Abstract
Phyllanthus amarus has been a cornerstone of traditional medicine in Africa, renowned for its hepatoprotective, antiviral, and antidiabetic properties. However, its therapeutic applications in modern medicine are limited by poor bioavailability due to challenges such as low solubility, rapid metabolism, and instability of its bioactive compounds. Addressing these limitations is essential for optimizing its pharmacological potential and enabling its broader integration into evidence-based healthcare systems. This review highlights various strategies to enhance the bioavailability of Phyllanthus amarus, including nanotechnology, phytosome technology, biopiperine supplementation, fermentation, and sustained-release formulations. These approaches not only improve solubility and absorption but also stabilize the herb’s phytochemicals, ensuring better therapeutic outcomes. Moreover, the review explores how bioavailability enhancement can transform Phyllanthus amarus into a standardized therapeutic agent, bridging the gap between traditional and modern medicine. Enhancing the bioavailability of Phyllanthus amarus has profound implications for healthcare in Africa. Improved formulations can amplify its therapeutic efficacy in traditional practices, while enabling its adoption in modern pharmacology through clinical validation and pharmaceutical-grade products. By addressing cost, accessibility, and regulatory challenges, these advancements can ensure that Phyllanthus amarus continues to be a vital, sustainable resource in addressing pressing health issues across the continent.
Keywords: Africa, bioavailability, modern medicine, Phyllanthus amarus, traditional medicine
Introduction
Phyllanthus amarus is a medicinal plant renowned for its diverse therapeutic applications, particularly in traditional medicine. Research highlights its antioxidant properties, hepatoprotective effects, and the presence of various bioactive compounds, making it a subject of interest for both traditional and modern medicine. P. amarus exhibits significant antioxidant activity, with studies showing a DPPH inhibition of up to 74.4% at optimal concentrations[1]. The total phenolic content (TPC) and total flavonoid content (TFC) are notably high, indicating its potential as a natural antioxidant source[1,2].The plant has demonstrated efficacy in protecting against liver damage, particularly in cases of gentamicin-induced hepatotoxicity in animal models[3]. Extracts have been shown to improve lipid profiles and reduce oxidative stress markers, suggesting a protective role against liver diseases[3,4].P. amarus contains a variety of bioactive compounds, including flavonoids, lignans, and terpenoids, which contribute to its medicinal properties[4,5].These compounds have been linked to both antioxidant and hepatoprotective activities, supporting its use in traditional remedies[4].
HIGHLIGHTS
Traditional significance: Phyllanthus amarus is widely used in African traditional medicine for its hepatoprotective, antiviral, and antidiabetic properties.
Bioavailability challenges: Low solubility, rapid metabolism, and phytochemical instability limit its therapeutic potential in modern medicine.
Enhancement strategies: Nanotechnology, phytosomes, piperine supplementation, and fermentation significantly improve absorption and stability.
Modern medicine integration: Bioavailability advancements enable clinical validation and pharmaceutical standardization for broader adoption.
Healthcare impact: Enhanced formulations can bridge traditional and modern medicine, promoting sustainable health solutions in Africa.
Aim
The aim of this review is to critically explore and synthesize current knowledge on strategies for enhancing the bioavailability of Phyllanthus amarus, a plant with deep roots in African traditional medicine, and to evaluate how such advancements could bridge traditional practices with modern healthcare systems.
Review methods
In developing this review on enhancing the bioavailability of Phyllanthus amarus and its implications for traditional and modern medicine in Africa, a systematic yet narrative-driven approach was adopted. The process began with a comprehensive literature search aimed at capturing the breadth of existing knowledge on P. amarus, its bioactive compounds, pharmacokinetics, and strategies for improving herbal bioavailability. Relevant scientific databases, including PubMed, Scopus, Google Scholar, and ScienceDirect, were searched using specific keywords such as “Phyllanthus amarus,” “bioavailability enhancement,” “nanotechnology and herbal medicine,” “traditional medicine in Africa,” and “phytochemical standardization.” Articles published between 2000 and 2025 were prioritized to ensure both historical context and contemporary insights were included. Studies focusing on the pharmacology, delivery systems, and clinical or preclinical evaluations of P. amarus were carefully reviewed. To maintain relevance and quality, preference was given to peer-reviewed journal articles, systematic reviews, meta-analyses, ethnobotanical reports, and clinical trial summaries. Grey literature, including theses and conference proceedings, was selectively used when they provided unique or region-specific insights, particularly about traditional African medicinal practices involving P. amarus.
Information was extracted and synthesized thematically. First, an overview of the pharmacologically active constituents of P. amarus was presented. This was followed by a detailed exploration of the challenges associated with its bioavailability. Subsequently, various strategies to overcome these barriers were organized into key categories such as nanotechnology applications, co-administration with bioenhancers, and novel delivery systems. Emphasis was placed on discussing not only the scientific underpinnings of these strategies but also their potential feasibility within the African context. Throughout the review process, an integrative lens was maintained, seeking to bridge traditional knowledge with modern biomedical advancements. Care was also taken to critically assess the robustness of the evidence, highlighting areas where data were strong as well as identifying gaps that require further research. While every effort was made to ensure a broad and balanced perspective, it is acknowledged that the dynamic and evolving nature of research in this field means that some emerging studies may not have been captured. Nevertheless, the methods employed aimed to produce a comprehensive and thoughtful narrative that informs both current understanding and future directions for the improved application of Phyllanthus amarus in healthcare systems across Africa.
Review limitations
While this review provides an extensive overview of strategies for enhancing the bioavailability of Phyllanthus amarus and explores their implications for traditional and modern medicine in Africa, certain limitations must be acknowledged. First, although numerous preclinical studies suggest promising techniques for improving bioavailability, there is a notable scarcity of clinical trials specifically focused on enhanced formulations of P. amarus. As a result, much of the discussion remains theoretical or extrapolated from broader research on phytomedicines, rather than being grounded in direct clinical evidence. This gap limits the immediate applicability of some of the strategies discussed. Additionally, the review heavily relies on data generated from in vitro and animal models, which may not fully predict human responses. Factors such as metabolism, immune system variations, and gut microbiota differences between species could significantly influence the absorption and therapeutic outcomes of P. amarus in human populations. Thus, while novel delivery systems and bioenhancement strategies show potential, their translation to real-world clinical success remains uncertain without further validation. Another limitation lies in the geographic and cultural diversity of traditional P. amarus use across Africa. Practices, formulations, and methods of administration vary widely between regions and ethnic groups, making it difficult to propose a universally applicable enhancement strategy. The review attempts to provide a general perspective, but deeper, localized ethnomedical studies would be necessary to tailor bioavailability enhancement approaches to specific communities without undermining traditional knowledge systems.
Moreover, economic and technological feasibility is an important consideration that could not be fully explored in this review. While nanotechnology-based systems and advanced delivery methods offer exciting possibilities, their cost-effectiveness, scalability, and accessibility in resource-limited African settings remain challenging. Without parallel efforts in capacity building and infrastructure development, these innovations might struggle to achieve widespread adoption. Although the review highlights the potential socio-economic benefits of enhancing P. amarus bioavailability, it does not deeply delve into the policy, regulatory, and intellectual property issues that could impact the integration of improved traditional medicines into formal healthcare systems. Addressing these complex factors will be crucial for ensuring that the advancement of P. amarus formulations truly benefits local communities and supports sustainable healthcare development.
Importance of bioavailability in determining pharmacological efficacy
The importance of bioavailability in determining pharmacological efficacy cannot be overstated, as it directly influences the therapeutic outcomes of drug therapies. Bioavailability refers to the proportion of a drug that enters systemic circulation and is available at the site of action, which is critical for achieving the desired therapeutic effects. Understanding and enhancing bioavailability is essential for optimizing drug efficacy and safety, particularly given the challenges posed by poor solubility and extensive first-pass metabolism in many pharmaceuticals. Bioavailability is defined as the rate and extent of drug absorption into systemic circulation[2]. Accurate measurement is vital for assessing a drug’s therapeutic potential. Various factors influence bioavailability, including solubility, stability, and the drug’s ability to penetrate biological membranes[6]. For instance, over 90% of drugs face limitations in oral bioavailability due to poor solubility[7]. Numerous strategies exist to improve bioavailability, such as size reduction, use of solubilizing excipients, and innovative drug delivery systems like nanotechnology[7,8]. These methods aim to increase the drug’s solubility and absorption efficiency. Ensuring adequate bioavailability is crucial for achieving therapeutic plasma concentrations, which directly impacts treatment efficacy and patient safety[6].
Importance of Phyllanthus amarus in African traditional medicine
P. amarus is widely recognized for its ability to protect the liver, making it a key remedy for jaundice and hepatitis[9,10].The plant exhibits antidiabetic properties and is effective against various microbial infections, addressing conditions like diarrhea and dysentery[10,11].It is employed in treating intermittent fevers, kidney disorders, and skin ailments, showcasing its versatility in traditional medicine[9,10].In many African cultures, P. amarus is integral to herbal remedies, reflecting its deep-rooted significance in local health practices[12].
Bioavailability and significance of Phyllanthus amarus
P. amarus contains various bioactive compounds such as quercetin, geraniin, and rutin, which contribute to its medicinal properties[9]. The herb’s extracts have shown the ability to modulate oxidative stress and inflammatory pathways, particularly through the inhibition of TNF-α and interleukins[13,14].
Health benefits
Studies indicate that P. amarus can restore liver integrity and function, particularly in conditions of oxidative stress and ischemia[14]. The plant has demonstrated efficacy against diabetes and viral infections, notably hepatitis B[9].
Objective of the review
To evaluate the bioavailability of P. amarus in Africa. This involves examining the factors influencing its bioavailability, pharmacokinetics, and therapeutic applications, with a focus on how these aspects affect its efficacy and integration into both traditional and modern medicine in Africa.
Description of Phyllanthus amarus and its distribution in Africa
The bioavailability of Phyllanthus amarus in Africa is supported by its diverse pharmacological properties and traditional uses, particularly in treating various ailments.
Phyllanthus amarus contains various bioactive compounds, including alkaloids, phenols, saponins, and tannins, which contribute to its medicinal properties[15]. These compounds are responsible for its antioxidant, anti-inflammatory, and antimicrobial activities, making it a valuable resource in traditional medicine. Studies demonstrate that the ethanol extract of Phyllanthus amarus effectively reduces parasitaemia in trypanosomiasis, improving clinical parameters in infected rats[15]. Additionally, its aqueous extract has shown antihypertensive effects and improved cardiac function in hypertensive models[16].
Summary of reported pharmacological activities of Phyllanthus amarus
Phyllanthus amarus exhibits significant antiviral properties, particularly against HIV. Extracts from the plant have been shown to inhibit HIV-1 attachment and the activity of key enzymes such as integrase and reverse transcriptase, demonstrating effectiveness both in vitro and in vivo[17].The plant has broad-spectrum antibacterial effects against both gram-positive and gram-negative bacteria. It has been found to inhibit drug-resistant strains, making it a potential candidate for treating bacterial infections[18,19].P. amarus is noted for its hepatoprotective properties, helping to restore liver function and protect against liver damage from toxins such as alcohol and certain medications[20].Research indicates that extracts of P. amarus can lower blood glucose levels and improve insulin sensitivity, making it beneficial for managing diabetes[21].The herb has shown promise in inhibiting cancer cell proliferation and inducing apoptosis in various cancer models. Its extracts have been linked to the prevention of chemically induced tumors and may possess anti-mutagenic properties[19,20].Phyllanthus amarus has been reported to reduce inflammation and pain, contributing to its use in traditional medicine for treating various inflammatory conditions[20]. Studies have demonstrated that P. amarus can protect against nephrotoxicity induced by drugs like gentamicin, helping to maintain kidney function[18-22]. The plant’s extracts are rich in antioxidants, which help combat oxidative stress and may contribute to its overall health benefits[20].Table 1 shows summary of key bioactive compounds in Phyllanthus amarus[23-27].
Table 1.
Summary of key bioactive compounds in Phyllanthus amarus
| Component class | Key compounds | Pharmacological activities |
|---|---|---|
| Lignans[19,20] | Phyllanthin, hypophyllanthin, niranthin, nirtetralin, phyltetralin | Hepatoprotective, antiviral, anticancer, antioxidant |
| Flavonoids[20,22] | Various subclasses like flavanones, quercetin, rutin | Antioxidant, anti-inflammatory |
| Alkaloids[23] | Various | Antimicrobial, antidiabetic |
| Terpenes[19] | Lupeol, oleanolic acid | Anti-inflammatory, antimicrobial |
| Tannins[19] | Amariin, ellagitannin, geraniin, corilagin, 1,6-digalloylglucopyranoside, rutin, quercetin-3-0-glucopyranoside | Antibacterial, antioxidant |
| Phenolic compounds[24] | Phyllanthusiin D, amariin, repansunic acid | Antioxidant |
| Other compounds[24] | Saponins, cardiac glycosides, phytol, hexadecanoic acid, ethyl ester, β-tocopherol, benzenamine,N-[2-(3,4-dimethoxyphenyl) thyl]-2-nitro-, 9,12,15-octadecatrienoic acid, 1-methyl ester, (Z,Z,Z)- | Immune modulation, cardiovascular effects, anti-inflammatory, hypo-cholesterolemic, cancer preventive, hepato-protective, bactericidal, antioxidant, diuretic, antitumor, antimicrobial |
Pharmacokinetic profiles of P. amarus reported in global studies
Phyllanthus amarus has garnered attention in pharmacological research for its potential herb-drug interactions and its impact on drug metabolism. Various studies have explored the pharmacokinetic profiles of this plant, particularly focusing on its effects on specific drugs and metabolic pathways. A study investigated the effect of Phyllanthus amarus extract on the pharmacokinetics of midazolam (MDZ), a substrate for cytochrome P450 3A (CYP3A) enzymes. Oral administration of P. amarus extract significantly increased the maximum concentration (Cmax) and area under the curve (AUC) of MDZ, with increases of 3.9-fold and 9.6-fold, respectively, while decreasing the clearance by 12% after a single dose. This suggests that P. amarus can inhibit intestinal CYP3A, enhancing oral bioavailability of MDZ[27-29]. In a study involving daily administration of P. amarus extract over 15 days, it was found to induce the activity and expression of CYP3A and CYP2B1/2 enzymes in rats. This dual action indicates that while acute exposure may inhibit certain metabolic pathways, chronic exposure could lead to an induction effect, potentially altering the metabolism of co-administered drugs[30-32].
A pharmacokinetic on Phyllanthus amarus revealed that its 80% ethanolic extract significantly inhibited the production of pro-inflammatory mediators such as TNF-α, IL-1β, and PGE2 in LPS-induced U937 human macrophages. The extract also downregulated COX-2 protein expression and the mRNA transcription of pro-inflammatory markers in a dose-dependent manner. Furthermore, it was found to suppress the phosphorylation of key signaling molecules involved in inflammation, including NF-κB, Akt, and various MAPKs (JNK, ERK, and p38). Additionally, P. amarus extract reduced the expression of upstream signaling molecules TLR4 and MyD88, which are crucial for activating NF-κB, MAPK, and PI3K-Akt pathways. The quantitative analysis identified significant levels of lignans and polyphenols in the extract, suggesting that these compounds may contribute to its anti-inflammatory effects[33-35].Additional 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[36,37]. The findings suggest that co-administration of P. amarus with drugs metabolized by CYP3A and other affected enzymes could result in therapeutic failure or adverse effects due to altered drug metabolism.
Therapeutic applications, with emphasis on conditions prevalent in Africa
Phyllanthus amarus has shown promising antimalarial properties, particularly against Plasmodium falciparum, the causative agent of malaria. Studies indicate that both ethanolic and aqueous extracts exhibit significant reductions in parasite growth, with the ethanolic extract demonstrating an inhibition rate of 76.8% and a half-maximal inhibitory concentration (IC50) of 5.80 μg/ml[38]. The plant is often prepared as a decoction, with traditional healers recommending its use for malaria treatment alongside other herbal remedies to enhance efficacy[39].P. amarus is traditionally used to treat liver-related ailments such as jaundice and hepatitis. Its bioactive compounds have been linked to hepatoprotective effects, helping to safeguard liver cells from damage caused by toxins and infections[40]. The presence of lignans like phyllanthin contributes to these protective effects, making it valuable in managing liver diseases prevalent in many African communities. The plant is also recognized for its antidiabetic effects, with studies suggesting that it can lower blood glucose levels and enhance insulin sensitivity[41]. Given the high prevalence of diabetes in Africa, P. amarus offers a potential natural remedy for managing this chronic condition and other ailments like gonorrhea, diarrhea and dysentery, respiratory issues like asthma, and skin ulcers[42].
Factors affecting bioavailability of P. amarus in Africa
The mineral content and overall quality of the soil where P. amarus is grown can impact the nutrient composition of the plant. Poor soil conditions may lead to lower concentrations of bioactive compounds such as lignans (phyllanthin and hypophyllanthin), which are critical for its pharmacological effects[43]. Temperature, rainfall, and humidity levels significantly influence the growth and biosynthesis of active compounds in P. amarus. Optimal conditions (20-35 °C) are necessary for effective germination and growth, which directly affects the plant’s medicinal properties[30].The method used to prepare extracts from P. amarus (e.g., aqueous, ethanol) can significantly influence the concentration and bioavailability of its active compounds. For instance, 50% ethanol extracts have shown effective antibacterial properties, indicating that solvent choice impacts the extraction efficiency of bioactive components[28]. Traditional methods of preparing herbal remedies may vary widely across regions and can affect the stability and bioavailability of active ingredients. Cooking or decocting the plant material may enhance or degrade certain compounds. The existing nutritional status of individuals consuming P. amarus can influence how well they absorb its active compounds. For example, individuals with deficiencies in specific nutrients may have altered absorption rates for certain phytochemicals present in the herb.
The metabolism of bioactive compounds from P. amarus can vary based on individual differences in liver enzyme activity (e.g., cytochrome P450 enzymes). This variability can lead to differences in how effectively these compounds exert their therapeutic effects[28]. Co-administration with other medications may alter the pharmacokinetics of P. amarus constituents, either enhancing or inhibiting their absorption and efficacy. The availability and quality of P. amarus may be affected by socioeconomic factors such as agricultural practices, market access, and conservation efforts. Poor harvesting practices can lead to degradation or contamination of plant materials. Knowledge about proper preparation methods and dosages among users can influence the effective use of P. amarus in traditional medicine. Table 2 shows challenges in bioavailability studies of Phyllanthus amarus[27,31,32]. Table 3 shows current bioavailability enhancement strategies[33-36].
Table 2.
Challenges in bioavailability studies of Phyllanthus amarus
| Challenge | Description |
|---|---|
| Limited water solubility[31] | Key bioactive components like lignans and flavonoids have poor water solubility, restricting their absorption and leading to reduced bioavailability, making it hard to achieve therapeutic concentrations in the bloodstream. |
| Extraction efficiency[27] | The choice of extraction solvent affects the yield and potency of active compounds. Polar solvents may not extract sufficient lipophilic compounds, potentially resulting in suboptimal therapeutic effects. |
| Variability in traditional practices[32] | Preparation methods for P. amarus vary widely across cultures, leading to inconsistencies in active ingredient concentrations, complicating comparisons across studies and limiting standardized dosages. |
| Crude extracts vs. isolated compounds[32] | Many studies focus on crude extracts without detailed chemical characterization, making it difficult to correlate bioactivity with specific compounds and hindering understanding of pharmacokinetics. |
| Limited animal and human trials[27] | Most research involves in vitro studies, which do not replicate complex interactions in living organisms, restricting insights into absorption, distribution, metabolism, and excretion (ADME) processes crucial for assessing bioavailability. |
| Individual differences[27] | Variability among individuals due to genetic factors, health status, and concurrent medications can affect metabolism and utilization of P. amarus, complicating predictions of therapeutic outcomes based on standard dosages. |
Table 3.
Current bioavailability enhancement strategies
| Bioavailability strategy | Description |
|---|---|
| Nanotechnology approaches[33,34] | Nanoparticles and nanocarriers: utilize nanoparticles like liposomes and solid lipid nanoparticles (SLNs) to enhance solubility and stability. Nanoemulsions and nanosuspensions: increase surface area for improved dissolution and bioavailability, especially for hydrophobic drugs. |
| Drug delivery systems[35] | Self-emulsifying drug delivery systems (SEDDS): promote emulsions upon contact with gastrointestinal fluids, enhancing solubility and absorption of lipophilic drugs. |
| Microspheres and liposomes: encapsulate drugs to protect from degradation and improve solubility through controlled release. | |
| Chemical modifications[34] | Prodrugs: modify drug structure to enhance solubility and permeability; prodrugs are metabolized into active forms in the body. Cyclodextrin complexation: form inclusion complexes with poorly soluble drugs to improve solubility and stability, particularly for oral bioavailability. |
| Solid dispersion techniques[34] | Disperse drugs within a polymer matrix to enhance dissolution rate, improving bioavailability of poorly soluble compounds. |
| Particle size reduction[36] | Micronization: reducing particle size increases surface area for dissolution, enhancing bioavailability of solid dosage forms. |
| Nanosizing: further reduction to nanoscale for greater improvements in solubility and absorption. | |
| Use of surfactants[36] | Incorporate surfactants to reduce surface tension and improve drug solubility; penetration enhancers facilitate transport across biological membranes. |
| Biochemical strategies[35]. | Targeted delivery systems: develop systems targeting specific tissues or cells to enhance efficacy and minimize side effects. |
| Environment-sensitive particles: respond to pH or temperature changes, releasing payloads in specific environments (e.g., tumor sites) for improved therapeutic outcomes. |
Conclusion
Enhancing the bioavailability of Phyllanthus amarus is essential for maximizing its therapeutic potential and integrating its traditional use into modern medicine in Africa. Despite its rich pharmacological profile, factors such as poor solubility, variable preparation methods, and metabolic differences pose significant challenges to its efficacy. Advanced strategies like nanotechnology, self-emulsifying drug delivery systems, and chemical modifications offer promising solutions to overcome these barriers. By addressing these bioavailability challenges, P. amarus can become a more effective and reliable treatment option, bridging the gap between its traditional applications and contemporary medical practices in Africa.
Footnotes
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Contributor Information
Arinze Favour Anyiam, Email: arinze21.favour@edouniversity.edu.ng.
Onyinye Cecilia Arinze-Anyiam, Email: onyinyejeco3@gmail.com.
Emmanuel Ifeanyi Obeagu, Email: emmanuelobeagu@yahoo.com.
Ethical approval
Not applicable as this a narrative review.
Consent
Not applicable as this a narrative review.
Sources of funding
The authors declare no conflict of interest.
Author contributions
E.I.O.: conceptualization, supervision, methodology, supervision, draft witting, editing, and approval before submission; O.G. and M.A.Z.: methodology, supervision, draft witting, editing, and approval before submission.
Conflicts of interest disclosure
The authors declare no conflict of interest.
Research registration unique identifying number (UIN)
Not applicable as this a narrative review.
Guarantor
Emmanuel Ifeanyi Obeagu.
Provenance and peer review
Not commissioned, externally peer-reviewed.
Data availability statement
Not applicable as this a narrative review.
References
- [1].Onyeukwu OB, Njideaka OT, Dibie DC. The antioxidant and phytochemical analysis of methanol extract of Phyllanthus amarus. FUDMA J Sci 2024;8:295–99. [Google Scholar]
- [2].Anyiam AF, Musa Muhibi MA, Iyare G, et al. Effects of different extracts of Phyllanthus amarus on selected haematological and haemostatic parameters of leukemic Wistar rats. Elite J Med Sci 2024;2:23–43. [Google Scholar]
- [3].Idowu S, Olaoye NAB, Awonegan P. The effect of Phyllanthus amarus leaf extract on the lipid profile of gentamicin-induced hepatotoxicity in albino rats. GSC Biol Pharm Sci 2024;28:233–39. [Google Scholar]
- [4].Pratima H, Shiraguppi A, Joojagar P, et al. Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review. J Pharm Pharmacol 2024;77:189–205. [Google Scholar]
- [5].Anyiam AF, Muhibi MA, Iyare GI, et al. Anti-inflammatory effects of Phyllanthus amarus extracts against benzene-induced leukemia in rats. Avicenna J Med Biochem 2024;12:114–22. [Google Scholar]
- [6].Sunday AG, Ifeanyi OE, Ezeja MI. Wound healing potentials of leaf and bark extracts of Delonix regia. World J Pharm Pharm Sci 2014;3:133–42. [Google Scholar]
- [7].Faeji C, Fasoro A, Oni O. Bioactive compounds in Phyllanthus amarus leaf extract and its toxicity in the treatment of Newcastle disease. Israa Univ J Appl Sci 2024;7:1–13. [Google Scholar]
- [8].Gabhane VT, Ashtankar AR, Dongre SV, et al. Bioavailability enhancement. World J Adv Res Rev 2023;18:224–27. [Google Scholar]
- [9].Stielow M, Witczyńska A, Kubryń N, et al. The bioavailability of drugs—the current state of knowledge. Molecules 2023;28:8038–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [10].Dash JR, GuruduttaPattnaik H, Pradhan G, et al. Novel approaches for the enhancement of bioavailability of drugs: an updated review. Curr Drug Discov Technol 2024;9:21. [Google Scholar]
- [11].Kargbo RB. Innovations in pharmacology: enhancing bioavailability and efficacy through novel compositions. ACS Med Chem Lett 2024;15:328–30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Bishoyi SK, Tripathy UP. Phytochemical, pharmacological potential and ethnomedicinal uses on Phyllanthus amarus: a review. Int J Sci Res Arch 2022;7:453–60. [Google Scholar]
- [13].Gupta M, Vaghela J. Recent advances in pharmacological and phytochemistry studies on Phyllanthus amarus. Pharm Biosci J 2019;7:01. [Google Scholar]
- [14].Vickram AS, Infant SS, Chopra H. AI-powered techniques in anatomical imaging: impacts on veterinary diagnostics and surgery. Ann Anat. 2024;258:152355 . [DOI] [PubMed] [Google Scholar]
- [15].Peng S, Xu C, He Q, et al. Fucoidan alleviates intestine damage in mice induced by LPS via regulation of microbiota. Pak Vet J 2024;44:517–25. [Google Scholar]
- [16].Sozen ME, Savas HB, Cuce G. Protective effects of selenium against acrylamide-induced hepatotoxicity in rats. Pak Vet J 2024;44:274–9. [Google Scholar]
- [17].Ahmad M, Ehsan N, Khan HA, et al. Ameliorative effects of rhamnetin against polystyrene microplastics-induced nephrotoxicity in rats. Pak Vet J 2023;43:623–27. [Google Scholar]
- [18].Bose A, Banerjee A, Chattopadhyay S. An insight into the potent medicinal plant Phyllanthus amarus Schum. and Thonn. The Nucleus 2022;65:437–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [19].Unigwe R, Okey SN. Medicinal values of the genus Phyllanthus – a review. J Curr Biomed Res 2023;3:1. [Google Scholar]
- [20].Olorunnisola OS, Fadahunsi OS, Adegbola PI, et al. Phyllanthus amarus attenuated derangement in renal-cardiac function, redox status, lipid profile and reduced TNF-α, interleukins-2, 6 and 8 in high salt diet fed rats. Heliyon 2021;7:e08106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [21].Afolabi AO, Akhigbe TM, Odetayo AF, et al. Restoration of hepatic and intestinal integrity by Phyllanthus amarus is dependent on Bax/Caspase 3 modulation in intestinal ischemia-/reperfusion-induced injury. Molecules 2022;27:5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [22].Sani MB, Muhammad HU, Abubakar M, et al. Efficacy of the whole plant ethanol extract of Phyllanthus amarus on Trypanosoma brucei-induced pathology in Wistar rat. Middle East Res J Biol Sci 2023;3:45–59. [Google Scholar]
- [23].Yao AN, Rasul Z, Najmanová I, et al. O10 beneficial effect of Phyllanthus amarus (Euphorbiaceae) on DOCA-salt-induced left ventricle cardiac hypertrophy and endothelial dysfunction in rats. Biochem Pharmacol 2017;139:112–13. [Google Scholar]
- [24].Mitropoulou G, Stavropoulou E, Vaou N, et al. Insights into antimicrobial and anti-inflammatory applications of plant bioactive compounds. Microorganisms 2023;11:1156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [25].Hajgude BS, Patil RP. Identification of bioactive compounds in Phyllanthus amarus Schumach. & Thonn. Using GC-MS method. Afr J Biol Sci 2025;7:881–89. [Google Scholar]
- [26].Danladi S, Idris M, Umar I. Review on pharmacological activities and phytochemical constituents of Phyllanthus niruri (Amarus). J Phytopharmacol 2018;7:341–48. [Google Scholar]
- [27].Ghosh A, Chattopadhyay S. A brief dig into the potent medicinal plant Phyllanthus amarus Schum. and Thonn. J Plant Sci Phytopathol 2024;8:025–8. [Google Scholar]
- [28].Meena J, Sharma RA, Rolania R. A review on phytochemical and pharmacological properties of Phyllanthus amarus Schum. and Thonn. Int J Pharm Sci Res. 2018;5:1377–86. [Google Scholar]
- [29].Nisar M, He J, Ahmed A, et al. Chemical components and biological activities of the genus Phyllanthus: a review of the recent literature. Molecules 2018;23:2567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].Modupe A, Morayo A, Olusola O, et al. Antimicrobial evaluation of Phyllanthus amarus leaf extracts against beta-resistance Escherichia coli isolated from Eidolon helvum. Res J Microbiol 2023;18:1–10. [Google Scholar]
- [31].Ajayi G, Olorunrinu T, Shittu M. Elucidation of bioactive compounds in hydroalcohol extract of Phyllanthus amarus Schum. and Thonn. Leaf using GC-MS analysis. J Sci Innov Res 2020;9:40–47. [Google Scholar]
- [32].Husain I, Abdulrahman B, Dale OR, et al. Interaction of Phyllanthus amarus extract and its lignans with human xenobiotic receptors, drug metabolizing enzymes and drug transporters. J Ethnopharmacol 2025;339:119142. [DOI] [PubMed] [Google Scholar]
- [33].Harikrishnan H, Jantan I, MdA H, et al. Anti-inflammatory effects of Phyllanthus amarus Schum. & Thonn. through inhibition of NF-κB, MAPK, and PI3K-Akt signaling pathways in LPS-induced human macrophages. BMC Complement Altern Med 2018;18:224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [34].Mohammed Y, Aliyu K, Abdullahi I, et al. In vitro antiplasmodial activity of Phyllanthus amarus against Plasmodium falciparum and evaluation of its acute toxicity effect in mouse model. Trop Parasitol 2021;11:31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [35].Bekoe EO, Kitcher C, Debrah P, et al. A study on Phyllanthus amarus; pharmacognostic, mycobactericidal and mutagenic properties. Pharmacogn J 2020;12:1732–39. [Google Scholar]
- [36].Mohammed A, Tajuddeen N. Antidiabetic compounds from medicinal plants traditionally used for the treatment of diabetes in Africa: a review update (2015–2020). S Afr J Bot 2022;146:585–602. [Google Scholar]
- [37].Sparzak-Stefanowska B, Krauze-Baranowska M. Phyllanthus amarus shoot cultures as a source of biologically active lignans: the influence of selected plant growth regulators. Sci Rep 2022;12:11505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [38].Khade U, Shinde M, Khatate M, et al. A review: herbal drug nanosuspension. Int J Enhanc Res Med Dent Care (IJERMDC) 2024;11:2349–1590. [Google Scholar]
- [39].Jantan I, MdA H, Ilangkovan M, et al. An insight into the modulatory effects and mechanisms of action of Phyllanthus species and their bioactive metabolites on the immune system. Front Pharmacol 2019;10:878. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [40].Choudhurie R. Formulation development – bioavailability enhancement strategies & opportunities. Drug Dev Deliv. 2013. Mar 13. Available from: https://drug-dev.com/bioavailability-enhancement-strategies-opportunities/
- [41].Kumari L, Choudhari Y, Patel P, et al. Advancement in solubilization approaches: a step towards bioavailability enhancement of poorly soluble drugs. Life 2023;13:1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [42].Al-Shoubki AA, Teaima MH, Rehab A, et al. Bioavailability enhancement strategies for rivaroxaban: a noteworthy review. Int J Appl Pharm. 2023;2023:33–37. [Google Scholar]
- [43].Bhalani DV, Nutan B, Kumar A, et al. Bioavailability enhancement techniques for poorly aqueous soluble drugs and therapeutics. Biomedicines 2022;10:2055. [DOI] [PMC free article] [PubMed] [Google Scholar]
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Data Availability Statement
Not applicable as this a narrative review.