raíz de glehnia

Glehnia Root (Glehnia littoralis): An Encyclopedic Reference

1. Identity

Botanical and Pharmaceutical Names

Glehnia littoralis Fr. Schmidt ex Miq. is the sole species in the genus Glehnia, belonging to the family Apiaceae (Umbelliferae). The medicinal drug derived from its dried root is known pharmaceutically as Glehniae Radix (sometimes rendered Radix Glehniae in older literature). This drug is known as Beishashen (北沙参) in China, Hamaboufu in Japan, and Heabangpoong in Korea.

In Chinese medicine, "Shashen" historically referred collectively to more than one root herb. Ancient medical books including the Xinxiu Bencao (Qing Dynasty, 1757 AD) and the Compendium of Materia Medica (1590 AD) include Beishashen and describe its therapeutic effects. Currently, the separate drug Nanshashen (Southern Sha Shen) originates from Adenophora stricta and is distinguished from Beishashen. It was not until the Qing Dynasty that the distinction between North and South varieties became standard, with Wu Yiluo's Ben Cao Cong Xin being among the first texts to describe Bei Sha Shen's specific properties in detail.

Natural Source and Morphology

G. littoralis is a perennial herb growing 20–70 cm in height. Its root is slender, cylindrical, or spindle-shaped and is yellowish-white in color. The above-ground stems are short and branched, whereas the underground part is elongated. It produces a slender, fleshy, cylindrical taproot that can extend up to 30 to 40 cm underground, which is the medicinal part.

G. littoralis is a perennial herb with the property of salt tolerance, which allows it to grow on the seashores of Northern Pacific countries, particularly China, Japan, Korea, the USSR, Canada, and the USA. This plant is a perennial herb endemic to the sandy seashores of Eastern Asia, mainly Eastern China, Korea, Japan, and far Eastern Russia. Due to a decline in the number of wild G. littoralis plants in China over the last few decades, it has been listed in the endangered plants of Chinese chronicles. It is now extensively cultivated in sandy loam soils in inland China for medicinal use.

Common Forms and Preparations

The dried roots can be used both as a dietary ingredient and a therapeutic element in nutritious food preparations. The recommended daily dosage of Glehniae Radix in TCM practice is 10–15 g when used as a decoction. This herb is often found in herbal prescriptions and in soups. Glehniae Radix and its supplements, such as pills and powder, can be found in herbal stores and Asian specialty markets. It is mild enough to use as a food ingredient in soups and teas, making it a popular choice for everyday health support. Bei Sha Shen is commonly added to soups and stews for nourishing effect and is classified as a food-medicine dual-use herb.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

The root of Glehnia littoralis (family Apiaceae) has been used as traditional medicine for thousands of years in China. Glehnia littoralis Fr. Schmidt ex Miq., the sole species in the genus Glehnia (Apiaceae), has long been used in traditional Chinese medicine to treat fatigue, weakness, stomach-yin deficiency, lung heat, cough, dry throat, and thirst.

The root is often used as a drug in clinics to invigorate yin. When dried, the roots are sweet, slightly bitter, and slightly cold and are used to nourish yin, moisten the lung, expel phlegm, and prevent cough. In TCM, G. littoralis has the traditional effects of clearing heat, tonifying yin, clearing lung, and nourishing stomach.

As a traditional herbal medicine, Glehniae Radix has a rich cultural heritage and is used in traditional healing practices to treat multiple symptoms including cough, fever, bloody phlegm, fatigue, dry throat, and thirst. It is commonly used to treat respiratory conditions (rhinitis and asthma), gastrointestinal conditions (gastric ulcer), and autoimmune-related diseases. It is also widely utilized in Japan, Korea, and other Asian nations. Since ancient times, more than 50 kinds of TCM prescriptions have been recorded in various ancient books.

Historical texts such as Bencao Congxin (New Compilation of Materia Medica) describe Bei Sha Shen for its ability to "nourish lung yin, clear lung heat, promote stomach fluids, and relieve dry coughs with little phlegm, dry throat, and thirst." The Depei Bencao further highlights its role in moistening the lungs, nourishing the stomach, clearing deficiency heat, and stopping night sweats.

Use in Korean and Japanese Medicine

Glehnia littoralis (Umbelliferae) is a traditional medicine used in Korea, China, and Japan to treat immune-related diseases. In Japan, it is known as hamabofu and has been recorded in traditional Kampo practice for respiratory and digestive complaints.

Ethnic Medicine: Mongolian and Tibetan Traditions

In Mongolian medicine, the dried root is mainly used to treat cough induced by lung heat, as well as fever, body fluid deficiency, thirst, and other conditions. In Tibetan medicine, the root is primarily used to treat rheumatism, paralysis, and skin diseases, among others.

Traditional Use as Food

G. littoralis has long been used in traditional Chinese medicine and has recently been incorporated into a wide range of Chinese vegetarian cuisines. The dual food-medicine status reflects its generally recognized mild nature within Asian culinary traditions.

3. Key Constituents and Active Compounds

Overview of Phytochemical Diversity

More than 186 components, including coumarins, lignans, polyacetylenes, organic acids, flavonoids, and terpenoids, have been isolated and identified from G. littoralis. The pharmacological activities of more than half of these chemicals are yet unknown. A phytochemical investigation revealed that the primary active compound classes are phenylpropanoids, coumarins, lignanoids, and flavonoids, organic acids and derivatives, terpenoids, polyacetylenes, steroids, nitrogen compounds, and others. In addition, G. littoralis also contains volatile oils, polysaccharides, and polyols.

Coumarins

Coumarins are among the most structurally diverse and pharmacologically significant classes of compounds identified in glehnia root. Both pyranocoumarins as well as furanocoumarins such as imperatorin, psoralen, and bergapten have been identified in glehnia. A total of 41 coumarins have been identified from Radix Glehniae extracts using advanced mass spectrometry methods. Among the various compound classes, polysaccharides and coumarins are regarded as important active components of Glehniae Radix; they are closely related to the traditional curative effect and modern pharmacological effect.

Furocoumarins xanthotoxin, bergapten, psoralen, and imperatorin are selective for CYP2A6 inhibition. Psoralen has also been reported as a phytoalexin in G. littoralis, suggesting a role in the plant's own defensive chemistry.

Lignans and Neolignans

From the underground parts of Glehnia littoralis, 26 compounds have been obtained including two new lignan glycosides (glehlinosides A and B), a new neolignan glycoside (glehlinoside C), and a new phenylpropanoid glycoside. Lignans of dibenzylbutyl-type and 8-O-4′-linked neolignan-type in Beishashen are biosynthesized from coumaric groups and are specified as glehlinosides.

Polyacetylenes

Polyacetylenes are fat-soluble compounds that are abundant in the Apiaceae family and have various biological activities including antibacterial, antifungal, and antitumor. These compounds can be used as important markers to evaluate the quality of G. littoralis. Key identified polyacetylenes from the root include falcarinol (also known as panaxynol), falcarindiol, and falcaindiol. The first isolation of two polyacetylene compounds with antibacterial activity from the root of G. littoralis, including (10E)1,10-heptadecadiene-4,6-diyne-3,9-triol and (9Z)1,9-heptadecadiene-4,6-diyne-3,8,11-triol, showed strong inhibitory effects against Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus.

Phenolic Acids and Flavonoids

A DPPH radical-scavenging assay disclosed quercetin, isoquercetin, rutin, chlorogenic acid, and caffeic acid as the major antioxidative constituents in the crude drug. Phytochemical investigation of the roots also led to the isolation of compounds including three β-carboline alkaloids, four phenylpropanoids, five phenolic acids, three polyacetylenes, and one fatty acid. The report of β-carboline alkaloids in G. littoralis was notably the first report of this compound class in the entire Umbelliferae family.

Polysaccharides

Glehnia littoralis polysaccharides (GLPs) constitute one of the primary active ingredients, demonstrating notable biological activities including immunomodulatory, antioxidant activity, and antitumor effects. A polysaccharide named GRP (Glehniae radix polysaccharide) isolated and purified from Glehniae radix by hot water extraction, ethanol precipitation, anion-exchange, and gel-filtration chromatography was found to be homogeneous with a molecular weight of 1.33 × 10⁴ Da.

4. Scientific Evidence by Area of Use

Important General Caveat

Lab studies suggest anti-inflammatory and antitumor properties, however, studies in humans have not been conducted. Although further studies are required, there is strong evidence of the antitumor and immunoregulatory potential of G. littoralis. More studies are needed to elucidate the mechanisms of action of its active compounds (e.g., falcarinol and panaxydiol) before any clinical studies can be carried out. All evidence summarized below is therefore preclinical (in vitro and animal) unless otherwise noted.

4.1 Anti-Inflammatory Activity

Evidence level: Preclinical (in vitro and animal models only).

A 2010 study investigated the effects of a 70% ethanolic extract of G. littoralis (GLE) on skin inflammation in mice. Researchers investigated the effects on skin inflammation in mice, examining production of proinflammatory cytokines (IL-1β and TNF-α), activation of myeloperoxidase (MPO), and histological indicators in acute and chronic skin inflammation using TPA-induced mouse ear edema and acetic acid-induced vascular permeability tests.

A 2024 in vitro study examined phenolic compounds from glehnia leaf extract in LPS-stimulated macrophage (RAW264.7) cells. Vital inflammatory cytokines, including COX-2, inducible nitric oxide synthase (iNOS), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB), were found to be down-regulated during treatment. The selected compounds also exhibited potent binding capacity to inflammatory factors through molecular docking studies. These results are preliminary, in vitro, and without clinical validation.

Pyranocoumarins isolated from G. littoralis have been reported to inhibit LPS-induced nitric oxide (NO) production in macrophage RAW 264.7 cells, further contributing to the mechanistic picture of anti-inflammatory action. All findings remain at the preclinical stage.

4.2 Antitumor / Anticancer Activity

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

Polysaccharide-mediated anticancer activity: The purpose of one study was to investigate the anticancer activity of polysaccharide (PGL) from G. littoralis on the human lung cancer cell line A549. Based on MTT assay, results suggested that PGL could significantly reduce A549 cell proliferation in a time- and dose-dependent manner. PGL also displayed inhibitory activity for A549 cell migration in Transwell migration assay, and flow cytometry indicated that PGL could promote apoptosis and induce cycle arrest of A549 cells. Immunofluorescence assay further showed PGL could down-regulate expression of proliferating cell nuclear antigen (PCNA), supporting the overall anticancer action through inhibiting migration, proliferation, and inducing cell apoptosis.

Glehnia littoralis polysaccharide effectively inhibits the proliferation and migration of A549 cell lines and induces cell apoptosis. An arabinan polysaccharide fraction (GLP90-2) demonstrated immunostimulatory antitumor effects: mechanistic studies showed that GLP90-2 promoted the maturation of DC2.4 cells and macrophages and enhanced the expression of immune-related cytokines, which may be attributed to interaction between GLP90-2 and TLR-4.

Polyacetylene-mediated cytotoxicity: In a preliminary screening, falcarinol and falcarindiol, C17 polyacetylenes from the roots of G. littoralis, displayed cytotoxic activity both against oxaliplatin-sensitive/resistant colorectal cancer (CRC) and gefitinib-sensitive/resistant non-small cell lung cancer (NSCLC) cells. Thirteen polyacetylenes including a novel compound were isolated and characterized. Oplopandiol showed cytotoxic activities against oxaliplatin-sensitive and -resistant CRC cells. However, both falcarinol and falcarindiol, previously evaluated, were found to have decomposed during testing, which seems to be the cause of inconsistent biological results, highlighting stability challenges with these compounds.

Although further studies are required, there is strong evidence of the antitumor and immunoregulatory potential of G. littoralis. However, all available evidence is in vitro or from animal models, and no human clinical trial data are available for oncological outcomes.

4.3 Immunomodulatory Activity

Evidence level: Preclinical (in vitro and animal models). No human clinical trials identified.

Experimental studies have demonstrated that GLPs significantly enhanced the NK cell cytotoxicity of spleen and promoted T lymphocyte activation in hyperthyroid yin-deficient mice. The biological activities of GRP upon proliferation of splenic lymphocyte, RAW264.7 cells, and A549 cells were investigated in vitro. The results showed that GRP exhibited promotion for proliferation of mouse spleen lymphocytes and RAW264.7 cells, which suggested that GRP may have potential immunoregulation, anti-inflammatory, and anti-tumor activity.

As an herbal medicine, G. littoralis has been employed for treating pulmonary interstitial inflammation, bronchial asthma, and allergic rhinitis. The decoction of G. littoralis combined with other herbs has been reported to have antitumor effects. These TCM combination-formula reports are observational or based on clinical experience records and have not been validated in controlled trials.

4.4 Neuroprotective Activity

Evidence level: Preclinical (animal and cell-based models only).

G. littoralis, described as a medicinal halophyte plant commonly used to treat strokes, has been investigated for neuroprotective and anti-neuroinflammatory effects using a 50% ethanol extract (GLE) on LPS-stimulated BV-2 cells and scopolamine-induced amnesic mice. In the in vitro study, GLE treatment at 100, 200, and 400 µg/mL markedly attenuated the translocation of NF-κB to the nucleus, with significant mitigation of LPS-induced production of inflammatory mediators including NO, iNOS, COX-2, IL-6, and TNF-α. These results suggest that GLE has potential neuroprotective activity that may ameliorate learning and memory impairment by regulating AChE activity, promoting CREB/BDNF signaling, and inhibiting NF-κB/MAPK signaling and neuroinflammation.

In a separate animal study, gerbils were subjected to transient global cerebral ischemia for 5 minutes. The extract of G. littoralis (GLE; 100 and 200 mg·kg⁻¹) was administered once daily before ischemic operations for 7 days. The neuroprotective effect was detected by immunohistochemistry and fluorescence staining; results showed that the ischemic injury area pretreated with 200 mg·kg⁻¹ GLE protected pyramidal neurons (P < 0.05), and the activation of astrocytes and microglia in ischemic CA1 area was significantly inhibited. GLE pretreatment significantly increased the expression of SOD-1 and BDNF in CA1 pyramidal neurons. These studies are entirely preclinical, and no human clinical data exist.

4.5 Antioxidant Activity

Evidence level: Preclinical (in vitro).

A DPPH radical-scavenging assay identified quercetin, isoquercetin, rutin, chlorogenic acid, and caffeic acid as the major antioxidative constituents in the crude drug. Biologically active compounds from GLE were purified to determine their ability to target COX-2 and DPPH; the results showed that significant compounds were identified, demonstrating binding affinity for both COX-2 and DPPH. In vitro antioxidant assays demonstrate radical-scavenging capacity, but no clinical data are available to translate this finding to a human health benefit.

4.6 Hepatoprotective Activity

Evidence level: Preclinical only.

This herb has been studied and shown to have hepatoprotective, immunomodulatory, antioxidant, antibacterial, antifungal, anti-inflammatory, and anticancer properties in preclinical models. No published controlled human trials examining liver-protective outcomes have been identified in the literature.

4.7 Antimicrobial Activity

Evidence level: Preclinical (in vitro).

Pharmacological analysis revealed strong inhibitory effects of polyacetylene compounds against Escherichia coli, Bacillus subtilis, Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. These results are from in vitro assays; no clinical antimicrobial efficacy studies in humans have been identified.

5. Body Systems and Health Areas

• Respiratory system: Glehniae Radix is commonly used to treat respiratory conditions including rhinitis and asthma, as well as symptoms of cough, bloody phlegm, and dry throat in traditional practice.
• Gastrointestinal system: GR is used to relieve coughs, moisten lungs, clear lung-heat, and as an antiphlogistic for the treatment of respiratory and digestive diseases. Its TCM indication for "nourishing stomach yin" places it centrally in the management of dry mouth, reduced appetite, and gastric discomfort attributed to yin deficiency.
• Immune system: GLPs demonstrate notable immunomodulatory and antitumor effects in preclinical models, with effects on NK cell function and T lymphocyte activation.
• Central nervous system: Preclinical evidence points to neuroprotective effects mediated through BDNF upregulation and NF-κB/MAPK pathway modulation, including in models of ischemia and scopolamine-induced memory impairment.
• Liver: Hepatoprotective activity has been noted in preclinical studies, though the specific mechanisms remain under investigation.
• Skin: In Tibetan medicine the root is used to treat skin diseases. Preclinical mouse studies also examined effects on cutaneous inflammation.

6. Dosage Forms and Reported Dosages

Dosage information below is drawn from TCM reference sources and, where available, from reported experimental dosages in preclinical research. No standardized human clinical dosing from controlled trials has been established, as human trials have not been conducted.

• Decoction (traditional oral use): The recommended daily dosage of Glehniae Radix is 10–15 g when used as a decoction. Some TCM references cite a range of 5–12 g per decoction for oral use.
• In formula preparations: In the classical formula Yi Guan Jian (Yiguan decoction), a single dose comprises 5.60 g of Glehniae Radix alongside other herbs.
• Preclinical animal dosages (reported in studies, not for human use):
  • In a cerebral ischemia model, GLE was administered at 100 and 200 mg·kg⁻¹ once daily for 7 days.
  • In an in vitro neuroinflammation study, GLE was tested at concentrations of 100, 200, and 400 µg/mL.
  • In the corresponding in vivo study, mice were orally administered GLE at 50, 100, and 200 mg/kg for 14 days.
• Acute toxicity reference in animal studies: At the maximum Glehniae Radix dosage of 0.04 mL·g⁻¹, no mice died. Another study found that the maximum dosage of the decoction was 32 g·kg⁻¹, which is 13.3-fold higher than that used in clinical practice, indicating that Glehniae Radix is almost nontoxic when used alone.

7. Safety Considerations and Interactions

General Toxicity Profile

At the maximum Glehniae Radix dosage of 0.04 mL·g⁻¹, no mice died in acute toxicity tests. A study found that the maximum dosage of the decoction of Glehniae Radix was 32 g·kg⁻¹, which is 13.3-fold higher than that used in clinical practice, indicating that Glehniae Radix is almost nontoxic when it is used alone.

Furanocoumarin-Associated Phototoxicity

Both pyranocoumarins as well as furanocoumarins such as imperatorin, psoralen, and bergapten have been identified in glehnia. Theoretically, glehnia may have phototoxic effects or CYP3A4 interactions due to furanocoumarin components. In theory, compounds in glehnia may cause increased skin sensitivity to light. Additional research is necessary to determine the safety and efficacy of this botanical.

CYP Enzyme Interactions

Glehnia root may theoretically inhibit CYP3A4 in a dose-dependent manner due to furanocoumarins; clinical relevance is not known. Furocoumarins xanthotoxin, bergapten, psoralen, and imperatorin are selective for CYP2A6 inhibition. Animal-based pharmacokinetic research has further shown CYP enzyme modulation: the decoction of Glehniae Radix can induce CYP2C9 activities in rats, and co-decoction with Radix et Rhizoma Veratri Nigri can significantly induce CYP1A2 and CYP2C9 activities. Furthermore, compared with Glehniae Radix alone, the co-decoction with Veratrum nigrum significantly inhibited CYP3A4 activity and significantly induced CYP1A2 activity. All data on CYP interactions are from animal studies; no human pharmacokinetic data for glehnia root are available.

Herb–Herb Interaction: Veratrum nigrum (Lilu)

According to historical records in China, the co-decoction of Glehniae Radix and Radix et Rhizoma Veratri Nigri (Lilu) might produce toxicity or side effects. Animal toxicity studies showed that the mortality rate of mice administered a mixed decoction was 25%, while the co-decoction produced a 65% mortality rate at the same dose. When the ratio of Glehniae Radix to Veratrum nigrum decoction increased from 1:1 to 1:4.19, the mortality of mice reached 90%. Promotion of the dissolution of the toxic component of Radix et Rhizoma Veratri Nigri in co-decoction may be the cause of the higher toxicity. Therefore, a prescription combining these drugs should be avoided in clinical practice. Glehniae Radix should not be used concurrently with species of Veratrum nigrum L.

TCM Contraindications

Glehniae Radix should not be used by individuals experiencing conditions of Wind-Cold or by individuals with a weak Cold Spleen according to TCM clinical doctrine. These are traditional contraindication frameworks without modern clinical validation.

Herb–Herb Pharmacokinetic Interaction: Ophiopogonis Radix

The combination of Glehniae radix and Ophiopogonis radix has long been widely used as a TCM herb pair for the treatment of respiratory and digestive diseases. The pharmacokinetic interaction mechanism of these two herbs has been investigated in rats. Increases in the AUCs of nine components of the GR–OR combination were observed and were attributed to herb–herb pharmacokinetic interaction. These results underscore the complexity of multi-herb formulations containing glehnia and the potential for pharmacokinetic changes when herbs are combined.

Conservation Status

Glehnia littoralis is an endangered plant species with significant medicinal, edible, and ecological value, and is now a central concern for conservation and sustainable utilization. Sourcing from wild populations is increasingly restricted in China, and cultivated material has become the norm for commercial preparations.

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