Psammosilene

Psammosilene (Psammosilene tunicoides W.C. Wu & C.Y. Wu)

1. Identity and Botanical Classification

Scientific Name and Taxonomy

Psammosilene tunicoides W.C. Wu & C.Y. Wu is a species of flowering plant in the carnation family, Caryophyllaceae, and the sole species in the monotypic genus Psammosilene. Known synonyms include Silene cryptantha Diels and Silene cryptantha Viv.

Common Names

The plant is also known by the common names Dudingzi, Kunming ginseng, and native ginseng. Its dried root, the medicinal part, is officially designated Psammosilenes Radix, and locally referred to as Jin-Tie-Suo (meaning "iron chain lock"), a name that alludes to its irritation to the respiratory tract. The tuberous roots are alternatively called "Jintiesuo" in some Chinese traditional medicine contexts.

Morphology and Natural Habitat

P. tunicoides is a perennial herb with a fleshy, turbinate (top-shaped) root reaching up to 30 cm in length. It is native to southeastern Tibet and the southwestern provinces of Sichuan, Yunnan, and western Guizhou in China, as well as to northern Thailand. The species grows usually on rocky mountain slopes, dry pastures, and in calcareous rock crevices, at elevations of 900–3,800 m.

Conservation Status

Through long-term excessive and destructive collection, wild population resources of the plant have declined, leading to it being listed as an endangered and nationally protected plant in China in 1991. P. tunicoides is currently classified in China as a Vulnerable species and a Grade II Protected Wild Plant. The plant is only distributed in southwest China, is slow-growing with limited saponin production, and due to high market demand and overexploitation, its natural resources have dwindled severely; it has been listed in the National Key Protected Plants in China.

Pharmacopoeial Status

The dried root, Psammosilenes Radix (Jin-Tie-Suo), is officially recorded in the Chinese Pharmacopoeia. P. tunicoides is recognized as a rare and endangered traditional medicinal herb with documented effects on multiple pathological conditions. It is one of the important ingredients of the Chinese traditional medicine formulation Yunnan Baiyao and has been listed in the Chinese Pharmacopoeia, where it is widely associated with the treatment of fractures, rheumatic arthralgia, and hemorrhagic diseases.

Common Preparations and Dosage Forms

The plant has been extensively used in traditional settings in different dosage forms including decoctions, pills, and powders for the treatment of rheumatism, inflammation, swelling, and pain. In modern patent medicines, P. tunicoides is an important medicinal material in habitually used Chinese patent medicines, such as Yunnan Baiyao, Fujian Bio-Tongxuekang Capsule, Guizhou Bio-Jingulian Capsule, and Eucommia Zhuanggu Pills. Psammosilenes radix is also among the key constituents in the commercial polyherbal preparation Yunnan Hongyao Capsule.

2. Traditional and Historical Use

Traditional Chinese Medicine

In traditional Chinese medicine, the dried roots of P. tunicoides have been used to treat haemostasis, rheumatism, and trauma haemorrhage. The roots are of great medicinal value in China and have been widely used to check bleeding, relieve pain, and promote blood circulation in folk medicine.

The plant is commonly used as an anodyne (pain-relieving) and hemostatic agent in the provinces of Yunnan, Guizhou, Sichuan, and Tibet in China.

Regional and Ethnic Uses

This herb is a well-known folk medicine in southwest China; its roots have been traditionally used to treat stomachaches, traumatic injuries, fractures, and rheumatic arthritis. It is also used by the Yi people living in Yunnan Province for treating paraplegia, numbness of the extremities, and coughing.

Documented Historical References

Historical botanical references to the plant appear as early as the 1945 work Icones Plantarum Medicarum e Libro Tien-Nan-Pen-Tsao Lanmaoano, which documents its medicinal applications in traditional Chinese herbal literature. This text, originating from the Yunnan regional herbal tradition, indicates the plant's deep integration into southwestern Chinese ethnomedicine, where it was regarded as a multifunctional remedy aligned with the classical Chinese medical concepts of stopping bleeding (zhi xue), moving blood (huo xue), and alleviating pain (zhi tong).

Formulation in Yunnan Baiyao

The tuberous roots of P. tunicoides (named "Jintiesuo") constitute an important ingredient in the famous traditional Chinese medicine Yunnan Baiyao. Yunnan Baiyao is a well-established polyherbal formula with a history spanning over a century, principally indicated for hemostasis and wound healing. The inclusion of P. tunicoides in this formula underscores the herb's enduring role as a hemostatic and analgesic agent in regional Chinese medical practice.

3. Key Constituents and Active Compounds

Primary Phytochemical Classes

Phytochemical studies have reported the presence of several types of compounds in P. tunicoides, including triterpenoid saponins, cyclic peptides, carboline alkaloids, lignans, and malt phenolic compounds. Triterpenoid saponins, cyclic peptides, and carboline alkaloids have been reported as the primary pharmacologically active ingredient classes.

Triterpenoid Saponins

Among these compound classes, triterpenoid saponins are considered the most characteristic metabolites and the main active components of P. tunicoides. Phytochemical research has found that the predominant bioactive components are oleanane-type triterpenoid saponins, of which quillaic acid (QA) and gypsogenin (GYP) constitute two representative aglycone types.

Multiple series of named saponins have been isolated and characterized:

• Two original oleanane-type triterpenoid saponins, tunicosaponin A (TSA) and tunicosaponin E (TSE), were among the first to be isolated from the roots of P. tunicoides.
• Seven oleanane-type triterpenoid saponins, tunicosaponins B–D and F–I, along with eight known triterpenoid saponins, were subsequently isolated from the roots.
• Five previously undescribed oleanane-type triterpenoid saponins, designated psammosaponins A–E, along with nine known compounds, were isolated in further phytochemical investigations of the roots.
• A quality control marker, the oleanane acid-type triterpene glucoside 3-O-6′-O-methyl-β-D-glucuronopyranoside of gypsogenin, has been used to measure the quality of extracts from P. tunicoides.

Cyclic Peptides

At present, approximately 20 cyclic peptides have been isolated and identified from P. tunicoides, including cyclo(Pro-Val), cyclo(Pro-Ala), cyclo(Pro-Pro), cyclo(Ala-Ala), cyclo(Ala-Val), cyclo(Ala-Leu), cyclo(Ala-Ile), psammosilenin A, psammosilenin B, and tunicyclins A through K.

Seven cyclic dipeptides have been found from the roots, and a series of cyclic heptapeptides (tunicyclins A–C, E–L, K) and a cyclic octapeptide (tunicyclin D) have been isolated; a few of these possess a unique tricyclic ring cyclopeptide skeleton and appreciable bioactivities including anti-acetylcholinesterase and antifungal properties.

Further investigation led to the isolation of a newer cyclic peptide, psammosilenin C, along with a ceramide and two phenolic compounds (dihydroferulic acid and vanillylacetone).

β-Carboline Alkaloids

β-carboline alkaloids are another pharmacologically active class extracted from the roots of P. tunicoides, and their antinociceptive activity has been the subject of dedicated study. β-carboline alkaloids as a class display a wide range of biological activities, including antitumor, antimicrobial, sedative, anxiolytic, and antidepressant activities.

Additional Minor Constituents

Ethanol extracts of P. tunicoides have also yielded additional compounds including methyl-4-hydroxybenzoate, N-methylsaccharin, 3-hydroxy-4-methoxybenzoic acid, germanicol, tricosanoic acid, octacosane, succinic acid, and stellarine A.

4. Established Mechanisms of Action

Analgesic (Antinociceptive) Mechanisms

β-carboline alkaloids from the roots of P. tunicoides have been shown to produce significant analgesic activity through both central and peripheral mechanisms, with studies suggesting that regulating the release of nitric oxide (NO), glutamate (Glu), or GABA_Aα1 receptor signaling are among the mechanisms involved.

In preclinical rodent experiments, four β-carboline alkaloids showed significant analgesic effects in both phases of the formalin test. All compounds suppressed Glu and NO levels in the brain cortex and spinal cord. Three of the four compounds extended the pain threshold in the hot-water tail-flick test, and two of them at 60 µmol/kg decreased GABA_Aα1 protein levels in the spinal cord.

The saponin constituents in P. tunicoides Radix are considered the major active ingredients for analgesia. Isolated saponins could significantly inhibit the production of nitric oxide and interleukin-6 (IL-6) and downregulate the expression levels of inducible NO synthase (iNOS), COX-1, and COX-2 in stimulated macrophages.

Anti-inflammatory Mechanisms

Two psammosaponin compounds have been shown to effectively inhibit the production of COX-1, iNOS, and IL-6.

In a collagen-induced arthritis (CIA) mouse model, the crude extract of P. tunicoides (CEPT) significantly decreased serum levels of IL-1β and IL-18, reduced arthritis score and paw edema, alleviated arthritic joint infiltration, and downregulated protein and mRNA levels of the NLRP3 inflammasome components, including ASC and caspase-1, suggesting the plant may reduce inflammatory joint disease by inhibiting NLRP3 inflammasome activation.

All tested β-carboline alkaloids from P. tunicoides exhibited anti-inflammatory effects by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW264.7 cells, with IC₅₀ values ranging from 1.1 to 34.9 µM.

In a further study, newly isolated compounds including psammosilenin C and a ceramide showed inhibitory activities on LPS-induced NO release in RAW264.7 macrophages.

Hemostatic Mechanism

The medicinal plant has demonstrated various therapeutic properties including pain-relief, haemostasia, anti-inflammation, and immunomodulation in experimental contexts. The hemostatic activity attributed to P. tunicoides in traditional usage has not yet been fully characterized at the molecular level in published research accessible through peer-reviewed literature; the pharmacological basis for its role in Yunnan Baiyao's hemostatic properties remains under investigation.

Immunomodulatory Mechanisms

Tunicosaponin A (TSA) and its semi-synthetic derivative TSA2 were evaluated for their adjuvant potential on cellular and humoral immune responses in ICR mice against ovalbumin (OVA), finding effects on OVA-induced IgG response and immune cell stimulation. The total triterpenoid saponins from P. tunicoides have demonstrated immunomodulatory activity, alongside antiarthritic, anti-inflammatory, antibacterial, and hemolytic activities in experimental models.

Antifungal Mechanism

Tunicyclin B contains an unusual α,β-dehydrotryptophan residue previously reported from marine sponges and bacteria. Tunicyclin D showed broad-spectrum antifungal activity against Candida albicans (two strains), Candida tropicalis, Candida parapsilosis, and Cryptococcus neoformans, with MIC₈₀ values of 4.0, 16.0, 0.25, 1.0, and 1.0 µg/mL, respectively.

5. Scientific Evidence by Area of Use

5.1 Pain and Analgesia

Evidence level: Preclinical (animal and in vitro) only; no human clinical trials identified.

Total triterpenoid saponins obtained from P. tunicoides have demonstrated significant analgesic effects in the acetic acid-induced writhing test model in rodents. At a dose of 40 mg/kg, isolated saponin compounds exhibited significant inhibitory effects on the mouse writhing response, with inhibitions ranging from 31.9% to 79.3%.

Isolated saponins also exhibited antinociceptive activities in hot plate and formalin tests on mice, and their antinociceptive mechanism was explored in LPS-stimulated RAW264.7 cells.

An ethyl acetate (EtOAc) extract of P. tunicoides displayed significant antinociceptive effects in mouse models, and four β-carboline alkaloids isolated from P. tunicoides exhibited significant antinociceptive activities.

All evidence in this area originates from in vitro cell models and rodent preclinical studies. No randomized controlled trials or other human clinical data have been published in accessible peer-reviewed literature.

5.2 Anti-inflammatory Activity

Evidence level: Preclinical (in vitro and animal) only; no human clinical trials identified.

Research has demonstrated that extracts and isolated compounds from P. tunicoides have analgesic, anti-inflammatory, and antioxidant activities in preclinical models. Crude saponins extracted from the roots were found to exhibit pain-relieving and anti-inflammatory activities. The mechanistic basis is multi-targeted, involving suppression of COX isoenzymes, iNOS, NO production, and multiple pro-inflammatory interleukins (IL-1β, IL-6, IL-18).

5.3 Rheumatic Diseases (Arthritis)

Evidence level: Animal model only; no human clinical trials identified.

Several reports have indicated that the water extract of P. tunicoides Radix is widely prescribed to manage rheumatic arthritis (RA) in traditional settings. In a controlled preclinical study, the crude extract of P. tunicoides (CEPT) was investigated for its mechanism in a collagen-induced arthritis mouse model, with treatment beginning on day 32 after primary immunization. Results suggested that P. tunicoides may reduce paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3 inflammasome components. This work provides a mechanistic basis for traditional use but does not constitute clinical evidence of efficacy in humans.

5.4 Hemostasis

Evidence level: Traditional use documented; preclinical evidence limited; no human clinical trials identified.

The roots of the plant have been widely used in folk medicine to check bleeding and promote blood circulation. The hemostatic application is one of the principal reasons for its inclusion in Yunnan Baiyao, a formula that has been studied for hemostatic effects in its composite form, though the independent contribution of P. tunicoides has not been isolated in clinical trials.

5.5 Antimicrobial and Antifungal Activity

Evidence level: In vitro only; no human clinical data.

Tunicyclin D showed a broad spectrum of antifungal activity against Candida albicans (SC5314), Candida albicans (Y0109), Candida tropicalis, Candida parapsilosis, and Cryptococcus neoformans with MIC₈₀ values of 4.0, 16.0, 0.25, 1.0, and 1.0 µg/mL, respectively, in in vitro assays. Total triterpenoid saponins from P. tunicoides have shown antibacterial activity in experimental models. In one study, succinic acid and stellarine A (compounds isolated from P. tunicoides) showed bacteriostatic activity to a certain extent. All evidence is in vitro; there are no clinical studies.

5.6 Immunomodulation and Vaccine Adjuvant Research

Evidence level: Animal (preclinical) only; no human clinical trials identified.

In a study of semi-synthetic tunicosaponin derivatives in ICR mice, TSA2 showed adjuvant potentials on cellular and humoral immune responses against OVA and had lower hemolytic activity than the reference adjuvant Quil A (P < 0.001). TSA2 did not cause any mortality and side effects when mice were administered subcutaneously at a dose up to 1.6 mg, and no significant hepatotoxic effect was observed in TSA2 groups at doses ranging from 0.05 mg to 0.8 mg. This line of research explores P. tunicoides saponins as potential vaccine adjuvants analogous to the better-known Quillaja saponin (Quil A), but has not progressed to human studies.

6. Dosages Reported in Studies

There are no established or clinically validated human dosage regimens for P. tunicoides as a standalone supplement. Dosages referenced in the available scientific literature are derived exclusively from preclinical (animal or in vitro) studies:

• In antinociceptive studies of isolated saponins in mice, a dose of 40 mg/kg produced significant inhibitory effects on the writhing response, with inhibition percentages ranging from 31.9% to 79.3%.
• In studies of β-carboline alkaloids, compounds 2 and 3 were administered at 60 µmol/kg to mice to evaluate effects on GABA_Aα1 protein levels in the spinal cord.
• In sub-acute oral toxicity studies, aqueous extracts of P. tunicoides parts (radix, radix with cortex, cortex) were administered to rats at doses of 0.3, 0.6, and 1.2 g/kg/day for 28 days.
• In immunological adjuvant research in ICR mice, TSA2 was evaluated subcutaneously at doses up to 1.6 mg for acute toxicity and from 0.05 mg to 0.8 mg for hepatotoxic evaluation.

In traditional ethnopharmacological practice, the plant is used in decoctions, pills, and powders, but standardized dosages for these preparations are not defined in currently accessible peer-reviewed publications.

7. Body Systems and Health Areas

The medicinal plant is associated with therapeutic properties spanning pain-relief, haemostasia, anti-inflammation, and immunomodulation. Based on the available peer-reviewed literature, the following body systems and health areas are associated with P. tunicoides:

• Musculoskeletal system: Traditional use for traumatic injuries, fractures, and rheumatic arthritis.
• Immune system: Immunomodulatory activity demonstrated in experimental models; potential interest as a vaccine adjuvant base compound.
• Hematopoietic / vascular (hemostasis): Widely used in folk medicine to check bleeding and promote blood circulation.
• Nervous system (pain pathways): β-carboline alkaloids from the roots have demonstrated analgesic activity through both central and peripheral mechanisms.
• Gastrointestinal system: Traditional use in folk medicine for the treatment of stomachaches.
• Respiratory system / neurological: The Yi people of Yunnan Province use it for treating paraplegia, numbness of the extremities, and coughing.

8. Safety Considerations

Documented Toxic Potential in Preclinical Studies

In formal toxicity evaluations, Psammosilene tunicoides has demonstrated toxic potential in both acute and sub-acute oral administrations. There was no direct relationship between toxicity and the cortex alone; daily oral administration of the three different parts (radix, radix with cortex, and cortex) may cause damage to the heart, lung, and kidney in rats.

Phytochemical studies have noted that medicinal plants with complex mixtures of saponins, flavonoids, and alkaloids can carry an increased risk of adverse reactions or synergistic chemical interactions; Psammosilene tunicoides may be one such medicinal plant with potential toxicity.

Hemolytic Properties

The triterpenoid saponins from Psammosilenes Radix are associated with potential health risks, mainly due to vascular stimulation and hemolytic properties. This is consistent with the known pharmacological behavior of many saponin-containing plants, in which membrane-disrupting properties of saponins can cause red blood cell lysis.

Respiratory Tract Irritation

The root is locally referred to as "choke hold" because of its irritation to the respiratory tract. This folk designation indicates that the dried root powder or concentrated preparations may cause respiratory irritation when handled or inhaled.

Hepatotoxicity Assessment of Saponin Derivatives

In studies of the semi-synthetic saponin derivative TSA2 (derived from tunicosaponin A), no significant hepatotoxic effect was observed at doses ranging from 0.05 mg to 0.8 mg in ICR mice. However, this positive finding applies to a specific semi-synthetic derivative in an animal model and cannot be extrapolated directly to crude extracts or other preparations of the plant.

Limited Toxicological Data

Currently, little toxicological information is available on its safety following prolonged use. All toxicity data originate from animal studies; no systematic human safety studies, pharmacovigilance data, or clinical trial safety reports have been published in accessible peer-reviewed literature. The absence of such data should be noted as a significant gap in the safety profile of this plant ingredient.

Conservation-Related Supply Concerns

P. tunicoides is a slow-growing plant with limited saponin production, and due to high market demand and overexploitation, natural resources have dwindled and become endangered. As an alternative to wild exploitation, hairy root cultures using genetic transformation by Agrobacterium rhizogenes have been developed for sustainable production of the bioactive components. These biotechnological approaches aim to reduce pressure on wild populations while enabling consistent supply of standardized extracts.

Adulteration and Authentication

Due to the similar morphology between Silene viscidula and P. tunicoides, botanical identification and phylogenetic studies of the plant are considered important for ensuring the integrity of material used in preparations. Misidentification of source material poses a potential risk in both traditional and commercial contexts.

References

• Wikipedia: Psammosilene tunicoides
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