Potential of traditional Chinese medicine in gastrointestinal disorders: Hericium erinaceus in chronic atrophic gastritis

Abstract

Traditional Chinese medicine (TCM) has been extensively explored with various naturally derived compounds as a potential therapeutic agent for chronic atrophic gastritis (CAG). In addition to the aspects discussed in the reviewed article, this invited commentary explores the initial available evidence on a fungus from TCM, Hericium erinaceus, in the context of CAG. Initial clinical data suggest the potential of this fungus in inducing clinical and histological improvements in patients with CAG, as well as a marked antimicrobial activity against Helicobacter pylori infection. Preclinical cellular evidence also indicates an antineoplastic role in gastric carcinogenesis, mediated by two components: Erinacine A and S. Further evidence is needed to propose this fungus as a potential complementary therapeutic approach for CAG.

Key Words: Traditional Chinese medicine; Chronic atrophic gastritis; Hericium erinaceus; Gastrointestinal disorders; Helicobacter pylori

Core Tip: Hericium erinaceus, a medicinal fungus in traditional Chinese medicine, has shown potential in chronic atrophic gastritis. Evidence suggests its anti-inflammatory, anti-Helicobacter pylori, and antineoplastic effects against gastric cancer, underlining its possible role as a complementary therapeutic option for gastrointestinal disorders, including gastric cancer prevention.

TO THE EDITOR

We have read with keen scientific interest the review entitled "Traditional Chinese Medicine for chronic atrophic gastritis: Efficacy, mechanisms and targets" by Wang et al[1], which examined the available evidence on the use of traditional Chinese medicine (TCM) approaches for the treatment of chronic atrophic gastritis (CAG). While commending the authors for their work, we believe there is still room for discussion regarding another component of TCM that was not included in their analysis. Specifically, we refer to the fungus Hericium erinaceus (H. erinaceus), for which some evidence related to CAG is available. We therefore take this invited letter as an opportunity to further expand on the discussion of this review by focusing on this basidiomycete of TCM. Our recent research demonstrated how H. erinaceus represents a promising tool in TCM as a gastrointestinal anti-inflammatory agent, particularly in models of chronic bowel inflammation[2,3]. The specifications of the fungus are presented in Table 1[2].

Table 1 General information on the Hericium erinaceus mushroom.

Parameter	Description
Phylum	Basidiomycota
Subphylum	Agaricomycotina
Class	Agaricomycetes
Order	Russulales
Family	Hericiaceae
Genre	Hericium
Species	Erinaceus
Common names	Lion’s Mane, Yamabushitake, Bearded Tooth Mushroom
Habitat	Deciduous forests, typically growing on hardwood trees such as oak, beech, and maple
Morphology	White, cascading spines resembling a lion’s mane, with a soft, fibrous texture

H. ERINACEUS AND CAG: WHAT EVIDENCE IS AVAILABLE?

CAG entirely fits within the described Correa cascade, which leads to progressive pathological changes affecting the gastric mucosa and ultimately results in the development of gastric carcinogenesis[4]. According to this model, a chronic inflammatory process in the stomach gives rise to chronic gastritis (triggered by various etiologies such as autoimmune mechanisms, Helicobacter pylori (H. pylori) infection, or chemical irritants like cigarette smoke), which progresses to CAG[4]. On this background, intestinal metaplasia develops, serving as the precursor to dysplasia, ultimately culminating in cancer[4].

Data on the potential of H. erinaceus in CAG has been available since the 1980s, with a study by Xu et al[5] reporting findings from a double-blind trial involving fifty patients with a histological diagnosis of CAG. The patients were randomly assigned in a 1:1 ratio to receive an oral supplement of H. erinaceus or a placebo and underwent gastric acidity analysis and gastroscopy after three months of treatment. The results showed that 63% of patients in the treatment group experienced a significant improvement in upper abdominal pain compared to 36% in the placebo group. This improvement was accompanied by endoscopic enhancements in 52% of treated patients vs 8% in the placebo group. Histological analysis also recorded improvements in dysplastic changes and inflammatory infiltrates in the treated group compared to the placebo. Later, Wang et al[6] used a polysaccharide, EP-1, extracted from the mycelium of H. erinaceus, demonstrating its inhibitory effect on the proliferation of MC cells (i.e., a cellular model of gastric atrophy) by arresting them in the G₀/G₁ phase of the cell cycle in a dose-dependent manner, ranging from 0.5 to 4 mg/mL of the substance used.

A further study by Gao et al[7] identified an additional polysaccharide from the cultivated mycelium of H. erinaceus(i.e., Hep-2), obtained through ultrafiltration, which was shown to reduce hydrogen peroxide-induced damage in cell models using the Cellosaurus cell line (i.e., GES-1), a cellular model also employed in studies on atrophic gastritis[8]. This effect appears to occur through the reduction of B-cell lymphoma 2/Bcl-2-associated X protein-mediated apoptosis and the induction of the expression of superoxide dismutase and glutathione peroxidase[7], which are well-known scavengers of oxygen free radicals, thereby demonstrating its evident antioxidant activity, in line with the established role of oxidative stress in the pathogenesis and progression of CAG[9,10].

H. ERINACEUS: HOW CAN IT INTERFERE WITH H. PYLORI AND GASTRIC CANCER?

H. pylori infection is highly prevalent, affecting approximately half the global population[11,12]. H. pylori-associated CAG results from sustained chronic inflammation, which induces atrophic damage to the gastric mucosa through the bacterium’s activation of innate immunity and, subsequently, adaptive immunity[13]. This process produces pro-inflammatory cytokines such as interleukin-1β and tumor necrosis factor-alpha, which promote atrophic damage[13]. Moreover, this bacterium can induce DNA damage through oxidative stress and epigenetic modifications by hypermethylation of tumor suppressor genes[13]. Altogether, these mechanisms contribute to an increased risk of gastric carcinogenesis[14,15]. This is indeed the reason why this bacterium has been classified as a Group 1 carcinogen for gastric cancer by the International Agency for Research on Cancer[16]. This necessitates prompt eradication, generally through a combination of multiple antibiotics and acid-suppressive drugs (such as proton pump inhibitors), as recommended by leading international guidelines[17,18]. However, these therapies are associated with a certain risk of adverse events, making studying natural substances highly desirable.

Various classes of compounds derived from H. erinaceus have demonstrated anti-H. pylori activity profiles[19-21], as we have shown in a narrative review[2]. Various minimum inhibitory concentrations have been reported for these compounds, ranging from 1.25 for culture filtrate-derived ethyl acetate fractions, as demonstrated by Thi My Ngan et al[19], to 400 for fractions II-64-78 (425.400 mg), as described by Liu et al[20]. However, this range of minimum inhibitory concentration is the result of different studies conducted under varying experimental conditions, with different compounds used as references for the calculation (i.e., colloidal bismuth subcitrate, metronidazole, tetracycline, or amoxicillin were employed)[2].

Additionally, H. erinaceus exhibits antineoplastic potential for gastric cancer, fundamentally summarized in Figure 1 and primarily mediated by two components, erinacines S and A[22,23].

Figure 1 Antineoplastic mechanisms of Hericium erinaceus erinacines against gastric cancer. Erinacine S has been shown in cellular models to induce a specific pathway through reactive oxygen species, leading to the phosphorylation of focal adhesion kinases (FAK)/protein kinase B, also known as AKT, as well as p21-activated kinase 1 (PAK1). This pathway promotes histone H3 trimethylation, facilitating the production of various molecules, including the TNF-related apoptosis-inducing ligand and Fas ligand receptors, which trigger the apoptotic cascade mediated by caspases 3, 8, and 9. Similarly, in gastric cancer cell models, erinacine A modulation of the FAK/AKT/PAK1 pathway can regulate two key proteins: Microtubule-associated scaffold protein 2 and the 14-3-3 sigma protein. This modulation negatively influences cell cycle regulation, particularly in the G2 and M phases. ROS: Reactive oxygen species.

CONCLUSION

In conclusion, in addition to what has already been discussed in the review by Wang et al[1], there is also some interesting evidence regarding H. erinaceus within the context of TCM for CAG. Further work, however, is still necessary to deepen the understanding of its pathophysiological and dynamic-mechanistic mechanisms and explore its translational potential at the clinical level. In particular, given that the available studies are predominantly preclinical and often limited to cellular models, there is a mandatory need to investigate the pathophysiological and dynamic mechanisms through which H. erinaceus may act in the pathogenesis of CAG in in vivo models. Moreover, considering that clinical data already exist on H. erinaceus-based products, it would be interesting to explore their effects on CAG from a clinical standpoint. For instance, our research group has demonstrated that a combination compound based on H. erinaceus significantly improved clinical remission rates in symptomatic uncomplicated diverticular disease[24] and ulcerative colitis[3], with a concomitant reduction in intestinal inflammatory burden (i.e., faecal calprotectin), suggesting marked anti-inflammatory properties of this basidiomycete.

All this, in our view, points towards an intriguing perspective of nutraceutical integration, given the promising potential of natural compounds, which, due to their intrinsic nature, are generally associated with a more favourable safety profile compared to conventional pharmacological therapies. This is particularly relevant in light of this specific pathology's repeatedly postulated nutraceutical potential[25–27].