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Stephania
Stephania cephalantha
Scientific classification Edit this classification
Kingdom: Plantae
Clade: Tracheophytes
Clade: Angiosperms
Clade: Eudicots
Order: Ranunculales
Family: Menispermaceae
Subfamily: Menispermoideae
Genus: Stephania
Lour.
Synonyms[1]
  • Byrsa Noronha
  • Clypea Blume
  • Homocnemia Miers
  • Ileocarpus Miers

Stephania is a genus of flowering plants in the family Menispermaceae. It includes 70 species native to tropical and southern Africa, eastern and southern Asia, Australia, and the tropical Pacific Islands.[1][2] They are herbaceous perennial vines, growing to around four metres tall, with a large tuber. The leaves are arranged spirally on the stem and are peltate, with the leaf petiole attached near the centre of the leaf. The name Stephania comes from the Greek, "a crown". This refers to the anthers being arranged in a crown-like manner.[3]

One species, S. tetrandra, is among the 50 fundamental herbs used in traditional Chinese medicine, where it is called han fang ji (漢防己, "Chinese fang ji"). Other plants named fang ji are sometimes substituted for it. Other varieties substituted include Cocculus thunbergii, C. trulobus, Aristolochia fangchi, Stephania tetrandria, and Sinomenium acutum. Notable among these is guang fang ji (廣防己, "(GuangDong, GuangXi) fang ji", Aristolochia fangchi. Because of its toxicity, it is used in TCM only with great caution.

Species

[edit]

70 species are accepted.[1][4][5]

Fossil species
Formerly placed here

Toxicity

[edit]
Female flowers of Stephania delavayi

There is evidence that a few species of Stephania are toxic.[7] However, the most commonly available species in the United States, Stephania tetrandra, has not been shown to be toxic. Any confusion regarding the possible toxicity of Stephania tetrandra was entirely due to an inadvertent shipment of Aristolochia fangchi sent in its stead to a Belgian clinic in 1993. The errant batch of Aristolochia was later confirmed via phytochemical analysis.[8]

Chemistry

[edit]

Chemical investigation of Stephania rotunda Lour. growing in Vietnam in 2005 led to the isolation and structural elucidation of three new alkaloids, 5-hydroxy-6,7-dimethoxy-3,4-dihydroisoquinolin-1(2H)-one, thaicanine 4-O-beta-D-glucoside, as well as (−)-thaicanine N-oxide (4-hydroxycorynoxidine), along with 23 known alkaloids.[9]

References

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Stephania

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from Grokipedia
Stephania is a of approximately 60 of herbaceous or woody climbing vines belonging to the Menispermaceae, distributed across tropical and subtropical regions of , , , and . These typically feature peltate leaves with long, swollen petioles inserted near the center of the blade, which is often triangular to orbicular and glabrous to sparsely hairy; rootstocks are frequently tuberous, and stems are striate and twining. Inflorescences consist of small, greenish-yellow, unisexual or bisexual flowers arranged in axillary or terminal umbels or compound racemes, with 4–8 sepals, 3–8 imbricate petals, and 3–6 stamens. Fruits are 1–3-seeded drupes borne on horseshoe-shaped endocarps that are typically rugose or crested externally. The genus is notable for its rich alkaloid content, including bisbenzylisoquinoline and types such as tetrandrine and stepholidine, which contribute to its pharmacological properties. Species of Stephania have long been employed in and other folk practices for treating diverse conditions, including , fever, , inflammatory diseases, , and infections. For instance, the root of S. tetrandra (known as han fang ji) is one of the 50 fundamental herbs in , valued for its and effects. Modern research has explored these alkaloids for potential applications in treating , cancer, and neurological disorders, though some species contain toxic compounds requiring careful use.

Taxonomy

Etymology and Classification History

The genus name Stephania derives from the Greek stephanos, meaning "" or "," alluding to the crown-like arrangement of the connate anthers in the male flowers or the peltate leaves that resemble a garland. Stephania was established by Joannes de Loureiro in his 1790 work Flora Cochinchinensis, with the initial descriptions of S. longa and S. rotunda based on collections from (present-day ). The genus belongs to the Menispermaceae and was initially distinguished by its dioecious habit, peltate leaves, and unique inflorescence structure. Early taxonomic expansions occurred through the work of John Miers, who in 1851 transferred several species from the related genus Cissampelos (such as C. glabra to S. glabra) and provided detailed revisions in subsequent publications (1851, 1864, 1871), broadening the circumscription of Stephania. Friedrich Diels further advanced the classification in his 1910 monograph within Das Pflanzenreich, recognizing additional species and establishing sectional divisions like Eustephania and Thamnothyrsa based on morphological traits such as leaf venation and fruit structure. In the late 20th century, Leslie Forman conducted extensive revisions of Asian Stephania species (1956–1988), including monographic treatments that recognized approximately 45 species, emphasizing regional floras in and Indochina. More recent molecular phylogenetic studies, such as those by Xie et al. (2015) and Ortiz et al. (2016), have reassessed subgeneric and sectional boundaries using nuclear and DNA markers, supporting the monophyly of Stephania and leading to updated estimates of around 60–70 species worldwide. A 2017 world checklist accepts 69 species, incorporating lectotypifications and synonymy resolutions from prior works.

Phylogenetic Relationships

Stephania is placed within the Tinosporoideae of the Menispermaceae, a classification supported by morphological evidence including apical style scars on fruits, bilateral seed curvature, and specific floral structures such as unisexual flowers with a single carpel in many . This is characterized by lianas or scandent shrubs predominantly distributed in tropical regions, with Stephania exhibiting these traits alongside genera like Tinospora and Cyclea. Molecular phylogenetic analyses using nuclear internal transcribed spacer (ITS) regions and plastid matK and trnL-F sequences have confirmed the monophyly of Stephania, with strong bootstrap support across sampled species, particularly those from and . These studies position Stephania as sister to Cyclea and Cissampelos within the Tinosporoideae, forming a well-supported defined by synapomorphies such as reduced carpels and specific morphology, as reconstructed from chloroplast ndhF data. Earlier analyses had suggested potential , but denser sampling in the and resolved this, emphasizing the genus's evolutionary coherence. Studies from the , aligned with the APG IV of angiosperms, have further illuminated Stephania's evolutionary history, highlighting its radiation in the tropical as part of Menispermaceae's diversification within during the Cretaceous-Paleogene transition. This radiation is evidenced by biogeographic patterns in molecular phylogenies, showing diversification centers in and , with dispersal to the Neotropics in related lineages. Chromosome counts in Stephania species typically range from 2n=22 to 2n=26. Such cytological variation aligns with inferred reticulate in Menispermaceae, though direct evidence of hybridization remains limited to phylogenetic incongruences between nuclear and markers.

Description

Morphological Characteristics

Stephania species are primarily herbaceous or woody vines, functioning as climbers or lianas that can reach lengths of up to 10 meters, often featuring striate (ridged) stems that are slightly twining and supported by a tuberous , which may occasionally be above ground; stems are sometimes succulent. The stems exhibit a slender , contributing to their climbing nature in tropical and subtropical environments. The leaves are alternate and simple, characteristically peltate with long petioles that are often swollen at both ends; the blade is typically deltoid, ovate, suborbicular, or deltoid-rotund in shape, measuring 5-15 cm in diameter, and ranges from papery to subleathery in texture with palmate venation, sometimes appearing palmately lobed or spirally arranged along the stem; leaves are glabrous or pubescent with multicellular hairs. These features provide structural support for climbing while optimizing light capture in forested understories. Inflorescences are unisexual, borne on dioecious , arising from axillary positions or short axillary stems in panicles, false umbels, or umbelliform cymes, with structures occasionally condensed into heads; the small flowers consist of sepals and petals that vary by , with flowers having 6-8 sepals in 1-2 whorls and 3-4 petals (rarely absent), and flowers having 3-6 sepals and 2-4 petals; flowers include a peltate synandrium of 2-6 stamens with transversely dehiscent anthers, while flowers feature a single carpel with a small style and slightly lobed or laciniate stigma. The fruits are drupaceous, ovoid to subglobose and slightly flattened, 5-10 mm in size, typically red or orangish-red, with a bony endocarp bearing transverse ridges or tubercles and a concave, sometimes perforate condyle; the seeds are horseshoe-shaped with fleshy , and the embryo is curved, a trait emblematic of the Menispermaceae family.

Reproductive Biology

Stephania species are dioecious, with flowers borne on separate , a characteristic trait throughout the Menispermaceae family. This sexual dimorphism ensures cross-pollination, as individual produce either staminate (male) or pistillate (female) inflorescences. Flowering is typically seasonal, occurring from spring through early autumn in some , aligning with favorable climatic conditions in their tropical and subtropical habitats. The inflorescences of Stephania are structured as compound umbelliform cymes, usually axillary or arising from short axillary branches, with peduncles up to 6 cm long and rays often short, forming dense umbellets. Male flowers feature 3–4 petals, with 2–6 (usually 4) stamens fused into a peltate synandrium that releases in tetrads, a feature common in Menispermaceae microsporogenesis. flowers exhibit a with 3–6 sepals and 2–4 petals, enclosing a single carpel. occurs primarily by , as the flowers are entomophilous. Following , female plants develop subglobose, slightly flattened drupes that ripen to red or orangish-red, aiding in primarily through zoochory by birds or mammals, with barochory () playing a secondary role in some cases. The seeds are horseshoe-shaped, with a fleshy and cotyledons that are subequal to or shorter than the , a trait emblematic of the .

Distribution and Habitat

Geographic Range

Stephania is native to the tropical and subtropical regions of the , encompassing eastern and southern (including countries such as , , and ), (notably and ), and tropical (for example, and ). The genus exhibits a center of diversity in ; endemism is particularly high in Indo-China biodiversity hotspots, where many species are restricted to localized areas. Some Stephania species have been introduced or naturalized in additional parts of and Pacific islands, often facilitated by human activities such as trade and cultivation for medicinal purposes. These expansions reflect both intentional dispersal and accidental spread, extending the genus's presence beyond its core native ranges in regions like the and .

Ecological Preferences

Species of the genus Stephania predominantly inhabit humid, lowland tropical and subtropical forests, often along riverbanks, in riparian zones, and on disturbed forest edges or thickets. These environments provide the necessary moisture and partial shade, with plants frequently observed in open woodlands, grasslands, and areas recovering from disturbance such as abandoned fields or roadsides. For instance, S. abyssinica thrives in shady, damp localities near rivers or swamps, avoiding dense rainforest interiors. Elevation preferences range from to approximately 1,500 meters, allowing to both coastal and montane settings within tropical biomes. In , species like S. japonica occur in beach forests, lowland s, shrublands, and forest margins up to 1,100 meters, while in , S. abyssinica extends to 1,500 meters in wooded grasslands. This elevational tolerance supports occupancy in diverse topographic niches, from coastal lowlands to upland slopes. Soil requirements vary but generally favor moist, well-drained substrates in a range of types, including loamy or sandy soils along watercourses that experience seasonal flooding. Stephania species demonstrate resilience in riparian habitats prone to periodic inundation, contributing to bank stabilization and recovery in successional forests. Adaptations such as twining stems enable access to light in shaded amid competing , facilitating establishment in competitive, low-light environments.

Species Diversity

Number of Species and Taxonomy

The genus Stephania is estimated to include 45–70 accepted species worldwide, with the current consensus from authoritative checklists recognizing approximately 70 taxa, though this number continues to evolve due to ongoing taxonomic revisions prompted by evidence of cryptic speciation revealed through molecular phylogenetics. While no formal subgenera are recognized within Stephania, infrageneric divisions are often delineated informally based on leaf morphology, particularly peltation; species cluster into clades characterized by consistently peltate leaves versus those with non-peltate or variably peltate leaves, reflecting underlying phylogenetic patterns supported by nuclear and chloroplast DNA analyses. Taxonomy of the genus is complicated by morphological convergence among its scandent species, which share similar climbing habits and vegetative traits that obscure species boundaries, necessitating the integration of molecular tools such as DNA barcoding with markers like the rbcL gene to resolve identifications and relationships.

Notable Species

Stephania tetrandra S. Moore, commonly known as han fang ji in traditional Chinese medicine, is a herbaceous perennial vine native to China, Taiwan, and Vietnam. The species name "tetrandra" derives from the Greek words for "four" (tetra) and "anther" (andros), referring to the four stamens in its male flowers. It was first described by Spencer Le Marchant Moore in 1875, with the type locality in Jiujiang, Jiangxi Province, China, based on a specimen collected in 1873. This slender climber reaches up to 3 meters in height, featuring simple, spiral-arranged, peltate leaves and twining stems that exude yellow latex when cut, making it a prominent species in subtropical forests. Stephania japonica (Thunb.) Miers is a widespread dioecious climber distributed across , including Japan, China, India, and Southeast Asia, often found in rainforests and coastal areas. The specific epithet "japonica" indicates its original description from Japanese material collected by . Named by John Miers in , it features peltate leaves that are broadly ovate to triangular, measuring 5-12 cm in length, with palmate venation. Renowned for its rich content, including compounds like epistephanine, the has been traditionally utilized in regions like and the for various remedies, highlighting its pharmacological significance. Stephania cephalantha Hayata is native to , central and southern , and , primarily occurring in mountainous regions of the Menispermaceae family. The name "cephalantha" combines Greek roots "kephalē" (head) and "anthos" (flower), likely alluding to the flower structure. Described by Bunzo Hayata in , its type locality is in , where it grows as a climbing vine. It serves as the primary natural source of the bisbenzylisoquinoline cepharanthine, extracted from its roots and stems. Due to extensive harvesting for medicinal purposes, the species faces endangerment from overexploitation and habitat loss. Stephania abyssinica (Quart.-Dill. & A. Rich.) Walp. represents one of the few African members of the , distributed from southward through eastern and in and habitats. The epithet "abyssinica" derives from , the historical name for , reflecting its type locality there. First described in 1847 and later transferred to Stephania by Wilhelm Walpers in 1848, it is a robust twining liane up to 10 meters long, with woody bases and peltate, broadly ovate to suborbicular leaves that are palmately veined. This species is distinguished by its adaptation to drier African ecosystems compared to the predominantly Asian congeners.

Phytochemistry

Alkaloid Composition

The Stephania is particularly noted for its rich content of bis s, which constitute the dominant class of s in many species, especially in the roots and tubers. These dimeric s are formed by the linkage of two units, typically through or bridges, contributing to their structural complexity and . A representative example is tetrandrine, a well-characterized bis isolated primarily from the roots of Stephania tetrandra, with the molecular formula C38H42N2O6; its structure features two moieties connected by two bonds, forming an 18-membered macrocyclic . Other notable bis s in Stephania include fangchinoline and berbamine, which share similar dimeric architectures and are often co-isolated from the same plant parts. In addition to bisbenzylisoquinolines, Stephania species produce a variety of other alkaloid types, including protoberberine, aporphine, and morphinane alkaloids. Protoberberine alkaloids, such as corydalmine and stepholidine, feature a tetracyclic ring system derived from precursors and are commonly found in tuberous roots. Aporphine alkaloids, exemplified by stephanine, possess a characteristic with a fully aromatized and are prevalent in several Stephania taxa. Morphinane alkaloids, structurally related to but lacking the double bond, include compounds like cephasamine. These alkaloid classes often co-occur, with their relative abundances varying by species and plant organ. The of these s in Stephania originates from L-, which is decarboxylated to and hydroxylated to ; these catecholic amines then undergo condensation to form (S)-norlaudanosoline, the central intermediate in pathways. From norlaudanosoline, enzymatic modifications such as , , and cyclization lead to monomeric units like aporphines or protoberberines, which dimerize to yield bisbenzylisoquinolines like tetrandrine through oxidative coupling mediated by enzymes. This pathway is conserved across Menispermaceae but shows species-specific variations, such as enhanced expression of methyltransferases in S. tetrandra roots that favor bisbenzylisoquinoline production. Studies using radiolabeled fed to cultured roots of Stephania cepharantha confirm incorporation into both benzyl and moieties, supporting the role of norlaudanosoline as a key branch point. Alkaloid profiles vary significantly among Stephania species, with over 20 distinct alkaloids reported in the roots of S. tetrandra alone, including multiple bisbenzylisoquinolines alongside aporphines and protoberberines. This diversity arises from differential gene expression in biosynthetic enzymes, leading to organ-specific accumulation; for instance, roots and tubers typically harbor higher concentrations than aerial parts. Extraction of these alkaloids is predominantly performed from dried tubers or roots using solvents like ethanol or deep eutectic solvents under ultrasound assistance, achieving yields of 1-5% of dry weight for total alkaloids, with tetrandrine often comprising 1-2% in optimized protocols.

Other Secondary Metabolites

In the Stephania, non-alkaloid secondary metabolites contribute to the plant's chemical diversity, encompassing , lignans, terpenoids, phenolics, and steroids. These compounds occur alongside alkaloids, with profiling studies indicating their co-occurrence in various extracts. , such as glycosides and derivatives, feature a characteristic 15-carbon skeleton consisting of two phenyl rings linked by a heterocyclic pyrone ring, and they provide properties through radical scavenging. Examples have been identified in like Stephania japonica and Stephania elegans, where total flavonoid content contributes to the polyphenolic profile. Lignans and terpenoids represent another key class, with lignans isolated from species such as Stephania cepharantha. For instance, four novel lignan glycosides were obtained from the stems, featuring diphenylbutane frameworks typical of this group, determined through spectroscopic methods including NMR and MS. Terpenoids, though less characterized, are reported in multiple species, adding to the structural variety. Phenolics and steroids occur as minor constituents, with phenolics including and simple detected in leaves and roots of Stephania japonica, while steroids like appear in broader screenings. Distribution varies across plant parts, with and phenolics often higher in aerial parts compared to roots, which tend to accumulate other metabolites. Analytical techniques such as high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS) have been employed to profile these metabolites, enabling identification and quantification in complex extracts from species like Stephania rotunda and Stephania hainanensis, thus revealing their diversity and potential synergistic interactions within the metabolome.

Traditional and Medicinal Uses

Historical Applications in Folk Medicine

In (TCM), Stephania tetrandra, known as Han Fang Ji, has been utilized since the , as recorded in the ancient text Shennong Bencao Jing (circa 100–200 CE), to treat conditions associated with wind-dampness, such as , , and beriberi, by dispelling dampness, alleviating pain, and promoting urination. The root is typically prepared as a by boiling 3-9 grams daily in water for oral consumption to address rheumatic pain and urinary issues. In Ayurvedic and Southeast Asian folk medicine, various Stephania species, including S. japonica and S. glabra, have been employed in decoctions to manage , fevers, and snakebites, with S. japonica specifically used in Indian traditions for and bowel disorders like . Roots and leaves are often boiled into teas or applied as poultices for these ailments, reflecting their role in heat-clearing and practices across these regions. Ethnobotanical records from African traditions highlight S. abyssinica, where roots are used in Ethiopian folk medicine to treat through extracts and to heal wounds via topical applications like poultices, drawing on its reputed and wound-healing properties in eastern African communities. These preparations underscore the plant's historical versatility in addressing infectious and inflammatory conditions without reliance on modern interventions. Active compounds, primarily alkaloids, are believed to contribute to these traditional effects (see ).

Pharmacological Studies and Bioactivities

Contemporary pharmacological research on alkaloids from the Stephania, particularly tetrandrine and cepharanthine, has highlighted their potential therapeutic applications in , cancer, cardiovascular conditions, and infectious diseases. These bisbenzylisoquinoline alkaloids, primarily isolated from species such as Stephania tetrandra and Stephania cepharantha, demonstrate multifaceted bioactivities supported by , , and limited clinical evidence. Studies emphasize mechanisms involving key signaling pathways, with a focus on modulating cellular responses without overlapping traditional empirical uses. Tetrandrine exhibits potent effects primarily through inhibition of the signaling pathway, a central regulator of pro-inflammatory cytokine production. In investigations have shown that tetrandrine suppresses activation induced by stimuli such as (LPS) or tumor necrosis factor-alpha (TNF-α), reducing the expression of downstream targets like interleukin-1β (IL-1β) and TNF-α in microglial and models. Dose-dependent inhibition occurs with IC50 values approximately 10-11 μM in human T-cell lines, where it attenuates nuclear translocation and DNA binding, thereby mitigating inflammatory responses in conditions like and . Cepharanthine demonstrates significant anticancer activity, notably by inducing in cells through activation and (ROS) generation. In human T-cell lines such as Jurkat and K562, cepharanthine at concentrations of 1-5 μM triggers mitochondrial dysfunction, upregulates Fas antigen expression, and promotes arrest at the G1/S phase, leading to . This mechanism has been corroborated in preclinical models of multidrug-resistant , where cepharanthine reverses resistance by inhibiting efflux. In , cepharanthine has been clinically employed since the 1950s to manage radiation- or chemotherapy-induced in cancer patients, with Phase II trials in the exploring its adjunctive role in enhancing chemotherapeutic efficacy against solid tumors and hematological malignancies, reporting improved in select cohorts. As of 2024, a Phase 1 for a reformulated cepharanthine (PD-001) was approved to evaluate its and . For cardiovascular benefits, tetrandrine acts as a non-selective , exerting hypotensive effects by relaxing vascular and reducing peripheral resistance. in spontaneously hypertensive rats (SHRs) have demonstrated that of tetrandrine at 30-60 mg/kg/day significantly lowers mean arterial blood pressure by 20-30% over chronic treatment periods, alongside decreases in and collagen deposition. This blockade of L-type calcium channels inhibits aldosterone synthesis and vascular remodeling, offering protective effects against hypertension-induced cardiac damage without substantial impact on . Stephania-derived alkaloids also possess antimicrobial and antiviral properties, with notable activity against Plasmodium species in malaria models. Cepharanthine inhibits the growth of chloroquine-resistant Plasmodium falciparum strains (D6 and W2) in vitro, with IC50 values in the micromolar range, by interfering with parasite development at the ring stage and potentiating antimalarial drugs like chloroquine through enhanced endolysosomal deacidification. In vivo, cepharanthine reduces parasitemia by up to 47% in Plasmodium berghei-infected mice, supporting its potential as an adjunct therapy. Broader antiviral effects include suppression of herpes simplex virus type 1 replication and inhibition of SARS-CoV-2 entry, underscoring the genus's relevance in infectious disease research. Recent studies as of 2025 have explored tetrandrine's mechanisms in treating diabetic kidney disease and enhancing cisplatin efficacy in non-small cell lung cancer.

Toxicity and Safety

Toxic Constituents and Mechanisms

Certain species of Stephania, particularly S. tetrandra, have been implicated in cases of (AA) exposure due to inadvertent substitution or contamination with species during herbal preparation, leading to the presence of nephrotoxic AA compounds rather than true analogs native to Stephania. AA, a nitrophenanthrene , exerts its toxicity primarily through metabolic to form DNA adducts, such as 7-(deoxyadenosin-N⁶)-yl-aristolactam I, which interfere with and repair, resulting in tubular cell , interstitial , and progressive renal failure known as aristolochic acid nephropathy. The primary alkaloids in Stephania, such as tetrandrine, exhibit low , with oral LD₅₀ values reported at approximately 2230 mg/kg in rats and 3700 mg/kg in mice, indicating relative safety at therapeutic doses. Pure Stephania extracts show low in use when uncontaminated, though high doses in models (e.g., 150 mg/kg intravenous in mice) can cause reversible liver, , and effects. Tetrandrine and related bisbenzylisoquinoline alkaloids also pose risks of via induction of , where (ROS) generated by (CYP450) enzymes, particularly , disrupt mitochondrial function, leading to permeability transition, ATP depletion, and . This mechanism can exacerbate in susceptible individuals. Additionally, tetrandrine undergoes primarily via CYP450 enzymes (e.g., ), potentially leading to herb-drug interactions by competing with substrates like cyclosporine or statins, thereby altering their and increasing toxicity risks.

Reported Incidents and Precautions

One of the most notable incidents involving Stephania occurred in the in , where a weight-loss regimen prescribed to over 100 young women included a preparation intended to contain Stephania tetrandra (known as Han Fang Ji in ). Due to a error and substitution with the nephrotoxic Aristolochia fangchi (Guang Fang Ji), patients developed aristolochic acid nephropathy, characterized by rapid progression to end-stage renal disease and a high incidence of urothelial carcinomas. This outbreak, often referred to as Chinese herbs nephropathy, affected approximately 128 individuals, leading to kidney transplants or dialysis for many, and heightened global awareness of adulteration risks in herbal products. While pure Stephania tetrandra has been used safely in traditional Chinese medicine, most reported severe toxicities stem from substitution with Aristolochia species rather than direct overdose of uncontaminated material. Animal studies indicate potential for organ toxicity (e.g., hepatotoxicity, nephrotoxicity) at high doses, but human data on direct adverse events from pure extracts remain limited. To mitigate these risks, species authentication is essential, often achieved through DNA barcoding or hyperspectral imaging to distinguish Stephania tetrandra from toxic look-alikes like Aristolochia species. Dosage guidelines in traditional Chinese medicine recommend no more than 3-12 grams per day of dried root in decoction for S. tetrandra, with limits under 15 grams to avoid cumulative toxicity; exceeding this can lead to renal and hepatic strain. Contraindications include pregnancy, due to potential teratogenic effects from alkaloids, and caution is advised for individuals with pre-existing kidney or liver conditions. Regulatory measures reflect these concerns: Aristolochia-containing herbs are banned across the due to nephrotoxic risks, and while pure Stephania tetrandra is permitted, some EU countries impose restrictions or require strict verification to prevent adulteration. In the United States, the FDA has issued warnings on herbal supplements potentially contaminated with , advising consumers to avoid unverified products containing Stephania or similar herbs, and emphasizing third-party testing for safety.

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