Application for traditional Chinese medicine in treating functional dyspepsia

Zhao-Jin Li＊

1Tianjin fifth central hospital,Tianjin,China.

Abstract Functional dyspepsia (FD) is a common disease in the department of gastroenterology, and its incidence tends to increase year by year. It has become one of the important diseases plaguing modern people. Western medicine is not ideal in clinical treatment, and this disease is easy to relapse. Traditional Chinese medicine (TCM) treatment FD has a unique potential advantage, mainly for the wide range of application, long-term application of small adverse reactions, and obtaining certain curative effect in clinical application. This paper summarizes the progress of TCM in the treatment of FD in clinical practice,so as to provide a reference for the clinical application of TCM in the treatment of FD.

Keywords:Functional dyspepsia,Gastroenterology,Traditional Chinese medicine

Background

Functional dyspepsia (FD) is one of the most common functional gastrointestinal disorders, which characterised by recurrent orchronic fullness in upper abdomen, belching, early satiety, bloating, epigastric algesia, vomiting, nausea, regurgitation, and loss of appetite and burning.The prevalence of FD in global is 21% [1] with a higher prevalence in women, smokers,users of non-steroidal antiinflammatory drugs and in those with Helicobacter pylori infection [2]. FD has now become a serious worldwide public health affecting patients’ physical and mental health [3].Based on the Rome IV criteria, FD can be divided into two subgroups, arepostprandial distress syndrome with postprandial fullness or early satiation, and epigastric pain syndrome with epigastric pain or epigastric burning[4].At present,the etiology of FD is not clear, which may be related to gastrointestinal motility abnormalities, visceral hypersensitivity,intestinal endocrine disorders, intestinal barrier dysfunction, genetic factors. Several studies have reported psychological distress, particularly anxiety, is also related to FD and might even precede the onset of FD symptoms; the psychosocial measures score of patients with FD was higher than average [5, 6]. The recently issued guidelines by international societies such as the American College of Gastroenterology(ACG) and Canadian Association of Gastroenterology(CAG) did not established the standard treatment due to the complexity of the syndrome [7]. H2 blockers,prokinetics, proton pump inhibitors, mirtazapine, and antidepressants, can only relieve symptoms of certain patients. However, these treatments do not achieve satisfactory relief due to certain side-effects with long-term application and easy recurrence after drug withdrawal.

Traditional Chinese medicine (TCM) has a unique therapeutic effect on relieving symptoms and reducing recurrence of FD. According to TCM theory, FD belongs to the category of "epigastric pain" (Wei Wan Tong) and "gastric distension" (Wei Pi) and is mainly caused by overwork,invasion of exogenous pathogens,irregular diet and emotional disorder [8].According to the Consensus Opinion of Experts in TCM Diagnosis and Treatment of Functional Dyspepsia [9], FD can be divided into five syndrome types: spleen deficiency and Qi stagnation syndrome,liver stomach disharmony syndrome, spleen stomach damp heat syndrome,spleen stomach deficiency and cold syndrome, cold and heat syndrome. Through invigorating spleen and invigorating Qi, regulating Qi and stomach, it can relieve the main symptoms such as postprandial fullness, early satiety, upper abdominal pain and burning sensation in the middle and upper abdomen.Some exciting evidence about the possible efficacy of TCM in treating FD has been reported [10-15]. The systematic review and meta-analysis including 292 studies, 19817 patients found that TCM was superior to western medicine in improving the overall symptom recovery rate, total effective rate, improving upper abdominal pain, early satiety, abdominal distension,regulating mood, which could significantly reduce the recurrence rate of patients, and no obvious adverse reactions were found [16]. The basic study confirmed that TCM showed effect in regulating gastric motility,compliance, visceral sensitivity and duodenal mucosal integrity[17-20].

This review summarizes the progress of TCM in the treatment of FD, so as to provide a reference for the clinical application of TCM in the treatment of FD.

The internal treatment of TCM

Chinese herbal medicine (CHM) ingredients treating FD

The possible efficacy of CHM ingredients in treating FD has been reported. Aurantii fructus immaturus flavonoid, the major effective constituent of Zhishi(Aurantii Fructus Immaturus), could promote gastric emptying process in FD rats [21]. It has been confirmed Weikang pian made of flavonoids extracted from Zhishi (Aurantii Fructus Immaturus) could effectively and safely alleviate the symptoms of FD[22].Artemisia rupestris L., which is the perennial herb of rupestris belonging to Artemisia (Compositae),can effectively improve the gastrointestinal motility of FD model rats by recovering gastrointestinal hormone levels and regulation of the peripheral and central nervous system and alter gut peptide levels[23].

Classic prescriptions treating FD

Based on the principle of syndrome differentiation and treatment, classic Chinese medicine prescriptions has achieved significant clinical effect in the treatment of FD. A data mining research showed the classical prescriptions for FD mainly included Sijunzi Decoction, Liujunzi Decoction, Xiangsha Liujunzi Decoction, Sini Powder, Chaihu Shugan powder,Zhizhu pill,Zhishi Xiaopi pill,etc[24].

Liu Jun Zi decoction.Liu Jun Zi decoction is a traditional Chinese compound herbal recipe, the record of which can be traced back toTaiping Huimin Hejiju Fangwritten by Shi-Wen Chen in Song Dynasty of China. It has the effect of invigorating the spleen and regulating Qi. The ingredients of the LiuJunZi decoction include Ren Shen (Radix Ginseng), Baizhu(Rhizoma Atractylodis Macrocephalae),Fuling(Poria),Gancao (Radix Glycyrrhizae), Chen Pi (Pericarpium Citri Reticulatae), Banxia (Rhizoma Pinelliae). A multi-center,randomized,double-blind study by Zhang SS, et al [25] showed that modified Liu Jun Zi decoction could improve symptoms associated with FD and gastric emptying; moreover,no adverse events were reported during the study.The mechanism of Liu Jun Zi decoction treating FD may be related to regulation of gastrointestinal function and hormone secretion [26]. Other experimental studies had shown that the active ingredients from the modified Liu Jun Zi decoction could improve gastrointestinal motility,regulate gastrointestinal function and have anti-Helicobacter pylori and anti-inflammatory action[27-32].

Chaihu Shugan powder.Chaihu Shugan powder is originated fromYixue Tongzhipublished in the Ming Dynasty of China. It is composed of Chenpi(Pericarpium Citri Reticulatae), Chaihu (Radix Bupleuri), Chuanxiong (RhizomaLigustici Chuanxiong), Xiangfu (Rhizoma Cyperi), Zhiqiao(Fructus Aurantii), Shaoyao (Radix Paeoniae Alba),Gancao(Radix Glycyrrhizae).Chaihu(Radix Bupleuri)and Shaoyao (Radix Paeoniae Alba) have the function of soothing the liver and relieving depression and regulating Qi. Chenpi (Pericarpium Citri Reticulatae)and Zhiqiao (Fructus Aurantii) have the function of regulating Qi. The combination of various drugs has the effect of soothing liver and regulating Qi,activating blood circulation to relieve pain. A systematic review concluded that the treatment of Chaihu Shugan powder on FD was better than that of western medicine control group, especially in improving clinical symptoms and has the advantage of small safety side effects[33].

Dalitong granule.Dalitong granule composed of Chaihu (Radix Bupleuri), Zhishi (Fructus Aurantii Immaturus), Muxiang (Radix Aucklandiae), Chenpi(Pericarpium Citri Reticulatae), Qingbanxia (Rhizoma Pinelliae Preparata), Pugongying (Herba Taraxaci),Shanzha (Crataegus pinnatifida Bunge), Binlang(Semen Arecae), Jishiteng (Paederia scandens Lour.Merr.), Dangshen (Radix Codonopsis), Yanhusuo(Rhizoma Corydalis), Liushenqu (Massa Medicata Fermentata) (fried). Dalitong granule has the effect of relieving depression and clearing heat. The double-blind, double-dummy and randomized controlled study showed Dalitong granule has the same clinical effect as cisapride with no obvious toxic-adverse effects[34].

Qizhi Weitong granule.Qizhi Weitong granule is composed of Chaihu (Radix Bupleuri), Yanhusuo(Rhizoma Corydalis), Zhiqiao (Fructus Aurantii),Xiangfu (Rhizoma Cyperi), Shaoyao (Radix Paeoniae Alba), Gancao (Radix Glycyrrhizae). It has the effect of soothing liver, regulating Qi and relieving stomach pain [35]. The randomized, double-blind,placebo-controlled trial showed Qizhi Weitong granule is an effective medicine for FD and is well tolerated with a good safety profile [36]. Modern pharmacological studies have shown that it has the functions of relieving spasmolysis and analgesia,inhibiting gastric acid secretion and promoting gastrointestinal motility.

Jiawei Xiaoyao pill.The Jiawei Xiaoyao pill consists of the following crude herbs: Danggui (Radix Angelicae Sinensis), Shaoyao (Radix Paeoniae Alba),Fuling (Poria), Baizhu (Rhizoma Atractylodis Macrocephalae), Chaihu (Radix Bupleuri), Mudanpi(Cortex Moutan Radicis), Shanzhi (Gardenia jasminoides), Gancao (Radix Glycyrrhizae). It has the effect of promoting Qi and blood as well as nourishing the spleen. Jiawei Xiaoyao pill has been approved by The China Food and Drug Administration to treat anxiety disorder [37] and psychological stress induced insomnia [38]. A multicenter, randomized,placebo-controlled, clinical trial showed Jiawei Xiaoyao pill was superior to the placebo in terms of improving the gastrointestinal symptom score in patients with FD[39].

Sini Powder.Sini powder (SNP) has effect of invigorating spleen and regulating Qi and was used to treat spleen-deficiency and Qi-stagnation syndrome in TCM.The herbal composition of SNP includes Chaihu(Radix Bupleuri),Zhishi(Fructus Aurantii Immaturus),Shaoyao (Radix Paeoniae Alba), Gancao (Radix Glycyrrhizae). Previous study showed that SNP had certain therapeutic effect in FD rats [40]. The intrinsic mechanism generating SNP benefits may related to alleviates the visceral hypersensitivity in FD model rat by regulation of the NO/cGMP/PKG signaling pathway in the spinal dorsal horn[41].The other study elucidated that the therapeutic effect of SNS on FD was achieved by restoring mucosal barrier integrity and suppressing low-grade inflammation in the duodenum via the CRF signaling pathway[42].

The external treatment methods of TCM

In recent years, external treatment of TCM has been widely used in clinic. A meta-analysis including 1424 patients showed the external treatment of TCM significantly reduced the symptom score, improved NDI (Nepean Dyspepsia Index) and the ghrelin level[43]. Commonly used TCM external treatment methods includes acupuncture, acupoint catgut embedding,etc.

Acupuncture therapy

As an internationally recognized alternative therapy,acupuncture therapy has been used in treatment of a variety of diseases. In recent years, many types of acupuncture therapies have been developed to treat FD,including manual acupuncture, warm acupuncture,electroacupuncture (EA), moxibustion, acupoint catgut embedding, and acupoint application. Acupuncture therapy is to improve the neurobiological function of patients by stimulating acupoints, so as to improve their clinical symptoms. The effectiveness of EA on FD has been investigated in several studies [44, 45].A systematic review and meta-analysis indicates that EA or acupuncture is superior to sham-EA,sham-acupuncture, western medication regarding the improvements in FD symptoms [46]. Ho et al.concluded that a combination of manual acupuncture and clebopride was the most effective approach of attenuating FD symptoms [47]. Tang YH, et al.observed the clinical effect of acupuncture combined with ginger-partitionmoxibustion on FD; the result showed acupuncture combined with ginger-partition moxibustion could improve the symptoms of FD, and had the advantages of easy operation and high safety[48]. Research has demonstrated that EA improves gastric slow waves and accelerates gastric emptying mediated via the autonomic and cholinergic mechanisms [49]. EA might be used as an effective and safe treatment for FD.

Acupoint catgut embedding

Acupoint catgut embedding is a kind of therapy to implant sheep's intestinal line into human acupoints,which has both physical and biological stimulation,that is, acupuncture, acupoints and "line ", which can stimulate meridian Qi and reconcile Qi and blood,thus treating diseases. Meta analysis showed that the treatment of FD by embedding thread was superior to the basic treatment in recovery rate,total effective rate,gastric half emptying time and gastric emptying time,and the incidence of adverse reactions was small[50].

Conbined treatment of TCM and western medicine

Xiangsha Liujunzi Decoction combined with quadruple therapy for FD of spleen stomach Qi deficiency type could effectively improve the clinical symptoms, improve the clinical efficacy, and had high safety and good long-term effect [51]. Ren Z, et al observed the clinical effect of Zhishi Xiaopi pills combined with trimebutine maleate for FD and the result showed Zhishi Xiaopi pills combined with trimebutine maleate could significantly reduce positive rates ofHelicobacter pyloriand effectively improve levels of gastrointestinal hormones [52]. Chaizhi Pinggan decoction is a classic prescription for the treatment of spleen and stomach weakness syndrome.It is composed of Hehuanhua (Flos Albiziae),Chuanxiong (Rhizoma Ligustici Chuanxiong), Foshou(Fructus Citri Sarcodactylis), Zhiqiao (Fructus Aurantii), Sharen (Fructus Amomi Villosi), Shaoyao(Radix Paeoniae Alba), Qingpi (Pericarpium Citri Reticulatae Viride), Chaihu (Radix Bupleuri), Gancao(Radix Glycyrrhizae). The study showed compared with domperidone alone, Chaizhi Pinggan decoction combined with domperidone not only has more significant therapeutic effect on FD, but also could reduce the recurrence rate of FD. The therapeutic mechanism may be related to improve the levels of gastrointestinal hormones motil and somatostatin[53].

Conclusion

TCM treatment FD has a unique potential advantage and obtains certain curative effect in clinical application.Because of the complexity and diversity of the herbs used in TCM prescriptions and the lack of quantitative studies, more evidences from properly controlled studies are needed.