Southern Tsangshu (Atractylodes lancea): A Comprehensive Reference
1. Identity and Botanical Characterization
Scientific Nomenclature and Taxonomy
Atractylodes lancea (synonyms: Atractylodes chinensis, Atractylodes japonica, Atractylodes ovata) is a species of flowering plant in the family Asteraceae, native to Vietnam, most of China, Korea, the southern Russian Far East, and Japan. The accepted full scientific authority is Atractylodes lancea (Thunb.) DC., where "Thunb." refers to the Swedish botanist Carl Peter Thunberg, who originally described the species, and "DC." to Augustin Pyramus de Candolle, who transferred it to the genus Atractylodes.
Among its many documented synonyms are Acarna chinensis Bunge, Atractylis chinensis (Bunge) DC., and Atractylis lancea Thunberg. The common name "Southern Tsangshu" is one of several English-language vernacular designations for the herb; other names include Lance-leaved Atractylodes, Cang zhu, Cangzhu, Mao cang zhu, and Nan cang zhu.
It is the source of cāng zhú (蒼朮), a Chinese herbal medicine sold to people suffering from a variety of ailments. The drug is also known by distinct names in other East Asian medical traditions: it is called "Cangzhu" in China, "Khod-Kha-Mao" in Thailand, and "So-jutsu" in Japan.
Morphology and Distribution
Atractylodes lancea is a perennial growing to 1 m (3 ft 3 in), flowering from July to October, with seeds ripening from August to October. It is a dioecious plant thought to be native to Asia and now cultivated globally. Successful cultivation requires adequate precipitation with moist, well-drained soil. It is found in wastelands and woodlands but does require sunlight, either direct or semi-shaded. A. lancea falls under the family Compositae and is a flowering perennial plant which blooms in late summer through early fall. The leaves are lance-like and produce seeds in late summer through the end of the growing season.
Atractylodes lancea is a perennial herb belonging to the Asteraceae family, primarily cultivated in regions like Jiangsu, Henan, Hebei, Shanxi, and Shaanxi in China, with the plant's dried rhizomes being the prized parts used in medicinal preparations. Its rhizome (3–10 cm) appears as a yellowish-brown color.
Pharmacopoeial Status and Related Species
A. lancea and A. chinensis are perennial plants, known to be widely distributed in China, and are prescribed in the Chinese, Japanese, and Korean Pharmacopoeias as the botanical origins of the crude drug Cangzhu (Sojutsu in Japanese), collectively termed Atractylodis Rhizoma. The dried rhizomes of Atractylodes lancea or Atractylodes chinensis are referred to as Atractylodis Rhizoma in the 2020 edition of the Chinese Pharmacopoeia.
In the Japanese Pharmacopoeia, Atractylodes Lancea Rhizome is defined as the rhizome of Atractylodes lancea De Candolle, Atractylodes chinensis Koidzumi, or their interspecific hybrids. In the Korean and Japanese Pharmacopoeias, the Atractylodis Rhizoma has been prescribed in traditional medicine as a diuretic and stomachic drug.
Common Forms and Preparations
The rhizome of Atractylodes lancea is extensively used in Chinese, Thai, and Japanese traditional medicines as crude extracts/decoctions or as a component in various herbal formulations. The rhizome is typically harvested, dried, and then processed in various ways depending on the intended use. Traditional processing included bran-frying and raw preparations; the dried rhizomes of the plant are commonly used to dry dampness, strengthen the spleen, disperse wind and cold, improve eyesight, and treat various gastrointestinal diseases. Modern pharmaceutical development has produced standardized capsule formulations of ethanolic extracts. The rhizome is rich in volatile oil, making up approximately 3.5–7% of the dried rhizomes.
2. Traditional and Historical Use
Classical Chinese Medicine and Earliest Records
The history of using rhizomes of A. lancea as a drug can be traced back to the Han dynasty (206 BC–220 AD), when it was described in Shen-nong-ben-cao-jing, the first Chinese pharmacopoeia. Atractylodis Rhizoma has been used as an important crude drug for the treatment of rheumatic diseases, digestive disorders, night blindness, and influenza in TCM, and was listed in the Shennong Bencao Jing, the first Chinese Pharmacopoeia.
According to the theory of TCM, Atractylodes lancea (Cangzhu) was attributed to the spleen, stomach, and liver meridians, with a rhizome that tastes pungent and bitter. Atractylodes lancea could be used to treat rheumatic diseases, digestive disorders, night blindness, and influenza. Historically, it occupied an important role in classical Chinese materia medica, appearing not only in the earliest pharmacopoeia but also in subsequent classical texts. In the Qing dynasty, the work Drug Interpretation of Yuqiu (Yuqiu Yaojie) noted that Cangzhu can digest food and eliminate lipids.
The herb also held significance outside strictly medical contexts. One manuscript in the Declarations of the Perfected (Zhen'gao), compiled by Tao Hongjing around 500 AD, celebrates a plant native to the Mao mountains: the herb atractylodes, cangzhu (蒼朮), or Atractylodes lancea Thunb.
Traditional Chinese Medicine (TCM) Framework
Atractylodes lancea is a common medicinal plant used in Traditional Chinese Medicine and in Japanese Kampo practices for a variety of complaints, but primarily as a general tonic and digestive aid. Today, the main functions in Chinese medicine for both baizhu (A. macrocephala) and cangzhu (A. lancea) are the ability to overcome moisture accumulation (damp impediment) and to promote digestion (disperse food). Traditional Chinese medicine theory states that both groups have a similar mode of action for invigorating the spleen and eliminating dampness.
Its use is primarily justified by historical and traditional medical texts, especially within the framework of TCM, where it is considered to "dry dampness" and "strengthen the spleen," which is believed to support digestive function and alleviate symptoms like belching, interpreted in TCM as signs of spleen qi deficiency or dampness obstructing the middle burner.
Atractylodes lancea was generally used in classical decoctions, notably Ermiao Powder and Simiao Powder. The rhizomes of A. lancea have mainly been used for digestive disorders and body fluid imbalance.
Japanese Kampo Medicine
Dried rhizomes of A. lancea are prescribed in Japanese and Chinese herbal medicines as the crude drug. In Japan, the crude drug is called "So-Jutsu," whereas in China it is called "Chang-zhu." Its dried rhizome has been used as an important crude drug in traditional Chinese and Japanese medicines, and in these medicines, various decoctions containing the crude drug have been used for the treatment of digestive disorders and body fluid imbalance.
Korean Traditional Medicine
Atractylodes lancea Thunb (AAL), commonly referred to as Changchul (Cangzhu in Chinese), is a perennial herb used extensively in Korean and Oriental medicine for its therapeutic properties. In Korea, atractylodes rhizome herbal medicines are called "Baekchul" and "Changchul" (analogous to Baizhu and Cangzhu, respectively).
Thai Traditional Medicine
In Thai traditional medicine, the main use of A. lancea is for the treatment of fever and cold. Thai researchers have more recently taken an active scientific interest in the plant, particularly regarding its potential against cholangiocarcinoma (bile duct cancer), which is endemic to the northeast region of Thailand.
3. Key Constituents and Active Compounds
Essential Oil Fraction
The major active compounds in A. lancea are essential oil compounds such as β-eudesmol, hinesol, atractylon, and atractylodin. The contents of these compounds in A. lancea exhibit high variability depending on their habitat. Previous phytochemical investigations revealed a series of sesquiterpenoids, monoterpenes, polyacetylenes, phenolic acids, and steroids from the rhizomes. The major constituents include atractylodin (14%), β-eudesmol (6%), atractylon (2%), and hinesol (1%). Other minor constituents include atractyloside A, atractyloside F, atractyloquinone, and atractylochromene.
The rhizome is rich in a volatile oil including atractylodin, β-eudesmol, hinesol, elemol, atractylone, and β-selinene. Sesquiterpenoid glycosides include atractyloside A 14-O-β-D-fructofuranoside and related compounds.
Sesquiterpenoids: β-Eudesmol and Hinesol
Major active ingredients in A. lancea are essential oil compounds, namely sesquiterpenoids (β-eudesmol, hinesol, atractylon) and polyacetylene (atractylodin). Its major active compounds are sesquiterpenoids such as β-eudesmol and hinesol, which have closely related chemical structures. As criteria for evaluating the quality of A. lancea, the β-eudesmol/hinesol content ratio is considered important. This ratio could be influenced by genetic factors, geographical environment factors, and their interactions.
The pharmacological activities of these two compounds are similar; however, the intensity of pharmacological activity and action mechanism may differ. For instance, both β-eudesmol and hinesol have mitigation effects against gastric ulcer, but their pharmacological action mechanisms are different. Additionally, hinesol has activity to induce apoptosis in human leukemia HL-60 cells, suggesting the possibility that hinesol may be a useful anticancer compound, while this activity is weak in β-eudesmol.
Atractylodin
Atractylodin is a polyacetylene compound and one of the most abundant bioactive constituents of the rhizome. Atractylodin and β-eudesmol, the major bioactive compounds in Atractylodes lancea, are considered promising candidates for anti-cholangiocarcinoma activity. The sesquiterpenoid compounds have been reported to have anti-ulcer activity, while atractylodin has been reported to ameliorate delayed gastric emptying.
Atractylon and Other Compounds
Recent in vitro studies have shown that sesquiterpenoids such as atractylone and β-selinene can modulate adipogenesis and lipid metabolism by activating AMPK (AMP-activated protein kinase), a critical regulator of energy homeostasis. Furthermore, atractylone has demonstrated anti-inflammatory effects by inhibiting NF-κB signaling and reducing pro-inflammatory cytokine expression in macrophages.
Among additional constituents, apigenin 7-glucoside flavonoids have been reported to have antioxidant and anti-inflammatory activity, and diosmetin 7-O-beta-D-glucuronopyranoside shows antioxidant activity.
Chemotype Variation by Geography
The A. lancea distributed in Hubei, Anhui, Shaanxi, and a region west of Henan province was classified as the Hubei Chemotype (HBA), characterized by a high content of β-eudesmol and hinesol with lower levels of atractylodin and atractylon. In contrast, the Maoshan Chemotype (MA) from Jiangsu, Shandong, Shanxi, Hebei, Inner Mongolia, and other northern regions exhibited high levels of atractylodin and atractylon. This chemotypic variation has direct implications for the pharmacological properties and quality assessment of commercial preparations.
4. Pharmacology and Mechanisms of Action
Overview of Demonstrated Pharmacological Activities
In vitro and in vivo studies in animal models demonstrate promising activities of the crude extracts (ethanolic, water, benzene, and methanol) of Atractylodis Rhizoma as well as its major constituents (β-eudesmol, atractylodin, hinesol, atractylon, atractylochromene, and quinone) on cancers, inflammation, fever and pain, gastrointestinal system, nervous system, cardiovascular system, and various microorganisms including Staphylococcus aureus, Escherichia coli, Saccharomyces cerevisiae, Candida albicans, Rhodotorula glutinis, and Saprolegnia. In addition, hepatoprotective and immunostimulating activity of A. lancea have also been demonstrated.
A. lancea rhizomes have been shown to exhibit pharmacological activities on nervous, cardiovascular, and gastrointestinal systems. Additionally, anticancer, anti-inflammatory, and antimicrobial activities have also been reported.
Gastrointestinal Mechanisms
The pharmacological activities of A. lancea and its constituents on the gastrointestinal system—including delay of gastric emptying, stimulation of intestinal motility, inhibition of gastric secretion, and antiulcer property—strongly support their clinical use for alleviation of digestive symptoms. A study in Journal of Ethnopharmacology (Kimura and Sumiyoshi, 2012, as cited in multiple PMC reviews) specifically investigated the effects of an Atractylodes lancea rhizome extract and a volatile component β-eudesmol on gastrointestinal motility in mice. Additionally, the anti-ulcer activity between the crude and bran-processed Atractylodes lancea was compared in a rat model of gastric ulcer induced by acetic acid (Yu et al., Journal of Ethnopharmacology, 2015).
Pharmacological effects include treating gastric ulcers, tumors, and inflammation, protecting the liver, regulating gastrointestinal (GI) activities, and inhibiting gastric acid secretion. It is particularly effective in the treatment of GI diseases.
Anti-Inflammatory Mechanisms
Resch, Steigel, Chen, and Bauer identified 5-lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes lancea in a 1998 study in the Journal of Natural Products. A laboratory study found 5-lipoxygenase and cyclooxygenase-1 (COX-1) inhibiting properties in lipophilic extracts of A. lancea rhizome.
Research on atractylodin has suggested a potential regulatory effect on inflammatory mediator expression through blockade of both the phosphorylation of MAPKs and the NPM-ALK signaling pathway. Research has also shown that A. lancea polysaccharide can reduce the expression levels of AST, ALT, and MDA in the liver, increase the activity of SOD and GSH-Px, and alleviate LPS-induced liver inflammation in mice by inhibiting the NF-κB signaling pathway.
Metabolic and Glucose-Lowering Mechanisms
Following 8 weeks of high-fat diet (HFD) feeding, mice receiving oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea showed reduced body weight; serum triglyceride, total cholesterol, and alanine aminotransferase levels; and hepatic lipid content. Furthermore, Atractylodes lancea significantly ameliorated fasting serum glucose, fasting serum insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) levels in response to HFD. A glucose tolerance test demonstrated improved glucose homeostasis.
Treatment with 5 or 10 mg/kg atractylodin also resulted in anti-obesity, anti-steatosis, and glucose-lowering effects. Atractylodin treatment resulted in the downregulation of key lipogenic genes (Srebf1, Fasn, Scd2, and Dgat2) and the upregulation of genes regulated by peroxisome proliferator-activated receptor-α.
In vitro studies have shown that sesquiterpenoids such as atractylone and β-selinene can modulate adipogenesis and lipid metabolism by activating AMPK (AMP-activated protein kinase), a critical regulator of energy homeostasis.
Cardiovascular Mechanisms
In laboratory studies, A. lancea has been reported to inhibit platelet aggregation. Research on atractyloside-type compounds from related Atractylodes species has further characterized how certain compounds can reduce agonist-induced platelet aggregation and ATP secretion, downregulate p-Akt and p-p38 MAPK levels, inhibit platelet proliferation and clot contraction, prolong the time to first occlusion, and prolong bleeding. The sesquiterpenoid extracted from A. lancea showed inhibition of blood vessel development in zebrafish embryos; β-eudesmol downregulated Vegfaa gene expression at all concentrations tested.
Hepatoprotective Mechanisms
Research has shown that A. lancea polysaccharides can prevent liver damage caused by harmful chemicals and toxins. Numerous pharmacological experiments, both in vivo and in vitro, have demonstrated that Atractylodis Rhizoma exhibits liver protection, lowers blood glucose, has diuretic properties, and anti-hypoxic effects, as it contains various sesquiterpenoids and other compounds.
Diuretic Activity
A. lancea has been reported to have a diuretic effect. Studies have found that intravenous injection or oral administration of 1.0 g/kg A. lancea solution can significantly increase the urine output of mice.
5. Scientific Evidence by Area of Use
5.1 Gastrointestinal Health
The gastrointestinal effects of A. lancea are the most extensively studied area. Evidence comes predominantly from preclinical animal models and in vitro work. Pharmacological effects include treating gastric ulcers, regulating gastrointestinal (GI) activities, and inhibiting gastric acid secretion. The rhizome has been shown to modulate intestinal motility in mouse models. A foundational 1990 study by Yamahara et al. in Journal of Ethnopharmacology documented an intestinal motility enhancing effect of Atractylodes lancea rhizome.
Research on the microbiome has also been conducted. One study aimed to explore the effect of an extract of Atractylodes lancea on antibiotic-induced intestinal tract disorder and the probable therapeutic mechanisms employed by this extract to ameliorate these disorders. All evidence in this area remains preclinical (animal and cell-based). No adequately powered, controlled clinical trials in humans specifically addressing gastrointestinal indications for A. lancea alone have been published to date.
Evidence strength: Preclinical only; supportive of traditional use but not confirmed by human trials.
5.2 Metabolic Syndrome, Glucose Regulation, and Obesity
Animal model data show promise for metabolic applications. Atractylodes lancea extract has been reported to attenuate obesity and improve glucose tolerance in high-fat diet-induced obese animal models. The active ingredients in A. lancea can improve glucose uptake, inhibit fat production, and regulate lipid metabolism in animals.
One small clinical observation in humans has been reported. A case report of 32 patients with senile obesity or overweight complicated with impaired glucose tolerance (IGT) found that in those treated with Atractylodes decoction versus control, body weight, waist circumference, hip circumference and waist-to-hip ratio, glucose tolerance, fasting serum insulin, and blood lipids improved significantly (P < 0.05 or P < 0.01). This 2006 study was published in the Journal of Traditional Chinese Medicine and is the primary human evidence in this area, but it is extremely limited: 32 subjects, non-randomized case-report design, and use of a compound formula rather than A. lancea alone.
A 2025 rat study in BMC Complementary Medicine and Therapies investigated cardiac and renal effects. Metabolic syndrome was induced in rats through an 8-week high-fat, high-fructose diet. After induction, experimental groups were orally administered aqueous extract of Atractylodes lancea (AAL) at 100 or 200 mg/kg/day for an additional 8 weeks. Body weight, fasting blood glucose, triglycerides, abdominal circumference, systolic blood pressure, and HDL-cholesterol levels were measured.
Evidence strength: Animal models are supportive; human evidence is limited to a very small, non-randomized observation using a compound formula.
5.3 Anti-Cancer (Cholangiocarcinoma and Others)
The most active recent clinical research on A. lancea has focused on cholangiocarcinoma (CCA, bile duct cancer), driven largely by a Thai research group. Modern pharmacological studies support broad pharmacological effects of A. lancea on various diseases. In vitro and in vivo studies in animal models demonstrate promising anticancer activities of the crude extracts and its major constituents.
In cell studies, β-eudesmol and atractylodin potently inhibited CL-6 (CCA) cell growth with mean IC50 of 21.5 ± 2.12 and 24.0 ± 1.98 μM, respectively. The cytotoxic activities of atractyloside III and hinesol were relatively weak (IC50 of 145.9 ± 14.4 and 91.0 ± 8.0 μg/ml, respectively). The interaction between β-eudesmol and atractylodin was additive.
At the human clinical level, phase I (safety/tolerability) trials have been conducted. Atractylodes lancea has been demonstrated in a series of studies to be a potential candidate for the treatment of cholangiocarcinoma. The aim of one study was to evaluate the safety and pharmacokinetics of the capsule formulation of the standardized AL extract in healthy Thai participants. Forty-eight healthy Thai participants were allocated to two study groups. Group 1 participants were randomized to receive a single oral dose of 1,000 mg of AL or placebo. Group 2 participants were randomized to receive daily oral doses of 1,000 mg AL or placebo daily for 21 days. The study was the first pharmacokinetics study of Atractylodes lancea in humans. AL was well tolerated as verified by clinical and laboratory investigations.
Atractylodin was rapidly absorbed but with low systemic exposure and residence time. There was no difference in the pharmacokinetic parameters of atractylodin following a single or multiple dosing, suggesting the absence of accumulation.
In a separate phase I immunomodulatory trial in healthy Thai volunteers, changes in pro-inflammatory (IL-2, IL-4, IL-6, IL-17A, TNF-α, and IFN-γ) and anti-inflammatory (IL-10) cytokine profiles, lymphocyte subpopulations, and cytotoxic activity against CCA cell line of peripheral blood mononuclear cells (PBMCs) following administration of a single and multiple dose regimens of a standardized AL extract were investigated. The confirmed immunomodulatory activity, in complementary with the direct action of AL on inducing CCA cell apoptosis, would support the potential of AL for further clinical development for CCA control.
Recent studies have shown that Atractylodes lancea could inhibit proliferation by cellular signaling pathways involved in gastric cancer cells, cholangiocarcinoma (CCA), and non-small cell lung cancer.
Evidence strength: Preclinical evidence is extensive but limited to cell lines and animal models. Phase I human trials demonstrate safety and tolerability at 1,000 mg/day for 21 days but do not assess efficacy. No phase II or III efficacy trials in cancer patients have been published as of 2025.
5.4 Inflammation and Rheumatic Conditions
The dried rhizomes of the plant are commonly used in traditional medicine to treat rheumatic diseases and colitis. Preclinical anti-inflammatory evidence includes inhibition of key inflammatory enzymes: 5-lipoxygenase and cyclooxygenase-1 (COX-1) inhibitory active compounds have been identified from Atractylodes lancea. Atractylone has demonstrated anti-inflammatory effects by inhibiting NF-κB signaling and reducing pro-inflammatory cytokine expression in macrophages. All evidence for rheumatic and inflammatory indications remains at the preclinical level.
Evidence strength: Preliminary, preclinical only.
5.5 Antimicrobial and Antifungal Activity
The antioxidant and antibacterial activities of Atractylodes lancea essential oil have been investigated. An essential oil was extracted by steam distillation from the rhizomes. Chemical components were determined by GC-MS. Antioxidant activities were investigated by DPPH radical scavenging, inhibition of lipid peroxidation, and effect on total antioxidant capacity in mice. Antimicrobial activities were determined by agar disc diffusion assay and double-broth dilution method, with antimicrobial mechanisms investigated based on cell membrane permeability and electron microscopy.
Studies have found that A. lancea has many biological functions, including anti-inflammatory, antioxidant, antiviral, and antibacterial properties. In vitro evidence shows activity against organisms including Staphylococcus aureus, Escherichia coli, Saccharomyces cerevisiae, and Candida albicans, but no clinical trials in humans for infection-related indications exist.
Evidence strength: In vitro only.
5.6 Night Blindness (Vitamin A Deficiency)
The rhizome of A. lancea is used for treatment of influenza, rheumatic diseases, night blindness, and a few digestive problems according to traditional sources. While the traditional indication of night blindness has a long history, no modern controlled clinical studies have evaluated A. lancea specifically for this purpose. The mechanistic basis for this traditional use has not been elucidated in peer-reviewed literature.
Evidence strength: Traditional use only; no modern clinical evidence identified.
6. Body Systems and Health Areas Associated with A. lancea
The pharmacological activities of A. lancea and their active constituents include anticancer, anti-inflammatory, antimicrobial, and antipyretic activities, as well as activities on the central nervous, cardiovascular, and gastrointestinal systems.
- Gastrointestinal system: Gastric acid inhibition, intestinal motility modulation, anti-ulcer activity, support for digestive function, treatment of gastrointestinal dysbacteriosis.
- Metabolic/endocrine system: Blood glucose modulation, lipid metabolism regulation, anti-obesity effects (primarily in animal models).
- Hepatic system: Hepatoprotection, including prevention of liver damage caused by harmful chemicals and toxins.
- Cardiovascular system: Inhibition of platelet aggregation, anti-thrombotic activity in preclinical models, modulation of blood pressure in metabolic syndrome animal models.
- Immune system: Immunomodulatory activity demonstrated in a phase I human trial.
- Musculoskeletal system: Traditional use in rheumatic diseases, supported by in vitro anti-inflammatory data.
- Renal system: Diuretic effects demonstrated in animal studies.
- Oncology (investigational): Cytotoxic activity against cholangiocarcinoma, gastric cancer, colorectal cancer, and non-small cell lung cancer cell lines in preclinical models.
7. Dosage Forms and Reported Dosages
A. lancea has historically been administered as a decoction (water extract) of the dried rhizome, either alone or as part of compound formulae. Modern preparations include standardized ethanolic extract capsules.
Dosages reported in cited scientific sources:
- Phase I clinical trial (safety/pharmacokinetics): A single oral dose of 1,000 mg of standardized AL capsule extract, or daily oral doses of 1,000 mg for 21 days, were evaluated in healthy Thai participants.
- Preclinical metabolic studies (high-fat diet mice): Oral doses of 30, 60, or 120 mg/kg of Atractylodes lancea were administered to mice following 8 weeks of high-fat diet feeding.
- Atractylodin (isolated compound, preclinical): Treatment with 5 or 10 mg/kg atractylodin resulted in anti-obesity, anti-steatosis, and glucose-lowering effects.
- Diuretic studies (animal): Intravenous injection or oral administration of 1.0 g/kg A. lancea solution was found to significantly increase the urine output of mice.
- Cardio-renal metabolic syndrome model (rat): Experimental groups were orally administered aqueous extract of Atractylodes lancea (AAL) at 100 or 200 mg/kg/day for 8 weeks.
- CYP450 modulation studies (mouse): The modulatory effects were investigated in mouse livers following a daily oral dose of atractylodin or β-eudesmol at 100 mg/kg body weight for 1, 7, 14, and 21 days.
No standardized or consensus human dosage has been established for any indication. The 1,000 mg/day capsule dose used in the Thai phase I trials represents the only human pharmacokinetic data available as of current literature.
8. Safety Considerations and Drug Interactions
General Safety Profile
Various pharmacological activities of A. lancea and its major constituents have been demonstrated in vitro, ex vivo, and in animal models. Results from toxicity studies in animal models suggest a safety profile of A. lancea and its active constituents. Despite extensive use with positive outcomes in many diseases, there has not been a clinical study that can conclusively support its efficacy and safety profile in humans.
In the phase I clinical trial in humans, AL was well tolerated as verified by clinical and laboratory investigations. There was no change in the pharmacokinetics of atractylodin (the AL active compound) when given as multiple dosing for 21 days, indicating an absence of accumulation in the short-term setting studied.
Platelet Aggregation and Anticoagulant Interactions
Atractylodes lancea has been reported to inhibit platelet aggregation in laboratory studies. Based on pharmacology, caution is warranted in individuals with bleeding disorders or those taking blood-thinning medications such as aspirin or warfarin.
Cytochrome P450 Enzyme Interactions
The inhibitory effects of atractylodin and β-eudesmol on human recombinant CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 enzymes were investigated. The inhibitory effects of both compounds on all rCYP450s were weak overall (IC50: 167 to >686 μM). β-Eudesmol showed the most potent inhibitory effect on rCYP2C19 (IC50 = 172.7 μM) and rCYP3A4 (IC50 = 218.6 μM).
Results of an ex vivo study showed that short exposure (1–7 days) of atractylodin and β-eudesmol resulted in the upregulation of mRNA. Prolonged exposure to the daily oral dose for at least 14 days significantly downregulated the expressions of mRNA and proteins, correlated with a decrease in the activities of mCYP1A2 and mCYP enzymes.
Based on these results, clinical uses of atractylodin or β-eudesmol for the treatment of cholangiocarcinoma are of concern for the risk of toxicity due to hCYP3A4 inhibition following chronic dosing, as well as the metabolic interaction with co-administered drugs metabolized by hCYP3A4. This is a significant consideration for any concurrent pharmaceutical drug therapies.
Evidence Gaps and Limitations
Despite extensive use with positive impressions in many diseases, there has not been a clinical study that can conclusively support the efficacy and safety profile of A. lancea in humans. The evidence base remains predominantly preclinical. Available human clinical data are confined to phase I safety and pharmacokinetic studies in healthy volunteers, conducted primarily for the specific cholangiocarcinoma research program of a Thai research group. No large-scale randomized controlled trials for any indication have been published as of the current literature base. Additionally, the contents of the major active compounds in A. lancea exhibit high variability depending on habitat, which means that the quality and potency of commercial preparations may vary considerably.
References
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