Siegesbeckia (Sigesbeckia orientalis and Related Species)
1. Identity: Botanical Classification, Nomenclature, and Natural Source
Siegesbeckia is an annual plant belonging to the family Asteraceae. The name is sometimes spelled "Siegesbeckia," though according to a paper published by The Royal Botanic Gardens, Kew, the technically correct spelling is Sigesbeckia. The genus is commonly represented by three medicinally recognized species that are used interchangeably under the collective herbal drug name Herba Siegesbeckiae (known in Chinese as Xi-Xian Cao, 豨莶草).
Herba Siegesbeckiae mainly includes Sigesbeckia orientalis L., Sigesbeckia pubescens Makino, and Sigesbeckia glabrescens Makino. Sigesbeckia pubescens carries the full scientific name Sigesbeckia orientalis L. subsp. pubescens (Makino) H.Koyama, and is more commonly known as Sigesbeckia, St Paul's wort, or in some circles as "pig pungent weed."
The Siegesbeckia genus (Compositae family) comprises about 20 species worldwide; they are distributed in the tropical, subtropical, and temperate areas of the world and mainly found in Central China, Northern Vietnam, and other South-East Asian countries. Three Siegesbeckia species have been popularly used as traditional medicines: S. orientalis, S. glabrescens, and S. pubescens.
In ancient medical books, Herba Siegesbeckiae was documented to be the dried aerial part of S. pubescens, which was also the only official origin of the drug in the 1963 edition of the Chinese Pharmacopoeia. The dried aerial parts of S. orientalis and S. glabrescens had been included as two additional origins in each edition of the Chinese Pharmacopoeia since 1977 (or 1997, depending on the source).
The branches of the Sigesbeckia plant are covered in purple-brownish hairs, as are the triangular leaves, which gives the subspecies its name pubescens. It has yellow tongue-shaped flowers that appear in late summer and early autumn. The herb is collected before or during blossom in summer and autumn.
Common Forms and Preparations
- The drug is cut into segments and used unprocessed, or steamed with yellow rice wine for medicinal use.
- The Chinese Pharmacopoeia (2025 Edition) records a single-herb preparation of Siegesbeckiae herba, namely Xixian Pills. This preparation is made from the herb processed with honey and wine.
- A traditional processing method known as the "nine cycles of steaming and shining" (jiuzhi jiupu) has historically been applied to Herba Siegesbeckiae, a procedure aimed at understanding its molecular mechanism from the viewpoints of modern pharmacochemistry and pharmacology.
- The most famous classical prescription containing Herba Siegesbeckiae is Xi-Tong pill, which consists of the herb combined with Folium clerodendri and is used to treat rheumatism and osteoarthritis.
2. Traditional and Historical Use
Traditional Chinese Medicine (TCM)
Herba Siegesbeckiae, also known as "Xi-Xian Cao," has been regarded as an important traditional Chinese medicine since the Tang dynasty. The dried aerial parts of Herba Siegesbeckiae are also used as herbal medicine in many countries such as Japan, Korea, and Vietnam.
The medicinal value of Herba Siegesbeckiae was first recorded in Xin-Xiu-Ben-Cao, written by Jing Su in 1061 A.D. Its medicinal values are recorded in 13 books and it is a constituent of 9 prescriptions.
Siegesbeckia orientalis L. was recorded as able to "eliminate wind-dampness and soothe painful joints" in the State Commission of Chinese Pharmacopoeia (2020), and was noted as being slightly toxic in Xinxiu Bencao (657–659 A.D., Tang Dynasty).
In China, Herba Siegesbeckiae has been used for the treatment of rheumatic arthralgia with aching and weakness of loins and knees, as well as numbness of limbs.
Within TCM theory, the herb is classified as pungent and bitter with a cold thermal property, and enters the liver and kidney meridians. Its actions are described as dispelling wind-damp, unblocking collaterals, clearing heat, and removing toxicity, making it suitable for arthralgia syndromes.
Broader Ethnobotanical Uses Across Asia and Beyond
Herba Siegesbeckiae, one of common Chinese medicinal foods, has been used to treat rheumatoid arthritis, malaria, and snakebite, based on its ability to dispel wind, eliminate dampness, and strengthen the sinews.
These plants have been used traditionally for treating various ailments such as hypertension, neurasthenia, rheumatoid arthritis, asthma, snakebites, allergic disorders, paralysis, soreness, cutaneous disorders, rubella, menstrual disorders, numbness of limbs, dizziness, headache, and malaria.
The whole plant has traditionally been used as a hypoglycemic agent.
3. Key Constituents and Active Compounds
Over 250 compounds have been identified and divided into three main groups: sesquiterpenoids (germacrane, guaiane, and cadinene types), diterpenoids (kaurane and pimarane types), and phenolics (flavone, flavanone, isoflavone, and chalcone). An earlier review reported an even higher count: at that time, 250 compounds had been separated from Siegesbeckia species, namely 128 diterpenoids, 71 sesquiterpenoids, 14 flavonoids, and 37 other compounds.
The full keyword listing from the comprehensive 2021 PubMed review of Herba Siegesbeckiae enumerates the following as documented constituents and markers: kirenol, darutoside, neodarutoside, siegesbeckiol, siegesbeckioside, orientalide, germacranolide, grandifloric acid, baicalin, luteolin, quercetin, 3-methylquercetin, orientin, caffeic acid, chlorogenic acid, ferulic acid, coumarin, oleanolic acid, ursolic acid, stigmasterol, D-mannitol, adenosine, succinic acid, syringaldehyde, palmitic acid, and heneicosanol, among others.
Principal Bioactive Compounds
- Kirenol: Kirenol is an ent-pimarane type diterpenoid that has been reported from Siegesbeckia orientalis, S. pubescens, and S. glabrescens (family Asteraceae). In recent years, kirenol has received great attention due to its diversified pharmacological activities. It is widely regarded as one of the primary bioactive markers of the herb.
- Darutoside: A diterpenoid glycoside co-occurring with kirenol. Kirenol and darutoside together are responsible for anti-inflammatory and antinociceptive effects through inhibiting COX-2 protein expression.
- Hesperidin: A flavanone glycoside present in the ethanol extract of S. pubescens. Kirenol, darutoside, and hesperidin were identified in the ethanol extract of S. pubescens, with relative proportions of 0.6%, 0.2%, and 0.01%, respectively; hesperidin was reported for the first time in this extract.
- Luteolin, chlorogenic acid, syringaldehyde, and related phenolics: Six phenolic components identified in S. orientalis extracts by HPLC include chlorogenic acid, syringic acid, p-coumaric acid, syringaldehyde, luteolin, and apigenin.
- Sesquiterpenoids: Sesquiterpene lactone, orientin, and diterpenes are bioactive chemical substances discovered in the aerial portions of S. orientalis.
Quantitative Content Variation
The contents of rutin, kirenol, and darutoside in S. pubescens ethanolic extract were determined to be 0.27 ± 0.01, 1.81 ± 0.02, and 0.28 ± 0.03%, respectively (n = 3) by HPLC analysis.
4. Mechanisms of Action
Siegesbeckiae Herba, noted for its therapeutic properties in alleviating rheumatism, enhancing joint function, and facilitating detoxification, has been identified as containing multiple bioactive components including sesquiterpenes, diterpenoids, flavonoids, and others.
Anti-Inflammatory Pathways
Research using in vitro and animal models has identified several molecular targets through which Siegesbeckia and its isolated constituents act on inflammation:
- NF-κB inhibition: Ethanolic extract of S. orientalis (SOE) inhibited LPS-induced NF-κB activation by blocking the degradation of IκB-α, and also reduced significantly the phosphorylation of ERK1/2, p38, and JNK in a dose-dependent manner.
- TLR1/TLR2-mediated NF-κB suppression: A study using S. pubescens extract in RAW 264.7 macrophages showed that the extract suppressed inflammation through TLR1/TLR2-mediated NF-κB pathway. The influence of the extract on NF-κB and MAPKs signaling relevant proteins was measured by Western blotting analysis, while intracellular nitric oxide generation and NF-κB/p65 nuclear translocation were determined using confocal microscopy.
- COX-2 inhibition: Both the ethanol extract of S. pubescens and its active ingredients could effectively alleviate the degree of swelling of the auricle and toes, increase the threshold of heat pain, decrease the overexpression of inflammatory protein cyclooxygenase-2 (COX-2) in the skin tissue, and reduce the number of writhes induced by acetic acid in mice.
- Suppression of pro-inflammatory cytokines: S. orientalis ethanol extract significantly reduced NO, IL-6, and TNF-α production in LPS-stimulated RAW264.7 cells. In vivo studies demonstrated that mice supplemented with 32 mg SOE/kg BW/day significantly lowered serum IL-6 levels and resulted in a higher survival rate compared to the control group (P = 0.019).
- Darutoside and macrophage polarization: Darutoside inhibited LPS-induced polarization and pro-inflammatory cytokine expression in macrophages by inhibiting the NF-κB signaling pathway.
Antioxidant Mechanisms
Siegesbeckia plants possess potent antioxidant activity and could scavenge hydroxyl free radicals in a dose-dependent manner. The ethyl acetate subfraction (SE-EA) of S. orientalis had the highest total phenolic content (76.9 ± 1.8 mg/g) and total flavonoid content (5.3 ± 0.3 mg/g), and exhibited the most significant antioxidant activities, including DPPH radical-scavenging capacity (IC50 = 161.8 ± 2.4 μg/mL).
Network Pharmacology Analysis for Rheumatoid Arthritis
Molecular docking simulation in a network pharmacology study indicated that CSF2, IL-1β, TNF, and IL-6 had good binding activity with corresponding compounds from Herba Siegesbeckiae (degree > 10). Six compounds (degree ≥ 5) of the herb and its essential oil had good interaction with five or more targets.
5. Scientific Evidence by Area of Use
5.1 Anti-Inflammatory and Analgesic Effects
Evidence level: Preclinical (in vitro and animal); limited human data.
A study aimed to clarify the mechanisms underlying the anti-inflammatory and analgesic influence of active components in the ethanol extract of S. pubescens Makino. Active ingredients were identified by HPLC-DAD. Four models — xylene-induced ear oedema, complete Freund's adjuvant (CFA)-induced hind paw oedema, acetic acid-induced pain writhing, and LPS-induced RAW264.7 cell migration — were used to clarify the anti-inflammatory and analgesic mechanisms. The study concluded that the extract and its active ingredients can effectively attenuate the expression of inflammatory factors induced by chemical inflammation, prevent the infiltration of inflammatory cells, and exert good anti-inflammatory and antinociceptive activities.
In CFA-induced acute inflammatory pain, kirenol reduces COX-2 expression and inflammation, increasing the threshold of thermal pain.
Oral administration of Sigesbeckia has been shown to have a mild effect at reducing pain in the acetic acid writhing test and in the hot plate test. In one study, methanolic extracts of Sigesbeckia significantly reduced stretch episodes by 32.3% in the writhing test — approximately half the analgesic effect of acetylsalicylic acid (aspirin).
These findings are restricted to animal and cell-based models. The strength of the anti-inflammatory evidence at a human clinical level remains weak, and further controlled trials are needed.
5.2 Rheumatoid Arthritis and Joint Disease
Evidence level: Preliminary human data (small, mostly Chinese-language clinical studies); mechanistic in vitro and animal research.
Siegesbeckia orientalis L. is a Chinese medicinal herb commonly used for treating rheumatoid arthritis (RA) in clinical practice, which is a common disease with a high disability rate.
Clinical trials conducted with Sigesbeckia have shown that subjects with rheumatoid arthritis had reductions in joint swelling and pain after taking Sigesbeckia for one month, and subjects with osteoarthritis in the knee receiving Sigesbeckia for five weeks had improved signs and symptoms. The endpoints of the rheumatoid arthritis study included improvements in joint swelling and pain as well as biochemical markers of arthritis and inflammation including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor (RF). Study medication was taken three times daily for one month.
An osteoarthritis trial is also noted: Shi (2008) examined the effects of Sigesbeckia, on its own and in combination with sodium hyaluronate, on early-stage osteoarthritis of the knee. Sixty patients with osteoarthritis were randomly divided into three groups receiving either Sigesbeckia plus intra-articular injection of sodium hyaluronate, Sigesbeckia alone, or sodium hyaluronate alone. Treatment was given over two courses, with each course lasting five weeks.
These clinical reports have significant limitations: they are small in scale, predominantly published in the Chinese-language medical literature, and lack the methodological detail required for rigorous assessment in systematic reviews. The mechanistic basis for the anti-rheumatic activity has been better established through network pharmacology and in vitro work.
5.3 Ischemic Stroke and Neuroprotection
Evidence level: Preclinical only (animal and cell studies).
Siegesbeckia orientalis L. is a traditional Chinese herbal medicine commonly used for inflammatory diseases; in ancient use it was applied for stroke, although the mechanisms were not previously clear. A study investigated whether the extract exerts neuroprotective effects by reducing microglia-related inflammatory injury after focal cerebral ischemia/reperfusion (I/R).
Herba Siegesbeckiae is a traditional herb with multiple pharmacological activities and evidence of cardiovascular protection; however, few data were previously available regarding its role in cardiac I/R. A study aimed to explore the effect and underlying mechanism of the herb's aqueous extract on cardiac I/R injury.
Previous studies had focused on the herb's ethanol extract, which could treat pressure overload-induced myocardial remodeling and global cerebral I/R damage. Additionally, the aqueous extract was reported to exhibit antioxidant activity by inhibiting the NOX2/ROS/NF-κB pathway and elevating SOD activity in rat knee osteoarthritis.
There are no published human clinical trials regarding Siegesbeckia for stroke or cardiac ischemia/reperfusion at this time. This area of research is animal model–based only.
5.4 Metabolic Syndrome, Antihyperglycemic, and Antihypertensive Activity
Evidence level: Preclinical in vitro.
A study using an in vitro approach assessed the potential of four extracts of Siegesbeckia orientalis on key enzymes relevant to metabolic syndrome, including carbohydrate-digesting enzymes such as pancreatic α-amylase and intestinal α-glucosidase, pancreatic lipase, and angiotensin I-converting enzyme (ACE). Plants containing phenolic compounds such as those identified in S. orientalis have been reported to have potent antioxidant, antihyperglycemic, antihyperlipidemic, and/or antihyperlipidemic activities.
No human trials exist confirming blood glucose or blood pressure-lowering effects in humans.
5.5 Anti-Hyperuricemic and Gout-Related Activity
Evidence level: Preclinical in vivo (animal models).
Aqueous ethanol extract of Siegesbeckia leaves, along with caffeic acid and chlorogenic acid, were able to reduce serum uric acid levels in hyperuricemic mice, probably through inhibition of liver xanthine oxidase activity, and significantly decreased paw edema induced by monosodium urate crystals.
Four newly isolated acyclic diterpenes (siegetalises A–D) from the aerial parts of Siegesbeckia orientalis were evaluated for xanthine oxidase inhibitory activity; at a concentration of 50 µM, compounds 1–4 exhibited xanthine oxidase inhibitory activity at levels of 13.59% ± 0.51%, 19.64% ± 1.54%, 17.45% ± 1.26%, and 21.36% ± 1.40%, respectively.
5.6 Anticancer Activity
Evidence level: Preclinical in vitro only; no human trials.
Siegesbeckiae Herba has demonstrated inhibitory effect on many kinds of tumors in cell-based studies. The ethyl acetate and n-butanol extracts of S. orientalis exhibit significant inhibitory effects on the in vitro proliferation of HeLa cells. The essential oil of S. pubescens obviously inhibited the proliferation of HepG2 cells in a dose-dependent manner. The aqueous extract of S. glabrescens exerted anti-proliferative action in human breast carcinoma cells (MDA-MB-231 and MCF-7).
The ethanolic extract of S. orientalis down-regulated anti-apoptotic Bcl-2 and migration-related proteins including matrix metalloproteinases (MMPs) and β-catenin in hepatocellular carcinoma (HCC) cells, suggesting promotion of HCC apoptosis and inhibition of migration. These findings indicated that the extract can delay the progression of HCC by increasing oxidative stress, promoting inflammatory response, inducing cancer cell apoptosis, and inhibiting their migration.
5.7 Skin Conditions and Wound Healing
Evidence level: Preclinical (animal and cell-based).
Herba Siegesbeckiae has been reported to have anti-inflammatory, anti-allergic, and wound-healing effects. Mechanistically, darutoside inhibited LPS-induced polarization and pro-inflammatory cytokine expression in macrophages by inhibiting the NF-κB signaling pathway. In vivo, darutoside was found to promote the growth of epithelial cells in wound tissue.
S. orientalis has been reported to have antirheumatic, antiallergic, and immunosuppressive activities. Kirenol, a pure component, was found to have topical application on the attenuation of skin inflammation in murine models.
5.8 Atopic Dermatitis
Evidence level: Animal (mouse model).
Atopic dermatitis is a common inflammatory skin disease characterized by skin barrier dysfunction and itching. Research aimed to investigate the anti-atopic dermatitis mechanism of Herba Siegesbeckiae using a metabolomic approach, establishing a mouse model of atopic dermatitis while conducting a metabolomics analysis on its metabolites. Kirenol, darutoside, and hesperidin were identified as contributing to the anti-inflammatory and analgesic activities of Siegesbeckia pubescens Makino by inhibiting COX-2 expression and inflammatory cell infiltration.
6. Body Systems and Health Areas of Association
Due to its diverse chemical constituents, Herba Siegesbeckiae displays numerous pharmacological activities, including anti-inflammatory, antitumor, antiallergic, antioxidant, antithrombotic, and antibacterial activities. Based on the aggregated preclinical and limited clinical literature, Siegesbeckia is associated with the following body systems and health areas:
- Musculoskeletal system: Rheumatoid arthritis, osteoarthritis, joint pain, and numbness of the limbs are the most historically and scientifically documented applications.
- Immune system: Extracts and pure compounds derived from Sigesbeckiae Herba are reported to present pharmacological activities including anti-inflammation, immunomodulation, and anti-cancer properties.
- Cardiovascular and cerebrovascular system: Cardiac ischemia/reperfusion injury and ischemic stroke in preclinical models.
- Dermatological system: Atopic dermatitis, wound healing, and skin inflammation, primarily documented in animal and cell-based models.
- Metabolic system: Hyperuricemia, hyperglycemia, dyslipidemia, and hypertension, documented in vitro and in limited animal models.
- Oncology (preclinical): Anti-proliferative activity against hepatocellular carcinoma, HeLa, and breast cancer cell lines in vitro.
7. Dosage Forms and Reported Dosages
The dosages described below are drawn entirely from the cited sources and are reported as observed in studies or traditional use records — not as prescriptive recommendations.
- In a 24-week rat toxicity study, Sprague–Dawley rats were intragastrically administered with Herba Siegesbeckiae aqueous extract (HSE) at 5, 1.67, and 0.56 g/kg (experimental groups), with 5 g/kg representing the maximum tolerated dose.
- In a murine anti-inflammatory model, mice were supplemented with 32 mg SOE/kg BW/day, which significantly lowered serum IL-6 levels and resulted in a higher survival rate compared to the control group.
- In a reported clinical study examining rheumatoid arthritis, study medication was taken three times daily for one month.
- In the osteoarthritis knee study, 60 patients were randomized to receive Sigesbeckia alone, in combination with sodium hyaluronate, or sodium hyaluronate alone. Treatment was given over two courses, each lasting five weeks.
- In a cardiac ischemia/reperfusion rat study, Herba Siegesbeckiae was administered intragastrically once daily for 7 days, followed by experimental surgery.
No standardized dosage for human supplemental use has been established in recognized international pharmacopeias. The Chinese Pharmacopoeia includes specifications for the raw herb and the Xixian Pills preparation.
8. Safety Considerations
Traditional Toxicity Notation
Siegesbeckia orientalis was noted as being "slightly toxic" in the Xinxiu Bencao (657–659 A.D., Tang Dynasty).
Hepatotoxicity
A formal preclinical study demonstrated for the first time that long-term oral administration of Herba Siegesbeckiae aqueous extract causes toxicities in rats evidenced by decreased body weight gain as well as liver and lung damage. Long-term oral administration caused toxicities including decreased body weight gain, elevated liver and lung relative weights, and histopathological alterations, with treatment-induced oxidative stress, inflammation, and MAPK activation involved in these toxicities.
The no-observed-adverse-effect level (NOAEL) could not be determined in that study, because the extract at all three dose levels (0.56, 1.67, and 5 g/kg) induced toxicities in rats.
Pulmonary Toxicity
Toxicological studies have demonstrated that the water extract of Siegesbeckia orientalis has acute toxicity in animals. In addition, reversible pulmonary toxicity of S. orientalis is observed in a subacute toxicity study in mice.
A metabolomics study further examined the pulmonary toxicity of raw S. orientalis and found that processing with rice wine reduced this toxicity. The contents of kirenol in raw SO and processed SO (PSO) were 0.13% and 0.07%, respectively — indicating that processing reduces the concentration of at least one major bioactive/potentially toxic diterpenoid.
Water Extract vs. Ethanol Extract
Because the water extract of Herba Siegesbeckiae is more toxic than its ethanol extract, and the herb is typically administered as a water decoction, this distinction is considered relevant to safety assessment.
Asteraceae Allergy Risk
As a member of the Asteraceae (Compositae) family, individuals with known allergies to related plants (e.g., chamomile, ragweed, chrysanthemum) may be at theoretical risk of cross-reactivity, as is recognized for plants in this family. However, specific allergenicity data for Siegesbeckia in the peer-reviewed literature was not identified in the sources reviewed.
Species and Processing Variability
Fewer experimental studies have focused on toxicity and quantitative study across the three official species. This suggests that further in-depth study of toxicity and quality control is critical for future evaluation of drug efficacy and safety.
Siegesbeckia orientalis is used as a long-term drug for treating chronic diseases such as RA and hypertension in clinical practice; however, the long-term toxicity of the plant remains insufficiently understood.
References
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