Since ancient times, pharmacologically active ingredients derived from natural sources, including plants and microbials have been used in the treatment of a wide array of diseases, such as atherosclerosis, diabetes mellitus and cancers. Herbal extracts and polyphenols are produced from herbs that contain a variety of ingredients, most of which exhibit anti-inflammatory, anti-oxidative and anti-microbial actions. Gingivitis is triggered by the infection of the periodontal tissues with periodontal disease-causing pathogens present in the dental biofilm. This is accompanied by weak inflammatory immune reactions in the gingiva. In periodontitis, prolonged and excessive inflammation results in the destruction of gingival connective tissue and in the resorption of alveolar bone, leading to tooth loss. There are a number of clinical reports showing the effectiveness of both herbal extracts and polyphenols on periodontal diseases when applied as a mouthwash or dentifrice into the oral cavity. However, to date, at least to the best of our knowledge, there is no clinical report available on the therapeutic effects of garlic or its extract on periodontal diseases, apart from a recent study, which reported that the intake of aged garlic extract (AGE) containing various pharmacologically active sulfur compounds, alleviated the symptoms of gingivitis clinically. The finding suggests that AGE may be a promising candidate for use in the treatment of periodontal diseases, although additional clinical trials are warranted to confirm this. In addition, further studies are required for the clarification of the basic molecular mechanisms through which AGE attenuates gingivitis. In this review, we summarize the beneficial effects of several natural compounds on periodontal disease and describe the possible applications of garlic ingredients in detail. Contents 1. Periodontal disease 2. Evidence of the inhibitory effect of various naturally occurring products on gingivitis and periodontitis 3. Conclusions and future perspectives
Aged garlic extract (AGE) contains various biologically active sulfur-containing amino acids, such as S-allylcysteine (SAC), S-1-propenylcysteine (S1PC) and S-allylmercaptocysteine (SAMC). These amino acids have been demonstrated to lower hypertension, improve atherosclerosis and enhance immunity through their anti-inflammatory and antioxidant activities. It was recently reported that the administration of AGE alleviated gingivitis in a clinical trial. In this study, to gain insight into this effect of AGE, the authors examined whether AGE and the three above-mentioned sulfur compounds influence the effects of tumor necrosis factor-α (TNF-α) in inducing intercellular adhesion molecule-1 (ICAM-1) expression and interleukin-6 (IL-6) secretion in Ca9-22 human gingival epithelial cells. It was found that S1PC reduced the level of ICAM-1 protein induced by TNF-α possibly through post-translational levels without affecting the TNF-α-induced mRNA expression. However, SAC and SAMC had no effect. It was also confirmed the inhibitory effect of an antimicrobial peptide [human-β defensin-3 (hβD3)] and found that the inhibitory effects of hbD3 and S1PC were synergistic. On the other hand, the TNF-α-induced IL-6 secretion was attenuated by SAC and SAMC in a dose-dependent manner, whereas S1PC was ineffective. In addition, SAC and SAMC, but not S1PC inhibited the phosphorylation of the transcription factor nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), which is involved in the expression of inflammatory molecules, suggesting that the anti-inflammatory effects of SAC and SAMC are mediated, at least partly, by NF-κB. On the whole, the findings of this study suggest that the three sulfur amino acids in AGE function synergistically in alleviating inflammation in human gingival epithelial cells.
Clinically, neurological disorders, such as cognitive impairments and dementia, have been reported as diabetic complications, which are remarkable, especially in children with diabetes. The blood-brain barrier (BBB) is a physiologically dynamic regulatory barrier that maintains the consistency of the fluid microenvironment composition of the brain. However, the differences in BBB conditions between children and adults and the contribution of the BBB to the severity of cognitive impairments remain unclear. We generated adult-onset diabetes mellitus (DM) and juvenile-onset diabetes mellitus (JDM) diabetic rat models and investigated BBB functions in these models during the early stages of type 1 diabetes. We performed a BBB permeability assay using sodium fluorescein, a small-molecule fluorescent dye, to evaluate endothelial transport from the blood to the central nervous system. One week after diabetes onset, BBB permeability increased in the hippocampus and striatum of JDM rats, but no changes were observed in the frontal cortex and hypothalamus of JDM rats or for any region of DM rats. The double staining of tight junction proteins and astrocytes revealed no changes in the hippocampus and striatum of JDM rats. These results suggested that the observed increase in BBB permeability during early-stage diabetes onset in JDM rats, which did not depend on the expression of the interendothelial tight junction protein, claudin-5, may affect stylized neural development and cognitive function.
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