Carry me seed

Carry Me Seed (Phyllanthus amarus Schum. & Thonn.): A Comprehensive Reference

1. Identity, Botanical Classification, and Natural Source

1.1 Nomenclature and Taxonomy

"Carry me seed" is the common English name for Phyllanthus amarus Linn., a member of the family Phyllanthaceae. The full author citation is Phyllanthus amarus Schumacher & Thonn., reflecting the original botanical authorities. The plant belongs to Infra Kingdom Streptophyta, Super Division Embryophyta, Division Tracheophyta, Subdivision Spermatophytina, and Class Magnoliopsida.

Common names for this plant include gale of the wind, carry me seed, seed on the leaf, pick-a-back, stonebreaker, and dukung anak (Malay). It is also known as "black catnip" and "hurricane weed." In Indian languages, it carries the Tamil name Keela Nelli and the Sanskrit name Bahupatra. In the Rongmei language it is called Chapa tarouthai, and in Manipuri Chakpa heikru. In Kannada it is known as Nela nelli, and in Ayurvedic literature it is called Bhumyaamalaki.

Note on nomenclature: Some sources, particularly those from West Africa and the Caribbean, use the name "carry me seed" interchangeably with Phyllanthus niruri L. These two taxa are morphologically and chemically similar and were historically confused in the literature. Contemporary botanical authorities treat P. amarus and P. niruri as distinct species, and P. amarus is very similar to two related congeners sharing the same habitat — Phyllanthus debilis and Phyllanthus urinaria — and can be distinguished from them by its blunt leaflet tips, shorter leaflets in length, and flowers with 5 sepals instead of 6.

1.2 Morphology and Distribution

Phyllanthus amarus is a small, annual plant that grows to a height of 30–60 cm. Its thin branches spread out, and each branch has two rows of small, elliptic-oblong leaves of 5–10 mm long that are arranged alternately. Its radial flowers are star-shaped and of about 2 mm in size. It grows well in soil of high moisture with light shade, and reaches maturity in 2–3 months.

Carry me seed has a fascinating way of spreading its seeds that inspired its name: when ripe, the plant's fruit bursts open explosively and its seeds are thrown some distance from the parent plant. It is a weed and produces flowers and fruits all year round.

Phyllanthus amarus is a leafy herbal plant found in tropical regions in the Americas, Africa, India, China, Sri Lanka, and Southeast Asia. It is a branching annual herb of 30–60 cm height widely spread throughout the tropics and sub-tropics as a weed.

1.3 Common Preparations and Forms

Across cultures, P. amarus is prepared and used in a range of forms. In South Indian Ayurvedic practice, it is used as a Kashaya (decoction). The whole plant is thoroughly washed and crushed, and a little cumin and pepper are added and boiled with water. Leaves crushed for decoction juice are given in leucoderma; leaf juice crushed and mixed with coconut milk is used as an appetizer and diuretic for children. In scientific and commercial settings, the plant is studied as aqueous extract, methanolic extract, ethanolic extract, whole-plant powder, and encapsulated supplement. P. amarus is ethnomedicinally used to treat gallbladder stones, kidney stones, and chronic liver diseases and is gaining popularity as an ingredient in many botanical dietary supplements.

2. Traditional and Historical Use

2.1 Duration and Extent of Traditional Use

P. amarus has a long history of use in the traditional system of medicine for over 2,000 years, owing to its wide array of secondary metabolites that confer significant medicinal attributes. Research on various aspects including ethnobotany, phytochemistry, bioactivity, and pharmacological studies has been conducted over several decades on this potent herb. Some sources place its traditional use even longer: Phyllanthus amarus Schum and Thonn has been in traditional medicine for more than 3,000 years and is commonly known by the names carry me seed, stone breaker, and gale of wind.

2.2 Ayurvedic Tradition (India and South Asia)

It is an important plant of the Indian Ayurvedic system of medicine, used in problems of the stomach, genitourinary system, liver, kidney, and spleen. It is widely used in traditional systems such as Ayurveda, Siddha, and Unani for hepatic, renal, and metabolic disorders.

In Indian folk medicine, the whole plant is used therapeutically. The whole plant is considered bitter, astringent, stomachic, diuretic, febrifuge, and antiseptic. The whole plant is used in gonorrhoea, menorrhagia, and other genital problems. It is useful for gastropathy, diarrhoea, dysentery, intermittent fever, ophthalmopathy, scabies, ulcers, and wounds. The plant was particularly well known as a folk treatment for jaundice in parts of South India. It is a plant well known to children as it is commonly used for treatment of jaundice.

2.3 Amazonian and Caribbean Traditions

Phyllanthus amarus has been used in the traditional medicine of various cultures, including Amazonian tribes, Ayurveda, and Sinhala folk medicine. This plant is a rainforest herb found in tropical and subtropical rainforests, including the Amazon, and is used in herbal medicine to eliminate gallstones and kidney stones.

2.4 Traditional Chinese Medicine

In Traditional Chinese Medicine (TCM) practice, Yexiazhu (the Chinese name for P. amarus) is traditionally prescribed for heat-clearing and detoxification, particularly in the management of liver- and kidney-related disorders, viral infections, and inflammatory conditions.

2.5 West African Traditions

Among the Yoruba tribe of Southwest Nigeria, water decoction of the leaf and seed of Phyllanthus amarus is reputably used for the local management of diabetes mellitus, obesity, and hyperlipidemia. The plant is widely used across West Africa in ethnomedicinal practice for various liver and kidney complaints.

3. Key Phytochemical Constituents

3.1 Overview of Chemical Classes

Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols, and alkaloids.

3.2 Lignans

Lignans are considered the most pharmacologically significant class of compounds in P. amarus. The highest amounts of phyllanthin (0.7% w/w) and hypophyllanthin (0.3% w/w) have been reported in the leaves, whereas in the stem these are present in minor quantities. Lignans isolated from P. amarus include phyllanthin, hypophyllanthin, niranthin, phyltetralin, nirtetralin, isonirtetralin, hinokinin, lintetralin, isolintetralin, demethylenedioxy-niranthin, and 5-demethoxy-niranthin.

Studies have shown that only P. amarus contains phyllanthin and hypophyllanthin in quantities that were correlated with the hepatoprotective activity of this species. Pharmacological research mainly focuses on phyllanthin, niranthin, and geraniin. Since lignans and tannins exhibit various activities, they are considered the most biologically active compounds of this genus.

3.3 Ellagitannins

Ellagitannins isolated from P. amarus include geraniin, amariin, furosin, geraniinic acid B, amariinic acid, amarulone, repandusinic acid A, corilagin, isocorilagin, elaeocarpusin, and phyllanthusiin A, B, C, and D. Methanolic extracts of the herb have been chromatographed and analyzed to isolate tannins such as geraniin, ellagic acid, and gallic acid, which possess significant medicinal value.

3.4 Flavonoids

Phyllanthus amarus contains flavonoids including quercetin-3-O-glucoside and rutin. A more complete list from chromatographic studies includes gallocatechin, rutin, quercetin-3-O-glucopyranoside, phyllanthusiin, quercetin, kaempferol 3-β-d-glucopyranoside, and kaempferol.

3.5 Alkaloids and Sterols

Phyllanthus amarus also contains alkaloids including phyllantine (quinolizidine type), securinine, norsecurinine, isobubbialine, and epibubbialine. Sterols isolated from the plant include amarosterol A and amarosterol B.

3.6 Principal Bioactive Compounds Summary

These pharmacological effects are primarily attributed to bioactive compounds such as phyllanthin, hypophyllanthin, geraniin, corilagin, and quercetin. Contemporary phytochemical investigations have revealed that P. amarus is rich in biologically active constituents, including lignans such as phyllanthin and hypophyllanthin, hydrolysable tannins such as geraniin and corilagin, flavonoids including quercetin derivatives, and various alkaloids.

4. Established Mechanisms of Action

4.1 Hepatoprotective Mechanisms

These compounds have been shown to exert hepatoprotective, antiviral, antioxidant, anti-inflammatory, and metabolic regulatory effects in numerous experimental models. In particular, antiviral activity against hepatitis B virus has been attributed to inhibition of viral DNA polymerase activity, suppression of HBV gene expression, and modulation of host transcription factors.

In cell-based models, P. amarus inhibited hepatitis B virus polymerase activity, decreased episomal hepatitis B virus DNA content, and suppressed virus release into culture medium. When P. amarus was administered to transgenic mice, hepatic HBsAg mRNA levels decreased, indicating transcriptional or post-transcriptional down-regulation of the transgene. Increase in hepatitis B virus mRNA expression after stimulation of the glucocorticoid responsive element was also suppressed by P. amarus, suggesting involvement of the hepatitis B virus enhancer in this response. These data support its role as an antiviral agent.

4.2 Antioxidant Mechanisms

The aqueous extract of the P. amarus whole plant has been investigated by various antioxidant assays, including DPPH (1,1-diphenyl-2-picrylhydrazyl radical), nitric oxide radical inhibition activity, and the β-carotene–linoleate method. P. amarus aqueous extract exhibited effective antioxidant activity in a dose-dependent manner, with IC₅₀ values calculated as 4.21±0.379, 426±0.512, and 126±0.348 for DPPH, nitric oxide radical inhibition, and the β-carotene–linoleate assay respectively. The effective in vitro antioxidant activity has been attributed to its total phenolics, with phyllanthin and hypophyllanthin considered as the active components.

4.3 Anti-inflammatory Mechanisms

In attempts to test phytoconstituents and extracts of P. amarus for anti-inflammatory effect using a carrageenan-induced paw oedema and neutrophil influx model of inflammation, the hexane extract and the lignan-rich fraction — specifically phyltetralin, nirtetralin, and niranthin — inhibited carrageenan-induced rat paw oedema, lowered the increase of interleukin (IL)-1β tissue levels induced by carrageenan, and inhibited neutrophil influx, bradykinin activating factor, platelet activating factor, and endothelin-1-induced paw oedema. These results showed that the hexane extract, the lignan-rich fraction, and the lignans niranthin, phyltetralin, and nirtetralin exhibited marked anti-inflammatory properties.

4.4 Antidiabetic / Hypoglycaemic Mechanisms

P. amarus has been shown to have an anti-hyperglycaemic impact via phosphorylating IRS and IR, which stimulates the insulin signalling pathway. According to in vitro research, GLUT4 translocation to the plasma membrane is the cause of P. amarus's hypoglycaemic impact.

In streptozotocin-induced diabetic rat models, Phyllanthus amarus significantly reduced blood glucose levels starting on the second week. The extract showed significant increase in plasma insulin and tissue glycogen contents. The antidyslipidaemic effect was demonstrated by a significant reduction in plasma total cholesterol, triglycerides, and LDL-cholesterol, while the cardioprotective lipid, HDL-cholesterol, was increased. P. amarus also modulated carbohydrate-metabolising enzymes by significantly increasing the activity of hexokinase and pyruvate kinase and significantly reducing the activity of glucose-6-phosphatase, fructose-1,6-diphosphatase, and glycogen phosphorylase.

5. Scientific Evidence by Area of Use

5.1 Hepatitis B Virus (HBV) Infection

Landmark early study (1988): In a preliminary study, carriers of hepatitis B virus were treated with a preparation of Phyllanthus amarus for 30 days. 22 of 37 (59%) treated patients had lost hepatitis B surface antigen when tested 15–20 days after the end of treatment, compared with only 1 of 23 (4%) placebo-treated controls. Some subjects were followed for up to 9 months, and in no case did the surface antigen return. Clinical observation revealed few or no toxic effects. These encouraging results recommended continued evaluation of this plant.

Subsequent clinical trial — failure to replicate (1991): In a subsequent randomized controlled trial, 65 adult asymptomatic chronic carriers of hepatitis B virus were enrolled. Thirty-four received Phyllanthus amarus 600 mg per day for 30 days, and 31 received placebo in identical capsules. The conversion rate of HBsAg was 6% in the study group at day 30. When 20 subjects in the P. amarus group were given a further 30-day treatment and 22 placebo recipients were given P. amarus 1,200 mg per day for 30 days, the conversion was observed in only 1 (5%) in the higher-dose group. Adverse effects were not observed in any patients receiving the plant.

Cochrane systematic review — HBV infection (2011, updated): Phyllanthus species for patients with chronic hepatitis B virus infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. When compared with placebo or no intervention, investigators were unable to identify convincing evidence that Phyllanthus species are beneficial in patients with chronic hepatitis B. Due to the limitations of the clinical trials included — small number of patients and high risk of bias — there is currently no strong evidence available on Phyllanthus species for chronic hepatitis B, and the previous Cochrane review also found no high-quality evidence to support Phyllanthus species.

Cochrane review — Phyllanthus versus antiviral drugs: Phyllanthus had no significant effect on clearance of serum HBsAg (RR 1.00; 95% CI 0.93 to 1.08) or HBV DNA (RR 0.83; 95% CI 0.53 to 1.31) when compared with antiviral drugs. Data on HBeAg seroconversion was reported in one trial and no significant difference was found comparing Phyllanthus versus lamivudine (RR 0.89; 95% CI 0.71 to 1.11). No data were reported on adverse events in the five trials. There is currently insufficient evidence to support or refute the use of Phyllanthus for patients with chronic hepatitis B.

Combination therapy findings: Fifteen trials comparing Phyllanthus plus an antiviral drug (such as interferon alpha, lamivudine, adefovir dipivoxil, thymosin, vidarabine, or conventional treatment) with the same antiviral drug alone found that combined treatment affected serum HBV DNA, serum HBeAg, and HBeAg seroconversion. The authors concluded that Phyllanthus in combination with an antiviral drug may be better than the same antiviral drug alone, but clinical trials with larger sample sizes and low risk of bias are needed to confirm these findings.

Evidence strength: Preliminary and conflicting. The seminal 1988 study showed a striking response, but subsequent trials have not consistently replicated this finding. Cochrane reviews conclude there is insufficient high-quality evidence. No large, well-powered RCT with low risk of bias exists as of the most recent reviews.

5.2 Hepatoprotection (Non-Viral Liver Injury)

P. amarus exhibits numerous medicinal properties including antihepatitis, antimalarial, antiviral, antibacterial, and antidiarrheal effects, as well as hepatoprotective, anti-carcinogenic, anti-inflammatory, antiasthmatic, and antidiabetic properties. In animal studies, the restorative potential of its leaves extract was investigated on hepatic and renal assault induced by CCl₄ and rifampicin. Animals administered 50–100 mg/kg b.w. of P. amarus following CCl₄ exposure, or 50–100 mg/kg after rifampicin exposure for 14 days, were evaluated. These are animal studies and cannot be directly extrapolated to human clinical outcomes.

Evidence strength: Predominantly preclinical (animal and in vitro). No large controlled human trials specifically on non-viral hepatoprotection have been identified in the peer-reviewed literature reviewed here.

5.3 Diabetes Mellitus and Glycaemic Control

In a one-week trial on non-insulin-dependent diabetic patients, an aqueous extract of the aerial portions of Phyllanthus amarus was found to be ineffective in decreasing fasting and postprandial blood glucose levels of untreated non-insulin-dependent diabetic patients. A separate study gave 21 non-insulin-dependent diabetic patients twice-daily 100 mL Phyllanthus amarus aqueous extract (prepared from 12.5 g dried aerial parts) for one week, after washout from oral hypoglycemics.

In rodent models, the aqueous extract caused a significant dose-related reduction in the fasting blood glucose of normoglycaemic rats, with maximum reduction occurring within 2 hours post-treatment with a 400 mg/kg dose. Single oral administration of the extract to normal rats reduced fasting blood glucose, suggesting an inherent hypoglycaemic effect. The extract also suppressed the postprandial rise in blood glucose in normal rats following a heavy glucose load.

A previous study reported the hypoglycaemic and hypocholesterolaemic effect of 150–600 mg/kg of the aqueous leaf and seed extract of Phyllanthus amarus in normal mice. A further study evaluated the effectiveness and mechanism(s) of action of 150–600 mg/kg of the aqueous leaf and seed extract in a type 2 diabetes model using 10% sucrose-induced hyperglycaemic rats.

Evidence strength: Animal and in vitro data are suggestive, but the limited human clinical data from a one-week trial showed no significant effect on fasting or postprandial blood glucose. Human clinical evidence is weak and preliminary.

5.4 Kidney Stones and Urolithiasis

P. amarus is ethnomedicinally used to treat gallbladder stones, kidney stones, and chronic liver diseases. Despite strong experimental support from in vitro and in vivo models, clinical findings remain limited, heterogeneous, and occasionally inconsistent. The plant's common name "stonebreaker" and its use for urolithiasis are well documented in traditional contexts across multiple continents, but robust human clinical trial data specifically on kidney stone dissolution or prevention for P. amarus specifically were not identified in the peer-reviewed sources surveyed.

Evidence strength: Traditional and ethnomedicinal evidence is strong. Peer-reviewed clinical trial evidence specific to urolithiasis is limited based on sources available for this review.

5.5 Antimalarial Activity

Phyllanthus amarus has shown promising antimalarial properties, particularly against Plasmodium falciparum, the causative agent of malaria. The evidence in this area is derived primarily from in vitro and animal experiments, and no large human clinical trial data specific to malaria have been identified in the sources reviewed.

Evidence strength: Preliminary; in vitro and animal models only based on sources surveyed.

5.6 Antimicrobial Activity

Extract yields and antibacterial activity have been demonstrated at concentrations from 250 to 1,000 mg/mL. The diameter of the inhibition zone for dried herbal extracts reached 16.75±0.96 to 21.25±0.50 mm at 250–1,000 mg/mL concentrations, with a statistically significant difference (p<0.05). The MIC values of dried and fresh extracts were defined at 125 mg/mL and 250 mg/mL respectively.

Evidence strength: In vitro laboratory evidence only. No controlled human trials on antimicrobial use were identified in sources reviewed.

5.7 Broad Pharmacological Activity Profile Summary

P. amarus extracts have shown a broad range of pharmacological activities including hepatoprotective, antioxidant, antiviral, antimicrobial, antidiabetic, anti-inflammatory, anticancer, antimalarial, nephroprotective, diuretic, and several other properties in laboratory and animal settings. The translation of these preclinical signals into demonstrated clinical efficacy in humans remains, overall, an area of active and ongoing research.

6. Body Systems and Health Areas of Association

• Hepatobiliary system: Most commonly used in the Indian Ayurvedic system of medicine in problems of the liver. Studied for hepatitis B, liver enzyme normalization, and general hepatoprotection.
• Urinary / renal system: Used in Ayurveda in problems of the genitourinary system, liver, kidney, and spleen. Specifically associated with kidney stone treatment and diuretic effects.
• Endocrine / metabolic system: Studied for antidiabetic, hypolipidaemic, and insulin-sensitizing effects in animal models.
• Immune / anti-infective: Used for viral infections (hepatitis B, HIV), bacterial infections (gonorrhoea, urinary tract infections), and parasitic infections (malaria).
• Gastrointestinal system: Traditionally used for gastropathy, diarrhoea, and dysentery.
• Dermatological: Traditionally used for scabies, ulcers, and wounds.
• Reproductive system: Traditionally used in gonorrhoea, menorrhagia, and other genital problems.

7. Dosage Forms and Dosages Reported in Studies

The following dosages are those reported in the primary literature. They are not recommendations.

• Capsules — chronic HBV, Thai RCT (1991): Thirty-four patients received Phyllanthus amarus 600 mg per day for 30 days; a second phase used 1,200 mg per day for 30 days.
• Capsules — acute hepatitis B trial: The study examined whether powders of Phyllanthus amarus plants favourably influenced the duration of disease in acute viral hepatitis B patients compared to placebo; the powders were given in capsule form at 300 mg.
• Capsules — recommended HBV protocol (patent-based summary): Based on a summary of clinical trials showing a mean HBsAg clearance rate of 25.6% and mean HBeAg seroconversion rate of 55.3%, a schedule of 500 mg dosage of P. amarus preparation in capsules given orally three times daily for six months was recommended.
• Aqueous extract — diabetes (human pilot): 21 non-insulin-dependent diabetic patients were given 100 mL Phyllanthus amarus aqueous extract (from 12.5 g dried aerial parts) twice daily for one week, after washout from oral hypoglycaemics.
• Aqueous leaf and seed extract — animal studies (antidiabetic): 150–600 mg/kg of the aqueous leaf and seed extract of Phyllanthus amarus was used in mice.
• Animal toxicology: Doses between 200 mg/kg and 500 mg/kg body weight were evaluated in rats, showing no acute toxicity and stable liver and kidney function parameters over 14 days. Administration to mice indicated that the plant is non-toxic even at the dose of 1,600 mg/kg body weight, showing it to be safe for medicinal use at this dose.

8. Safety Considerations and Drug Interactions

8.1 CYP Enzyme Inhibition and Herb-Drug Interactions

The most scientifically well-characterized safety concern with P. amarus involves its interactions with cytochrome P450 (CYP) drug-metabolizing enzymes.

Phytochemicals in P. amarus may interact with cytochromes P450 (CYP). Both ethanolic and aqueous extracts inhibited CYP1A2, CYP2D6, CYP2E1, and CYP3A4 in a dose-dependent manner. The IC₅₀ values of the ethanolic and aqueous extracts on testosterone 6β-hydroxylation were higher than that of ketoconazole but lower than those of erythromycin and clarithromycin. Both extracts were weak inhibitors of CYP1A2, CYP2D6, and CYP2E1. Phyllanthin and hypophyllanthin were potent mechanism-based inhibitors of CYP3A4 with K_I values of 1.75±1.20 µM and 2.24±1.84 µM respectively. These results suggest that co-administration of P. amarus with drugs metabolized by CYP3A4 may potentially result in herb-drug interactions.

A 2024 study funded by the U.S. FDA confirmed additional receptor-mediated interactions: overconsumption of P. amarus or P. amarus-containing botanical supplements may change CYP homeostasis, which could alter the pharmacokinetics of substrate drugs, thereby elevating the risk of herb-drug interactions when taken concomitantly with conventional medications. Further studies are warranted to strengthen the clinical relevance of these findings.

P. amarus has been found to interact with CYP3A4, a key enzyme in drug metabolism. This induction reduces the efficacy of medications such as oral contraceptives, anticoagulants, and immunosuppressants.

Research has indicated that P. amarus may also inhibit other cytochrome P450 enzymes such as CYP1A2, CYP2C9, and CYP2D6, which are crucial for phase I drug metabolism. This inhibition could lead to significant herb-drug interactions when P. amarus is co-administered with medications metabolized by these enzymes. The findings suggest that co-administration with drugs metabolized by CYP3A and other affected enzymes could result in therapeutic failure or adverse effects due to altered drug metabolism.

8.2 Potential Interactions with Specific Drug Classes

P. amarus can interact with medications, either amplifying or diminishing their effects, potentially leading to issues such as increased bleeding risk with anticoagulants or uncontrolled blood sugar levels. The mechanism-based inhibition of CYP3A4 documented in vitro raises particular concern for drugs with narrow therapeutic windows that depend on CYP3A4 metabolism.

8.3 Acute Toxicity Data

Ethanolic extracts studied at doses between 200 mg/kg and 500 mg/kg body weight in rats showed no acute toxicity and stable liver and kidney function parameters over 14 days. Administration to mice at 1,600 mg/kg body weight indicated that the plant is non-toxic at this dose.

In the hepatitis B trials that have been conducted, adverse effects were not observed in all patients receiving the plant across published RCTs; however, the small sample sizes and short durations of these trials limit conclusions about long-term safety.

8.4 Broader Safety Context

The evidence supporting the use of botanicals to treat chronic liver diseases is insufficient, and only a few are well standardized and free of potential serious side effects; most of these medications are not recommended outside clinical trials. This applies to P. amarus: while acute toxicity appears low in animal models, standardization of commercial preparations is variable, and the herb-drug interaction profile (particularly via CYP enzymes) requires clinical attention when it is used alongside pharmaceutical drugs.

References

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