Advances in research on the mechanism of traditional Uyghur herbs on inflammatory bowel disease
June 19, 2017 Source: Chinese Herbal Medicine Magazine
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are common gastrointestinal diseases with clinical manifestations of diarrhea. , abdominal pain, bloody stools, anemia and body weight reduction [1]. According to reports, the incidence of IBD in China was the highest in Asia in 2013, at 3.44/100,000, of which UC patients were about twice as many as CD patients [2]. At present, the etiology and pathogenesis of IBD are still unclear, and it is generally considered to be caused by environmental factors, genetic factors, and immune factors [3]. Therapeutic drugs for IBD include 5-aminosalicylic acid, glucocorticoids, immunosuppressive agents, cyclosporine and monoclonal antibodies to biological agents, but it is difficult to cure IBD [1]. IBD patients often need long-term and adequate control of the disease [4], studies have shown that IBD disease is not easy to control, the risk is usually irreversible negative consequences or even death [5-7]. In addition, IBD medications can cause adverse reactions, and treatment-related risks can lead to poor compliance in IBD patients [8]. As a common multiple disease, it is undoubtedly important to find anti-IBD drugs or active ingredients from traditional medicine.
Uyghur has a long history of medicine. It is a scientific accumulation and summary of the process of inheriting various diseases in the long-term production and life practice of the ancient Chinese people in Xinjiang and the Uighur people who later moved to Xinjiang. According to Uyghur medical theory, colitis is caused by complex or abnormal body fluids producing specific or non-specific reactions in colonic mucosal capillaries. It is often used clinically to eliminate abnormal body fluids, enhance immunity, stop bleeding, promote ulcer healing and promote The treatment of intestinal mucosal regeneration, digestion and antibacterial treatment. In this paper, through the literature retrieval analysis and visiting Uyghur medical clinicians, the 10 medicinal herbs with anti-IBD effect were screened out, and the research progress on the pharmacological action and mechanism of anti-IBD was systematically reviewed for the subsequent exploration of Uyghur drugs against IBD. The mechanism of action provides a reference.
1. Factors related to the pathogenesis of IBD
1.1, the immune system
Regarding the pathogenesis of IBD, it is believed that the intestinal mucosal immune system is abnormally regulated by intestinal mucosal antigens including "normal" intestinal flora. Studies have shown that patients with IBD have congenital and acquired immune abnormalities [9], and immune system regulatory factors such as neutrophils, macrophages, dendritic cells and natural killer cells have changed. Abnormal mucosal Th cells and cytokines such as interleukin-1β (IL-1β), IL-6β, IL-12β, tumor necrosis factor-α (TNF-α) and interferon-gamma (IFN-γ) in patients with IBD. Have a higher expression [10].
1.2, oxidative stress
Oxidative stress is a potential cause and trigger of IBD due to its damage to reactive oxygen species (ROM) during inflammation [11]. Compared with healthy people, the molecular oxidation rate of patients with IBD is accelerated [12]. Studies have shown that patients with IBD have decreased antioxidant capacity and increased the number of reactive oxygen species [13].
1.3, microorganisms
Elevated microbial concentration in the gastrointestinal tract is one of the mechanisms of IBD pathogenesis. In general, non-pathogenic gut bacteria can cause host susceptible IBD in chronic enteritis, immunoregulatory abnormalities, bacterial clearance or mucosal dysfunction. The concentration of intestinal flora in patients with IBD is higher than that in normal subjects, and the concentration of intestinal flora increases with the severity of the disease [14-15].
1.4, nuclear transcription factor-κB (NF-κB)
NF-κB belongs to a family of structurally related eukaryotic transcription factors that promote the expression of more than 150 genes, such as cytokines, enzymes, cell adhesion molecules, etc., most of which play an important role in inflammation and apoptosis. . NF-κB can accelerate the process of inflammation by coordinating the activation process between various inflammatory genes, and is an enlarged continuation mechanism of inflammatory diseases [16]. The expression of NF-κB in the colonic mucosa of patients with IBD is significantly increased, and is associated with its disease activity and severity [17]. IL-10 can inhibit the activity of NF-κB by inhibiting the activity of NF-κB inhibitor α (IκBα) [18]. It has been found that IL-10 has a significant anti-inflammatory effect on IBD [19]. Therefore, inhibition of NF-κB activity can be used as a pathway for the treatment of IBD [12].
1.5, nitric oxide (NO)
NO is a short-lived molecule synthesized by NO synthase (NOS), which is produced in the process of converting arginine and oxygen into citrulline and NO. There are three subtypes of NOS: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). Three lines of evidence suggest that iNOS plays a decisive role in the inflammatory process. First, NO is produced by two kinds of cNOS subtypes related to iNOS. Accelerating NO nitrosation, oxidative damage and increasing inflammatory factors lead to inflammation [12]. Second, iNOS expression pattern is associated with inflammation. Third, inhibition of iNOS is reduced. Inflammation [20]. There is evidence that IBD is associated with the excessive production of NO by iNOS [20]. The amount of NO in the intestinal and saliva of patients with IBD increased [21]. This suggests that inhibition of iNOS also attenuates dextran sulfate sodium (DSS)-induced mouse colitis [22].
1.6, cyclooxygenase-2 (COX-2)
COX-2 is caused by the exposure of transformed colon cell lines to pro-inflammatory cytokines including IL-1 and TNF-α [14], which usually does not respond to early inflammatory gene expression, but can induce inflammation in response to inflammation. Stimulation, these stimuli are produced by inflammatory cells, including IL-1a/b, IFN-g, and TNF-α [23], and therefore, it is another factor involved in the synthesis of prostaglandins associated with inflammation-related factors in IBD, COX -2 selective inhibitors such as celecoxib are an effective drug for IBD [24].
1.7, leukotriene B4 (LB4)
LB4 is a metabolite of arachidonic acid, a potent proinflammatory regulator that plays an important role in certain inflammatory diseases such as rheumatoid arthritis, asthma, psoriasis and IBD [25]. Overproduction of LB4 is observed in patients with IBD, therefore, inhibition of LB4 reduces inflammation and improves IBD [14].
2. The mechanism of action of Uyghur drugs on IBD
2.1, yellow scorpion skin (color Riheel Elyss)
The yellow scorpion skin is a mature dry peel of the Gentianaceae plant scorpion Terminaliachebula Retz. It contains polyphenols, amino acids and other components, and has immunomodulatory, antibacterial, anti-oxidant and anti-inflammatory effects [26]. Studies have found that acetic acid-induced colonic mucosal injury in the mouse colitis model leads to elevated levels of myeloperoxidase (MPO), which activates neutrophils, thereby increasing levels of pro-inflammatory factors and reactive oxygen species; In addition, colonic mucosal damage can also increase NO levels, leading to elevated levels of reactive oxygen species and inflammation [27]. Scutellariae can also significantly reduce lipid peroxide (LPO) and NO levels in colitis mice, and increase superoxide dismutase (SOD), catalase (CAT), and glutathione associated with antioxidant activity. Glycopeptide peroxidase (GSH-Px) levels; Gram-negative gut bacteria such as Escherichia coli, Shigella, and Shigella flexneri have low concentrations of Scutellariae Radix extract in the sensitivity to gut microbes. Higher sensitivity [28].
2.2, Solanum lyrium (Etiope Zu honey)
Solanum nigrum L. is a near-mature fruit of the Solanaceae Solanum nignum L. Solanum nigrum contains flavonoids, polyphenols, saponins and other substances, which have anti-oxidation, anti-inflammatory and damage repair effects [29]. Solanum nigrum fruit extract Longan glycoprotein can attenuate the activity of NF-κB and AP-1 by inhibiting mitogen-activated protein kinase (MAPK), down-regulate the expression of COX-2 and NO, thereby inhibiting IBD. The inhibition of IBD is dose dependent [30].
2.3, no food (Moza)
The larvae are the parasitic insects of the bee larvae. The larvae of the bee larvae are parasitic on the genus Quercus infectoria Oliv. Gallop is rich in polyphenols, which have antioxidant, damage repair, anti-inflammatory and antibacterial effects [31]. Gallopans reduce inflammatory damage by reducing MPO secretion and down-regulating LPO, and enhance the antioxidant activity of colon tissue by scavenging free radicals to enhance antioxidant enzyme activity [32]. In the traditional Uyghur medicine, there is a drug, Xipaiyi, which is mainly composed of galls [33]. Studies have shown that ulceration can reduce the amount of NF-κB, IL-1β and transforming growth factor-β1 (TGF-β1) in the colonic mucosa and attenuate the expression of Toll-like receptor 2 (TLR2). In addition, xipayi can also improve the imbalance between pro-inflammatory factors and inflammatory cytokines, restore colonic epithelial cells, and repair damaged sites [34].
2.4, cinnamon (Klinda Riccione)
Cinnamon is the old bark of the sapling plant Cinnamomumcassia Presl. The main component of cinnamon is enamel, which has anti-inflammatory, damage repair, anti-oxidation effects [35]. Cinnamon extract can effectively improve colonic tissue damage, immune cell infiltration and inflammation in mice after treatment with colitis. These effects are through inhibition of macrophage inflammatory protein-2 (MIP-2), TNF, IFN. Up-regulation of gamma and chemokines CCL2, CCL3, CCL4 and IL-1β, MC-CPA, monocyte chemoattractant protein-1 (MCP-1) and MCP-4, but does not inhibit tight junction proteins Expression [36].
2.5, pomegranate
The pomegranate is derived from the fruit of the pomegranate Punicagranatum L., including the sour pomegranate (Querman Anar) and the sweet pomegranate (Tatrik Anar), the seeds (Pomegranate/Analo Ouhe), Peel (Pomegranate peel / Arnald's), flowers (Pomegranate / Anal Gully), root bark (Anaer's Philippe) can be used as medicine. Pomegranate is rich in anthocyanins and tannins, which are decomposed into urolithin A under the action of intestinal flora. Urinin A induces mitochondrial autophagy, fights muscle degeneration and anti-aging effects [37].
Pomegranate extract can effectively relieve the symptoms of colonic submucosal edema in rats and eliminate mononuclear inflammatory infiltration [38]. Histamine is a vascular amine produced by mast cells, and its release can lead to the decline of mast cells. Pomegranate can stabilize mast cells and prevent its decline, which may be one of its anti-ulcer mechanisms [39]. Pomegranate and pomegranate-rich pomegranate food can rapidly reduce the overexpression of COX-2 and iNOS, reduce MAPKs diisopropyl protein kinase and prevent NF-κB transcription in the nucleus, resulting in a significant decrease in MPO activity and TNF-α levels. [40].
Ellagic acid is an important compound in the pomegranate that has a therapeutic effect on IBD. In IBD, activated neutrophils and macrophages are the main factors of colitis active lesions, which can induce NOS to produce a large amount of NO at the site of inflammation, and NO reacts rapidly with oxygen free radicals to produce various cytotoxins. Lipid peroxidation and oxidative stress response to the treatment of colitis by scavenging free radicals to inhibit oxidized nitrate [41]. In terms of anti-inflammatory, ellagic acid can act on the NF-κB pathway and inhibit its action, thereby reducing the expression of inflammatory factors COX-2, iNOS, TNF-α and IL-6 [42]. In addition, ellagic acid can also inhibit the decline of IκBα and prevent the phosphorylation of p38 MAPK kinase, JNK and ERK1/2 MAPKs, all of which indicate that ellagic acid may be effective in colitis [43].
Pomegranate is mainly found in pomegranate seeds. Its target is peroxisome proliferator-activated receptor (PPAR), which inhibits the production of TNF-α and MCP-1 through the expression of PPARγ and PPARδ in mucosal and epithelial cells, and inhibits inflammatory bowel disease. [44]. In addition, punicic acid can target p38 MAPK kinase/serine 345-p47 phox-axis and MPO release inhibits TNF-α-induced NSDPH oxidase, producing anti-inflammatory activity [45].
2.6, Acacia (Enuddijk)
Acacia is a seed of the leguminous Abrasii Abrusprecatorius L., which mainly contains saponins, flavonoids, terpenoids and polyphenols, and has antioxidant, anti-inflammatory and anti-ulcer effects [46]. Its water extract can inhibit the production of reactive oxygen species. The experimental results show that the colonic injury histological score (CMDI) decreased, malondialdehyde (MDA) decreased, NO, SOD, GSH after colitis mice treated with Acacia extract. CAT activity is elevated, thereby protecting the colon [47].
2.7, ocean olive oil
Ocean olive oil is the fatty oil of Olea europaea L. mature fruit, contains volatile compounds, polyphenols, etc., has anti-inflammatory, anti-oxidant and anti-cancer effects [48-49], polyphenols can significantly improve colitis Symptoms of inflammation in mice. The experimental results show that olive oil has a protective effect on colitis mice. By up-regulating PPARγ and inhibiting NF-κB and p38 MAPK signaling pathways, the expressions of MCP-1, TNF-α, COX-2 and iNOS are decreased, thereby reducing disease activity index (DAI) and reducing tissue damage [50].
Hydroxytyrosol is an important chemical component in olive oil and has anti-microbial, anti-oxidant and anti-inflammatory effects [48, 51]. Colonic animal experiments show that hydroxytyrosol acetate (HTy-Ac) has a significant protective effect on colitis mice, can down-regulate JNK phosphorylation and reduce p65 levels, and reduce protein expression of MPO, COX-2 and iNOS. Improve tissue damage and reduce DAI index [52]. In addition, a mixture of olive oil, olive oil and hydroxytyrosol was compared. It was found that the mixture of hydroxytyrosol and olive oil had a more protective effect on colitis, and the cytokine level and COX-2 were down-regulated by p38 MAPK pathway. The amount of iNOS [53].
2.8, Apple (Ali)
Apple is the mature fruit of Rosaceae apple MaluspumilaMill. It is rich in flavonoids, vitamin C, proanthocyanidins, etc. It has damage repair, anti-inflammatory, anti-oxidation and immune regulation [54-55]. Apple polyphenol extract can significantly improve colonic injury, reduce COX-2, TNF-α and calpain activity in colon tissue, accelerate tissue-transfer glutaminase (tTG) overexpression, balance calpain with tTG, and pass Inhibition of calpain accelerates the repair of the fibroblast layer [56]. In addition, there is a study on the mechanism of action of apple polyphenol extract on T cells. Apple oligomer polyphenols can alleviate the inflammation of TCRα/mouse through the activation of white blood cells, thereby increasing the pro-inflammatory cytokines; The pro-inflammatory effect is regulated by T cells in normal mice, and the expression of CXC chemokine receptor 3 (CXCR3) in the colon is inhibited by TCRαβ cells, thus protecting the colitis mice [57]. Oral apple proanthocyanidin extract can increase the ratio of TCRαβ-CD8α in TCRγδ cells and epithelial lymphocytes in colitis mice, inhibit the synthesis of IFN-γ in epithelial lymphocytes, and thus protect colitis mice [54].
2.9, grapes
The grape is the dried fruit of the grape plant Vitisvinifera L., including the seedless grape (European åˆ åœ åœ åœ ) ) ) ) ã€ ã€ ã€ ã€ ã€ ã€ ã€ è¨ è¨ è¨ è¨ è¨ è¨ è¨ è¨ è¨ è¨ è¨ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ ã€ A variety of cultivars, including flavonoids, polyphenols, proanthocyanidins and other compounds, have antioxidant, anti-inflammatory, antibacterial effects [58]. Grape extract can significantly reduce the increase of pro-inflammatory factor TNF-α and regulate iNOS expression [59]. Macroscopically, it can reduce the ileal villus height and mucosal thickness and reduce the degree of tissue damage in colitis mice, but there is no colon crypt. Significant inhibition [60].
Resveratrol is one of the active constituents of grape anti-IBD. Resveratrol inhibits intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM) in experimental colitis mice. -1), restore mucosal NO levels, inhibit leukocyte adhesion and reduce leukocyte adhesion [61]; and down-regulate COX-2 expression associated with inflammatory response and injury, but have no effect on COX-1 expression Inhibition of prostaglandin D2 (PGD2) synthesis and inhibition of prostaglandin E2 (PGE2); in addition, resveratrol also accelerates colonic apoptosis in experimental colitis mice [62]. In addition, resveratrol regulates the expression of TNF-α and IFN-γ by CD3+ T cells, and down-regulates p53 and p53-dioxyphosphoryl-serine, showing significant protective effects on IBD [59].
Proanthocyanidins are concentrated enamel that eliminates intestinal inflammatory responses in certain media such as neutrophil infiltration, oxygen free radicals, IL-1β, IL-2 and IL-4, and promotes the repair of colonic injury tissue [63]. In addition, proanthocyanidins can eliminate free radical production, reduce the decline of endogenous antioxidant enzymes, and resist the defects of GSH [64].
2.10, saffron (Refar)
The saffron is the upper part of the style and the stigma of the saffron Crocussativus L. Tibetan acid is an important component of saffron and has anti-oxidant and anti-inflammatory effects [65]. The experiment found that crocetin has a significant protective effect on colitis mice, and its mechanism of action is to down-regulate the inflammatory factor Th1 response, leading to inhibition of iNOS and reduction of neutrophil proliferation, reducing lipid peroxidation and tissue damage [ 66].
3, the conclusion
3.1, 10 kinds of vitamins mainly resist anti-inflammatory and anti-oxidation effects IBD
Uyghur medicine has a variety of drugs for the treatment of IBD, and studies have shown that they or a component of it can alleviate the symptoms of colonitis in rodent models. At present, the research on the role of vitamins against IBD is mainly focused on anti-inflammatory and anti-oxidation. In terms of anti-inflammatory effects, pomegranate and other vitamins can inhibit TNF and NF-κB pathways, and apples can inhibit the expression of inflammatory factors and oxytocin pathways. Vitamins such as olive oil can also inhibit PPARγ and MAPK pathways in immune response. The response achieves an anti-IBD effect. In terms of antioxidation, anti-IBD effects are mainly achieved by inhibiting NO, MPO and reducing free radical production (Tables 1, 2). Through the above mechanism, the Uyghur medicine achieves the purpose of promoting ulcer healing and intestinal mucosal regeneration, eliminating abnormal body fluids, enhancing immunity, stopping bleeding, assisting digestion and anti-microbial.
3.2, the toxic effects of vitamins have rarely been reported
In the current study, only literature has shown that ip apple polyphenols ≥ 3 mg / kg will have toxic effects and no protective effect on DSS-induced IBD mice, mice showed rapid reduction in body mass and decreased body temperature [57] . Oral apple polyphenols have no toxic effects on IBD mice, probably due to intestinal regulation of oral apple polyphenol intake, preventing blood levels from reaching toxic levels [67]. The toxic effects of other plants on IBD have not been reported.
3.3. Part of the pathway of some medicinal materials is worth studying, and the research work of LB4 has yet to be carried out.
In the anti-IBD effect of Uyghur herbal medicine, the research of 10 plants involved anti-inflammatory and anti-oxidation effects, and other activities such as damage repair and immune regulation were only involved in some plants. It has not been studied to achieve anti-IBD effects by inhibiting LB4 (Table 2). Existing studies have shown that LB4 overproduction can be observed in patients with IBD, and inhibition of LB4 can reduce inflammation and improve IBD.
References (omitted)
This article is excerpted from: Qin Huiyu, Ma Shangzhi, Yu Wei, Long Fei, Chen Haijun, Chen Wen, Tian Xing, Han Bo.Research progress on the mechanism of traditional Uyghur herbs on inflammatory bowel disease[J]. Chinese Traditional and Herbal Drugs, 2017, 48(11) :2327-2334.
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