Stemona

Synopsis

Stemona (Baibu / Radix Stemonae): A Comprehensive Reference

1. Identity and Botanical Classification

Taxonomic Position

Stemona is a genus of vines and subshrubs in the family Stemonaceae, described as a genus in 1790. It is native to China, the Indian subcontinent, Southeast Asia, Papuasia, and northern Australia. Stemona alkaloids represent a unique class of natural products exclusively known from the three genera Stemona, Stichoneuron, and Croomia of the monocotyledonous family Stemonaceae.

Pharmacopoeial Species

Stemonae Radix consists of the dried roots of Stemona japonica (Bl.) Miq., Stemona sessilifolia (Miq.) Miq., and Stemona tuberosa Lour., and is a widely used traditional Chinese medicine (TCM) also known as "Baibu" (Chinese: 百部). These three species are listed in the 2020 edition of the Chinese Pharmacopoeia as an antitussive herb.

Beyond these three pharmacopoeial species, the genus comprises many more members. The genus Stemona comprises 27 species and is widely distributed in Asia and Australia. Notable non-pharmacopoeial species used regionally include Stemona curtisii Hook.f., the most frequently used medicinal species in Thailand, with a remarkable reputation for resisting various insects. S. burkillii Prain occurs in Thailand and Myanmar; S. cochinchinensis Gagnep. in Vietnam; S. collinsiae Craib in Thailand and Vietnam; and S. curtisii Hook.f. in Sri Lanka, Nicobar, and Thailand.

Stemona tuberosa (Chinese: 百部; pinyin: bǎi bù) is one of the 50 fundamental herbs used in traditional Chinese medicine. S. japonica and S. sessilifolia grow on hillsides in eastern China, whereas S. tuberosa has a wider distribution.

Common Names and Drug Names

The principal drug prepared from the roots of the three pharmacopoeial species is known by several names across traditions: Baibu (百部) in Chinese medicine; Radix Stemonae or Stemonae Radix in pharmacopoeial Latin; and "stemona root" in English. Radix Stemonae, also known as Baibu, is one of the most popular herbal medicines used in many Asian countries, including China, Korea, Japan, Thailand, and Vietnam, where it has been used for the treatment of various respiratory diseases such as bronchitis, pertussis, and tuberculosis.

Botanical Form and Drug Preparation

Processing of the crude drug involves eliminating foreign matter, washing clean, softening thoroughly, cutting into thick slices, and drying. The drug occurs in irregular thick slices or irregular slat-shaped oblique slices, externally greyish white or brownish yellow, with deep longitudinal wrinkles; cut surface greyish white to yellowish white; texture flexible and soft. A honey-processed form also exists: the slices are stir-fried with honey (using 12.5 kg of refined honey for 100 kg of drug) until not sticky to the fingers.

2. Traditional and Historical Use

Traditional Chinese Medicine (TCM)

The herb Radix Stemonae, called Baibu in Chinese, has been used as an antitussive and anthelmintic in traditional Chinese medicine for some 2,000 years, and as an insecticide in the Orient. It first appeared in the herbal Additional Records of Famous Physicians (Mingyi Bielu), compiled in the 6th century A.D., where Baibu is indicated for treating cough and noted for its mild toxicity.

According to records of medical books, the roots of Stemona species have been traditionally and ethnobotanically used to relieve itching and expel parasites, stop cough, resolve phlegm and asthma. In TCM, Stemona sessilifolia, Stemona tuberosa, and Stemona japonica have been widely used to relieve cough and asthma, and expel parasites.

According to pharmacopoeial indications, the action of the drug is to moisten the lung and relieve cough, and to kill insects and worms. Indications include acute and chronic cough, cough in phthisis, and whooping cough. For external use, the drug is applied to treat pediculosis capitis, pediculosis corporis, oxyuriasis, and pudendal itching. The honey-fried form is specifically indicated for cough in phthisis. The standard dosage stated in the pharmacopoeia is 3 to 9 g, decocted in water; for external use, an appropriate quantity decocted in water or infused in wine.

The roots of Stemona sessilifolia, a traditional medicine of China, have been used to relieve cough, bronchitis, and tuberculosis, and also as an anthelmintic agent to treat respiratory disorders and bronchitis in animals.

In the Chinese pharmacopoeia, the dried root of Stemona sessilifolia has been recorded for centuries as an antitussive and antiasthmatic herb, most often taken as a decoction. Japanese Kampo practitioners also employ the same underground tuber, simmering it in water for 20–30 minutes to relieve chronic cough and bronchial irritation.

Southeast Asian Traditions

The tuberous roots of various Stemona species are used throughout Southeast Asia, China, and Japan as insecticides and therapeutic agents (especially for coughs). In Southeast Asia, S. tuberosa is by far the most important species. In the Moluccas, the ground fresh tuberous roots are used to repel lice from body and clothing. In Thailand, the tuberous roots, crushed and soaked in water, are topically applied to treat scabies and kill head lice. In Vietnamese folk medicine, the tuberous roots are used internally as an antitussive and anthelmintic, and externally as an insecticide. As an anthelmintic, it is applied as an enema or as a decoction in combination with a purgative.

Stemona species have been used in Asia as traditional medicines to treat skin and respiratory diseases, diminish inflammation, ease pain, and as biological pesticides to kill pests for thousands of years. In Thailand, Stemona curtisii Hook.f. is the most frequently used medicinal plant, with a remarkable reputation for resisting various insects, such as Parasarcophaga ruficornis, Rhipicephalus microplus, and Plutella xylostella. The extract of this species is lethal to maggots, mosquitoes, mandarin aphids, and cutworms.

Processing in Traditional Practice

Processing is an important and crucial part of traditional oriental medicine. Traditional ingredients were processed on the basis of Yin Yang theory, Five Elements theory, and folk experiences. Among many processing techniques, honey-frying is a process enhancing the effects of traditional herbs on the Spleen and Stomach organs. The inclusion of honey in Stemona tuberosa-based treatments greatly reduces the plant's toxicity and enhances its cough suppressant activity.

3. Phytochemistry: Key Constituents and Active Compounds

Overview of Secondary Metabolites

To date, the major chemical constituents, including 12 types of the 286 secondary metabolites, have been extracted, separated, and identified from plants of the genus Stemona in the past 60 years. Phytochemical assessments have revealed that plants of genus Stemona contain alkaloids (pyridoazepines, pyrroloazepines, and miscellaneous alkaloids), stilbenoids (phenylbenzofurans, stilbenes, phenanthrenes, and tocopherols), and others. Up to now, more than 170 compounds have been isolated and identified from the three official species of Stemonae Radix, mainly including Stemona alkaloids. A 2024 review reported that more than 250 Stemona alkaloids have been isolated and identified.

Stemona Alkaloids: Structure and Classification

The Stemona alkaloids are structurally characterized by the presence of either an exposed or hidden pyrrolo[1,2-a]azepine (n=1) moiety, also named perhydroazaazulene or 4-aza-azulene, or a pyrido[1,2-a]azepine (n=2) nucleus. Stemona alkaloids constitute a unique chemical feature of the Stemonaceae and cannot be detected so far in any other plant families. So far, such alkaloids are not found elsewhere in the plant kingdom except in the four genera in Stemonaceae. Notably, the same structural nucleus has been found in the skin of the Colombian poison frog Dendrobates lehmanni.

Stemona alkaloids are mainly divided into eight types: stenine (I), stemoamide (II), tuberostemospironine (III), stemonamine (IV), parvistemoline (V), stemofoline (VI), stemocurtisine (VII), and miscellaneous alkaloids (VIII).

The major individual alkaloids of pharmacological interest include tuberostemonine, neotuberostemonine, croomine, stemoninine, stemofoline, protostemonine, and stemonamine. Based on biosynthetic considerations, the alkaloids can be classified into stichoneurine/tuberostemonine types, protostemonine types, and croomine types. The tuberosa group contains stichoneurine- and croomine-type alkaloids demonstrating antitussive activity, while the non-tuberosa group contains protostemonine-type alkaloids that promote potent insecticidal activity.

Tuberostemonine was the first Stemona alkaloid to have its biological activity tested. The anthelmintic activity of this alkaloid was detected against Angiostrongylus cantonensis, Dipylidium caninun, and Fasciola hepatica with an effect on the motility of these helminthic worms.

Stemofoline alkaloids occur in the stems and leaves of Stemona species, particularly S. japonica, and have been investigated for use as pharmacological and pesticidal compounds. Remarkably, the chemical structure of the commercial insecticide flupyradifurone was inspired by stemofoline.

Stilbenoids

Biological testing showed that the insecticidal and antitussive activities of Stemona are dependent on Stemona alkaloids, while antifungal activity against plant-pathogenic fungi is dependent on the presence of stilbenoids. The 2-arylbenzofurans characteristic of Stemona are found in only seven known plant families, including Stemonaceae. Antibacterial stilbenoids have been isolated specifically from the roots: twelve dihydrostilbenes (stilbostemins N–Y) and a phenanthraquinone (stemanthraquinone) were isolated and identified from roots of Stemona tuberosa. Dihydrostilbene 8 exhibited strong activity against Bacillus pumilus (MIC 12.5–25 µg/mL), and many tested compounds exhibited moderate antibacterial activities.

Intra- and Inter-Species Chemical Variability

Significant intra- and inter-specific chemical diversities are found among the three pharmacopoeial species. HPLC analyses demonstrated that the total alkaloid profiles could be grouped into four types, represented as the major component by stenine-type Stemona alkaloids such as tuberostemonine and neotuberostemonine, or by non-stenine types such as croomine and stemoninine. Chemical variation between specimens may result from environmental factors such as differences in age, seasons of collection, and geographic distributions. Alkaloids are the main active ingredient in stemonae radix, so their composition and concentration levels are directly linked to clinical effects.

In terms of raw total alkaloid content across species, studies have found: the content of total alkaloids in Stemonae Radix ranges from 0.26 to 3.1%; in Stemona sessilifolia from 0.26 to 2.17%; in S. japonica from 0.83 to 1.43%; and in S. tuberosa from 0.53 to 3.1%.

4. Mechanisms of Action

Antitussive Mechanisms

Preclinical studies, primarily using guinea pig models, have characterized how distinct alkaloids act on different sites of the cough reflex. Neotuberostemonine, tuberostemonine, and stemoninine act on the peripheral cough reflex pathway, while croomine acts on the central part. Croomine also shows obvious central respiratory depressant effects.

Croomine, neotuberostemonine, and stemoninine showed similar antitussive potency, while tuberostemonine showed much weaker antitussive potency. Croomine was the most potent compound, showing a dose-dependent inhibition of coughing with an ID50 value of 0.18 mmol/kg.

Regarding central action: biodistribution studies showed higher levels in liver and lung; croomine was detected in brain and showed that it could cross the blood–brain barrier, indicating it has an antitussive effect by acting on the central nervous system.

Studies on S. sessilifolia further confirm the multi-pathway activity: protostemonine, maistemonine, and the croomine-type derivative stemospironine were investigated using the citric acid-induced cough model. All three alkaloids showed significant antitussive activity following peripheral administration.

Insecticidal Mechanisms

Follow-up studies on the significant insecticidal activities focused on the mode of action using biochemical and electrophysiological approaches. Screening for acetylcholinesterase inhibitory properties revealed a much higher potency for stemofoline derivatives compared to pyridoazepines, but also showed significant activity for isomers of stenine with a stichoneurine skeleton.

Compounds including stemofoline acted as agonists, whereas protostemodiol and demethoxy-dihydroprotostemonine acted as antagonists of insect nicotinic acetylcholine receptors (nAChRs). The remarkable potential of these stemofolines might be related to the defense system of the Stemona plants.

Tuberostemonine was pointed out as the bioactive principle responsible for the insecticidal activity of S. tuberosa, with activity levels comparable to those of azadirachtin, after being tested against the larvae of Spodoptera littoralis.

Anti-inflammatory Mechanisms

The anti-inflammatory activity of some derivatives was identified as an inhibition of the expression of inflammatory mediators. Research on new alkaloids from S. japonica has indicated anti-inflammatory activity: three new Stemona alkaloids, stemajapines A–C, were discovered from the roots of Stemona japonica, along with six known alkaloids; these compounds showed potential anti-inflammatory activity, suggesting a new direction for Stemona alkaloids beyond their traditional antitussive and insecticide properties.

Multidrug Resistance Reversal

Evaluating synergistic growth inhibitory effects with cancer chemotherapeutic agents, stemofoline exhibited the most potent effect in the reversal of permeability glycoprotein (P-gp)-mediated multidrug resistance. Comparing the diverse bioactivities of Stemona alkaloids, stemofoline-type derivatives are the most versatile compounds, representing promising lead structures for further development as commercial agents in agriculture and medicine.

Acetylcholinesterase (AChE) Inhibition

AChE inhibition is an important bioactivity of the Stemona alkaloids. Sessilistemonamines A–C and dihydrostemoninine isolated from the roots of Stemona sessilifolia were examined for AChE inhibitory properties; compounds 153 and 154 displayed moderate activity with IC50 values of 68.8 ± 9.5 µM.

5. Scientific Evidence by Area of Use

5.1 Antitussive and Respiratory Effects

This is the best-studied pharmacological activity of Stemonae Radix. The evidence base, however, consists predominantly of preclinical (animal) work rather than registered human clinical trials.

Although Radix Stemonae has been in use for two millennia and is included in the China Pharmacopoeia, hardly any experimental study is available to document the antitussive functions of this herb in humans. Cong and Xu (1997) claimed that the total alkaloids of the three species had antitussive effects; however, their study was based on mice as the animal model with cough induced by ammonia aerosol.

A key preclinical investigation tested four major alkaloids of S. tuberosa in guinea pigs using a citric acid aerosol cough model: the study aimed to determine whether alkaloids contribute equally to antitussive functions, act on the same sites of cough reflex, and play any role in inducing central respiratory depressant effects. Antitussive potency of four major alkaloids was evaluated in guinea pigs with citric acid aerosol to induce cough, and the action sites on the cough reflex pathway were tested with electrical stimulation of the superior laryngeal nerve. The four major Stemona alkaloids in Stemona tuberosa do not contribute equally to antitussive potency in guinea pigs. Neotuberostemonine, tuberostemonine, and stemoninine target the peripheral cough reflex pathway. Croomine acts on central sites in the cough reflex pathway and demonstrates central respiratory depressant effects, which can partly account for the adverse reactions reported for the herb.

A separate study examined different chemical profiles of S. tuberosa: all samples demonstrated different degrees of antitussive properties in guinea pigs. Both crude alkaloidal extracts and different types of alkaloids exhibited strong antitussive activity while also showing different side effects. S. sessilifolia growing in Chuzhou, recorded in ancient medicinal books as the geo-authentic species, contains a major alkaloid with the most potent antitussive activity and the least side effects.

Evidence strength: The antitussive effect of Stemonae Radix alkaloids is well-supported at the preclinical (animal) level, with mechanistic elucidation of peripheral and central sites of action. No randomized controlled human clinical trials specifically evaluating isolated Stemona alkaloids as antitussives have been identified in the literature. The herb's inclusion in the Chinese Pharmacopoeia rests on two millennia of traditional use and extensive preclinical data.

5.2 Insecticidal and Antiparasitic Effects

Numerous studies have shown that the extracts and secondary metabolites isolated from these plants have a wide range of pharmacological activities, including insecticidal and antifeedant activity.

Against pest insects: lipophilic crude extracts of the roots of Stemona curtisii and Stemona cochinchinensis exhibited significant insecticidal activity against Spodoptera littoralis, whereas moderate activity was observed for S. kerrii. Stemofoline and didehydrostemofoline isolated from extracts exhibited stronger activities than those of pyrethrum extract.

Against ectoparasites (cockroaches): S. collinsiae dichloromethane extract, which contained the highest didehydrostemofoline content, exhibited the highest contact toxicity against final-instar nymphs (41.0–100.0% corrected mortality) and adult Periplaneta americana (23.0–46.0% corrected mortality).

Against helminths: the anthelmintic activity of tuberostemonine was detected against Angiostrongylus cantonensis, Dipylidium caninun, and Fasciola hepatica with an effect on the motility of these helminthic worms.

Evidence strength: Insecticidal and antiparasitic activities are robustly demonstrated at the in vitro and in vivo (invertebrate/animal model) level, with clear mechanistic data involving nAChR modulation and acetylcholinesterase inhibition. Clinical evidence in humans for antiparasitic therapeutic applications is not available in the peer-reviewed literature.

5.3 Anti-inflammatory Activity

In previous studies on Stemona tuberosa, several alkaloid types have been isolated that have shown many biological activities, such as antitussive and anti-inflammatory activities. Anti-inflammatory mechanisms involve inhibition of inflammatory mediator expression. Evidence at the preclinical level includes in vitro cell studies and animal models; the available literature is primarily composed of cell-based assays.

Evidence strength: Anti-inflammatory evidence is preliminary and based on in vitro and animal model studies. No human clinical trials specifically testing anti-inflammatory endpoints for Stemona preparations have been identified.

5.4 Antimicrobial Activity

Antifungal activity against plant-pathogenic fungi is dependent on the presence of stilbenoids. For antibacterial activity, dihydrostilbene 8 exhibited strong activity against Bacillus pumilus (MIC 12.5–25 µg/mL), and many tested compounds exhibited moderate antibacterial activities.

Evidence strength: Antimicrobial activity is demonstrated in vitro (MIC assays). No human clinical trials have evaluated Stemona preparations for antimicrobial endpoints.

5.5 Anticancer Activity

Preliminary tests on anticancer and antioxidant activities of some Stemona species have been reported. Stemofoline exhibited the most potent effect in the reversal of P-gp-mediated multidrug resistance in cancer chemotherapy models.

Evidence strength: Anticancer-relevant evidence is confined to in vitro cytotoxicity and drug-resistance reversal assays. No human clinical data exist.

5.6 Anti-pulmonary Fibrosis Activity

A TCM formula called Baibu Tang, which uses Baibu (root of Stemona tuberosa) containing different components (neotuberostemonine, tuberostemonine, and stemoninine), could significantly reduce hydroxyproline levels and collagen deposition in the lung tissue of bleomycin-induced mice, showing anti-fibrosis activity. The result showed that changes in the chemical composition of Stemona tuberosa have little effect on the anti-fibrosis activity of Baibu Tang, and its mechanism and material basis require further investigation.

Evidence strength: Preliminary, animal (mouse) model data only.

6. Body Systems and Health Areas Associated with Stemona

Respiratory system: Stemonae Radix has a wide range of pharmacological effects, mainly used to treat respiratory diseases. Indications include cough, bronchitis, asthma, pertussis, and tuberculosis-associated cough.
Parasitic/ectoparasitic conditions: Baibu was also used for killing cattle parasites, agricultural pests, and domestic insects.
Skin: Traditional topical applications for scabies, pediculosis capitis, and pediculosis corporis, as documented in Asian folk medicine.
Gastrointestinal system (anthelmintic): Used via enema or oral decoction to expel intestinal parasites.
Immune/Inflammatory: Preliminary preclinical evidence for anti-inflammatory properties involving inhibition of inflammatory mediator expression.
Potential oncology: In vitro evidence for reversal of multidrug resistance in cancer cells.

7. Dosage Forms and Reported Dosages

The Chinese Pharmacopoeia specifies the dose of Radix Stemonae (crude form) as 3 to 9 g for internal use, decocted in water. For external use, an appropriate quantity is decocted in water or infused in wine. The honey-fried form (Radix Stemonae stir-fried with honey) is specifically indicated for moistening the lung and relieving cough.

The primary preparation forms used in research and practice include:

Decoction of dried root slices — the classical TCM preparation, made by simmering root slices in water; standard pharmacopoeial dose 3–9 g per day.
Honey-processed (honey-fried) slices — the inclusion of honey greatly reduces the plant's toxicity and enhances its cough suppressant activity.
Ethanol or alkaloid extracts — used in pharmacological research. In one analytical study, 5 g of chopped roots of Stemona tuberosa were refluxed with 95% ethanol (100 mL) for one hour to prepare total alkaloid fractions.
Topical preparations — crushed fresh root soaked in water or infused in wine, for application to skin to treat ectoparasites.
Wine infusion — used externally for insecticidal applications as stated in pharmacopoeial monographs.

8. Safety Considerations

Known Adverse Effects

Stemona tuberosa may cause nausea, vomiting, headache, and even respiratory distress and depression. The inclusion of honey in Stemona tuberosa-based treatments greatly reduces the plant's toxicity and enhances its cough suppressant activity.

The mechanistic basis for respiratory toxicity is well-characterized in animal studies: croomine acts on central sites in the cough reflex pathway and demonstrates central respiratory depressant effects, which can partly account for the adverse reactions reported for the herb.

Variability and Quality Control Challenges

The heterogeneous and variable nature of the chemical constitution of Stemona plants causes difficulties in quality control of the herb. Pharmacological reports most often attribute activities to various extracts rather than specific compounds. This hampers the establishment of a connection between chemical constituents and pharmacological activities.

Potential Drug Interactions (Theoretical/Preclinical)

No well-documented pharmaceutical drug interactions have been established for Baibu in clinical studies. However, based on its pharmacological profile, croomine — one of the major alkaloids in Baibu (particularly in S. tuberosa) — has demonstrated central respiratory depressant effects in animal studies, raising a theoretical concern regarding co-administration with central nervous system depressants and sedatives, though this has not been studied clinically.

Use in Vulnerable Populations

Pediatric doses should be proportionally reduced based on age and body weight, typically one-third to one-half of the adult dose. The honey-processed form is preferred for children as it is gentler on the digestive system. Very young infants should only receive Baibu under direct practitioner supervision due to the mild toxicity of Stemona alkaloids and their potential respiratory depressant effects.

General Limitations of the Evidence Base

Though plants of genus Stemona have been put to enormous traditional uses, the pharmacological studies conducted were insufficient. Therefore, more secondary metabolites need to be studied for more detailed pharmacological evaluation. Presumably, activities demonstrated in preclinical work can help explain the traditional medicinal application of these plants, although further pharmacological studies are needed. The review literature confirmed pharmacological activities including antitussive, antiviral, insecticidal, antitumor, and antioxidant effects, but highlighted that most pharmacological studies attribute activity to extracts rather than specific compounds, complicating interpretation.