Clerodendrum trichotomum (Harlequin Glorybower)
1. Identity
Botanical Classification and Nomenclature
Clerodendrum trichotomum Thunb. is a shrub or tree of the genus Clerodendrum, family Lamiaceae, which is widely distributed in China, Korea, India, Japan, and the Philippines. The plant belongs to the genus Clerodendrum; it is still debated whether this genus belongs to the Lamiaceae family or the Verbenaceae family. The genus was assigned to family Verbenaceae traditionally by Engler and Prantl, a classification also adopted in the Flora of China. However, modern taxonomic systems mostly place it in the family Lamiaceae.
The species Clerodendrum trichotomum was first scientifically described by the Swedish botanist Carl Peter Thunberg in 1784, based on specimens collected during his travels in Japan, and the description was published in his Flora Japonica.
Common Names
- English: Harlequin glory bower, Chance tree
- Chinese (TCM): Chou-Wu-Tong (referring to the unpleasant smell of the leaves and twigs)
- In traditional Chinese medicine, the plant is also known as Haizhou Changshan
- Japanese: Kusagi, meaning "bad-smelling tree"
- German: Japanischer Losbaum
Plant Description and Natural Source
C. trichotomum occurs naturally in lowland and mountainous areas in Japan, Korea, and eastern China, where it grows as a shrub or small tree, reaching heights of 1.5–10 m. Its sweet-smelling flowers have a white or pink crown. The calyx turns from green to pink–purple over time, providing an especially decorative touch around the ripe deep-blue fruits that persist until winter. In Europe, it is cultivated primarily as an ornamental plant.
Plant Parts Used and Common Preparations
As a traditional Chinese medicine, C. trichotomum is used to treat various diseases and conditions, inspiring research on the pharmacological activities of its different parts, including roots, stems, leaves, flowers and fruits. In the areas of its natural occurrence, the leaves and young shoots of C. trichotomum, and sometimes the roots, flowers and fruits, are used in folk medicine.
The young leaves of C. trichotomum are a kind of green wild vegetable favored by local residents in Guizhou, Hubei, Sichuan, Yunnan and other places of China because of their unique flavor, fresh taste, and slightly sweet aftertaste. The leaves are described as non-toxic, bitter and cold in taste, with special flavor and rich in pectin, vegetable protein, and a variety of amino acids. They are used as essential raw materials for Enshi Tujia people to make "fairy tofu" and can also be made into special drinks.
The plant blossoms in August with many white flowers and the fruits assume a sky-blue pigment when they ripen in October. Formerly, the blue pigment of the fruit was used to color clothes sky-blue and its extract was used as a herbal medicine.
Preparations documented in the scientific and ethnobotanical literature include:
- Aqueous decoctions of roots, stems, and leaves
- Methanol and ethanol extracts (used in laboratory and preclinical research)
- Infusions (teas) of dried leaves and young shoots
- Resin of Clerodendron trichotomum, which has diverse reported pharmacological activities including blood pressure reduction, sedation, soothing, and paralysis activity
2. Traditional and Historical Use
Traditional Chinese Medicine (TCM)
The first mention of C. trichotomum was recorded in the book Bencao Tujing of the Song Dynasty. Historically, due to its origin in the Haizhou area of Lianyungang, Jiangsu province, it was once used as Changshan, another kind of Chinese medicine.
In traditional Chinese medicine, documented as early as the Song Dynasty in texts like Bencao Tujing, the plant, known as "Haizhou Changshan," is employed to nourish the liver, reduce blood pressure, dispel wind, and eliminate dampness.
C. trichotomum is mainly used as a folk remedy for the treatment of rheumatism, hemiplegia, hypertension, migraine, malaria, and dysentery. Its roots, stems, leaves, flowers, and fruits can all be used as medicine.
C. trichotomum is widely used in Chinese folk medicine to nourish the liver, reduce blood pressure, dispel wind, and eliminate dampness. In China, relevant studies mainly focused on the mechanisms of reducing blood pressure, sedation, and analgesia, most of which were conducted in the 1950s and 1960s.
Traditional Use by Plant Part
Documented traditional uses by plant part and geographic region include: leaves — for asthma, inflammatory skin conditions, headache, hypertension, anti-rheumatic use, rheumatism and rheumatic articular pain, and rheumatism fever (China, Taiwan, Korea, Japan, Nepal); flowers — for inflammatory conditions, headache, and hypertension (China, Taiwan, Korea, Japan); fruits — for anticancer purposes (China, Japan); raw material — for eczema (China); decoctions — for rheumatoid arthritis, joint pain, numbness, and paralysis (China); and all parts collectively — for anti-diabetic, neuralgia, arthritis, cough, abdominal lump, anti-hypertensive, and sedative purposes (China, Korea).
Japanese and Korean Traditional Medicine
Clerodendrum trichotomum has been utilized in traditional medicine across East Asia, particularly in Chinese and Japanese folk practices, for treating various ailments including rheumatism, hemiplegia, hypertension, migraine, malaria, and dysentery. Japanese ethnopharmacological traditions similarly incorporate it for inflammatory conditions such as headaches.
Studies from other countries mainly concentrated on anti-inflammatory, antioxidant, and other mechanisms of action, with more reports in South Korea and Japan, most of which were carried out in the 21st century.
Food Use
C. trichotomum is a kind of medicinal and edible plant which integrates ecological afforestation, garden greening, herbal medicine, and flavored wild vegetable use. The plant thus occupies a dual role in East Asian tradition, serving simultaneously as a folk medicine and as a culinary ingredient in certain regions of China.
3. Key Constituents and Active Compounds
Overall Phytochemical Profile
A total of 164 secondary metabolites have been isolated from C. trichotomum, and their structural types are mainly terpenoids, flavonoids, steroids, phenylpropanoids and phenylpropanoid glycosides, phenylethanosides, phenolic glycosides, anthraquinones, polyketones, cyclohexylethanoids, alkaloids, and acid amides. The presence of a variety of phytochemicals, especially abietane diterpenes, clerodane diterpenes, phenylpropanoid glycosides, and flavonoid glycosides, plays an important role in the activity diversity of this plant.
Among the 164 secondary metabolites, there are 74 terpenoids (including 4 monoterpenes, 3 sesquiterpenes, 51 diterpenes, and 16 triterpenes), 11 flavonoids, 16 steroids, 24 phenylpropanoids, 3 phenylethanosides, 2 phenolic glycosides, 3 anthraquinones, 2 polyketones, 7 cyclohexylethanoids, 7 alkaloids, 2 acid amides, and 13 other compounds including acids, alcohols, aldehydes, esters, an alkane, and a peroxide.
Preliminary research on the composition of the raw material suggests that its health-promoting effect is associated with the presence of numerous secondary metabolites, including phenylpropanoids, flavonoids, lignans, terpenoids, steroids, alkaloids, and anthraquinones.
Phenylpropanoid Glycosides
The dominant group of phenolic compounds in C. trichotomum are phenylpropanoids. In 1983, Sukarai and Kato confirmed the presence of the most representative phenylpropanoid, acteoside (also known as verbascoside or kusaginin), in the leaves of the species.
Acteoside (compound 102) is considered the plant's major phytochemical, with rich pharmacological activities including anti-hypertension, antitumor, antioxidant, antiviral, and whitening effects. Other important phenylpropanoid glycosides identified from the shoots include leucosceptoside, plantainoside C, jionoside D, martynoside, isoacteoside, and isomartynoside.
Terpenoids: Diterpenoids
C. trichotomum research on chemical composition mainly focuses on terpenoids, phenylpropanoids, flavonoids, and steroids. Most of the terpenoids are diterpenoids, and the main structural types are abietane-type and clerodane-type.
Chemical studies on the species have reported the isolation of several diterpenes including clerodendren A, B, D, and I. Clerodane-type diterpenes clerodendrin B, clerodendrin D, clerodendrin H, and clerodendrin I were found to have insect feeding stimulant activity toward the turnip sawfly Athalia rosae ruficornis.
Trichotomone was first isolated from Clerodendrum trichotomum roots. This diterpenoid is a rare phenolic ketal of a regular abietane derivative and demonstrates moderate cytotoxic activity against some tumor cell lines (A549, Jurkat, BGC-823, and 293T WT) with IC50 values ranging between 7.51 and 19.38 µM.
Flavonoids
Chemical studies have reported the isolation of three flavonoids: clerodendrin, clerodendroside, and acetin-7-β-d-glucurono-β-(1→2)-d-glucuronide. Additional studies have identified flavonoids including hispidulin and luteolin-based compounds within the species.
Sterols and Triterpenes
From the petroleum ether extract of the leaves, ten compounds were isolated and identified, including four triterpenes (lupeol, friedelin, betulinic acid, and taraxerol) and four sterols (22-dehydroclerosterol, clerosterol, stigmasterol, and sitosterol).
Blue Pigments: Trichotomines
Trichotomine is a bright blue pigment found in the berries of Clerodendrum trichotomum. It has a novel chromophore structure which differs from previously studied plant pigments. Two blue pigments, trichotomine and trichotomine G1, have been isolated from the species. The blue-colored bis-indole alkaloid pigment trichotomine and two glycosides thereof were isolated and characterized from the berries.
Cyclohexylethanoids
A series of cyclohexylethanoids, including rengyolone, cleroindin C, cleroindin B, and rengyol, have been isolated from the leaves of C. trichotomum.
Volatile Compounds
Volatile compounds of C. trichotomum have been analyzed and reported by gas chromatography-mass spectrometry (GC-MS), and most of these studies were focused on the leaves, flowers, and fruits. The analysis showed that the components of volatile oil differ with different parts of the plant, geographic origin, and extraction methods.
4. Mechanisms of Action
Antihypertensive Mechanisms
Kang et al. isolated a series of phenylpropanoid glycosides from the stems of C. trichotomum and found that acteoside, martynoside, leucosceptoside A, isoacteoside, and isomartynoside had significant angiotensin-converting enzyme (ACE) inhibitory activity, with IC50 values of 373.3 ± 9.3 µg/mL, 524.4 ± 28.1 µg/mL, 423.7 ± 18.8 µg/mL, 376.0 ± 15.6 µg/mL, and 505.9 ± 26.7 µg/mL, respectively. The antihypertensive effect of C. trichotomum may be, at least in part, due to ACE inhibitory activity of these phenylpropanoid glycosides.
A flavonoid glycoside, clerodendroside, isolated from the leaves of C. trichotomum, was found to have a hypotensive effect on anaesthetised rats.
Anti-inflammatory Mechanisms
A study found that the methanol fraction of the leaf extract of C. trichotomum significantly reduced the amount of prostaglandin E2 (PGE2) in a dose-dependent manner, with isoacteoside and acteoside identified as the main compounds exhibiting this activity.
Anti-inflammatory constituents isolated from Clerodendron trichotomum leaves inhibit pro-inflammatory gene expression in LPS-stimulated RAW 264.7 macrophages by suppressing NF-κB activation.
A ferment mixture containing C. trichotomum was found to inhibit the activity of COX and 5-LO enzymes, which are generators of pro-inflammatory mediators.
Antioxidant Mechanisms
The phenylpropanoid glycoside trichotomoside effectively scavenges intracellular reactive oxygen species (ROS) and DPPH radicals and increases the viability of cells exposed to γ-radiation and H2O2. Like jionoside D, trichotomoside scavenged intracellular radicals more effectively than DPPH radicals, suggesting that it acts not only as a conventional radical scavenger but also indirectly stimulates the cellular defense system.
Skin-Whitening / Tyrosinase Inhibition
Acteoside and isoacteoside, isolated from C. trichotomum, showed whitening activity by inhibiting tyrosinase activity and tyrosinase expression.
Active Substances for Sedation and Analgesia
The active substances responsible for the analgesic and sedative effects of C. trichotomum are still unclear, and the question of which specific constituents are responsible remains an open area of research.
5. Scientific Evidence by Area of Use
5.1 Cardiovascular / Antihypertensive Effects
Evidence type: Preclinical (in vitro and animal studies); no clinical (human) trials identified.
The stems of Clerodendron trichotomum have been traditionally used for treatment of hypertension in far East Asia including China, Korea, and Japan. Preclinical investigations have provided pharmacological support for this use. Bioassay-guided fractionation of the EtOAc-soluble extract of Clerodendron trichotomum afforded acteoside, leucosceptoside A, martynoside, acteoside isomer, and isomartynoside. The ACE activities were significantly inhibited by these phenylpropanoid glycosides in a dose-dependent manner, with IC50 values of 373±9.3, 423±18.8, 524±28.1, 376±15.6, and 505±26.7 µg/mL, respectively. These results suggest that the antihypertensive effect of Clerodendron trichotomum may be, at least in part, due to the ACE inhibitory activity of phenylpropanoid glycosides.
Limitations: All identified mechanistic studies are in vitro (enzymatic ACE inhibition assays) or conducted on anaesthetised animals. Most biological studies were based on simple in vitro tests. Studies conducted on animals were few and only fragmentary, and none were clinical studies. No human clinical trials investigating the antihypertensive effects of C. trichotomum have been published in the peer-reviewed literature reviewed.
5.2 Anti-inflammatory Effects
Evidence type: In vitro and animal (rodent) studies; no clinical trials identified.
Leaves of Clerodendron trichotomum have been used for centuries in Chinese folk medicine for their anti-inflammatory properties. Anti-inflammatory effects of the leaf extracts were studied in rats, mice, and in RAW 264.7 cells. At 1 mg/kg, the 30% and 60% methanol extracts of the leaf, and 1 mg/kg of indomethacin as a positive standard, were administered to rats; carrageenan was injected subcutaneously to induce hind paw edema. The result showed that 1 mg/kg of the 30% and 60% methanol fractions of the leaf and 1 mg/kg of indomethacin inhibited hind paw edema by 19.5%, 23.0%, and 20.5%, respectively.
A mixture of six plant ferments, including one obtained from C. trichotomum, was administered to mice with allergic rhinitis induced by egg albumin. A product fermented for 4 days reduced allergic symptoms with a similar effectiveness to cetirizine. It also significantly reduced the levels of histamine and immunoglobulin E in the blood.
Limitations: Available anti-inflammatory studies are predominantly in vitro or use rodent models with variable dosing and preparation methods. No controlled human trials have been performed. Before C. trichotomum can be used in modern medicine, further research is necessary regarding the safety and efficacy of the raw material, its mechanisms of action, and dosage.
5.3 Antitumor / Anticancer Effects
Evidence type: In vitro cell-line studies only; no animal or human studies identified for the whole plant.
The compounds of C. trichotomum show a variety of in vitro anti-tumor activities, including against breast cancer cells MCF-7 and 4T1, lung cancer cells A549, hepatocellular carcinoma cells HepG2, and cervical cancer cells.
All compounds isolated from one study were evaluated for cytotoxic activities against cultured K562, MCF-7, A549, and HepG2 cell lines; none of them showed good antitumor activities. This illustrates that results across studies are inconsistent, and some isolated constituents fail to demonstrate meaningful cytotoxicity in cell-line testing.
The plant's major phytochemical, acteoside, has rich pharmacological activities including antitumor effects, and relevant studies have shown that it exists in various stages of clinical trials for anti-nephritic, hepatoprotective, and osteoarthritic activity — though these trials apply to acteoside as an isolated compound, not to C. trichotomum preparations as a whole.
Limitations: Available anticancer evidence is strictly limited to in vitro cell-line experiments. No clinical data exist for C. trichotomum extracts or preparations in human oncology.
5.4 Antioxidant Effects
Evidence type: In vitro assays; no clinical trials identified.
Several studies describe the evaluation of antioxidant activity of the methanolic extract of C. trichotomum and its constituent compounds. The first report examined the antioxidant activity of jionoside D based on its ability to scavenge intracellular free radicals and neutralize DPPH radicals.
The antioxidant properties of trichotomoside were also examined. It was found to effectively scavenge intracellular ROS and DPPH radicals, and it increased the viability of cells exposed to γ-radiation and H2O2, with greater efficacy observed against the former. Trichotomoside scavenged intracellular radicals more effectively than DPPH radicals, suggesting that it acts not only as a conventional radical scavenger but also indirectly stimulates the cellular defense system.
Limitations: All antioxidant assessments are in vitro and based on chemical or cell-based radical scavenging assays. Translating in vitro antioxidant results to human clinical benefit requires further investigation.
5.5 Sedative and Analgesic Effects
Evidence type: Early preclinical data; active compounds not yet identified.
In China, relevant pharmacological studies focused on the mechanisms of reducing blood pressure, sedation, and analgesia, most of which were conducted in the 1950s and 1960s. The active substances responsible for analgesic and sedative effects of C. trichotomum are still unclear.
Limitations: The early preclinical research on sedative and analgesic effects predates modern pharmacological standards. The specific active constituents have not been definitively characterized, and no modern controlled studies or human clinical trials have investigated these endpoints.
5.6 Antiviral (HIV-1 and Respiratory Viruses)
Evidence type: In vitro only.
The antiviral activities of Clerodendrum trichotomum extract were shown to be very strong against RSV (respiratory syncytial virus) infection in HEp-2 cells, making it a promising agent for antiviral research. Additionally, studies have reported HIV-1 integrase inhibitory activity from phenylpropanoid glycosides isolated from the species.
Limitations: All antiviral evidence is restricted to in vitro cell-based assays. No animal or human antiviral studies have been conducted.
5.7 Antibacterial Effects
The active compounds isolated from C. trichotomum, including abietane diterpenoids, phenylpropanoid glycosides, flavonoid glycosides, clerodane diterpenoids, and steroidal compounds, showed activities including antibacterial effects. These findings are likewise limited to in vitro settings.
6. Body Systems and Health Areas Associated with C. trichotomum
The following body systems and health areas have been associated with C. trichotomum in the traditional and scientific literature:
- Cardiovascular system: Traditionally used for hypertension across East Asia; preclinical data suggest ACE inhibitory activity from phenylpropanoid glycosides.
- Musculoskeletal and connective tissue: Products based on Harlequin glory are used in the treatment of rheumatoid arthritis, joint pain, and skin inflammation.
- Central nervous system: Roots, stems, leaves, and flowers of the plant are used medicinally for their sedative and analgesic effects.
- Immune and inflammatory system: Used in folk medicine for anti-inflammatory, analgesic, and anticancer purposes; also employed in the treatment of asthma.
- Respiratory system: Leaves are used traditionally for asthma in China, Taiwan, Korea, Japan, and Nepal.
- Skin: Acteoside and isoacteoside have demonstrated skin-whitening activity by inhibiting tyrosinase. Traditional use also includes treatment of eczema and inflammatory skin conditions.
- Oncology (preclinical only): Multiple compounds from C. trichotomum show in vitro anti-tumour activities against various cancer cell lines including breast, lung, hepatocellular carcinoma, cervical, melanoma, and hematological cancer cells.
- Metabolic/endocrine: Anti-diabetic uses have been documented among traditional users in China and Korea.
7. Dosage Forms and Dosages Reported in Studies
There are no established official therapeutic indications, administration forms, dosages, or safety profiles for C. trichotomum and its bioactive compounds.
The following dosages have been reported in specific preclinical studies:
- Anti-inflammatory (animal): 1 mg/kg of 30% and 60% methanol extracts of the leaves (CTL) were administered to rats with carrageenan-induced hind paw edema; 1 mg/kg of indomethacin was used as a positive control. The 30% and 60% methanol fractions inhibited edema by 19.5% and 23.0%, respectively.
- ACE inhibition (in vitro): IC50 values for phenylpropanoid glycosides ranged from 373±9.3 µg/mL (acteoside) to 524±28.1 µg/mL (martynoside).
- Cytotoxicity (in vitro): Trichotomone demonstrated moderate cytotoxic activity against tumor cell lines with IC50 values ranging between 7.51 and 19.38 µM.
No standardized oral dosage for human use has been established in official pharmacopeias or clinical guidelines. Modern requirements for medicinal raw materials necessitate the use of only detailed, tested, and standardized products, and there are currently no established official therapeutic indications, administration forms, dosages, or safety profiles for C. trichotomum and its bioactive compounds.
8. Safety Considerations and Interactions
Toxicological Data
The extracts and isolated compounds of C. trichotomum have showed many pharmacological effects, but their toxicological studies have rarely been reported. Although no toxicological data currently exist on C. trichotomum and its products, some reports exist for other species in the genus, suggesting they may be safe for use.
Requirement for Further Safety Research
Before C. trichotomum can be used in modern medicine, further research is necessary regarding the safety and efficacy of the raw material, its mechanisms of action, and dosage.
Overall Evidence Gaps
In one comprehensive systematic review of the literature from 1970–2022, 39 published reviews and experimental studies were selected. Most biological studies were based on simple in vitro tests. Studies conducted on animals were few and only fragmentary, and none were clinical studies. This reflects the near-complete absence of human clinical trial data for this plant and its preparations.
The major constituent acteoside exists in various stages of clinical trials for anti-nephritic, hepatoprotective, and osteoarthritic activity — but these trials pertain to the isolated compound acteoside, not to standardized C. trichotomum extracts or preparations.
Taxonomic Considerations
It is still debated whether the genus Clerodendrum belongs to the Lamiaceae family or the Verbenaceae family. The genus was traditionally assigned to Verbenaceae by Engler and Prantl, but modern taxonomic systems mostly place it in Lamiaceae. This taxonomic ambiguity may affect regulatory classification and safety assessments in different jurisdictions.
References
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