Bletilla

Bletilla (Bletilla striata): A Comprehensive Encyclopedic Reference

1. Identity and Botanical Description

Taxonomic and Nomenclatural Identity

Bletilla striata (Thunb.) Reichb. f. (family Orchidaceae), also known as Hyacinth Orchid and Baiji (Simplified Chinese: 白及), is best recognized medicinally for its efficacy in arresting bleeding with astringent action and for topical application to overcome ulcers, sores, swellings, and chapped skin. Its other informal English-language names include Chinese ground orchid. Bletilla striata is native to Japan, Korea, Myanmar (Burma), and China — specifically the provinces of Anhui, Fujian, Gansu, Guangdong, Guangxi, Guizhou, Hubei, Hunan, Jiangsu, Jiangxi, Shaanxi, Sichuan, and Zhejiang. Also known as Bletillae Rhizoma, it is considered merely an ornamental plant in Europe and the USA, but it is widely distributed across China, Japan, Korea, Mongolia, and Myanmar, where it is important for its use in traditional Chinese medicine.

The plant has diverse vernacular nomenclature across cultures: in China it is called Baiji, Gangen, Zhulan, or Zilan; in Korea, Jaran; in Japan, Shiran; in Denmark, Mikodoblomst; in Sweden, Mikadoblomma; and in Germany, Japanorchidee. The Latin specific epithet striata means "striped," in reference to the plant's ribbed leaves.

Bletilla striata (Thunb.) Rchb.f. is a perennial medicinal orchid with a well-documented history in traditional Chinese medicine spanning millennia. It is a terrestrial orchid with pleated, spear-shaped leaves, breaking dormancy in early spring, with each tuber of the previous year potentially sending out multiple shoots. It is most commonly found growing in clumps alongside grassy slopes with sandy soil. It thrives in warm, humid, shaded environments but demonstrates low frost tolerance and photophobic characteristics.

Medicinal Part and Common Preparations

The tuberous roots of B. striata constitute the primary medicinal component, containing a complex array of bioactive compounds. In TCM practice, the dried tuber (rhizome) is the official pharmacopoeial part. The polysaccharide extracted from these tubers (BSP) has been widely used in the manufacture of adhesives, wound dressings, gels, food, cosmetics, and tissue engineering scaffolds. Various extraction techniques — including hot water, ultrasonic-assisted, and microbial fermentation methods — have been developed to isolate Bletilla polysaccharides, with extraction parameters significantly influencing their structural features. Modern dosage forms include decoctions, powders, liniments, microspheres, hydrogels, and injectable embolic materials.

2. Traditional and Historical Use

China

Bletilla striata is a plant that has been employed as a traditional Chinese medicine (TCM) for thousands of years in China. According to the earliest pharmacopeia of TCM, Shennong's Materia Medica Classic, Chinese scholars were the first to describe the morphological features and medicinal value of B. striata. Other Chinese pharmacopeias have recorded the effect of its astringency upon hemostasis and analgesia, as well as its use for treating traumatic bleeding, ulcers, and swelling and chapped skin.

In classical TCM, B. striata has been widely used for the treatment of hematemesis (vomiting blood), hemoptysis (coughing blood), and traumatic bleeding due to its astringent hemostatic action, and has been applied topically to overcome ulcers, sores, swellings, and chapped skin. Additional medical applications include the treatment of tuberculosis, malignant ulcers, hemorrhoids, anthrax, eye diseases, and silicosis.

According to ancient Chinese medicinal books, Bletilla was used to treat a wide variety of conditions including coughing, bruising, and bleeding, but among the most commonly mentioned uses in ancient Chinese texts is skin whitening and freckle removal. Since ancient times, Bletilla species have been used consistently for skin care and whitening, and there are many well-known skincare products related to Bletilla.

In TCM, B. striata is often used with other medicinal drugs to offset the toxicity of one drug or enhance the bioavailability of another — known as the "correspondence of prescription and syndrome." For example, Bai Ji San (B. striata liniment) is frequently used as an astringent hemostatic medicine.

Japan and Korea

Physicians in Korea and Japan have used B. striata to treat tuberculosis, whooping cough, bleeding of the stomach and duodenal ulcers, abscesses, swellings, and parasitic diseases.

Non-Medical Traditional Uses

Bletilla striata is used in Asian traditional medicine for problems with the lining of the alimentary canal, such as ulcers. It has also been used as a natural glue for making silk strings for traditional Chinese instruments such as the guqin.

3. Key Constituents and Active Compounds

Overview of Phytochemistry

More than 200 compounds have been isolated and identified from the tubers, fibrous roots, and flowers of B. striata, falling into nine major categories including polysaccharides, malic acid derivatives, bibenzyls, and phenanthrenes. Approximately 158 compounds extracted from B. striata tubers with clarified molecular structures have been classified as glucosides, bibenzyls, phenanthrenes, quinones, biphenanthrenes, dihydrophenanthrenes, anthocyanins, steroids, triterpenoids, and phenolic acids. Modern research has shown that the principal chemical components of Bletilla striata include amino acids, spirostane-type steroidal saponins, stilbenes, bibenzyls, bis-phenanthrenes, carotenoids, dihydrophenantrofurans, glycosides, phenanthrenes, anthraquinones, and others.

Polysaccharides (BSP)

The major bioactive component, Bletilla striata polysaccharide (BSP), is a water-soluble heteropolysaccharide composed primarily of mannose and glucose. Cumulative evidence confirms BSP fractions are primarily composed of glucose (Glu) and mannose (Man), with variable proportions of galactose (Gal), rhamnose (Rha), arabinose (Ara), and glucuronic acid (GluA). BSP is essentially a natural soluble glucomannan, consisting of α-mannose, β-mannose, and β-glucose. Among the plant's constituents, Bletilla striata polysaccharides have emerged as the primary pharmacologically active components, demonstrating remarkable anti-inflammatory activity, wound healing, hemostatic activity, antioxidant activity, and antimicrobial activity.

Bibenzyls and Phenanthrenes (Stilbene-type Compounds)

Chemical isolates from Bletilla species belong to the stilbenes (bibenzyls and phenanthrenes), flavonoids, triterpenoids, steroids, simple phenolics, and glucosyloxybenzyl 2-isobutylmalates classes of compounds. The stilbene compounds present in B. striata exhibit antibacterial, anti-inflammatory, and antitumor properties. Novel compounds named blestanols A–M — thirteen undescribed phenanthrene and bibenzyl derivatives — have been isolated from the plant's tubers; these include one pair of biphenanthrene enantiomers, two bis 9,10-dihydrophenanthrene ethers, five pairs of 9,10-dihydrophenanthrene/bibenzyl atropisomers, one racemic 9,10-dihydrophenanthrene/bibenzyl dimer, one 9,10-dihydrophenanthrenebibenzyl ether, two pairs of bibenzyl derivatives, and one stilbene, together with 12 known analogues.

Key identified anti-inflammatory bibenzyl constituents include coelonin, batatasin III, 3′-O-methylbatatasin III, and 3-hydroxy-5-methoxy bibenzyl.

Triterpenoids, Steroids, and Other Compounds

Phytochemistry studies have revealed that polysaccharides, bibenzyls, and phenanthrenes are the main constituents of this species, with triterpenoids, steroids, anthraquinones, and organic acids also detected in B. striata. Studies focusing on secondary metabolites have resulted in the isolation of bibenzyls, dihydrophenanthrenes, biphenanthrenes, phenanthrenes, triterpenoids and their saponins, steroids and their saponins, cyanidin glycosides and anthocyanins, phenanthraquinones, anthraquinones, lignans, organic acids, and glucosyloxybenzyl 2-isobutylmalates.

4. Mechanisms of Action

Hemostasis

BSP-derived microparticles (BSMPs), upon coming into contact with a bleeding surface, form aggregations or sealants at wound surfaces that quickly spur hemostasis. In vitro coagulation studies revealed BSMP-blood aggregate formation via stereoscope and texture analyzers, and in vivo studies based on rat injury models illustrated the BSMP capabilities under conditions of hemostasis. This hemostatic action is physical in nature and functions independently of the classical coagulation cascade.

Bletilla polysaccharides are valued by researchers for their excellent hemostatic performance and good reactivity. The extensive quantity of hydroxyl groups present on BSP engage in cross-linking reactions with boron atoms in borax, forming borate ester bonds; carboxymethyl chitosan (CMCS), equipped with amino and carboxyl groups, is capable of forming hydrogen bonds with borax, serving to fortify and stabilize the hydrogel network; owing to the inherent pharmacological properties of BSP, it is thus enabled to fulfill crucial functions such as hemostasis.

Anti-Inflammatory Activity and Signaling Pathways

Integrated mechanistic analyses demonstrate that B. striata compounds exert anti-inflammatory effects through coordinated modulation of core signaling pathways, including NF-κB, MAPK (suppression of p38 and JNK phosphorylation), and the NLRP3 inflammasome (inhibition of caspase-1 activation and GSDMD-mediated pyroptosis). These pathway-level effects translate into reduced production of pro-inflammatory mediators (NO, PGE2, TNF-α, IL-1β, IL-6) across multiple in vitro and in vivo models, including acute lung injury, gastric ulcers, colitis, skin wounds, and metabolic dysfunction. Approximately 65 compounds in total have been reported to possess anti-inflammatory activity.

The inhibitory effect of BSP and BSP-2 on IL-6 showed no significant difference compared with that of a positive control (p < 0.05) and exhibited a dose-dependent trend. Western blot results indicated that both BSP and BSP-2 suppressed NF-κB activation markers (p-p65, p-IκBα); BSP-2 reduced iNOS expression, whereas BSP showed clearer inhibitory effects on COX-2. The anti-inflammatory activities of BSP and BSP-2 appear to be mediated through the inhibition of NF-κB pathway-related proteins.

Wound Healing

The wound-healing mechanism of Bletilla polysaccharide may operate through promoting the formation of new blood vessels, regulating inflammation, and promoting the process of epithelialization. In animal studies of diabetic wound models, BSP was evaluated for its effects on the production of interleukin-1β (IL-1β), tumor necrosis factor-α, macrophage infiltration, angiogenesis, and the activation of the NLRP3 inflammasome, as well as insulin sensitivity in wound tissues.

Anticancer Mechanisms

In vitro studies showed that isolated phenanthrene compound(s) inhibited cell proliferation and migration and promoted cell apoptosis in A549 lung cancer cells. The mechanisms may correlate with regulation of the Akt, MEK/ERK, and Bcl-2/Bax signaling pathways, suggesting that the phenanthrenes of B. striata might be important and effective substances in the treatment of non-small cell lung cancer (NSCLC).

Butyrylcholinesterase (BChE) Inhibition

The 95% ethanol extract from tubers of Bletilla striata showed promising butyrylcholinesterase inhibition (IC50 = 8.6 μg/mL). Extracts with different polarities were evaluated for their inhibition of cholinesterases, and the most active ethyl acetate extract was subjected to bioassay-guided isolation and afforded twenty-two bibenzyls and phenanthrenes. Five phenanthrenes presented promising capacity for BChE inhibition (IC50 < 10 μM). Further kinetic studies indicated their modes of inhibition: compounds 6, 8, and 14 were found to be mixed-type inhibitors, while compounds 10 and 12 could be classified as non-competitive inhibitors. These findings are preliminary and based on in vitro assays only; no clinical data in cognitive disease contexts exist.

5. Scientific Evidence by Area of Use

5.1 Hemostasis and Bleeding Control

Evidence level: Moderate (animal/laboratory models; limited human clinical data in interventional settings).

The chemical constituents of B. striata support pharmacological properties of hemostasis and wound healing, and also exhibit anti-oxidation, anti-cancer, anti-viral, and anti-bacterial activities. Laboratory and animal evidence for hemostatic activity is extensive. The facile production of BSMPs (Bletilla striata micron particles) shows promise as an effective hemostatic agent. However, well-controlled clinical trials specifically isolating the hemostatic effect in human subjects remain limited, and most evidence comes from in vitro coagulation studies and rat injury models.

5.2 Wound Healing

Evidence level: Moderate (preclinical — animal and in vitro; some clinical trial reports, largely in Chinese literature).

B. striata is a rich source of polysaccharides, which have been used as a variety of biomedical materials for wound healing or as vehicles for drug delivery. Studies have shown that Bletilla polysaccharide hydrogel can promote the repair of wounds in diabetic mice, and this may operate through promoting the formation of new blood vessels, regulating inflammation, and promoting the process of epithelialization. The B. striata polysaccharide hydrogel has demonstrated effectiveness in promoting wound healing and can be used as an efficient wound dressing. The 2021 PMC study on diabetic foot ulcer models found that BSP treatment over 12 days in streptozocin-induced diabetic mice accelerated wound closure and reduced NLRP3 inflammasome-mediated inflammation. Although clinical evidence remains limited, preliminary studies support its efficacy in conditions such as peptic ulcer disease and postoperative wound healing.

5.3 Gastrointestinal Mucosal Protection and Peptic Ulcer Disease

Evidence level: Limited clinical (some controlled trials, predominantly in Chinese-language literature; mechanistic data in animals).

Bletilla striata, as a traditional Chinese medicinal herb, contains diverse chemical constituents and exhibits multiple pharmacological effects. As a key component in various TCM compound formulations, it has demonstrated notable clinical efficacy, and it has a solid research foundation and broad application prospects in the treatment of gastrointestinal diseases. Research has found that Bletilla striata may treat peptic ulcers by targeting specific proteins involved in promoting the release of inflammatory cytokines, reducing oxidative stress, accelerating ulcer healing, and protecting the gastrointestinal mucosa. B. striata polysaccharide has been reported to reduce the levels of pro-inflammatory cytokines and suppress MAPK/NF-κB signaling pathway activity in rats with gastric ulcer induced by ethanol. Large-scale, prospective, well-controlled human trials specifically attributable to B. striata alone (rather than multi-herb formulas) are not yet established in the peer-reviewed English-language literature.

5.4 Embolization (Interventional Oncology)

Evidence level: Moderate (controlled case series in humans; animal model data; limited formal RCTs).

Various clinical trials conducted on B. striata have demonstrated its marked activities as an embolizing and mucosa-protective agent, and its application in novel biomaterials, quality control, and toxicology. A noteworthy clinical application involves the use of B. striata as an embolizing material in transarterial embolization for hepatocellular carcinoma. A Chinese herb, Bletilla striata, was used as an embolizing agent in order to improve the therapeutic results of intervention treatment of liver cancer. From October 1991 to January 1995, 56 cases of hepatic carcinoma were treated with Bletilla striata by hepatic artery embolization, with conventional gelfoam embolization in 50 cases as control. Patients were followed up for 10–48 months; embolization with Bletilla striata led to extensive and permanent vascular obstruction, accompanied with marked shrinkage of tumor size and significant decrease in serum AFP levels. Collateral circulation was established late, allowing treatment intervals to be prolonged with an average of 7 months. The 1-, 2-, and 3-year survival rates were 81.9%, 44.9%, and 33.6%, respectively, with a median survival time of 19.8 months — all clinical parameters were reported as superior to conventional gelfoam embolization. These findings are from an unblinded comparative case series rather than a randomized controlled trial, limiting their interpretive strength.

B. striata polysaccharide microspheres (BSPMs) have been proposed as promising transarterial chemoembolization carriers for cancer treatment, showing favorable drug-loading, swelling, suspension, drug-entrapment, and release characteristics. Biocompatibility studies in rabbits found that BSMs exhibited no cytotoxicity in cultured mouse fibroblasts and human umbilical vein endothelial cells, showed high compatibility with red blood cells, and produced no hemolysis. Intramuscular implantation with BSMs resulted in a gradually lessening mild inflammatory reaction that disappeared after eight weeks, and occlusion of small renal vessels was associated with only a mild perivascular inflammatory reaction without significant renal and liver function damage. These findings support BSMs as a high-biocompatibility embolic agent.

5.5 Anticancer Activity

Evidence level: Preliminary (in vitro cell lines and animal models only; no human clinical data).

The tubers of Bletilla striata are regarded as "an excellent medicine for lung diseases." In studies, seventeen phenanthrene derivatives, including two new compounds, were isolated from the tubers of B. striata, and most showed cytotoxicity against A549 non-small cell lung cancer cells. The crude extracts and pure compounds derived from Bletilla species have reportedly exhibited a wide spectrum of in vitro and in vivo pharmacological effects, including hemostatic, anti-inflammatory, anti-tumor, and anti-microbial activities. Studies have demonstrated that the extracts and compounds from B. striata exhibit a wide range of pharmacological activities including anti-cancer, antiviral, anti-melanin, antibacterial, anti-ulcer, anti-aging, anti-fibrosis, anti-inflammatory, antioxidant, immunomodulatory, wound-healing, neuroprotective, and haemostasis effects. These anticancer effects remain at the laboratory stage with no established human clinical evidence.

5.6 Antimicrobial Activity

Evidence level: Preliminary (in vitro only).

The phenanthrenes isolated from B. striata root ethanol extract showed bioactivity against Staphylococcus aureus. Pharmacological research demonstrated that the components of Bletilla species exhibit a variety of bioactivities including anti-inflammatory, cytotoxic, antimicrobial, and antioxidant activities. No controlled clinical trials have evaluated B. striata as a systemic antimicrobial in human infections.

5.7 Anti-Inflammatory and Pulmonary Effects

Evidence level: Preliminary (in vitro and animal only).

In vitro studies using RAW264.7 macrophages found that an effective fraction of B. striata (EFB) pretreatment decreased inflammatory cytokines in macrophages, significantly attenuated PM2.5-induced proinflammatory protein expression, and downregulated the levels of phosphorylated NF-κBp65, IκB-α, JNK, ERK, and p38, demonstrating the potential effectiveness of B. striata extracts for treating PM2.5-triggered pulmonary inflammation.

5.8 Drug Delivery and Biomaterial Applications

Evidence level: Active preclinical development; some early clinical translation in embolization.

Owing to its favorable biodegradability and biocompatibility, BSP shows promise as a nanocarrier for drug delivery. The first reported preparation of novel dissolving microneedles (MNs) using Bletilla striata polysaccharide (BSP), a natural glucomannan material, has been reported as a transdermal drug delivery vector, with excellent moldability and easy detachment from the mold. BSP-based nanomicelles have also been developed as targeted drug delivery vehicles; for example, one 2024 Frontiers in Immunology study described BSP-coated andrographolide nanomicelles (AG@BSP-VES) prepared via the dialysis method, with drug loading, entrapment efficiency, stability, and safety assessed, and tumor targeting ability evaluated through targeted cell uptake and in vivo imaging.

6. Body Systems and Health Areas Associated with Bletilla

• Cardiovascular / Hematological: Hemostasis, blood coagulation support, pro-coagulant and platelet-aggregating mechanisms via BSP and microparticle formation.
• Gastrointestinal: TCM use and some clinical data for epistaxis, gastrointestinal bleeding, cough and hemoptysis, gastric and duodenal ulcers, and traumatic injuries.
• Dermatological / Wound Healing: Topical use for burns, ulcers, chapped skin; polysaccharide hydrogels as wound dressings; skin whitening and cosmetic applications.
• Respiratory: Effective use for tuberculosis, silicosis, and hemoptysis caused by lung vessel damage has given B. striata the reputation of "an excellent medicine for lung diseases."
• Oncological (Interventional): Use as an embolic agent in hepatic arterial embolization for liver cancer, and as a microsphere drug carrier in chemoembolization.
• Immunological / Inflammatory: Modulation of innate immune responses via NF-κB and MAPK signaling pathways; NLRP3 inflammasome inhibition.
• Neurological (Exploratory): In vitro BChE inhibition; anti-neuroinflammatory effects of phenanthrene/bibenzyl dimers at the research stage only.
• Metabolic / Gut Microbiota: In vitro fermentation studies have shown that BSP carbohydrates can promote the growth of beneficial gut bacteria, such as Streptococcus and Veillonella species, while simultaneously reducing the abundance of harmful microorganisms.

7. Dosage Forms and Reported Dosages

Clinically, B. striata is employed for treating mucosal injuries, ulcers, trauma, and burns. The following dosage-related information comes directly from research sources:

• Hepatic artery embolization: In rabbit model embolization experiments, the right renal artery was embolized with BSMs 200 μm in diameter. In reported human clinical series, no standardized dose in grams is available in the English-language peer-reviewed literature reviewed here; the dosing is procedure-dependent.
• In vitro anti-inflammatory (EFB): The effective fraction of B. striata (EFB) at a dose range of 0–40 μg/mL did not cause significant change in RAW264.7 cell proliferation, and was used across this range in inflammatory cytokine inhibition experiments.
• Polysaccharide hydrogel compositions (preclinical wound dressing): In hydrogel studies, preparations designated M2Bx, M5Bx, and M8Bx were explored, with the BSP component studied at variation percentages of 0.5%, 1%, and 2%.
• Oral preparations in TCM: No specific oral dose validated in a peer-reviewed English-language clinical trial was identified in the sources reviewed. Because there are insufficient studies on its clinical properties, its efficacy and safety cannot be fully established from a scientific point of view.
• Polysaccharide extraction yields: The crude polysaccharides obtained from Bletilla striata using hot water extraction, alkali-assisted extraction, boiling water extraction, and ultrasonic-assisted extraction showed different molecular weights, monosaccharide compositions, glycosidic bond compositions, and zeta potentials.

8. Safety Considerations and Interactions

Acute Toxicity

The existing literature indicates that the biological safety profile of B. striata is relatively favorable. Acute oral toxicity studies in mice have shown that the LD50 in female Kunming mice exceeded 10.0 g/kg, suggesting a high level of oral safety. No skin irritation, allergic reactions, or phototoxic responses have been observed, and no significant adverse effects were reported in human skin tests.

TCM Traditional Safety Classification

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.

The "Eighteen Incompatibilities" — Interaction with Aconite

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. 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.

Gaps in Toxicological Knowledge

Significant knowledge gaps persist regarding in vivo metabolism, pharmacokinetic profiles, systematic toxicological evaluation, and direct target identification. Future research should prioritize integrated pharmacokinetic-pharmacodynamic studies, regulatory-grade toxicity assessments, chemical proteomics for target discovery, mechanism-based quality control standards, and rigorous clinical trials to translate this traditional resource into evidence-based therapeutics.

Most studies have primarily relied on simplified in vitro cell models or basic animal disease models to evaluate its bioactivities. Future investigations should adopt more clinically relevant approaches to elucidate its mechanisms of action comprehensively; to ensure safe and effective clinical application of B. striata, it is strongly recommended that forthcoming research prioritize toxicity assessments and pharmacokinetic profiling.

Conservation Status

As a rare and endangered species, its cultivation and conservation strategies warrant further investigation to support the sustainable utilization of this valuable resource.

9. Overall Evidence Assessment

Various clinical trials conducted on B. striata have demonstrated its marked activities as an embolizing and mucosa-protective agent, and its application for use in novel biomaterials, quality control, and toxicology. It has also been widely used as a constituent of many preparations in TCM formulations, but because there are insufficient studies on its clinical properties, its efficacy and safety cannot be established from a scientific point of view.

The strongest and most clinically advanced evidence for Bletilla striata lies in its applications as a vascular embolic biomaterial in interventional radiology/oncology and in the development of BSP-based wound dressings and hydrogels. Mechanistic evidence from in vitro and animal studies robustly supports hemostatic, anti-inflammatory, and wound-healing activities. Anticancer, antimicrobial, and neuroprotective activities remain entirely at the in vitro stage. Despite extensive studies, the structure–activity relationships and toxicological profile of BSPs remain incompletely understood. Rigorous, placebo-controlled human clinical trials across most therapeutic categories are currently absent from the literature.

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