Pagoda tree

Pagoda Tree (Styphnolobium japonicum / Sophora japonica): A Comprehensive Reference

1. Identity: Botanical Classification, Nomenclature, and Natural Source

Styphnolobium japonicum (synonym: Sophora japonica L.), commonly called the Japanese pagoda tree, Chinese scholar tree, or simply pagoda tree, is a species of deciduous tree in the subfamily Faboideae of the pea family Fabaceae. It was formerly included within a broader interpretation of the genus Sophora. Styphnolobium japonicum is now generally accepted as the correct botanical name, although in commerce the older name Sophora japonica is often retained. The nomenclature change is based on chromosome numbers as well as morphological and cytological differences.

Despite the species epithet and common name, Sophora japonica is native to China and Korea, not Japan. The common name "Japanese pagoda tree" is the result of its being planted on the grounds surrounding Buddhist temples in Japan. In Chinese, the tree is known as huái (槐). It is one of the 50 fundamental herbs used in traditional Chinese medicine.

The tree is deciduous, 15–25 m tall, usually branching low when growing in the open. The bark of mature trees is grey and corrugated. Leaves are pinnate and composed of 7–17 ovate to oval leaflets. Flowers are creamy white, about 1 cm long, held in showy clusters at the ends of branches. The hairless, necklace-like fruits are 3–12 cm long and 1–8-seeded.

It is a popular ornamental tree in Europe, North America, and South Africa, grown for its white flowers, borne in late summer after most other flowering trees have long finished flowering. It was introduced to Britain in 1753 by the famous nurseryman James Gordon.

Plant Parts Used Medicinally

Several parts of the plant are used pharmaceutically as Sophorae fructus (fruit), Sophorae flos (flower), and Sophorae gemmae (flower bud). Three entries are listed in the Chinese Pharmacopoeia: Huaimi (Flos Sophorae Immaturus) is the dry flower buds collected in summer; the rutin content in the flower buds should be not less than 20%, and it is used mainly as a hemostatic agent. Huaihua (Flos Sophorae) is the dry flowers collected in summer when the plant has flowered; the rutin content in flowers should be not less than 8%, with similar indications. Huaijiao (Fructus Sophorae) is the dry ripe fruits collected in winter, used for treatment of intestinal hemorrhage.

Common Preparations and Forms

• The plant is rich in nutritional ingredients and bioactive compounds that can be directly used for preparing teas, dishes, and powders, or can be processed into ingredients and additives for functional food, pharmaceuticals, health products, and cosmetics.
• The buds and fruits are used internally as decoctions or extracts, and externally in some topical preparations to soothe bruises, swelling, and skin inflammation.
• Preparations include decoctions (boiling 5–10 grams of dried flowers or buds in water), as well as powders and honey pills for oral administration.
• The dried flower and flower bud are also marketed as dietary supplements in the United States for their antioxidative properties and as a source of flavonoids, including rutin and quercetin.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

Known in Chinese as Huai (槐), S. japonica is a medium-sized deciduous tree commonly found in China, Japan, Korea, Vietnam, and other countries. The use of this plant has been recorded in classical medicinal treatises of ancient China, and it is currently recorded in both the Chinese Pharmacopoeia and European Pharmacopoeia.

Their use has been documented in the Five Dynasties period, as mentioned in the "Da Ming Ben Cao" pharmacopoeia. In the Chinese Pharmacopoeia, Flos Sophorae (FS) and Flos Sophorae Immaturus (FSI) are recorded to exhibit a bitter taste and a slightly cold nature, possessing hemostatic properties and the ability to clear liver heat.

The flower buds and fruits are most commonly used in Asia (especially in China) to treat hemorrhoids, hematochezia, hematuria, hematemesis, hemorrhinia, uterine or intestinal hemorrhage, arteriosclerosis, headache, hypertension, dysentery, dizziness, and pyoderma.

In traditional medicine in Asia, the flower buds are used for their haemostatic and astringent properties. Historical TCM texts suggest that Japanese sophora may be used to "cool the blood" and treat conditions such as bloodshot eyes, eye bleeding, or conjunctival congestion, especially when these are associated with heat or toxicity syndromes in TCM theory.

In TCM doctrine, these preparations were known to eliminate "heat" and purge "fire," cool the blood, and stop bleeding, and were used to treat a variety of diseases in ancient China.

Use in Korea and Japan

Sophorae Flos has also been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation. The flowers and leaves are sometimes used for teas, such as by families in Laoshan Village, Shandong Province, China.

Cultural and Historical Significance

In its native China, the pagoda tree was typically planted around Buddhist temples. As Buddhism spread into China, the tree was used as a grave-marker for Buddhist monks. As the official tree of Beijing, China, it demonstrates the common theme of aesthetic beauty shared between East and West.

The Guilty Chinese Scholartree is a historic pagoda tree in Beijing, from which the last emperor of the Ming dynasty, Chongzhen, hanged himself in 1644. In East Asian culture, the tree is associated with scholar-officials, and a pagoda tree in the courtyard was a symbol of high-ranking status.

Despite their strong purgative properties, extracts of the leaves and fruits were once used in China to adulterate opium. A yellow dye can be obtained from the flower buds; ancient Japanese prints used this dye.

Food Use

The flowers are edible and used in Chinese cuisine as well as in traditional Chinese medicine. Styphnolobium japonicum is native to Korea, Japan, and China, where it grows in dryish forests and thickets. The S. japonica flower has been commonly consumed in Asia (China, Japan, Korea, and Vietnam), and in China has been used to make desserts and dishes. The leaves and flowers are edible; however, the pods and seeds are toxic and should not be consumed.

3. Key Constituents and Active Compounds

Chemical investigations of S. japonica have led to the isolation and identification of at least 153 constituents, including flavonoids, isoflavonoids, triterpenoids, alkaloids, mineral elements, and amino acids. Main components include flavones, tetraglycosides, isoflavones, isoflavone tetraglycosides, triterpene glycosides, phospholipids, alkaloids, amino acids, and polysaccharides.

Major Flavonoids and Isoflavonoids

Among the secondary metabolites, kaempferol, quercetin, rutin, isorhamnetin, genistein, and sophoricoside are the major active constituents of S. japonica.

Rutin and quercetin have been identified as the two main active components responsible for various pharmacological functions of S. japonica, including antibacterial and antioxidant activities. Rutin is the main active ingredient in the S. japonica flower, accounting for 4%–20% of the dry weight of the flower. The dried flower buds may contain as much as 20% rutin with some quercetin.

Flos Sophorae Immaturus (FSI) is the dried flower bud and contains various phytochemicals, including rutin, quercetin, kaempferol, isorhamnetin, genistein, and Flos Sophorae saponins. The active components of FSI have anti-cancer, antithrombotic, analgesic, antibacterial, antiviral, anti-aging, anti-inflammatory, anti-allergic, and antioxidant pharmacological and nutritional properties.

Rutin is a flavonoid glycoside composed of quercetin and the disaccharide rutinose. Sophora japonica is among the most important species that contain rutin as one of their major constituents.

Further active constituents include sophoricoside (an isoflavone glycoside), alkaloids, and polysaccharides, which contribute to the plant's anti-inflammatory, antioxidant, vascular-protective, and hemostatic effects.

Isoflavone Content

Phytochemical investigations have revealed that natural products from S. japonicum fruit extracts contain various flavonoids, including sophoricoside, genistin, genistein, kaempferol, rutin, and quercetin. Additional flavonoids present in the plant are kaempferol, quercetin, and their derivatives, such as kaempferol 3-O-β-rutinoside and tamarixetin.

Alkaloids

In toxicology, S. japonica is classified as toxic; in particular, alkaloids of the matrine type are thought to be poisonous. While the alkaloid content of S. japonica proper is lower and less clinically prominent than that of closely related species such as Sophora flavescens, the genus Sophora is broadly characterized by the presence of quinolizidine alkaloids. The primary alkaloidal constituents of Sophora are classified as matrine-, lupinine-, lupanine-, macrocyclic bisquinolizidine-, cytosine-, sparteine-, and tetrahydrocytisine-type alkaloids.

Polysaccharides

The polysaccharides of Sophora japonica have been found to scavenge hydroxyl and superoxide anion free radicals.

4. Established Mechanisms of Action

Antioxidant Activity

Both quercetin and rutin demonstrate free radical scavenging activity; quercetin offers better protection, and has been found to protect rabbit erythrocytes with normal and high cholesterol content against lipid peroxidation. Rutin in an iron-rutin complex inhibits the conversion of superoxide anion to hydroxyl radicals in normal and iron-overloaded rats.

Anti-inflammatory Signaling

Flavonoids from Sophora japonica inhibit pro-inflammatory transcription factors such as NF-κB and AP-1, lowering production of cytokines like TNF-α, IL-1β, and IL-6. The inactivation of the NF-κB pathway by S. japonica flower extract or rutin may contribute to anti-colitis effects.

Vasoprotective and Microcirculatory Mechanisms

Rutin and its derivatives improve venous tone, reduce capillary permeability, and decrease edema in chronic venous insufficiency models and clinical use. This is thought to involve modulation of nitric oxide pathways, improved lymphatic drainage, and stabilisation of endothelial tight junctions.

Rutin's most celebrated property is its ability to strengthen capillary walls and reduce their permeability and fragility. This is achieved by inhibiting the breakdown of collagen in the blood vessel walls and by providing antioxidant protection against damage.

Hemostatic Mechanisms

Sophora japonica contains both anti-hemorrhagic and anti-hemostatic substances. The hemostatic action in TCM is attributed to the flower buds' capacity to "cool the blood," consistent with the astringent properties documented for the raw herb. In traditional medicine in Asia, the flower buds are specifically used for their haemostatic and astringent properties.

Bone Metabolism

Sophora Flos extract showed inhibitory effects on IκBα phosphorylation in vitro, resulting in a reduction of the NF-κB pathway activation induced by RANKL at concentrations of 0, 50, 100, and 200 μg/mL. As a result, NFATc1 was downregulated, and osteoclast differentiation brought on by RANKL was inhibited. These results suggest that Sophora Flos extract might be a potent candidate for managing inflammatory bone disorders, including osteoporosis, rheumatoid arthritis, and periodontitis.

Neuroprotective Mechanisms

Styphnolobium japonicum fruit extract activated the SKN-1/Nrf2 pathway, resulting in oxidative stress resistance, and revealed promising pharmacological activities towards treatment of Huntington's, Parkinson's, and Alzheimer's diseases. Polyphenolics from Styphnolobium japonicum may be a promising route towards treatment of CNS disorders, but need to be tested in other in vivo systems.

5. Scientific Evidence by Area of Use

5.1 Cardiovascular and Vascular Health

Background and traditional rationale: Extracts from flower buds and the isolated rutin are used in phytotherapy to treat symptoms of capillary and venous insufficiency, including swollen legs, varicose veins, cramps, and piles.

Clinical and preclinical evidence: Earlier clinical studies revealed that rutin has the potential to reduce the increased hypertension-associated capillary fragility to normal and hence prevents retinal haemorrhage and cerebral accidents in patients. In the circulation and vein-health realm, Sophora japonica's rutin-derived compounds overlap with the broader class of "venoactive" flavonoids used for chronic venous insufficiency, varicose veins, and hemorrhoids. Hydroxyethylrutosides and other rutoside preparations — synthetic derivatives of rutin often originally sourced from plants like Sophora — have demonstrated improvements in leg swelling, heaviness, cramps, and night pain in chronic venous disease.

Evidence strength: Some clinical literature on rutin evaluates vascular markers and blood pressure parameters, but results vary by baseline health, dose, duration, and study design. The most robust human evidence pertains to semi-synthetic rutoside derivatives rather than S. japonica extract as a whole; direct clinical trials on the whole flower extract for venous insufficiency are limited. Evidence at the mechanistic and preclinical level is well established, but dedicated large-scale randomized controlled trials using standardized Sophora japonica extract in humans remain scarce.

5.2 Cerebral Infarction and Neuroprotection

Animal and preclinical studies: Sophora japonica reduces cerebral infarction partly as a result of its anti-oxidative and anti-inflammatory activities. Previous studies found that Sophora japonica reduced the size of cerebral infarction and neurological deficits, and reduced microglial activation, interleukin-1β release, and number of apoptotic cells in ischemia-reperfusion injured Sprague-Dawley rats.

A review of the effects of Sophora japonica on cerebral infarction was published based on literature from Medline, PubMed, Cochrane Library, and the China National Knowledge Infrastructure (CNKI). The authors note that further study is required to determine the relationship between Sophora japonica-mediated reduction in cerebral infarction size and the effects of Sophora japonica on platelet aggregation.

C. elegans and mouse models: A 2019 study published in Molecules used the Caenorhabditis elegans nematode model and a trimethyltin-induced neurotoxicity mouse model to evaluate the antioxidant properties of S. japonicum fruit extract. The ability of the extract to enhance stress resistance was manifested through increasing survival rate by 44.7% and decreasing basal reactive oxygen species (ROS) levels by 72.3% in C. elegans. In addition, the extract increased the levels of the stress response enzyme superoxide dismutase-3 (Sod-3) by 55.5%. Using a mouse model, the extract significantly decreased the expression of the oxidative stress marker malondialdehyde (MDA), and an elevation in the levels of the antioxidant markers glutathione (GSH), SOD, and heme oxygenase-1 (HO-1) was observed.

A 2023 study in BMC Complementary Medicine and Therapies evaluated neuroprotective activities of a hydroalcoholic extract from S. japonicum fruits in C. elegans. The findings identified S. japonicum extract and its components as a source of promising novel neuroprotective compounds. It was described as the first study to report that S. japonicum extract shows great potential towards modulating protein homeostasis and decreasing the development of age-related diseases such as Huntington's, Parkinson's, and Alzheimer's diseases.

Evidence strength: All published neuroprotective evidence is preclinical (in vitro, nematode model, or rodent model). No human clinical trials exist for neurological endpoints.

5.3 Anti-inflammatory and Gastrointestinal Effects

Animal studies: A 2022 study in Food Chemistry administered S. japonica flower extracts (SFE) or rutin to chemically induced-colitic mice. The results showed that SFE or rutin regulated inflammation and oxidative stress in colitic mice. Colonic permeability was significantly improved by SFE or rutin, characterized by higher levels of tight junction proteins and lower serum levels of FITC-Dextran and endotoxins. The inactivation of the NF-κB pathway by SFE or rutin may contribute to the anti-colitis effects.

In colitic mice, SFE or rutin partially restored gut microbiota dysbiosis, as seen by increases in potential probiotics (e.g., Faecalibaculum rodentium) and decreases in potentially disease-related bacteria.

Evidence strength: Translating this to humans is not straightforward, but it supports traditional use where Sophora is combined with other herbs for bleeding or inflamed intestines. All evidence at this time is animal-based; no randomized human trials specifically on S. japonica flower extract for inflammatory bowel disease have been identified.

5.4 Hypertension and Renal Protection

Animal studies: A PMC-indexed study examined the effects of combining Scutellaria baicalensis and Sophora japonica in spontaneously hypertensive rats. SB and SJ significantly ameliorated the severity of renal injury induced by hypertension. The combination also decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and the intestinal barrier was improved. SB and SJ increased short-chain fatty acids (SCFAs) production, inhibited inflammatory factor release, and regulated blood pressure by decreasing the expression of Olfr78 and increasing that of GPR41, then alleviated kidney damage.

Evidence strength: This evidence is animal-based and from a combination product (not S. japonica alone). No high-quality human clinical trials specifically for hypertension using S. japonica extract as a sole agent have been identified in the reviewed sources.

5.5 Bone Health (Osteoporosis)

In vitro and animal studies: Sophorae Flos has been used in traditional Korean and Chinese medicine for the treatment of hemostasis and inflammation, and has been found to possess anti-obesity properties, as well as anti-allergic, anti-proliferative, and anti-inflammatory activities.

A 2017 study published in BMC Complementary and Alternative Medicine (PMC5364702) examined Sophora Flos extract (SFE) in cultured mouse-derived bone marrow macrophages. SF extract showed inhibitory effects on IκBα phosphorylation in vitro, resulting in a reduction of the NF-κB pathway activation induced by RANKL at different concentrations (0, 50, 100, 200 μg/mL). As a result, NFATc1 was downregulated and the differentiation of osteoclasts was inhibited.

Administration of Sophorae fructus extract at a dose of 0.556 g/kg/day in ovariectomized rats decreased serum Ca and TBA levels and increased the levels of Dpd. These findings showed that this extract efficiently prevented bone loss.

Sophora flavonoids and isoflavonoids, especially genistein, sophoricoside, sophorabioside, 2′-methoxykurarinone, 8-prenyl kaempferol, formononetin, maackiain, sophoraflavonoloside, nicotiflorin, and rutin, showed anti-osteoporosis effects through several pathways.

Evidence strength: Evidence is limited to in vitro and animal models. No human clinical trials for osteoporosis outcomes are available from the reviewed sources.

5.6 Antioxidant Activity

Modern pharmacological studies have shown that the active components and/or crude extracts of S. japonica exhibit a wide range of pharmacological actions, including cardiovascular effects as well as anti-inflammatory, anti-osteoporotic, antioxidant, antitumor, antibacterial, antiviral, hemostatic, and anti-atherosclerotic effects. Most of the antioxidant evidence is from cell-based and animal studies. Rutin's radical scavenging properties have been confirmed in multiple in vitro systems, and there is preclinical in vivo data, but large-scale human antioxidant trials using whole S. japonica extract are absent from the published literature reviewed.

5.7 Antibacterial Activity

In broth dilution and agar well diffusion methods, crude methanol extracts from roasted S. japonica buds were able to induce stronger antibacterial effects than isolated rutin or quercetin, suggesting the important roles of other minor compounds in the total effects of these plants. Synergisms among different constituents have been proposed for various therapeutic functions, supporting the concept that employing whole plant materials is more advantageous than applying only isolated active ingredients.

Evidence strength: Antibacterial evidence is predominantly in vitro. No human clinical trials for infection management using S. japonica extract have been identified.

5.8 Cancer / Antitumor Research

In vitro biological experiments showed that isorhamnetin and quercetin, the main active components of Sophora japonica, had a significant inhibitory effect on liver cancer cells HepG2. In both pharmacological studies and clinical practice, S. japonicum exhibits anti-tumor, anti-inflammatory, anti-platelet, and anti-obesity activities. However, the available data is predominantly preclinical and in vitro; no registrational clinical trials of S. japonica extract as an anticancer agent have been identified in the reviewed sources.

6. Body Systems and Health Areas of Association

• Cardiovascular and vascular system: Extracts from flower buds and isolated rutin are used in phytotherapy to treat symptoms of capillary and venous insufficiency, including swollen legs, varicose veins, cramps, and piles. Extracts have also shown astringent, antibacterial, antispasmodic, hypotensive, anticholesterolemic, and anti-inflammatory properties.
• Gastrointestinal tract: It is widely known for its use in traditional Chinese medicine for treating dizziness, headache, hypertension, hematemesis, intestinal hemorrhage, and hemorrhoids.
• Musculoskeletal system (bone): Preclinical evidence supports potential anti-osteoporotic effects via inhibition of RANKL-induced osteoclastogenesis and osteoclast differentiation, as detailed in Section 5.5.
• Nervous system: Preclinical data in nematode and mouse models support potential neuroprotective effects via Nrf2/SKN-1 pathway activation and reduction in ROS, as detailed in Section 5.2.
• Immune and inflammatory pathways: The active components have anti-allergic and anti-inflammatory pharmacological properties.
• Skin: Skin health benefits, including reduced UV-induced damage and support for collagen preservation and pigmentation balance, have led to the inclusion of Sophora japonica extracts in cosmeceuticals.

7. Dosage Forms and Dosages Reported in Studies

To prevent toxic effects, the 2015 edition of the Chinese Pharmacopoeia recommends an exact dose of 5–10 g for Flos Sophorae Immaturus and 6–9 g for Fructus Sophorae.

In TCM decoctions, a standard preparation involves boiling 5–10 grams of dried flowers or buds in water for oral administration.

In preclinical experimental settings, the following dosages have been reported:

• Sophorae fructus extract was administered at a dose of 0.556 g/kg/day in ovariectomized rats in the osteoporosis model.
• In osteoclast differentiation cell assays, SF extract was tested at concentrations of 0, 50, 100, and 200 μg/mL.

The dried flower and flower bud are commercially available as dietary supplements in the United States primarily for their antioxidative properties and as a source of flavonoids, including rutin and quercetin. Standardized extracts sold in Western markets are typically standardized to a declared percentage of rutin (often 20% or higher, reflecting the pharmacopoeial standard), though no single standardized clinical dosage has been established in the reviewed human literature.

8. Safety Considerations and Drug Interactions

Overall Safety Profile (Flower and Flower Bud)

A United States Pharmacopeia comprehensive safety review focused on the safety of S. japonicum flower and flower bud as dietary supplement ingredients. No serious adverse events or toxicity were reported in the clinical or experimental animal studies reviewed.

Information on the side effects and safety evaluations for S. japonica is limited, although this plant is frequently used in TCM. The limited evidence base means that gaps in safety knowledge remain, particularly for long-term use and in special populations.

Alkaloid-Mediated Toxicity

In toxicology, S. japonica is classified as toxic; alkaloids of the matrine type in particular are thought to be poisonous. In clinical samples, toxic effects such as severe palpitations, dyspnea, and spasms were observed with Sophora alkaloids. In animal studies, toxic effects have been shown for oxymatrine.

Toxicity of Seeds and Pods

The pods and seeds are toxic and should not be consumed. This represents an important distinction from the approved medicinal use of dried flower buds and flowers, which carry a significantly different safety profile from the seeds.

Potential Drug Interactions

Although some studies indicated that rutin or quercetin may have potential for drug interactions, none were specifically identified for S. japonicum flower or flower bud in the USP safety review. The drug interaction data relating to rutin is relevant because rutin is the principal constituent of the marketed supplement form. Rutin's inhibitory effects on platelet aggregation could theoretically potentiate anticoagulant or antiplatelet drugs, though this has not been confirmed in direct human herb-drug interaction studies using S. japonica flower preparations.

Possible Reproductive Toxicity (In Vitro)

A study indicated that Sophora japonica extract induces oxidative/nitrosative stress-mediated impairment of the mechanism for free radical scavenging, which may provoke genotoxic events in germ cells through cell cycle arrest and micronuclei formation. Toxicological studies are considered urgently needed to confirm the safety of Sophora japonica extracts for clinical use. The study addressed potential reprotoxicity of Sophora japonica extract in respect to mouse germ cells (GC-1 spg, GC-2 spd) in vitro. This finding is limited to an in vitro model and has not been replicated or confirmed in human studies; it should be interpreted with caution.

Pharmacopeial Dose Limits

To prevent toxic effects, the 2015 edition of the Chinese Pharmacopoeia recommends exact dose limits: 5–10 g for Flos Sophorae Immaturus and 6–9 g for Fructus Sophorae. These limits reflect the recognition that at higher doses, adverse effects may occur, particularly from the purgative properties of leaves and fruits noted in the historical literature.

Limited Information on Special Populations

No human data from the reviewed sources specifically characterizes safety in pregnancy, breastfeeding, pediatric populations, or severe hepatic/renal impairment. While the use of this plant has been recorded in classical medicinal treatises of ancient China, and it is currently recorded in both the Chinese Pharmacopoeia and European Pharmacopoeia, formal clinical safety studies across these populations have not been identified in the current review.

9. Regulatory and Pharmacopoeial Status

The use of this plant is recorded in both the Chinese Pharmacopoeia and the European Pharmacopoeia. As a health supplement, S. japonica extracts have already been approved for clinical use in the Chinese Pharmacopoeia. While the medicinal use of S. japonicum is not yet recognized in European pharmacopeial monographs per se, it is included in the Chinese Pharmacopoeia as a raw material, underscoring its longstanding use in traditional medicine. In the United States, dried flower and flower bud preparations are marketed as dietary supplements.

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