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Subjects:
Gastroenterology & Hepatology
慢性胃炎（CG）是一种常见的临床消化系统疾病，不易治愈，容易复发。中医药（TCM）在CG的治疗中发挥着重要作用，并越来越受到临床应用的关注。大量报道表明，中医对CG有很好的治疗效果。
- chronic gastritis
- classical prescription
- proprietary Chinese medicine
- active components
1. Clinical Observation of TCM in the Treatment of CG
1.1. Classical Prescriptions
Classical prescriptions are the outstanding representatives of traditional Chinese medicine prescriptions, summarizing the clinical experience of previous generations of medical practitioners. The classical prescription has characteristics of relatively stable ingredients, clear curative effects, profound historical and cultural accumulation, and so on. In addition, it possesses unparalleled advantages in theoretical basis, prescription laws, dose control, drug administration, and other aspects. It is an important carrier to reflect the clinical experience and academic thoughts of famous ancient doctors [5].
Banxia Xiexin decoction is a classic prescription of TCM, which was first recorded in the Treatise on Febrile Diseases in the Medical Code of the Eastern Han Dynasty. This ancient prescription is composed of seven kinds of Chinese herbal medicine, including Pinellia ternate (Thunb.) Breit., Coptis chinensis Franch., Scutellaria baicalensis Georgi, Zingiber officinale Rosc., Panax ginseng C. A. Mey., Ziziphus jujuba Mill., Glycyrrhiza uralensis Fisch. In clinical practice, it has been widely used in the treatment of patients with the cold-heat syndrome of CAG. A recent study demonstrated that the clinical effective rate of Banxia Xiexin decoction in the treatment of chronic non-atrophic gastritis and improving gastritis symptoms is significantly better than that in the control group [36]. In addition, Banxia Xiexin decoction plays a more significant role in inhibiting Hp infection, improving Hp-related inflammation, reducing glandular atrophy, intestinal metaplasia, and gastric mucosal dysplasia [37]. It has been found that many kinds of Chinese herbs in this prescription can protect the gastric mucosa and inhibit Hp. In addition, it also relieves pain by inhibiting the central nervous system [5,38,39]. Numerous bioactive components in the above traditional Chinese medicines, including gingerol, soybean oil alcohol, stigmasterol, β-sitosterol, berberine, palmatine, baicalein, ginsenoside, polysaccharides and glycyrrhizin, have been found to play a direct or indirect role in the treatment of chronic gastritis [40].
Huangqi Jianzhong Decoction is derived from the Synopsis of the Golden Chamber written by Zhang Zhongjing in the Eastern Han Dynasty. It is composed of seven traditional Chinese medicines, including Astragalus membranaceus (Fisch.) Bge., Cinnamomum cassia Presl, Paeonia lactiflora Pall., Zingiber officinale Rosc., Glycyrrhiza uralensis Fisch., Ziziphus jujuba Mill., and Saccharum Granorum, which are used to treat various chronic inflammatory gastrointestinal diseases [41,42]. The study showed that Huangqi Jianzhong Decoction has a significant effect on the treatment of Hp-related gastritis with spleen and stomach deficiency and cold type. After treatment, nausea, vomiting, and upper abdominal discomfort were effectively improved, and the negative conversion rate of Hp was significantly increased [43]. In addition, in the treatment of chronic superficial gastritis, the efficacy was similar to that of omeprazole sodium in the improvement of stomachache, stomach distension, and nausea, with good safety, and no adverse reactions were found. In terms of effect duration, the effect of Huangqi Jianzhong Decoction was superior to that of the omeprazole treatment group [44]. In summary, the effect of Huangqi Jianzhong Decoction on chronic gastritis is outstanding, which is worthy of extensive clinical promotion.
Shenling Baizhu Powder comes from the “Prescription of peaceful benevolent dispensary,“ which consists of ten kinds of herbs: Panax ginseng C. A. Mey., Poria cocos (Schw.) Wolf, Atractylodes macrocephala Koidz., Dioscorea opposita Thunb., Dolichos lablab L., Nelumbo nucifera Gaertn., Coix lacryma-jobi L.var.ma-yuen (Roman.) Stapf, Amomum villosum Lour., Platycodon grandiflorum (Jacq.) A.DC., and Glycyrrhiza uralensis Fisch. [45]. The prescription has a bidirectional regulatory effect on gastrointestinal movement, which plays an important role in the treatment of gastric diseases. The evidence from this study suggested that Shenling Baizhu Powder can significantly relieve the clinical symptoms of patients with CAG and relieve gastric discomfort. It was mainly manifested in increasing the serum levels of PG Ⅰ, G-17, and PG Ⅱ, reducing gastric injury, and improving prognosis [46].
盛阳益味汤最早出现在《内外伤害歧视 ·卷“，这是李高的名方。该处方由黄芪（Fisch.）Bge.， Pinellia ternate （Thunb.）Breit.， Panax ginseng C. A. Mey.， Glycyrrhiza uralensis Fisch.， Paeonia lactiflora Pall.， Saposhnikovia divaricata （Turcz.）Schischk.， Notopterygium incisum Ting ex H. T. Chang， Angelica pubescens Maxim.f.biserrata Shan et Yuan， Citrus reticulata Blanco， 茯苓 （Schw.） Wolf， Alisma orientale （Sam.） Juzep.， Bupleurum chinense DC.， Atractylodes macrocephala Koidz.， and Coptis chinensis Franch.[47]. 一项研究表明，胃炎患者在接受西药三联疗法的同时，采用圣阳益味汤治疗，可显著改善上腹痛、嗳气、胃酸反流、恶心、呕吐，提高治疗效果和Hp清除率。两者结合可发挥协同作用，不易产生副作用[48]。
吴竹汤最早出现在张仲京的《发热病论》中。它由Euodia rutaecarpa（Juss.）组成。Benth.，Zingiber officinale Rosc.，人参C.A.Mey.，Ziziphus jujuba Mill.，对治疗胃寒患者有很好的效果。在肝寒侵入胃的胃炎治疗中，通过比较乌竹鱼汤与雷贝拉唑胶囊联合铝镁加混悬液，发现乌竹鱼汤治疗肝寒侵胃的胃炎有更高的有效率。此外，缩短了患者的症状改善时间，不良反应的发生率更低[49]。
1.2. 中成药
中成药是中医药临床实践的重要组成部分，在全球医疗实践中发挥着重要作用。具有生物利用度高、储存和概率方便、质量可控等优点。近年来，中成药种类的增加和剂型的不断创新，使其在世界范围内广受欢迎。
威苏颗粒由紫苏（紫苏）、圆柱栾（Cyperus rotundus L.）、网状柑橘（Citrus reticulata Blanco）、柑橘（Citrus medica L.）、柑橘（Citrus medica L.）、柑桔（Citrus medica L.）、柑桔（Citrus medica L.）、槟榔（Citrus aurantium L.）、槟榔（Arecica catechu L.）、家养紫苏（Gallus gallus domesticus Brisson）组成，具有消炎、消除Hp、改善胃损伤的作用。有证据表明，威素颗粒联合三联疗法可显著改善CG患者的胃功能，修复胃黏膜，降低炎症因子水平。进一步的研究发现，陈皮中的川醚具有破坏细菌结构的作用[50]。Xiang Fu抑制炎症趋化因子的产生，以抑制炎症的发生并延缓疾病的发展[51]。三九威泰颗粒主要由吴茱萸（Spreng.）组成。Merr.， 黄芩 （Scutellaria baicalensis Georgi）， Murraya exotica L.， Zanthoxylum nitidum （Roxb.）DC.、奥克兰芍、茯苓、芍药、 芍药、熟地黄。 各种草药的组合应用起到清热、祛湿、消炎、止痛的作用。三九威泰颗粒联合雷贝拉唑钠肠溶性胶囊治疗慢性浅表性胃炎的研究发现，联合应用组临床有效率明显高于单独使用雷贝拉唑钠肠溶性胶囊，不良反应发生率降低[52]。京华威康胶囊是在中医理论指导下，以现代药学技术提取的挥发油制成的一种胶囊。研究发现，晶华威康胶囊在体内外均有很好的抗Hp作用，对Hp引起的胃黏膜损伤有一定的修复和保护作用。其机制可能与抑制NF-κB介导的炎症通路有关。此外，在改善耐药性方面也有一定的作用[53]。Qi等[54]探讨了晶华威康胶囊联合Rebaport片治疗CAG的临床疗效。结果表明，晶华伟康胶囊联合瑞卑德片的总有效率、前列腺素E2（PGE2）、胃泌素-17（G-17）、胃蛋白酶原比值（PGR）和胃蛋白酶原I.（PG I.）均高于单独瑞卑胺片治疗组。此外，血清可溶性白细胞介素-2受体（SIL-2R）和白细胞介素-1 β（IL-1 β）水平均低于单独使用利巴匹德治疗组，表明京华伟康胶囊联合瑞巴匹片可提高慢性萎缩性胃炎的疗效，减轻胃黏膜炎症损伤，调节胃肠道激素分泌，安全性好，临床应用良好。Yangwei颗粒由黄芪（Fisch.）组成。Bge.， Codonopsis pilosula （Franch.）Nannf.， 芍药 lactiflora Pall.， Glycyrrhiza uralensis Fisch.， Citrus reticulata Blanco， Cyperus rotundus L.， Prunus mume （Sieb.）Sieb.etZucc.和Dioscorea opposita Thunb。现代药理学研究发现，它可以降低胃蛋白酶活性，抑制胃酸分泌，改善胃蠕动，增加疼痛阈值[55,56]。研究表明，杨威颗粒联合抗HP四联疗法比单独四联疗法更快地缓解了HP感染的CAG临床症状。此外，阳威颗粒联合抗HP四联治疗显著提高临床疗效和HP根除率，安全性好，临床价值高[57]。
2. 中药治疗慢性胃炎的有效成分
2.1. 生物碱
生物碱是植物中含氮的基本有机化合物。它们是中草药中重要的有效成分之一，大多具有复杂的环状结构。研究表明，生物碱具有广泛的药理活性，通过抗炎、抗氧化、抗凋亡、保护胃粘膜、抗菌等来保护胃损伤。小檗碱和棕榈碱是从黄连等中草药中提取的天然异喹啉生物碱，数百年来一直被广泛用于治疗。在过去的几十年里，许多研究表明，小檗碱和棕榈碱及其衍生物在消化系统中具有抗炎、抑菌和黏膜保护活性[58,59]。同时，越来越多的报道明确指出，它们在治疗HP感染引起的CG方面具有巨大的潜力。Yang及其同事的研究表明，小檗碱对Hp引起的CAG有很好的治疗效果[60,61]。其机制可能部分与干扰素调节因子8（IRF8）-干扰素-γ（IFN-γ）信号轴的抑制以及白细胞介素-4（IL-4）信号转导和转录激活因子6（STAT6）信号通路的激活有关。在小檗碱的干预下，血清白细胞介素-17（IL-17）、趋化因子1（CXCL1）和趋化因子9（CXCL9）水平下调，G-17显著升高。Hp对胃黏膜的损害也得到了缓解。同时，小檗碱可以改善GES-1细胞的细胞活力和形态变化。另一方面，小檗碱治疗抑制促炎基因和IRF8-IFN-γ信号轴相关基因。此外，小檗碱干预抑制肿瘤坏死因子-α（TNF-α）、iNOS（NOS2）、趋化因子受体7型（CCR7）和IRF-8的mRNA表达，增加IL-4、STAT6和白细胞介素-10（IL-10）的mRNA表达。另一项研究表明，棕榈碱显着减弱了 Hp 诱导的胃粘膜损伤和 GES-1 细胞的形态学变化。进一步的研究表明，棕榈碱显著抑制EGFR活化的配体基因的表达，包括分解的金属蛋白酶17（ADAM17）和肝素结合的表皮生长因子样生长因子（HB-EGF）。此外，帕马汀可减轻CD8+T细胞的炎症浸润，抑制趋化因子16（CXCL-16）和白细胞介素8（IL-8），从而增强宿主防御能力[62]。脱氢吴芸香碱是从吴茱萸中分离得到的一种关键的喹唑啉类生物碱，在治疗胃肠道疾病中起着重要作用。温团队的结果表明，脱氢吴萸苷通过抑制HIF-1α/VEGF血管生成途径改善了体内CAG大鼠MNNG诱导的胃损伤和体外GES-1细胞迁移[63]。
2.2. 多酚
多酚类是具有多个酚羟基的复杂次生代谢产物，广泛分布于植物中，具有抗氧化、清除自由基、镇痛、抗炎、抗菌等药理作用。越来越多的证据表明，多酚化合物对胃损伤有一定的治疗和改善作用。姜黄是一种属于生姜科的亚热带植物，含有姜黄素，姜黄素是促成其许多生物学功能的主要成分。研究表明，姜黄素具有广泛的生物学功能，如抗炎、抗氧化、抗菌、神经保护和胃保护特性[64,65]。研究表明，姜黄素可以通过增加基质金属蛋白酶-2（MMP-2）的表达和降低基质金属蛋白酶-9（MMP-9）的活性来保护和治愈胃，从而导致粘膜的再上皮化和重塑[66]。此外，Hp诱导的胃部炎症与NF-κB活化增加有关。NF-κB 通路参与这些炎症介质（TNF-α、IL-6 和 IL-1β）的产生，这些介质通过补充姜黄素而减少。此外，姜黄素降低了一组趋化因子（CCL20、CCL5、CXCL1、CXCL10、CXCL11、CCL25）的表达。此外，Hp 可激活上皮细胞和树突状细胞 （DC） 上的几种 TLR。TLR 是介导 Hp 和 DC 之间相互作用的关键分子，这在很大程度上依赖于除 TLR3 之外的所有 TLR 使用的接头蛋白 MyD88 信号转导。激活的 TLR4 通过 MyD88 依赖性途径激活 NF-κB，以调节炎性细胞因子的产生。姜黄素降低TLRs和MyD88的表达，从而表现出抗炎作用。该机制部分被认为是改善Hp诱导的胃炎小鼠中炎症细胞因子、趋化因子以及toll样受体（TLRs）和髓系分化因子88（MyD88）的表达[67]。临床上，与三联疗法组相比，姜黄素联合三联疗法组显著降低了丙二醛和谷胱甘肽过氧化产物的标志物，提高了胃黏膜的总抗氧化能力。此外，姜黄素联合三联治疗组DNA的氧化损伤显著低于基线组和三联治疗组。进一步研究表明，姜黄素联合三联治疗组所有活动性炎症、慢性炎症和胃镜炎症的评分均显著低于三联治疗组[68]。白藜芦醇主要来源于Polygoni Cuspidati Rhizoma et Radix，是一种天然存在的植物营养素多酚化合物，用于治疗多种疾病，包括疼痛、组织损伤和炎症性疾病。众所周知，白藜芦醇可以调节Hp诱导的各种毒力因子的蛋白表达。这种活性的机制部分与通过上调核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号通路来抑制Hp诱导的胃炎模型中IL-8和iNOS的水平有关[69]。
2.3. 黄酮类化合物
黄酮类化合物广泛存在于各种植物中，通常与糖结合形成糖苷。大量研究发现，黄酮类化合物具有多种药理活性，如抗胃溃疡、抗炎、抗氧化、镇痛等。研究发现，槲皮素通过调节TNFR-c-Src-ERK1/2-c-Fos和NF-κB通路，降低TNF-α诱导的GES-1细胞中MMP-9的表达，保护胃黏膜上皮细胞[70]。另一项研究进一步揭示了山奈酚通过调节刺猬信号通路和降低IL-6和IL-1β水平，在慢性萎缩性胃炎的治疗中发挥作用，为揭示山奈酚治疗慢性萎缩性胃炎提供了理论依据[71]。黄芩苷是一种天然类黄酮化合物，具有抗氧化、抗炎和免疫调节活性。Ji 等人报道，黄芩苷参与丝裂原活化蛋白激酶 （MAPK）、磷脂酰肌醇 3 激酶 （PI3K）-Akt 和 NF-κB 等多种途径，以减少 IL-2、IL-8 和 TNF-α 的产生，并增加表皮生长因子和 B 细胞淋巴瘤-2 的表达。上述结果为发现治疗CG的潜在靶蛋白提供了重要的见解[72]。
2.4. 萜类化合物
Terpenoids are important natural organic compounds contained in TCM, which are composed of isoprene as the basic structural unit. Terpenoids play an important role in treating gastritis by regulating related signal pathways, improving inflammation and gastric mucosa injury. Gentiopicrin is the main active ingredient of gentian. It was found that treatment with gentiopicrin significantly improved alcohol-induced gastritis in mice, mainly by decreasing the production of pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, and increasing the level of anti-inflammatory cytokine IL-10. This research finally found that regulating the MMP-10 and pERK1/2 signaling pathway is the crucial mechanism of gentiopicroside in alcohol-induced gastritis [73]. Ginsenoside Rg1 is the main active ingredient of Panax notoginseng with the highest content. A study demonstrated that ginsenoside Rg1 could improve the pathological condition of chronic atrophic rats and effectively inhibit the occurrence of atrophy and inflammation. Furthermore, ginsenoside Rg1 increased the expression of SHH and Ptch in gastric tissue, suggesting that ginsenoside Rg1 may improve gastric mucosal lesions in CAG by activating the Hedgehog pathway [74].
2.5. Polysaccharides
Polysaccharides widely exist in a variety of Chinese herbal medicine, which have a significant effect on the protection of gastric mucosal damage. They are characterized by multi-angle and multi-institutional coordination. Astragalus polysaccharides, as the main active component of Astragalus membranaceus, are one of the important material bases of its pharmacological action. It was found that astragalus polysaccharides have a certain therapeutic effect on CAG rats by down-regulating cyclooxygenase-2 (COX-2) and MMP2. The gastric morphology of chronic non-atrophic gastritis rats was significantly improved after treatment with astragalus polysaccharide. In addition, astragalus polysaccharide significantly increased the levels of gastrin in plasma and decreased PGE2 in CAG rats but had no significant effect on motilin levels [75]. Glycyrrhiza polysaccharides are one of the main components of Glycyrrhiza uralensis Fisch. The research found that the significant pharmacological effects of antioxidation and anti-apoptosis were related to increasing the ratio of Bcl-2/Bax and the content of SOD and GSH in gastric mucosa [76] (Figure 1).
Figure 1. Chemical structure of active components of traditional Chinese medicine. Note: these chemical structural formulas are derived from PubChem.
This entry is adapted from the peer-reviewed paper 10.3390/ph16091308
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