Mechanism of action of heat-clearing and detoxifying herbs in the treatment of erosive gastritis

Abstract

This article focuses on the clinical efficacy and mechanism of action of heat-clearing and detoxifying traditional Chinese medicines (TCMs) in the treatment of erosive gastritis, providing a reference for the treatment of this disease. In the clinical treatment of erosive gastritis, TCM combinations such as Qing Gastric San, Semixia Diarrheal Heart Soup, and single-flavored heat-clearing and detoxifying drugs such as dandelion and Huanglian have specific efficacies and effectively improve the patient's symptoms, including killing or inhibiting Helicobacter pylori, reducing inflammatory reactions, protecting the gastric mucosa, inhibiting gastric acid secretion, regulating gastrointestinal hormones, and regulating immune function, playing therapeutic roles through multi-level and multi-target mechanisms. Thus, heat-clearing and detoxifying TCMs have broad application prospects in clinical practice for erosive gastritis.

Key Words: Heat-clearing and detoxifying medicines; Chronic gastritis with erosion; Clinical efficacy; Mechanisms of action; Traditional Chinese medicine etiology and pathogenesis

Core Tip: Erosive gastritis, also known as chronic gastritis with erosion, can be divided into two types: "Atrophic gastritis with erosion" and "non-atrophic gastritis with erosion". As a common digestive system disease, the onset of erosive gastritis is related to various factors such as pathogen infection, daily routines, and emotional stress, which seriously affect patient health. The clinical efficacy of heat-clearing and detoxifying traditional Chinese medicine in treating erosive gastritis is definite, and their mechanism of action requires further in-depth research.

INTRODUCTION

The so-called "toxin-heat" etiology primarily results from Helicobacter pylori (H. pylori) infection, excessive emotional stress that transforms into heat and accumulates into toxins, the abnormal reflux of bile into the stomach, or certain medications. The long-term accumulation of toxins can damage the gastric mucosa, resulting in erosion and ulceration. Based on the symptoms and characteristics of the gastric mucosa, some scholars believe that this disease is similar to gastric abscess. The causes are often due to external contraction of wind-cold, internal injury from improper diet, and other factors such as emotional distress, which lead to the accumulation of heat-toxin in the stomach, stagnation of qi and blood, and impaired flow in the collaterals, eventually resulting in blood decay and tissue necrosis. Other scholars argue that, in addition to gastric injury from an improper diet and liver qi invading the stomach, the main cause of this disease is the invasion of toxic pathogens into the stomach. After the toxins accumulate and generate heat, the heat-toxin combines with stasis blood, damaging the gastric collaterals and ultimately leading to erosion of the gastric network vessels and the onset of disease[1,2]. Professor Xue-Wen Zhou, a master of traditional Chinese medicine (TCM)[3], in the active stage of gastric ulcer, the innovative etiology of "toxin-heat" and the therapeutic strategy of "treating as carbuncle" (i.e., clearing heat-toxin, eliminating carbuncle, and promoting granulation) have demonstrated remarkable clinical efficacy. Chinese medicines, such as Coptis chinensis, Sophora flavescens, Taraxacum mongolicum, and Fritillaria thunbergii, can help clear toxins from the body and reduce damage to the gastric mucosa. Pathological changes in erosive gastritis include gastric mucosal erosion, congestion, edema, and infiltration of inflammatory cells. Clinical symptoms include burning pain in the stomach, heartburn, acid reflux, and bitter taste in the mouth. According to TCM syndrome differentiation, it is "toxin-heat damaging the stomach.” Therefore, heat-clearing and toxin-resolving Chinese medicines have good curative effects.

CLINICAL EFFICACY OF HEAT-CLEARING AND DETOXIFYING TCMS IN TREATING EROSIVE GASTRITIS

Clinical efficacy of heat-clearing and toxin-resolving Chinese medicine compounds

Heat-clearing and toxin-resolving Chinese medicines can clear heat pathogens and toxins in the body, relieving pathological changes and clinical symptoms caused by toxin-heat. Heat-clearing and toxin-resolving Chinese medicines are commonly used to treat erosive gastritis. Multiple drugs are combined and work synergistically to enhance therapeutic effects.

Qingwei San (from "Treatise on the Spleen and Stomach") is a commonly used compound for clearing heat and detoxifying, mainly composed of Coptis chinensis, Rehmannia glutinosa, Angelica sinensis, Moutan cortex, and Cimicifuga racemosa. This formula has the effect of clearing stomach heat and cooling blood and is applicable for erosive gastritis caused by the upward attack of stomach fire. Qingwei San can effectively inhibit the growth of H. pylori, reduce the inflammatory response of the gastric mucosa, and promote the repair of the gastric mucosa. A randomized controlled trial (RCT) involving 120 patients with excessive stomach fire syndrome and H. pylori-negative erosive gastritis demonstrated that the total effective rate of the TCM group (modified Qingwei San) was 91.67%, which was higher than that of the Western medicine group (78.33%; P < 0.05). The TCM group showed better performance in improving specific symptoms, such as thirst and halitosis, and the recurrence rate after discontinuing the medication for 6 months was only 6.67%, which was significantly lower than that in the Western medicine group (20%). This study indicated that modified Qingwei San is highly effective and safe for treating erosive gastritis[4].

Banxia Xiexin Decoction (from "Treatise on Febrile Diseases")[5] is also a classic compound for the treatment of erosive gastritis. It is composed of Pinellia ternata, Scutellaria baicalensis, Zingiber officinale, Ginseng radix, Coptis chinensis, Ziziphus jujuba, and Glycyrrhiza uralensis. This formula regulates cold and heat, resolves abdominal fullness and discomfort, and dissipates nodules. It has a significant effect on erosive gastritis of the type of spleen-stomach deficiency and cold-heat complex. Banxia Xiexin Decoction regulates gastrointestinal function, promotes gastric emptying, inhibits gastric acid secretion, and reduces gastric mucosa damage. Concurrently, this formula can also regulate the immune function of the body and enhance the body's resistance. One study applied the Banxia Xiexin Decoction to treat patients with erosive gastritis for 8 weeks; the patients’ clinical symptoms significantly improved after treatment[6]. Gastroscopy revealed a marked reduction in gastric mucosal erosion and inflammation, and a high rate of negative conversion for H. pylori.

Modified Huanglian Wendan Decoction (from "Differentiation of Six - Factor Pathogenesis")[7] is a commonly used compound preparation for the treatment of erosive gastritis. It comprises Coptis chinensis, Bambusa inermis, Aurantii Fructus Immaturus, Pinellia ternata, Citri Reticulatae Pericarpium, Glycyrrhiza uralensis, Zingiber officinale, and Poria cocos. It has the effects of clearing heat, drying dampness, regulating qi, resolving phlegm, harmonizing the stomach, and benefiting the gallbladder. When treating erosive gastritis, adding flavors according to the specific symptoms of the patient can enhance the therapeutic effect. Zhang et al[8] treated 50 patients with erosive gastritis using a modified Huanglian-Wendan decoction. In this formula, Coptis chinensis has anti-inflammatory, heat-clearing, and toxin-resolving properties and is effective in inhibiting H. pylori. The combination of Evodia rutaecarpa and Coptis chinensis can relieve liver fire and treat root causes by regulating the ascending and descending qi. Bupleurum chinense, Scutellaria baicalensis, and Pinellia ternata can reconcile the Shaoyang meridian, making qi flow smoothly and calming the spleen and stomach. Bambusa inermis, Citri Reticulatae Pericarpium, and Poria cocos harmonize with the stomach function and relieve nausea. In addition, heat-clearing and toxin-resolving herbs, such as Taraxacum mongolicum and Hedyotis diffusa, as well as acid-reducing and pain-relieving drugs, such as Concha Arcae, Sepiellae seu Sepiae Endoconcha, and Bletilla striata powder, which can promote tissue regeneration, reduce swelling, stop bleeding, and form a protective film on the erosive surface, were added. The effect was significantly greater in the treatment group than in the control group. The total efficacy rate in the treatment group was 96.7%. After a 6-month follow-up, 28 patients in the treatment group showed no recurrence, whereas 12 patients in the control group had recurrence. This indicates that the modified Huanglian-Wendan decoction has obvious advantages in improving the symptoms of patients with erosive gastritis, promoting repair of the gastric mucosa, and reducing the recurrence rate.

Zhou et al[9], created the Huazhuo Jiedu Formula to treat erosive gastritis. The basic formula is as follows: Artemisia capillaris 15 g, Scutellaria baicalensis 15 g, Coptis chinensis 15 g, Citri Reticulatae Pericarpium 9 g, Bambusa inermis 10 g, Pinellia ternata 9 g, Bupleurum chinense 15 g, Cyperus rotundus 15 g, Perilla frutescens stem 12 g, and Citri Reticulatae Viride 15 g. It resolves turbidity and toxins, clears heat, and promotes diuresis. Its characteristics include resolving dampness and toxins with aromatic herbs, promoting diuresis, resolving toxins with bland-tasting herbs, removing foul-smelling substances, resolving turbidity and toxins, attacking toxins, and dissipating nodules.

Compared to single-herb medicines, the application of compound medicines has the advantage of multi-target and multi-pathway treatments. The drugs in the compound synergistically exert antibacterial, anti-inflammatory, gastric mucosa-protecting, and immune-regulating effects, thereby treating erosive gastritis more comprehensively.

The TCM classification of erosive gastritis and representative prescriptions are shown in Table 1.

Table 1 Traditional Chinese medicine syndromes and representative prescriptions for erosive gastritis.

Syndrome	Symptoms	Treatment method	Prescription
Damp-heat in the spleen and stomach	Distending epigastric pain, bitter taste in the mouth and halitosis, nausea and vomiting, sticky stools, yellow and greasy tongue coating, and slippery and rapid pulse	Clearing heat, drying dampness, regulating qi, and harmonizing the middle	Qingwei San
Mixed cold and heat	Distending epigastric pain, alternating chills and fever, bitter taste in the mouth, dry throat, unsatisfactory bowel movements, yellow and greasy tongue coating, and wiry and slippery pulse	Harmonizing cold and heat, regulating qi, and harmonizing the middle	Banxia Xiexin Tang
Liver and stomach with depressed heat	Distending epigastric pain radiating to hypochondria, which is exacerbated by emotional stress, irritability, and anger; bitter taste in the mouth; dry throat; red tongue with yellow coating; and wiry and rapid pulse	Soothing the liver, resolving depression, clearing heat, and harmonizing the stomach	Chaihu Shugan San
Blood stasis blocking the collaterals	Piercing epigastric pain that is localized and worse at night; dark purple tongue or ecchymosis; and choppy pulse	Activating blood, transforming stasis, regulating qi, and relieving pain	Jinlingzi San
Spleen and stomach deficiency	Dull epigastric pain that is relieved by warmth and pressure, fullness after eating, poor appetite and early satiety, fatigue, loose stools, pale tongue with white coating, and thin and weak pulse	Strengthening the spleen, invigorating qi, warming the middle, and harmonizing the stomach	Guipi Tang

Common heat-clearing and toxin-resolving Chinese patented medicines used for the treatment of erosive gastritis are shown in Table 2.

Table 2 Efficacy and mechanisms of action of heat-clearing and toxin-resolving Chinese patent medicines in the treatment of erosive gastritis.

Drug name	Main ingredients	Efficacy	Action mechanisms	Dosage and duration
Kuidekang Granules[43]	Coptis chinensis, Taraxacum mongolicum, Sophora flavescens, Notoginseng, Astragalus membranaceus, Zhejiang Fritillaria, Bletilla striata, etc.	Clearing heat, harmonizing the stomach, neutralizing acid, and relieving pain[44]	Anti-inflammatory, protect the gastric mucosa, inhibit gastric acid secretion, and regulate gastrointestinal function	10 g per dose, three times daily, for 4-8 weeks
Kangfuxin Liquid[45]	Ethanol extract of dried Periplaneta americana	Promoting blood circulation and nourishing yin to generate tissue	Promote gastric mucosa repair, inhibit inflammatory responses, improve gastric mucosa microcirculation, and regulate immune function	10 mL per dose, three times daily, for 4-6 weeks
Sanjiu Weitai Granules[46]	Evodia lepta, Murraya exotica, Zanthoxylum nitidum, Aucklandia lappa, Scutellaria baicalensis, Poria cocos, Rehmannia glutinosa, Paeonia lactiflora, etc.	Clearing heat, drying dampness, promoting qi, activating blood, soothing the liver, and relieving pain	Inhibit gastric acid secretion, reduce gastric mucosa inflammation, and protect the gastric mucosa barrier	1 bag (15 g) per dose, three times daily, for 4-6 weeks
Weikangling Capsules[47]	Paeonia lactiflora, Bletilla striata, Glycyrrhiza uralensis, Poria cocos, Corydalis yanhusuo, Sepiellae seu Sepiae Endoconcha, Notoginseng radix, Belladonna extract, etc.	Soothing the liver, harmonizing the stomach, dispersing blood stasis, and relieving pain immediately	Inhibit gastric acid secretion, neutralize stomach acid, reduce the irritative effect of stomach acid on the erosive gastric mucosa, anti-inflammatory, and reduce swelling	4 capsules per dose, three times daily, for 4-8 weeks
Lanqin Oral Liquid[48]	Isatis indigotica, Scutellaria baicalensis, Gardenia jasminoides, Phellodendron amurense, Platycarya strobilacea	Clearing heat, detoxification, relieving sore throat, and reducing swelling	Regulate immunity, inhibit inflammatory factors, and reduce gastric mucosa inflammatory response	10 mL per dose, three times daily, for 4-6 weeks
Lianpu Shuangqing Tablets[49]	Berberine hydrochloride, Taraxacum mongolicum extract	Clearing heat, detoxification, drying dampness, and stopping dysentery	Inhibit various gastrointestinal pathogenic bacteria, reduce gastric mucosa inflammation, and promote gastric mucosa repair	4 tablets per dose, three times daily, for 4-6 weeks

Research on single TCMs and their active ingredients

The main components of Rhizoma coptidis[10] include alkaloids such as berberine and palmatine, among which berberine has the highest content and significant antibacterial, anti-inflammatory, and gastric mucosal protection effects. A previous study used berberine extract in the treatment of patients with erosive gastritis, and the results showed that the total effective rate of the treatment group was 90.0%, which was significantly higher than that of the control group (73.3%); the patients’ symptoms of gastric pain, gastric distension, belching, and acid reflux were significantly improved, and related symptoms, such as dry mouth, bitter taste of the mouth, and yellowish and greasy tongue coating among others, were also significantly improved[11]. Gastroscopy revealed that the gastric mucosal erosion and inflammation were significantly reduced. Further studies found that berberine inhibited the urease activity of H. pylori and reduced the production of ammonia, thus reducing the damage to the gastric mucosa and the inflammatory response of the gastric mucosa by inhibiting the inflammatory signaling pathway and reducing the expression and release of inflammatory factors[12].

The main components of Scutellaria baicalensis[10] include flavonoids such as baicalin, baicalein, and hanhuangqin. Scutellaria baicalensis has the effects of clearing heat and drying dampness, diarrhea, and detoxification; stopping bleeding; and tranquilizing the fetus. The main effects of Scutellaria baicalensis in the treatment of erosive gastritis are anti-inflammatory, antibacterial, and protective effects on the gastric mucosa. Baicalin and baicalein, the main active components of Scutellaria baicalensis, have significant anti-inflammatory effects, which can reduce the expression and release of inflammatory factors and reduce the inflammatory response of the gastric mucosa by inhibiting the NF-κB signaling pathway[13]. Meanwhile, Scutellaria baicalensis also has an inhibitory effect on bacteria, such as H. pylori, which can reduce the damage caused by bacterial infection to the gastric mucosa[14]. In addition, Scutellaria baicalensis promotes the proliferation and repair of gastric mucosal cells and enhances the barrier function of the gastric mucosa[15].

The primary components of honeysuckle include chlorogenic acid, isochlorogenic acid, lignans, and inositol[10]. Honeysuckle extract reduces the serum levels of PGE2 and histamine in animal models of inflammation and inhibits the infiltration of inflammatory cells, thus reducing the inflammatory response. In addition, honeysuckle can regulate inflammation-related signaling pathways, such as the mitogen-activated protein kinase (MAPK) signaling pathway[16], and inhibit the expression of inflammatory genes, further exerting anti-inflammatory effects. It can promote the proliferation and differentiation of immune cells, such as T-lymphocytes and B lymphocytes, and improve the immune response of the body[17]. In the treatment of erosive gastritis, honeysuckle promotes repair and healing of the gastric mucosa by regulating immune function and enhancing the body's defense abilities[18].

The main components of officinale[10] include taraxasterol, taraxacin, caffeic acid, and chlorogenic acid, and modern pharmacological studies have shown that Taraxacum officinale possesses a variety of pharmacological effects[19]. Taraxacum officinale (dandelion) enhances the activity of antioxidant enzymes such as superoxide dismutase (SOD) through its rich flavonoid content, effectively eliminating reactive oxygen species (ROS) and significantly reducing the damage caused by oxidative stress. In addition to directly scavenging ROS and enhancing the activity of antioxidant enzymes to alleviate oxidative stress, dandelion can also disrupt the vicious cycle of mutual exacerbation between oxidative stress and inflammation. This is achieved by modulating inflammatory signaling pathways, gut microbiota, and cytokine networks, thereby exerting its anti-inflammatory and immunomodulatory effects[20,21].

The main components of forsythia[10] include forsythia glycoside, forsythia ester glycoside A, rutin, and volatile oils. Forsythia is effective in clearing heat, removing toxins, subduing swelling, dispersing knots, and evacuating wind heat. Forsythia exerts anti-inflammatory, antibacterial, and antiviral effects in erosive gastritis. Forsythia glycoside and forsythia ester glycoside A have anti-inflammatory activities that can reduce the inflammatory reaction in the gastric mucosa by inhibiting the activity of inflammation-related enzymes and reducing the synthesis of inflammatory mediators. Forsythia has an inhibitory effect on a variety of bacteria and viruses, such as Staphylococcus aureus, Escherichia coli, and influenza virus, which can reduce damage to the gastric mucosa caused by pathogen infections. In addition, by scavenging free radicals in the body and protecting the gastric mucosa from oxidative damage, forsythia shows antioxidant effects[22].

The main components of Radix et Rhizoma Ginseng[10] include Radix et Rhizoma Ginseng alkaloids, sophocarpine, Radix et Rhizoma Ginseng flavonoids, isoflavonoids, and Radix et Rhizoma Ginseng polysaccharides. Bitter ginseng flavonoid components can reduce the activity of inflammation-related enzymes such as COX-2, which catalyzes the generation of inflammatory mediators such as prostaglandins from arachidonic acid, and bitter ginseng flavonoids inhibit their activity[23], which in turn reduces the generation of inflammatory mediators and exerts anti-inflammatory effects[24]. Several studies have shown[25] that bitter ginseng polysaccharides can promote the secretion of mucus by gastric mucosal cells and increase the thickness of the mucus layer, which can isolate the erosion of the gastric mucosa by gastric acid and pepsin and play a physical protective role. The active ingredients in bitter ginseng can also upregulate the expression of tight junction proteins, such as occludin and ZO-1, in gastric mucosal cells. These proteins are essential for maintaining the tight junctions of gastric mucosal epithelial cells, can enhance the barrier function of the gastric mucosa, and prevent the invasion of harmful substances into the gastric mucosal tissues[26].

Antipyretic and detoxifying TCMs have shown significant therapeutic effects in the treatment of erosive gastritis. However, their cold and cool components may lead to gastrointestinal discomfort and liver function impairment. Therefore, when using these herbs, it is essential to control the dosage strictly, avoid excessive or long-term use, and monitor liver function regularly to ensure medication safety. Moreover, it is crucial to follow the principles of TCM syndrome differentiation and treatment, adjusting the dosage according to the specific conditions of the patient.

Common heat-clearing and detoxifying TCM s used to treat erosive gastritis are listed in Table 3.

Table 3 Efficacy and mechanisms of action of heat-clearing and detoxifying traditional Chinese medicines and their active ingredients in the treatment of erosive gastritis.

Herbs	Main ingredients	Efficacy	Action mechanisms	Common dosage (g)
Coptis chinensis[12]	Berberine, coptisine, etc.	Clearing heat, drying dampness, purging fire, and detoxification	Inhibit inflammatory signaling pathways, reduce the release of inflammatory factors, regulate gastric acid secretion, and protect the gastric mucosa	2-5
Scutellaria baicalensis[15]	Baicalin, baicalein, wogonin, etc.	Clearing heat, drying dampness, cooling blood, and detoxification	Inhibit the production of inflammatory mediators, exert antioxidant effects, scavenge free radicals, and alleviate oxidative damage to the gastric mucosa	3-9
Lonicera japonica[18]	Chlorogenic acid, luteolin, neochlorogenic acid, etc.	Clearing heat, detoxification, and dispersing wind-heat	Antioxidant, reduce free radical damage; luteolin inhibits inflammation and regulates immunity	10-15
Taraxacum mongolicum[21]	Taraxasterol, taraxacum saponins, etc.	Clearing heat, detoxification, reducing swelling, and dispersing nodules	Anti-inflammatory, reduce gastric mucosal congestion and edema, and promote digestion and absorption	10-15
Sophora flavescens[26]	Matrine, oxymatrine, etc.	Clearing heat, drying dampness, killing parasites, and promoting diuresis	Inhibit the infiltration of inflammatory cells and the release of inflammatory mediators, regulate immunity, and enhance resistance	3-9
Hedyotis diffusa[50]	Flavonoids, terpenoids, anthraquinones, etc.	Clearing heat, detoxification, promoting diuresis, and relieving stranguria	Antioxidant, protect gastric mucosal cells; regulate immunity; inhibit inflammatory responses; and promote gastric mucosal repair[51]	15-30
Isatis indigotica[52]	Indirubin, indigo, polysaccharides, etc.[10]	Clearing heat, detoxification, cooling blood, and relieving sore throat	Anti-inflammatory and antibacterial, regulate immunity, enhance antiviral and repair capabilities[53]	10-15
Patrinia scabiosaefolia[54]	Patrinoside, volatile oils, etc.	Clearing heat, detoxification, removing blood stasis, and discharging pus.	Anti-inflammatory and antibacterial, promote gastric mucosal repair, and regulate gastrointestinal function[55]	10-15

ACTION MECHANISMS OF HEAT-CLEARING AND TOXIN-RESOLVING CHINESE MEDICINES IN THE TREATMENT OF EROSIVE GASTRITIS

Killing or inhibiting H. pylori

H. pylori infection is a major cause of erosive gastritis. It is present in approximately 70%-90% of patients with chronic gastritis and is more prevalent in those with erosive gastritis. Various components of heat-clearing and detoxifying herbs and detoxifying drugs have significant inhibitory effects on H. pylori. Berberine in Huanglian is the main antibacterial active ingredient, and berberine can inhibit the growth and reproduction of H. pylori by disrupting its metabolic processes and destroying its cell wall and cell membrane structure[27]. In an in vitro experiment, different concentrations of berberine were applied to H. pylori[28]. The growth of H. pylori was significantly inhibited with an increase in berberine concentration; its minimum inhibitory concentration (MIC) could be up to 0.125-0.5 mg/mL. This suggests that berberine has strong inhibitory activity against H. pylori, can effectively reduce the colonization of H. pylori in the gastric mucosa, and can alleviate the inflammatory response. Baicalin and baicalin in Scutellaria baicalensis also have antibacterial and therapeutic effects against gastritis and gastric ulcers caused by H. pylori infection. Baicalein can inhibit the urease activity of H. pylori, which is the key enzyme for the survival and pathogenicity of H. pylori. It can decompose urea to produce ammonia, neutralize gastric acid, and create a suitable environment for the survival of H. pylori. By inhibiting urease activity, baicalein destroys the survival environment of H. pylori, thereby inhibiting its growth. In addition, baicalein has anti-inflammatory and antioxidant effects, which can reduce gastric mucosal inflammation and oxidative stress damage caused by H. pylori infection. Chlorogenic acid and lignans in honeysuckle have inhibitory effects on a variety of pathogenic bacteria. Although erosive gastritis is mainly associated with H. pylori infection, infection by other pathogenic bacteria may also aggravate the condition. The antimicrobial effect of honeysuckle can effectively prevent and control infection by other pathogenic bacteria and create a favorable environment for the repair of the gastric mucosa. Honeysuckle extract had an obvious inhibitory effect on the growth of common pathogenic bacteria such as Staphylococcus aureus and Escherichia coli. Its antibacterial mechanism mainly involves the inhibition of bacterial protein synthesis and nucleic acid metabolism, which interferes with the normal growth and reproduction of bacteria. In recent years, with the increasing prevalence of drug resistance in H. pylori, the application of antipyretic and detoxifying TCMs in treating H. pylori infection has attracted significant attention. For example, Coptis chinensis (Huanglian) contains berberine as its main active component, which has a remarkable antibacterial effect against H. pylori, with an MIC of 12.5 mg/mL. Berberine can also reduce the pathogenicity of H. pylori by inhibiting urease activity. Moreover, Coptis chinensis may decrease drug resistance by modulating the expression of efflux pump genes; however, there is currently limited research data on whether long-term use of Coptis chinensis could lead to gene mutations in H. pylori. Therefore, long-term clinical trials are needed in the future to monitor changes in drug resistance and to evaluate its safety and efficacy comprehensively[29,30].

Reducing inflammatory reaction

In addition to their direct inhibitory effects on H. pylori, heat-clearing and detoxifying herbs can also mitigate inflammatory responses, which are crucial components in the pathogenesis of erosive gastritis. Under the stimulation of inflammation, the gastric mucosa may exhibit pathological changes, such as congestion, edema, and erosion. The main component of Huanglian, berberine, has demonstrated significant potential in inhibiting the inflammatory response induced by H. pylori. Research has shown that berberine significantly alleviates chronic atrophic gastritis induced by H. pylori through the inhibition of the IRF8-IFN-γ signaling axis[31]. The underlying mechanisms include reducing the levels of inflammatory cytokines (such as IL-17, CXCL1, and CXCL9) in the serum, upregulating the expression of gastrin-17, inhibiting the expression of IRF8 and genes related to the IFN-γ signaling pathway, decreasing the release of inflammatory cytokines, and improving the function of gastric mucosal cells, thereby exhibiting significant anti-inflammatory and antibacterial potential. Furthermore, N4BP3 plays a key role in the inflammatory response by promoting K48-linked ubiquitination of IκBα, thereby activating the TLR4-NF-κB signaling pathway. Similarly, SAA1 significantly induces the secretion of inflammatory cytokines by activating this pathway, thereby exacerbating the inflammatory response[32,33]. The active components in heat-clearing and detoxifying herbs such as honeysuckle (Lonicera japonica) and forsythia (Forsythia suspensa) (e.g., chlorogenic acid and forsythoside) can inhibit the release of inflammatory mediators (such as TNF-α and IL-6), thereby alleviating the inflammatory response in erosive gastritis. These components work by inhibiting the NF-κB signaling pathway, reducing the expression of inflammatory genes, and exhibiting antioxidant effects. They enhance the activity of SOD and glutathione peroxidase and decrease the content of malondialdehyde, thus protecting the gastric mucosa. In addition, they can inhibit the growth of H. pylori and promote the repair of the gastric mucosa, demonstrating multi-target and multi-pathway antibacterial and anti-inflammatory effects. This provides an effective strategy for the treatment of erosive gastritis.

Protecting gastric mucosa

The gastric mucosal barrier is a crucial defense mechanism that protects the gastric mucosa from damage caused by harmful substances such as gastric acid, pepsin, and bacteria. Heat-clearing and detoxifying herbs can enhance the function of the gastric mucosal barrier through multiple pathways and promote the repair and regeneration of gastric mucosal cells, thereby protecting the gastric mucosa and treating erosive gastritis. Berberine in Coptis chinensis can promote the proliferation and migration of gastric mucosal cells and enhance the barrier function of the gastric mucosa. Studies have found that berberine can upregulate the expression of tight junction proteins such as ZO-1 and occludin in gastric mucosal cells, strengthen intercellular tight junctions, as well as reduce the permeation of harmful substances such as gastric acid and pepsin into the gastric mucosa[34]. Heat-clearing and detoxifying herbs can also promote the secretion of mucus from the gastric mucosa and enhance the barrier function of the gastric mucosa. The mucus layer is an important protective structure of the gastric mucosa, which can isolate gastric acid and pepsin and reduce their damage to the gastric mucosa. Baicalin in Scutellaria baicalensis can stimulate gastric mucosal cells to secrete mucus and increase the thickness of the mucus layer. Baicalin can upregulate the expression of mucin genes in gastric mucosal cells and promote the synthesis and secretion of mucin, thereby enhancing the barrier function of the gastric mucosa. In addition, glycyrrhizic acid in licorice also has a similar effect[35]. It can promote the secretion of PGE2 from gastric mucosal cells, and PGE2 can stimulate the secretion of mucus and bicarbonate, further enhancing the protective effect of the gastric mucosa.

Inhibiting gastric acid secretion

Taraxasterol, a compound found in dandelion (Taraxacum mongolicum), can inhibit gastric acid secretion. Studies have shown that taraxasterol can act on gastric mucosal cells, modulate intracellular signaling pathways, and inhibit the activity of enzymes and ion channels related to gastric acid secretion, thereby reducing the secretion of gastric acid[36]. In animal experiments, rats with excessive gastric acid secretion were administered dandelion extract by gavage, and the content of gastric acid in the gastric juice of the rats was significantly reduced, along with a decrease in pepsin activity. This indicates that dandelion, by inhibiting gastric acid secretion, alleviates the damage caused by gastric acid to the gastric mucosa and has a certain therapeutic effect on erosive gastritis[37].

Regulating gastrointestinal hormones

Heat-clearing and detoxifying herbs can indirectly inhibit gastric acid secretion by regulating the neuroendocrine system. The secretory function of the stomach is finely regulated by the neuroendocrine system. Gastrin, an important hormone, promotes gastric acid secretion, while somatostatin has an inhibitory effect on it. Berberine, found in Huanglian, can regulate the secretion of gastrin and somatostatin and reduce gastrin levels while increasing the secretion of somatostatin, thereby decreasing gastric acid secretion. After experimental animals were injected with berberine, the levels of gastrin in their blood decreased, those of somatostatin increased, and the secretion of gastric acid in the gastric juice was significantly reduced[38]. This indicates that Coptis chinensis effectively inhibits gastric acid secretion by regulating the neuroendocrine system, which helps alleviate the symptoms of patients with erosive gastritis.

Heat-clearing and detoxifying herbs can work synergistically with other drugs to enhance the effect of inhibit gastric acid secretion. A study that included 35 research projects covering 4667 patients conducted an in-depth analysis of the therapeutic effects of 11 traditional Chinese patent medicines combined with Western medicine in treating H. pylori infection. The study found that the combination of traditional Chinese patent medicines and Western medicine showed remarkable performance in improving eradication rates, reducing adverse reactions, and alleviating symptoms, significantly outperforming Western medicine alone. In particular, the combination of heat-clearing and detoxifying traditional Chinese patent medicines with proton pump inhibitors demonstrated significant clinical advantages. Systematic reviews and meta-analyses further confirmed that the integration of traditional Chinese and Western medicine has significant effects in increasing H. pylori eradication rates and reducing adverse reactions. More high-quality RCTs are needed to validate these findings further and explore their mechanisms of action in depth[39,40].

Regulating immune function

Heat-clearing and detoxifying TCMs exert immunomodulatory effects by regulating the balance of Treg/Th17 cells and the gut microbiota through multiple pathways. The mechanisms mainly include the following aspects: These TCMs directly regulate T-cell differentiation, promoting the development of Treg cells and inhibiting the differentiation of Th17 cells. Meanwhile, they modulate the cytokine network by reducing the levels of pro-inflammatory cytokines (such as IL-6, IL-23, TNF-α) and increasing the levels of anti-inflammatory cytokines (such as IL-10, TGF-β), thereby maintaining the balance of Treg/Th17 cells. Additionally, they regulate the structure of the gut microbiota, increasing the proportion of beneficial bacteria (such as Bifidobacterium and Lactobacillus) and reducing the number of harmful bacteria (such as Escherichia coli and Enterobacter). They also regulate the metabolic products of microbiota by increasing the levels of short-chain fatty acids. Through the interaction between the gut microbiota and immune cells and their immunomodulatory effects, they indirectly influence the balance of Treg/Th17 cells. In addition, heat-clearing and detoxifying TCMs inhibit inflammatory signaling pathways (such as NF-κB and MAPK), improve the structure of the gut microbiota, and significantly reduce inflammatory responses. They demonstrate strong immunomodulatory potential, providing new strategies for the treatment of chronic inflammatory diseases[41,42].

CONCLUSION

In summary, erosive gastritis is often triggered by the pathogenic factor of “toxic heat”, characterized by gastric mucosal erosion and inflammation. Clinical studies have shown that compound prescriptions such as Qingwei San and Banxia Xiexin Tang can improve symptoms and repair the gastric mucosa. Individual herbs like Huanglian and Taraxacum mongolicum (Pugongying), as well as traditional Chinese patent medicines like Kaidikang Granules, are also highly effective. The mechanisms of action of heat-clearing and detoxifying TCM compound prescriptions, patent medicines, and individual herbs mainly include inhibiting H. pylori, reducing inflammatory responses, protecting the gastric mucosa, regulating gastric acid secretion, and modulating immune function. These therapeutic effects are achieved through multi-level and multi-target actions. Future research should focus on exploring the associations between specific microRNAs and the therapeutic effects of heat-clearing and detoxifying TCMs, with the aim of identifying biomarkers that can predict treatment responses and thereby promote the development of personalized treatment plans, as well as the role that the gut microbiota plays in inflammation and immune regulation. The use of heat-clearing and detoxifying TCMs in combination with probiotics may further enhance therapeutic efficacy by modulating the gut microbiota. Heat-clearing and detoxifying TCMs have significant advantages in the treatment of this disease. Therefore, it is necessary to continue exploring integrated traditional Chinese and Western medicine treatment models to organically combine heat-clearing and detoxifying medicines with Western medical treatments, and to complement each other's strengths in order to enhance the therapeutic effect of erosive gastritis and provide a new pathway for the development of more efficient and safer drugs.