Clinical efficacy and mechanism of Bletilla striata and Chinese herbal compounds in treatment of peptic ulcer

Abstract

Peptic ulcer (PU) is characterized by inflammation, necrosis, and erosion of the gastrointestinal mucosa caused by various pathogenic factors, leading to ulcer formation. The stomach and duodenum are the most commonly affected sites. Bletilla striata, a traditional Chinese medicinal herb, contains diverse chemical constituents and exhibits multiple pharmacological effects. As a key component in various traditional Chinese medicine compound formulations, it has demonstrated notable clinical efficacy. Moreover, it has a solid research foundation and broad application prospects in the treatment of gastrointestinal diseases. This paper systematically elaborates on the clinical efficacy and mechanisms of action of Bletilla striata in the treatment of PUs, drawing from ancient medical literature and traditional formula applications to provide support for clinical use.

Key Words: Bletilla striata; Related traditional Chinese medicine compound formulations; Peptic ulcer; Mechanism of action; Clinical efficacy

Core Tip: Bletilla striata has shown notable effects in the treatment of peptic ulcers. Clinical studies indicate that it can not only alleviate ulcer symptoms but also promote ulcer healing and enhance patients’ quality of life. The mechanisms of action of Bletilla striata and its traditional Chinese medicine compound formulations require further investigation and are believed to involve multiple processes, including anti-inflammatory activity, antioxidant effects, and promotion of gastric mucosal repair.

INTRODUCTION

This paper aims to systematically review the clinical efficacy and mechanisms of action of Bletilla striata in the treatment of peptic ulcers (PUs), drawing on evidence from both ancient medical literature and contemporary compound formulations. By exploring these aspects, the study seeks to provide a robust foundation for the clinical application of Bletilla striata in gastrointestinal disorders, emphasizing its potential as a valuable therapeutic agent.

PU is a pathological condition characterized by inflammatory reactions, necrosis, and erosion of the gastrointestinal mucosa caused by various pathogenic factors. These processes lead to ulcer formation, which may penetrate the muscularis mucosae, muscularis propria, or even the serosa. Lesions can occur in the esophagus, stomach, or duodenum, as well as near the gastrojejunal anastomosis or within Meckel’s diverticulum containing gastric mucosa, with the stomach and duodenum being the most commonly affected sites[1,2]. Clinically, the disease presents with an insidious onset and a chronic, protracted course. Epigastric pain typically displays periodicity and rhythmicity and is often accompanied by acid regurgitation, belching, and localized tenderness in the epigastric region. In traditional Chinese medicine (TCM), this condition corresponds to the diagnostic categories of epigastric pain (weitong in Chinese), gastric upset (caoza in Chinese), and gastric ulcer (GU; weiyang in Chinese)[3].

Xiao and Zhou[4], a National Master of Chinese Medicine, proposed—based on the clinical manifestations and endoscopic morphological features of active PUs—that these presentations closely resemble the "redness, swelling, heat, and pain" associated with external abscesses (waiyong). Consequently, he classified this condition as an internal abscess (neiyong) and named it "stomach abscess" (weiyong). Ji et al[5] developed the "toxic-heat etiology" theory, identifying "stomach toxic-heat syndrome" as the fundamental pathological pattern. He adopted the principle of "treating it as an abscess" and applied the therapeutic strategy of "clearing heat and detoxifying, eliminating necrotic tissue, and promoting tissue regeneration," which has demonstrated favorable clinical outcomes. Among the therapeutic agents used, Bletilla striata is primarily indicated for malignant sores and abscesses. It is especially valued for its effects in resolving abscesses and promoting tissue regeneration, making it an indispensable herb in clinical practice.

BLETILLA STRIATA AND RELATED COMPOUND FORMULATIONS, CHEMICAL COMPOSITION

Historical records of Bletilla striata in classical Chinese medical texts

Bletilla striata (Chinese: Baiji), the dried tuber of the orchid species Bletilla striata (Thunb.) Rchb.f.[6], is a perennial terrestrial herb belonging to the family Orchidaceae. It is also known as Baiji Zi or Baiji Fen and is primarily distributed in the humid mountainous regions of southwestern China—including Sichuan, Yunnan, and Guizhou provinces—with smaller populations found in Anhui, Zhejiang, and Jiangsu provinces along the southeastern coast[7]. Its medicinal use was first recorded in Shennong’s Classic of Materia Medica[8], where it was classified as a lower-grade herb: “Bletilla striata has a bitter and neutral nature; it treats abscesses, malignant sores, necrotic ulcers, damaged yin, dead tissue, and pathogenic factors in the stomach. It also addresses wind-induced injuries and paralysis. Alternate names include Gan Gen and Lian Ji Cao. It grows in valleys”. This early record briefly outlined its properties, therapeutic indications, aliases, and habitat. Subsequent herbal texts have primarily referred to it as Bai Ji, a name that has remained in common use. The Compendium of Materia Medica[9] from the Ming Dynasty noted, “Its roots are white and grow interconnected, hence the name Bai Ji (white connection)”. Bletilla striata is slightly cold in nature, and bitter, sweet, and astringent in taste. It enters the lung, liver, and stomach meridians. It functions to astringe bleeding, reduce swelling, and promote tissue regeneration. It is commonly used to treat traumatic bleeding, hematemesis, hemoptysis, sores, ulcers, and skin fissures, demonstrating broad clinical utility[10]. Huang’s[11] Bencao Qiuzhen (Truth of Materia Medica, 1769) from the Qing dynasty further noted that Bletilla striata “not only arrests pulmonary bleeding but also treats traumatic fractures, burns and scalds, malignant sores and abscesses, and resolves gangrenous tissues or necrotic muscles”.

Ancient records of Bletilla striata (Baiji) in TCM formulations

Bletilla striata serves as the sovereign herb (Jun Yao) in numerous TCM formulas. It is primarily indicated for ulcerative sores, hematologic disorders, and related conditions. Representative formulations containing Bletilla striata are summarized in Table 1.

Table 1 Bletilla striata-sovereign herbal compound formulations.

Formula name	Composition	Source	Actions and indications
Bletilla striata Powder (Baiji San)	Bletilla striata, Ampelopsis japonica, Os Sepiae, Salvia chinensis, Scutellaria baicalensis, Os Draconis	Volume 290, Puji Fang (Universal Relief Manual), Ming Dynasty	Promotes tissue regeneration, alleviates pain, stops bleeding, closes ulcerations, and dispels pathogenic wind. Indicated for abscesses, boils, sores, and toxic-heat lesions[37]
Bletilla striata Ointment (Baiji Gao)	Bletilla striata, Alpinia officinarum, asphalt	Volume 314, Puji Fang (Universal Relief Manual), Ming Dynasty	Treats furuncles[37]
Baiji Pipa Wan	Bletilla striata, loquat leaf, lotus node	Classified Prescriptions from Standards for Diagnosis and Treatment, Vol 3, Ming Dynasty (Dai's formulas)	Treats hemoptysis[38]
Baiji Lianhua San	Bletilla striata, lotus stamen, Platycladus orientalis leaf, Adenophora stricta	Classified Prescriptions from Standards for Diagnosis and Treatment, Vol 3, Ming Dynasty (Dai's formulas)	Treats hemoptysis[38]
Baiji Xionghuang San	Bletilla striata, realgar	Volume 10, Dongtian Ao Zhi (Mysterious Revelations of the Heavenly Abode), Qing Dynasty	Treats neonatal skin lesions (tà pí chuāng) in infants, attributed to maternal excessive consumption of pungent, heat-inducing foods during pregnancy[39]
Baiji Tang	Bletilla striata, Rubia cordifolia, rehmannia, Moutan bark, Achyranthes bidentata, tangerine peel, Angelica sinensis tail	Ancient and Modern Comprehensive Medicine, Vol 2, Qing Dynasty	Sed for hematemesis due to internal injury[40]

Main chemical components and pharmacological activities of Bletilla striata

Modern research has shown that the principal chemical components of Bletilla striata include amino acids, spirostane-type steroidal saponins, stilbenes, bibenzyls, bis-phenanthrenes, carotenoids, dihydrophenanthrofurans, glycosides, phenanthrenes, anthraquinones, and others[12,13]. These compounds exhibit a wide range of pharmacological activities, including hemostatic effects, immunomodulatory functions, wound healing promotion, antibacterial properties, gastrointestinal mucosal repair, anti-inflammatory effects, antitumor activity, antioxidant capacity, anti-ulcer effects, hematopoietic stimulation, and antiviral activity[14-17].

Potential toxicity or drug interactions of Bletilla striata

In TCM theory, Bletilla striata is considered a relatively safe medicinal substance, commonly used for the treatment of malignant sores and abscesses, to stop bleeding through astringency, and to reduce swelling and promote tissue regeneration. There are no explicit records of toxicity associated with its traditional use. However, in classical Chinese pharmacology, the theory of the “Eighteen Incompatibilities” (Shiba Fanfan) notes an incompatibility between Bletilla striata and Aconite (Wutou). Modern research suggests that when Bletilla striata is co-administered with Aconite-based medicinal substances, it may inhibit hepatic drug-metabolizing enzymes such as CYP3A and CYP1A2. This inhibition can slow the metabolic clearance of aconitine, thereby increasing systemic exposure and enhancing toxicity[18]. Therefore, although Bletilla striata is generally safe when used at therapeutic doses, special attention must be paid to avoid its combination with Aconite-derived compounds to prevent adverse interactions.

MODERN RESEARCH ON THE CLINICAL EFFICACY OF BLETILLA STRIATA AND RELATED COMPOUND FORMULATIONS

Clinical efficacy of Bletilla striata monotherapy

The use of single-herb Bletilla striata powder in combination with conventional Western medicine for the treatment of PUs has demonstrated significant efficacy in inhibiting inflammation, promoting ulcer healing, reducing bleeding, and lowering recurrence rates. It is also employed as an adjunct in cancer therapy and in the management of dermatological conditions (Table 2).

Table 2 Clinical efficacy of Bletilla striata.

Drug combination	Clinical application	Specific effects	Supporting research
Bletilla striata powder combined with esomeprazole or omeprazole	Treatment of peptic ulcer	Inhibits inflammation, promotes ulcer healing, and reduces recurrence	Combination with proton pump inhibitors significantly enhances therapeutic efficacy[19,20]
Combined with rhubarb	Treatment of burns and scalds	Promotes wound contraction and tissue regeneration, and accelerates healing	Synergistic use enhances heat-clearing, detoxification, swelling reduction, and analgesic effects[41]
Ointments and gels containing Bletilla striata	Treatment of skin injuries	Used for chapped skin, acne, and other skin conditions. Demonstrates whitening, anti-inflammatory effects, and serves as an effective wound dressing	Bletilla striata-based topical preparations exhibit significant therapeutic efficacy in dermatological applications[42-44]
Bletilla striata polysaccharide	Antitumor, gastroprotective, and hemostatic effects	Exhibits adjuvant effects against various tumor types, reduces gastric ulcer index, enhances healing rate, and demonstrates significant hemostatic efficacy for pulmonary, gastric, and traumatic bleeding	Bletilla striata polysaccharides show antitumor activity, gastroprotective effects, shortened coagulation time, and enhanced platelet aggregation[45-48]
Other active components	Protection against acute lung injury	Demonstrates significant protective effects against LPS-induced lung injury by reducing neutrophil infiltration and downregulating pro-inflammatory cytokine expression	Bioactive extract EFBS of Bletilla striata exhibits potent anti-inflammatory activity in acute lung injury models[49,50]
Combined with Coptis chinensis and borneol	Other applications	Clinically used in the treatment of herpes zoster, pressure ulcers, and related conditions	Combination therapy enhances anti-inflammatory and analgesic outcomes[51,52]

LPS: Lipopolysaccharide; EFBS: Esophageal foreign body.

Wang et al[19] investigated the effects of Bletilla striata powder combined with esomeprazole on serum inflammatory factors, intestinal flora, and quality of life in patients with GU. The study included 70 patients in the control group and 80 in the observation group. The control group received esomeprazole monotherapy, while the observation group was treated with esomeprazole in combination with Bletilla striata powder. Outcomes compared between the two groups included total efficacy rate, levels of serum inflammatory markers, composition of intestinal flora, and quality of life metrics. After seven days of treatment, the observation group exhibited a significantly higher total efficacy rate than the control group. Serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8, and C-reactive protein were lower in the observation group. In addition, reductions were observed in the abundance of Enterobacteria, Enterococci, Staphylococci, and Bacteroides, alongside increased levels of Bifidobacteria. Furthermore, scores across all dimensions of the EuroQol 5-Dimension questionnaire were significantly higher in the observation group.

Wei and Ma[20] investigated the clinical efficacy of Bletilla striata combined with omeprazole (OME) in the treatment of GU. The study enrolled 34 patients in the treatment group and 34 in the control group. The control group received OME monotherapy, while the treatment group received OME plus 6 g of Bletilla striata powder, administered in capsules, in addition to the control regimen. After four weeks of treatment, the Helicobacter pylori (H. pylori) eradication rate in the treatment group was 16 cases (47.06%), compared with 6 cases (17.65%) in the control group. The eradication rate in the treatment group was significantly higher than in the control group. These findings suggest that the combination of Bletilla striata and OME demonstrates confirmed therapeutic efficacy in the treatment of GUs, particularly in enhancing H. pylori eradication.

Clinical efficacy of Bletilla striata compound formulations

Zhao[21] developed Huoxue Yuyang Granules, a compound formulation composed of multiple herbal ingredients including Bletilla striata, Dendrobium, Gynostemma pentaphyllum, Pseudostellariae Radix, Aucklandiae Radix, cuttlebone, Corydalis Rhizoma, Gallus gallus domesticus endothelium, Lilii Bulbus, Fritillaria thunbergii, Paederia scandens, Cynanchi paniculati Radix, Geranium wilfordii, Panax notoginseng, Angelica sinensis, Salvia miltiorrhiza, Curcuma phaeocaulis, and Glycyrrhizae Radix, among others. This formulation exhibits a range of therapeutic effects, including harmonizing the stomach and resolving blood stasis, analgesic and sedative actions, activating blood circulation and clearing heat, as well as tonifying qi (vital energy) and strengthening the spleen and stomach.

Studies have shown that, in a comparative analysis of the clinical efficacy of ranitidine, hydrotalcite tablets, and Huoxue Yuyang Granules, the study group treated with Huoxue Yuyang Granules demonstrated superior cure and overall effectiveness rates in patients with blood stasis-type GUs compared to the control group. The granule formulation effectively alleviated clinical symptoms such as gastric distension, epigastric pain, halitosis, anorexia, irritability, and bitter or dry mouth. It also improved patients’ quality of life, reduced recurrence rates, and showed no significant adverse drug reactions. In conclusion, Huoxue Yuyang Granules exhibit notable therapeutic efficacy in the treatment of blood stasis-type GUs.

Liu[22] conducted a randomized controlled trial to assess the clinical efficacy of integrating Sanqi Baiji Powder with standard quadruple therapy in the management of PUs. The study enrolled 100 patients with PU, who were equally assigned to two groups: A control group receiving quadruple therapy alone, and a combined treatment group receiving Sanqi Baiji Powder alongside quadruple therapy. Comparative analysis revealed that the combined treatment group achieved a significantly higher total efficacy rate (96.00%) compared to the control group (80.00%). Additionally, the integrated treatment group demonstrated significant reductions in symptom resolution time, ulcer healing duration, and length of hospital stay. These findings suggest that adjunctive use of Sanqi Baiji Powder enhances therapeutic outcomes, accelerates recovery, mitigates systemic inflammation, and improves patients’ quality of life. The study highlights the potential of this integrated approach as a promising clinical strategy for PU treatment.

Qin and Deng[23] conducted a comparative study to evaluate the therapeutic effects of the Zhuang medicine Yuyang Powder in the treatment of PU. In this randomized controlled trial, patients were assigned to two groups: One receiving Yuyang Powder—composed of Ilex rotunda, Panax notoginseng, Taraxacum mongolicum, Bletilla striata, Astragalus membranaceus, Sepiella maindroni, among others—and the other receiving conventional Western medications (OME capsules, clarithromycin tablets, and metronidazole tablets). Post-treatment evaluations included follow-up gastroscopy and H. pylori detection. The results revealed similar ulcer healing rates between the two groups, with total efficacy rates of 90% in the Yuyang Powder group and 87.5% in the control group. Notably, the H. pylori eradication rate was significantly higher in the Yuyang Powder group (95%) than in the control group (82.5%). These findings suggest that Yuyang Powder provides comparable ulcer-healing efficacy to conventional therapy while offering superior H. pylori clearance, supporting its potential as an effective alternative treatment for PUs.

Li et al[24] conducted a study to evaluate the clinical efficacy of Shugan Yuyang Decoction in the treatment of GU. The decoction includes stir-fried Bupleurum (Chaihu), White Peony Root (Baishao), Chinese Honeylocust Spine (Zaojiaoci), Trogopterus Dung (Wulingzhi), stir-fried Immature Bitter Orange (Zhishi), Bletilla Striata (Baiji), Chinese Angelica (Danggui), Cuttlefish Bone (Haipiaoxiao), and Astragalus (Huangqi). A total of 110 GU patients were randomly divided into an observation group and a control group. The observation group received Shugan Yuyang Decoction, while the control group was treated with conventional Western medications. The results demonstrated that the total effective rate in the observation group was 89.09%, significantly higher than the 72.73% observed in the control group. These findings indicate that Shugan Yuyang Decoction provides distinct therapeutic benefits for patients with GUs compared to Western treatments.

Chen et al[25] investigated the clinical efficacy of TCM in the treatment of H. pylori–positive PU and its anti-inflammatory effects on the gastric mucosa. Sixty patients with PU were randomly divided into a treatment group and a control group, with 30 patients in each group. The treatment group received a TCM decoction, while the control group was treated with conventional Western medication, including anti-H. pylori therapy. The TCM decoction consisted of the following herbs: Bletilla striata (10 g), Bupleurum (15 g), Paeonia lactiflora (12 g), Citrus reticulata (10 g), Pinellia ternata (10 g), Pseudostellaria heterophylla (15 g), Poria cocos (15 g), stir-fried Atractylodes macrocephala (15 g), Sepiella maindroni (15 g), and Glycyrrhiza uralensis (6 g). Mechanistically, Bletilla striata forms a thin film over ulcerated areas, covering the ulcer surface to provide a protective barrier. It stimulates granulation tissue proliferation at damaged sites, facilitating tissue repair and promoting ulcer healing. Bletilla striata and Sepiella maindroni act synergistically to form this protective layer, thereby alleviating mucosal inflammation, improving microcirculation, accelerating mucosal repair, and enhancing ulcer healing. These herbs exhibit multiple therapeutic actions, including astringing ulcers, protecting the mucosa, inhibiting gastric acid secretion, and promoting tissue regeneration, as shown in Table 3.

Table 3 Clinical efficacy of Bletilla striata compound formulations.

Ref.	Study focus	Herbal formula composition	Control group treatment	Research findings
Zhao et al[21]	Huoxue Yuyang Granule in treating gastric ulcers with stomach collateral blood stasis pattern	Bletilla striata, Dendrobium, Gynostemma pentaphyllum, Pseudostellaria heterophylla, Aucklandia lappa, Sepia esculenta, Corydalis yanhusuo, Gallus gallus domesticus, etc.	Ranitidine, hydrotalcite tablets	The treatment group exhibited significantly higher complete healing and total effectiveness rates than the control group, along with notable improvements in multiple clinical symptoms
Liu[22]	Treatment of peptic ulcers using Pseudo-ginseng Rhizoma Bletillae Powder combined with quadruple therapy	Bletilla striata, Panax notoginseng	Standard Western quadruple therapy	The integrated Chinese-Western treatment group achieved a higher total effectiveness rate, along with faster symptom resolution and ulcer healing, compared to the control group
Qin and Deng[23]	Treatment of peptic ulcer with Zhuang Yao Yuyang San	Ilex rotunda, Panax notoginseng, Taraxacum mongolicum, Bletilla striata, Astragalus membranaceus, Sepia esculenta, etc.	Omeprazole capsules, clarithromycin tablets, metronidazole tablets	The treatment group demonstrated a higher Helicobacter pylori eradication rate compared to the control group, with comparable ulcer healing efficacy
Li et al[24]	Use of Shugan Yuyang Decoction in managing gastric ulcers	Bletilla striata, stir-fried Bupleurum chinense, Paeonia lactiflora, Trogopterus dung, stir-fried Aurantii Fructus Immaturus, Angelica sinensis, etc.	Conventional Western medicine	The observation group showed a significantly higher overall effectiveness rate than the control group
Chen et al[25]	Clinical efficacy of traditional Chinese medicine for Helicobacter pylori-positive peptic ulcers	Bletilla striata, Bupleurum chinense, Paeonia lactiflora, Citrus reticulata, Pinellia ternata, Pseudostellaria heterophylla, Poria cocos, etc.	Anti-H. pylori agents and other conventional Western treatments	Bletilla striata forms a protective film over ulcers, reduces mucosal inflammation, improves microcirculation, accelerates mucosal repair, and promotes ulcer healing

Experimental study and mechanisms of action of Bletilla striata compounds in the treatment of PUs

Gao et al[26] investigated the therapeutic effects of Bletilla striata on aspirin-induced GUs in rats. Animals were randomly divided into a normal group, a model group, high-, medium-, and low-dose Bletilla striata groups, and a positive control group. Except for the normal group, all rats were administered aspirin solution intragastrically to induce GU formation. After eight weeks, the positive control group received OME via gavage, while the Bletilla striata dose groups were administered suspensions of Bletilla striata at the corresponding doses, also via gavage. After four weeks of treatment, the GU index of each group was evaluated. Hematoxylin and eosin (H&E) staining was used to observe gastric histopathological changes. Serum levels of TNF-α, IL-6, prostaglandin E2 (PGE2), and endothelin (ET) in the gastric mucosa were also measured. The results showed that all Bletilla striata-treated groups exhibited reduced ulcer indices, decreased serum expression of TNF-α and IL-6, increased levels of gastric mucosal PGE2, reduced ET expression, upregulated cyclooxygenase-1 (COX-1) gene and protein expression, downregulated cyclooxygenase-2 (COX-2) gene and protein expression, and alleviated histopathological damage to the gastric mucosa. The high-dose group demonstrated the most pronounced therapeutic effects. It was concluded that Bletilla striata effectively mitigates aspirin-induced gastric mucosal injury in rats by significantly reducing the expression of proinflammatory cytokines TNF-α and IL-6, regulating the expression of COX-1 and COX-2 in gastric mucosa, promoting PGE2 production, and inhibiting ET generation—thereby contributing to the treatment of GUs.

Fan et al[27] discovered that Bletilla striata may treat PUs by targeting specific proteins involved in promoting the release of inflammatory cytokines, reducing oxidative stress, accelerating ulcer healing, and protecting the gastrointestinal mucosa—thereby exerting anti-ulcer effects. Studies have demonstrated that the primary active components of Bletilla ochracea exhibit strong binding affinity with key molecular targets including IL-6, TNF, interleukin-1β (IL-1β), and nuclear factor kappa B (NF-κB)[28]. This interaction effectively ameliorates gastric mucosal injury in rats with GU and significantly reduces the expression of inflammatory mediators—IL-6, IL-1β, TNF-α, and myeloperoxidase (MPO)—while increasing epidermal growth factor (EGF) levels (P < 0.05) in ulcerated rats. Therefore, it was concluded that Bletilla ochracea suppresses tissue inflammation by modulating signaling pathways mediated by IL-17, NF-κB, TNF, and mitogen-activated protein kinase (MAPK). Molecular docking analysis confirmed the reliability of these network pharmacology predictions, suggesting that the therapeutic effects of Bletilla ochracea on GUs are achieved through coordinated regulation of IL-6, TNF, IL-1β, EGF, and MPO within these signaling pathways.

Li et al[29] conducted a study to evaluate the therapeutic potential of OME–loaded Bletilla striata polysaccharide (BSP) nanoparticles (NPs) in the management of GUs. Through comprehensive histological analysis using H&E and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling staining, the researchers observed that OME-BSP NPs conferred multiple therapeutic benefits. These included a significant reduction in ulcer area, suppression of gastric acid secretion, and marked attenuation of tissue damage and apoptosis. Further biochemical analyses demonstrated enhanced efficacy, as evidenced by the modulation of oxidative stress markers—superoxide dismutase (SOD) and malondialdehyde (MDA)—and inflammatory cytokines (IL-6 and TNF-α) in ulcer-induced rat models. Collectively, these findings indicate that the OME-BSP NP system represents a promising therapeutic approach for GU treatment, exerting anti-secretory, tissue-protective, and anti-apoptotic effects.

In summary, Bletilla striata exhibits broad pharmacological effects and diverse clinical applications. It effectively treats PUs through multi-component, multi-target, and multi-pathway mechanisms, as shown in Table 4.

Table 4 Mechanisms of Bletilla striata in peptic ulcer treatment.

Mechanism of action	Specific manifestations	Research support
Anti-H. pylori activity	Inhibits the growth of H. pylori and reduces ulcer recurrence	Reduces H. pylori-associated ulcers[53]
Inhibition of inflammatory response	Downregulates pro-inflammatory cytokine secretion and alleviates gastric mucosal inflammation	Suppresses the inflammatory cascade and limits inflammatory cell infiltration[54]
Enhancement of mucosal blood flow	Decreases nitric oxide activity and endothelin-1 Levels in gastric tissue	Improves mucosal perfusion and promotes tissue repair[55]
Promotion of cell proliferation and repair	Upregulates EGF and EGF receptor expression	Stimulates gastric epithelial proliferation and maintains mucosal integrity[55]
Immune modulation	Regulates cytokine secretion balance	Enhances the gastric mucosa’s defense against inflammation[56]
Antioxidant effect	Increases superoxide dismutase activity and reduces malondialdehyde content	Enhances antioxidant defense and limits oxidative tissue damage[57,58]

H. pylori: Helicobacter pylori; EGF: Epidermal growth factor; SOD: Superoxide dismutase; MDA: Malondialdehyde.

Experimental study on the therapeutic efficacy of Bletilla striata compound in PU

Wang et al[30] investigated the therapeutic mechanisms of Sanqi Baiji San in the treatment of GUs with blood stasis in rats, focusing on its modulation of the PI3K/AKT signaling pathway. Experimental animals were divided into five groups: Control, model, low-dose Sanqi Baiji San, high-dose Sanqi Baiji San, and high-dose Sanqi Baiji San combined with the PI3K activator 740Y-P. Parameters assessed included ulcer size, ulcer index (UI), gastric mucosal blood flow (GMBF), histopathological changes (examined using H&E staining), serum concentrations of inflammatory mediators (IL-6, PGE2, TNF-α), and expression levels of PI3K/AKT pathway components. The results showed that administration of high-dose Sanqi Baiji San significantly reduced gastric lesion area, UI, blood viscosity (high-, medium-, and low-shear rates), plasma viscosity, inflammatory cytokine levels (IL-6, PGE2, TNF-α), MDA content, and the phosphorylation ratios of PI3K/AKT proteins. Concurrently, this treatment increased GMBF and enhanced the activities of glutathione peroxidase (GSH-Px) and SOD in gastric tissues. In contrast, co-administration with 740Y-P reversed these therapeutic effects. These findings suggest that Sanqi Baiji San exerts protective effects against gastric mucosal injury in blood stasis–type ulcers primarily through inhibition of the PI3K/AKT signaling pathway. This mechanism attenuates inflammatory responses, reduces oxidative stress, improves hemorheological parameters, and enhances microcirculation—collectively contributing to gastric mucosal repair.

Experimental study on active ingredients from Bletilla striata in the treatment of PUs

Gong et al[31] conducted a systematic study to investigate how BSPs modulate c-JNK and p38 MAPK signaling pathways and their associated inflammatory mediators—TNF-α, IL-1β, and IL-6—in a GU rat model. Wistar rats were initially divided into healthy controls and GU model groups. The GU model rats were further randomized into five treatment groups: Untreated model controls, a positive control group receiving ranitidine hydrochloride (0.3 g/kg), and three groups receiving BSPs at low (0.125 g/kg), medium (0.25 g/kg), and high (0.5 g/kg) doses. After 15 days of treatment, comprehensive analyses were performed to evaluate concentrations of inflammatory cytokines and activity of the JNK/p38 MAPK signaling pathways in gastric tissue. Quantitative PCR was used to assess gene expression, while Western blotting quantified corresponding protein levels. The high-dose polysaccharide group (0.5 g/kg) showed substantial mucosal improvement, characterized by enhanced glandular regeneration and reduced inflammatory cell infiltration. All treatment groups exhibited dose-dependent reductions in pro-inflammatory cytokines and JNK/p38 MAPK pathway expression, with the highest efficacy observed in the high-dose group. These findings demonstrate that BSPs exert gastroprotective effects through selective inhibition of the JNK/p38 MAPK signaling cascade, thereby normalizing the expression of TNF-α, IL-1β, and IL-6. This study provides mechanistic evidence supporting the therapeutic potential of these natural polysaccharides in the management of GUs.

Fang et al[32] employed an integrated network pharmacology and experimental approach to elucidate the therapeutic mechanisms of Bletilla striata’s non-polysaccharide components in the treatment of GUs. The study first identified 47 chemical constituents in the non-polysaccharide fraction, highlighting several key bioactive compounds—gymnoside I, gymnoside II, militarine, bletilloside A, and shancigusin I—as potential therapeutic agents. Using systematic network analysis, the researchers constructed comprehensive component–target–pathway relationships. Protein–protein interaction network analysis identified albumin, AKT serine/threonine kinase 1, TNF, and EGFR as central molecular targets. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the non-polysaccharide components primarily exert their effects through modulation of the PI3K–AKT, MAPK, and Ras signaling pathways. Experimental validation using an ethanol-induced GU murine model demonstrated significant therapeutic efficacy, as evidenced by increased ulcer inhibition rates and modulation of inflammatory mediators. Treatment significantly suppressed serum levels of TNF-α, IL-1β, IL-6, vasoactive intestinal peptide and thromboxane B2, while upregulating anti-inflammatory interleukin-10 (IL-10) and mucosal protective factors including PGE2, EGF, and vascular endothelial growth factor (VEGF). Western blot analysis confirmed mechanistic involvement via differential regulation of PI3K-AKT pathway components, with downregulation of total PI3K and AKT and upregulation of their phosphorylated forms. This multidisciplinary investigation provides mechanistic evidence that Bletilla striata’s non-polysaccharide fraction exerts gastroprotective effects through pleiotropic actions involving multiple active compounds, molecular targets, and signaling cascades. The study successfully integrated computational predictions with experimental validation, offering a robust framework for elucidating the mechanisms of traditional herbal medicines in GU management.

In a mechanistic investigation of gastric mucosal protection, Shi et al[33] evaluated the therapeutic potential of ethanolic extracts derived from Bletilla striata fibrous roots using an ethanol-induced GU rat model. The experimental design included six distinct groups: Healthy controls, ulcer model controls without treatment, a reference drug control group, and three intervention groups receiving graded doses of the herbal extract. Following ulcer induction with absolute ethanol, researchers conducted macroscopic assessments of gastric lesions using digital imaging techniques. Subsequent biochemical analysis via enzyme-linked immunosorbent assay (ELISA) quantified serum concentrations of key inflammatory mediators, including IL-1β, TNF-α, and IL-10, to elucidate potential mechanisms of action. The results demonstrated that the ethanol extract of Bletilla striata fibrous roots significantly reduced ulcer area. ELISA data showed significant alterations in serum levels of IL-1β, TNF-α, and IL-10 compared to the model group. These findings indicate that the ethanolic extract of Bletilla striata fibrous roots exerts anti-GU effects by downregulating pro-inflammatory factors such as IL-1β and TNF-α while upregulating anti-inflammatory and mucosal repair factors, including IL-10 and VEGF.

Fan et al[34] developed an in situ gel system incorporating sodium alginate, deacetylated gellan gum, calcium citrate, and BSP for the treatment of GUs. Their pharmacological evaluation involved five experimental groups in an animal study: A blank control, an OME-treated positive control, a BSP-only group, a blank gel group, and a BSP-loaded in situ gel group. Following a 10-day pretreatment phase, severe acute GUs were induced in rats via administration of 95% ethanol. The results demonstrated that the BSP-incorporated in situ gel group exhibited significantly improved outcomes compared to the model group across multiple parameters, including gross morphological appearance, histopathological features, inflammatory response regulation, and modulation of apoptosis. Experimental findings revealed that the BSP-based in situ gel formulation effectively reduced tissue necrosis and inflammatory cell infiltration, preserved gastric mucosal integrity, normalized cytokine profiles, and attenuated inflammation-associated apoptotic activity. These results indicate that the developed gel system ameliorates pathological changes in the inflammatory microenvironment of PU while maintaining a favorable safety profile, with no observable adverse effects, as shown in Table 5.

Table 5 Mechanisms of Bletilla striata compound formulations and their active components in treating peptic ulcers.

Ref.	Research content	Experimental model & grouping	Key findings
Wang et al[30]	Effects of Sanqi Baiji powder on blood stasis-type gastric ulcers in rats	A rat model of blood stasis-type gastric ulcer was established and divided into five groups: Control, model, low-dose Sanqi Baiji San, high-dose Sanqi Baiji San, and high-dose Sanqi Baiji San + PI3K activator (740Y-P)	Sanqi Baiji powder alleviates inflammation and oxidative stress by inhibiting the PI3K/AKT signaling pathway. It improves hemorheological parameters (e.g., blood viscosity) and gastric mucosal blood flow, thereby reducing gastric mucosal injury
Gong et al[31]	Effects of BSPs on gastric ulcer in rats	A gastric ulcer rat model was established and divided into a blank control, model, ranitidine hydrochloride group, and low-, medium-, and high-dose BSP groups	BSPs protect the gastric mucosa by downregulating JNK and p38 MAPK gene and protein expression, and by inhibiting abnormal secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6)
Fang et al[32]	Therapeutic effects and mechanisms of Bletilla striata non-polysaccharide components in gastric ulcer	An ethanol-induced gastric ulcer mouse model was established and divided into blank control, model, Yunnan Baiyao, and high-, medium-, and low-dose Bletilla striata alcohol extract groups	Bletilla striata non-polysaccharide components exert synergistic therapeutic effects via multiple bioactive compounds, targets, and signaling pathways
Shi et al[33]	Anti-ulcer activity and mechanisms of Bletilla striata fibrous root ethanol extract in ethanol-induced ulcers	Ethanol-induced acute gastric ulcer rat models were divided into normal, model, positive control, and low-, medium-, and high-dose Bletilla striata fibrous root ethanol extract groups	The fibrous root extract reduces serum levels of IL-1β and other pro-inflammatory markers while increasing IL-10 and VEGF expression, thereby exhibiting protective effects against ethanol-induced gastric ulcers
Fan et al[34]	Protective effects of sodium alginate/BSP in situ gel on alcohol-induced ulcers	Rats were divided into blank control, omeprazole-treated positive control, BSP group, blank gel group, and BSP-loaded in situ gel group	The BSP-loaded in situ gel reduces tissue necrosis, mitigates inflammatory cell infiltration, preserves mucosal barrier integrity, modulates cytokine imbalance, and suppresses apoptosis related to inflammation. No significant adverse effects were observed, supporting its potential for peptic ulcer treatment

BSP: Bletilla striata polysaccharide; VEGF: Vascular endothelial growth factor; TNF-α: Tumor necrosis factor-alpha; IL-1β: Interleukin-1β; IL-6: Interleukin-6.

CONCLUSION

PU disease is a prevalent condition. While many patients remain asymptomatic, dyspepsia is the most common and characteristic symptom. In some cases, the disease may first present with complications such as upper gastrointestinal bleeding, perforation, or obstruction[35]. As a traditional Chinese medicinal herb, Bletilla striata exhibits diverse bioactivities and holds broad application potential. Extracts and key active components of Bletilla striata promote ulcer and tissue repair through hemostatic, anti-inflammatory, antibacterial, and antioxidant pharmacological effects[36]. It demonstrates notable efficacy in clinical practice and warrants further systematic investigation. Additionally, Bletilla striata and its compound formulations, as herbal preparations, require comprehensive evaluation regarding cost-effectiveness, standardization, and personalized clinical application. Optimizing supply chain management, improving standardization of production processes, and enhancing quality control can significantly improve the cost-efficiency and stability of Bletilla striata preparations. Moreover, integrating TCM theories with clinical practice to support rational, individualized use of Bletilla striata and its compound formulas may further maximize their value in modern healthcare.