provide evidence that STW 5, but not STW 6 interacts with A(2A)R, which is involved in the anti-inflammatory action of STW 5. STW 6 did not contribute to adenosine A(2A)R-mediated anti-inflammatory effect of STW 5. Other signaling pathways could be involved in the mechanism of action of STW 6.