Bhumi Amla (Phyllanthus Niruri)

Recent Research on Phyllanthus urinaria

• Yeo, Sang-Gu & Song, Jae & Hong, Eun-Hye & Lee, Bo-Ra & Kwon, Yong & Chang, Sun-Young & Kim, Seung & Lee, Sang-Won & Park, Jae-Hak & Ko, Hyun-Jeong. (2014). Antiviral effects of Phyllanthus urinaria containing corilagin against human enterovirus 71 and Coxsackievirus A16 in vitro. Archives of pharmacal research. 38. 10. 1007/ s12272- 014- 0390-9. Human enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are major causative agents of hand, foot, and mouth disease (HFMD) especially in infants and children under 5 years of age. Despite recent outbreaks of HFMD, there are no approved therapeutics against EV71 and CA16 infection. Moreover, in a small percentage of cases, the disease progression can lead to serious complications of the central nervous system. In this study, we investigated the antiviral effect of corilagin and Phyllanthus urinaria extract, which contains corilagin as a major component, on EV71 and CA16 infection in vitro. Our results indicate that corilagin reduces the cytotoxicity induced by EV71 or CA16 on Vero cells with an IC50 value of 5.6 and 32.33 μg/ mL, respectively. We confirmed the presence of corilagin in EtOAc and BuOH fractions from P. urinaria extract and this correlated with antiviral activity of the fractions against EV71 or CA16. Future studies will be required to confirm the antiviral activity of corilagin and P. urinaria extract in vivo. Challenging a model with a lethal dose of viral infection will be required to test this. Collectively, our work provides potential candidates for the development of novel drugs to treat HFMD.
• Praseno, Praseno. (1998). Anti-herpes simplex virus property of Phyllanthus urinaria (L) as shown by plaque reduction assay. Medical Journal of Indonesia. 7. 29. 10. 13181/mi. v7i1. 794. Traditional medicine has been popular in Indonesia. Many of them are effective in curing various diseases. Based on that the antiviral activity of the Herpes Simplex Virus of an aqueous phase of extract of Phillantus urinaria (L) plant was investigated in vitro by a plaque reduction assay. Results showed that Iino was achieved by the extract at concentrations of 6% and 4% v/v for HSV-2 and HSV-1 respectively. 
• Chung, Chueh- Yao & Liu, Ching- Hsuan & Burnouf, Thierry & Wang, Guey- Horng & Chang, Shun-Pang & Jassey, Alagie & Tai, Chen- Jei & Tai, Cheng- Jeng & Huang, Ching- jang & Richardson, Christopher & Yen, Ming- Hong & Lin, Chun- Ching & Lin, Liang-Tzung. (2016). Activity-Based and Fraction-Guided Analysis of Phyllanthus urinaria Identifies Loliolide as a Potent Inhibitor of Hepatitis C Virus Entry. Antiviral research. 130. 10. 1016/ j. antiviral. 2016. 03. 012. Without a vaccine, the hepatitis C virus (HCV) remains a global medical and socio-economic burden, predisposing about 170 million carriers worldwide to end-stage liver diseases including cirrhosis and hepatocellular carcinoma. Although the recently developed direct-acting antivirals (DAAs) have revolutionized hepatitis C treatment, most of them are unsuitable for monotherapy due to risks of resistance, thus necessitating combination with interferon (IFN)-alpha, ribavirin, or additional DAAs. More importantly, the high cost associated with the DAAs restricts their access to most parts of the world. Developing novel cost-effective anti-HCV therapeutics may help expand the scope of antivirals and treatment strategies against hepatitis C. Herein, we applied an activity-based and fraction-guided analysis of extracts from the medicinal plant Phyllanthus urinaria (P. urinaria), which yielded fraction 13 (F13) as possessing the most potent inhibitory activity against early viral entry of cell-culture HCV infection. Chemical analysis (silica gel chromatography followed by ESI LC-MS plus 1H and 13C NMR) of F13 identified collide (LOD), a monoterpenoid lactone, as a novel inhibitor of HCV entry. Specifically, LOD could efficiently inactivate HCV-free virus particles, abrogate viral attachment, and impede viral entry/fusion, with minimal effect on viral replication/translation, particle production, and induction of type I IFN host antiviral immune response. The ELISA-based binding analysis confirmed the monoterpenoid’s ability to efficiently block HCV particle attachment to the host cell surface. Furthermore, LOD could inhibit infection by several genotypic strains of HCV. This is the first report characterizing P. urinaria and its bioactive compound LOD as potent HCV entry inhibitors, which merit further evaluation for development as candidate antiviral agents against hepatitis C.
• Huang, Sheng-Teng & Pang, Jong-Hwei & Yang, Rong-Chi. (2009). Anti-cancer effects of Phyllanthus urinaria and relevant mechanisms. Chang Gung Medical Journal. 33. 477- 87. Phyllanthus urinaria (P. urinaria), a widely used herbal medicine, has been reported to possess various biological activities. This report aimed to characterize the whole P. urinaria plant, present the anticancer effects of P. urinaria both in vivo and in vitro, and explore relevant mechanisms. The water extract of P. urinaria significantly reduces the cell viability of various cancer cell lines from different origins and suppresses tumor development in C57BL/ 6J mice after the implantation of Lewis lung carcinoma (LCC) cells. The anticancer activity of P. urinaria extract is mainly due to induced apoptosis of cancer cells as demonstrated by DNA fragmentation and increased caspase-3 activity through both intrinsic and extrinsic pathways. The decrease in viability with P. urinaria treatment might be partially associated with the down-regulation of telomerase activation and induction of the apoptotic process. In addition, P. urinaria also exhibits anti-angiogenic activity that is mediated, at least in part, by suppression of matrix metalloproteinase 2 (MMP-2) secretion and inhibition of MMP-2 activity through zinc chelation.
• Cheng, Hua-Yew & Yang, Chien-Min & Lin, Ta-Chen & Lin, Liang-Tzung & Chiang, Lien-Chai & Lin, Chun-Ching. (2011). Excoecarianin, Isolated from Phyllanthus urinaria Linnea, Inhibits Herpes Simplex Virus Type 2 Infection through activation of Viral Particles. Evidence-based complementary and alternative medicine: eCAM. 2011. 259103. 10. 1093/ ecam/ nep157. Phyllanthus urinaria Linnea (Euphorbiaceae) is one of the traditional medicinal plants widely used by Oriental people to treat various diseases. We have previously demonstrated that the acetone extract of P. urinaria inhibits herpes simplex virus type 2 (HSV-2) but not HSV-1 infection. In a continuing effort to clarify the antiviral mechanisms of P. urinaria, we isolated the pure compound excoecarianin from the whole plant of P. urinaria through acetone extraction and investigated its anti- HSV- 1 and HSV- 2 activities. Our results indicated that excoecarianin protected Vero cells from HSV- 2 but not HSV- 1 infection, and its 50 % inhibitory concentration (IC (50)) was 1.4 ± 0.1 μM. The antiviral effective concentration of excoecarianin did not affect the viability or the morphology of Vero cells. Although excoecarianin inhibited HSV-2 infection, the inhibitory effect, however, was most prominent when excoecarianin was concurrently added to the virus. Pretreatment of Vero cells with excoecarianin with removal of the drug before infection did not yield any antiviral effects, and the same observation was made for post-viral entry treatment. Subsequent studies revealed that excoecarianin inactivated HSV- 2 virus particles to prevent viral infection. A synergistic antiviral effect against HSV-2 was also observed when Vero cells were treated with a combination of acyclovir (ACV) and excoecarianin. These results suggested that excoecarianin merits be further explored as an entry inhibitor against HSV- 2 and could potentially be investigated for combinatorial drug treatment with nucleoside analogs such as ACV in the therapeutic management of HSV- 2 infection.
• Saahene, Roland & Agbo, Elvis & Barnes, Precious & Yahaya, Ewura & Amoani, Benjamin & Nuvor, Samuel Victor & Okyere, Perditer. (2021). A Review: Mechanism of Phyllanthus urinaria in Cancers- NF- κB, P13K/ AKT, and MAPKs Signaling Activation. Evidence-based complementary and alternative medicine: Volume 2021. 10. 1155/ 2021/ 4514342. Phyllanthus urinaria has been characterized by its several biological and medicinal effects such as antiviral, antibacterial, anti-inflammatory anticancer, and immunoregulation. In recent years, Phyllanthus urinaria has demonstrated the potential to modulate the activation of critical pathways such as NF- κB, P13K/ AKT, and ERK/ JNK/ P38/ MAPKs associated with cell growth, proliferation, metastasis, and apoptotic cell death. To date, much evidence indicates that modulation of cellular signaling pathways is a promising approach to consider in drug development and discovery. Therapies that can regulate cancer-related pathways are longed for in anticancer drug discovery. &is review’s focus is to provide comprehensive knowledge on the anticancer mechanisms of Phyllanthus urinaria through the regulation of NF- κB, P13K/ AKT, and ERK/ JNK/ P38/ MAPKs signaling pathways. 
• Lin, Shyr-Yi & Wang, Ching- Chiung & Lu, Yeh- Lin & Wu, Wen- Chun & Hou, Wen- Chi. (2008). Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinaria. Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association. 46. 2485- 92. 10. 1016/ j. ft. 2008. 04. 007. The wrinkle-fruited leaf flower (Phyllanthus urinaria L.) (Euphorbiaceae) is widely used as a traditional folk medicine for inflammatory relief. Geraniin, the hydrolyzable tannin, was purified by a series of chromatographic processes from the 70% aqueous acetone extracts of P. urinaria and identified by NMR [1H (500 MHz) and 13C NMR (126 MHz)] spectra and mass spectroscopy. The scavenging activities of geraniin against DPPH radicals (half-inhibition concentration, IC50, were 0.92 and 1.27 microM, respectively, for pH 4.5 and pH 7.9), hydroxyl radicals (IC50 was 0.11 microM by deoxyribose method and 1.44 microM by electron spin resonance method), and superoxide radicals (IC50 were 2.65 micro M) were determined in comparison with positive controls. The inhibitory activities against xanthine oxidase (IC50 were 30.49 micro M) were measured. Geraniin also showed dose-dependent inhibitory activities against semicarbazide-sensitive amine oxidase (SSAO, IC50 were 6.58 micro-M) and against angiotensin converting enzyme (ACE, IC50 were 13.22 micro M). For kinetic property determinations, Geraniin showed competitive inhibitions against SSAO (the apparent inhibition constant, Ki, was 0.70 micro M) and mixed noncompetitive inhibitions against ACE. Spontaneously hypertensive rats (SHR, 10- week age) were orally administered once (5 mg geraniin/ kg SHR), and changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured over 24 h and compared with the positive control of captopril (2 mg/ kg SHR). The geraniin showed antihypertensive activity in lowering SBP and DBP and showed a significant difference from the blank (distilled water) at 2, 4, 6, 8, and 24 h. Healthy food products could use geraniin for antioxidant protection and therapeutic effects in the future.
• Chularojmontri, Linda & Wattanapitayakul, Suvara & Herunsalee, Angkana & Charuchongkolwongse, Suphan & Niumsakul, Somchit & Srichairat, Supatra. (2005). Antioxidative and Cardioprotective Effects of Phyllanthus urinaria L. on Doxorubicin-Induced Cardiotoxicity. Biological & pharmaceutical bulletin. 28. 1165- 71. 10. 1248/ bob. 28. 1165. Cardiac toxicity is a major adverse effect caused by doxorubicin (DOX) therapy. Many recent studies have shown that DOX toxicity involves the generation of reactive oxygen species (ROS). Although protection or alleviation of DOX toxicity can be achieved by the administration of antioxidant vitamins such as ascorbic acid and vitamin E, their cardioprotective effect remains controversial. Thus, alternative naturally occurring antioxidants may potentially be candidates for antioxidant therapy. In this study, we investigated the antioxidative and cytoprotective effects of Phyllanthus urinaria (PU) against DOX toxicity using H9c2 cardiac myoblasts. The total antioxidant capacity of PU (1 mg/ml) was 5306.75 +/- 461.62 FRAP value (micro- M). DOX IC50 values were used to evaluate the cytoprotective effects of PU ethanolic extract (1 or 10 microg/ml) in comparison with those of ascorbic acid (VIT C, 100 micro-M) and N-acetylcysteine (NAC, 100 micro- M). PU treatments (1 or 10 microg/  ml) dose-dependently caused rightward DOX IC50 shifts of 2.8- and 8.5-fold, respectively while treatments with VIT C and NAC increased DOX IC50 by 3.3- and 4.2-fold, respectively. Additionally, lipid peroxidation and caspase-3 activity were parameters used to evaluate the cytoprotective effect. All antioxidants completely inhibited cellular lipid peroxidation and caspase-3 activation induced by DOX (1 micro-M). Endogenous antioxidant defense such as total glutathione (tGSH), catalase, and superoxide dismutase (SOD) activity was also modulated by the antioxidants. PU treatment alone dose-dependently increased t-GS, and this effect was retained in the presence of DOX. Similar effects were observed in the assessment of catalase and SOD enzyme activity. The nuclear factor kappa- B (NF- kappa B) transcription factor assay demonstrated that all antioxidants significantly inhibited DOX-induced NFkappaB activation. Our results suggest that PU protection against DOX cardiotoxicity was mediated through multiple pathways and this plant may serve as an alternative source of antioxidants for prevention of DOX cardiotoxicity.
• Disoriya, Boby & Jadon, Arvind & Bhadauriya, Poonam. (2022). IN-VITRO SCREENING OF PHYLLANTHUS URINERIA FOR ANTIMICROBIAL ACTIVITY USING DISK DIFFUSION METHOD. WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES. 10. 1632. 10. 20959/ apps. 202210- 23395. Leaves with Arial parts and fruits of the plant Phyllanthus urinaria were collected and dried under shade. Powdered plant materials were subjected to extraction, and after the extraction, pharmacognostic evaluation was done. Extracts were tested for phytochemicals and found leaf extract contains tannins, flavonoids, glycosides, alkaloids, saponins and phenolics and fruit extract contains flavonoids, glycosides, saponins, phenolics, anthraquinones, and alkaloids. Gradual increasing percentage inhibition with increasing concentration was observed as antioxidant activity by DPPH assay. Extracts of Phyllanthus urinaria were evaluated against Gram-positive (B. subtilis) and Gram-negative bacteria (E. coli). The ethanolic extract of the leaf was effective against E. coli but minutely active against B. subtilis bacteria. The Aqueous extract of the leaf is moderately effective against both Gram-positive and Gram-negative bacteria. Ethanolic extract of Seed was moderately effective against both Gram-positive and Gram-negative bacteria. Aqueous extract of seeds was moderately effective against both Gram-positive and Gram-negative bacteria. Extracts of Phyllanthus urinaria were evaluated against A. niger and C. albicans. The ethanolic extract of the leaf was effective against A. niger but moderately effective against C. albicans, Aqueous extract of the leafless was effective against both Candida albicans and A. Niger. Ethanolic extract of Seed was moderately effective against Candida albicans but less effective against A. Niger. Aqueous extract of seeds was moderately effective against Candida albicans but less effective against A. Niger.
• Jantan, Ibrahim & Haque, Md & Ilangkovan, Menaga & Arshad, Laiba. (2019). An Insight Into the Modulatory Effects and Mechanisms of Action of Phyllanthus Species and Their Bioactive Metabolites on the Immune System. Frontiers in Pharmacology. 10. 878. 10.3389/fphar.2019.00878. Phyllanthus species (family; Euphorbiaceae) have been intensively studied for their immunomodulating effects due to their wide-ranging uses to treat immune-related diseases in indigenous medicine, which primarily lack a scientific basis. The focus of this review is on the significance of Phyllanthus species and their bioactive metabolites particularly corilagin (1), geraniin (2), gallic acid (3), phyllanthin (4), hypophyllanthin (5), ellagic acid (6), phyltetralin (7), niranthin (8), catechin (9), quercetin (10), astragalin (11), and chebulagic acid (12) in the modulation of both innate and adaptive immune systems through various mechanisms and their possible therapeutic benefits for treatment of immune-related diseases. 
• Ramanujam, Srirama & Deepak, H & Umapathy, Senthilkumar & Ravikanth, Gudasalamani & Gurumurthy, bukkambudhi Rudrappa & Byrappa, Shivanna & Chandrasekaran, C.V. & Agarwal, Amit & Shaanker, R. (2012). Hepatoprotective activity of Indian Phyllanthus. Pharmaceutical Biology. 50. 948- 53. 10. 3109/ 13880209. 2011. 649858. Phyllanthus (Euphorbiaceae) species are traditionally well-known for their medicinal properties including hepatoprotective activity. The study assessed the hepatoprotective and antioxidant activities of 11 Phyllanthus species, P. amarus Schumach., P. urinaria L., P. debilis Klein ex Willd, P. tenellus Roxb., P. virgatus G. Forst., P. maderaspatensis L., P. reticulatus Poir., P. polyphyllus Willd., P. emblica L., P. indofischerii Bennet. and P. acidus (L.) Skeels. The dried leaves and stems of each plant species were extracted in methanol and successively in water. The extracts were screened for hepatoprotective activity at a concentration of 50 µg/ mL against tert-butyl hydroperoxide (t-BH) induced toxicity in HepG2 cells. Seven extracts from five species that showed hepatoprotective activity were assessed for their 50 % effective concentration (EC (50)) values and their antioxidant activity using a DPPH assay. Phyllanthin and hypophyllanthin contents were also determined in these Phyllanthus species. The methanol extracts of P. polyphyllus, P. emblica, and P. indofischeri showed high levels of hepatoprotective activity with EC (50) values of 12, 19, and 28 µg/ mL and IC (50) of 3.77, 3.38 and 5.8 µg/ mL for DPPH scavenging activity respectively against an IC (50) of 3.69 µg/ mL for ascorbic acid. None of these activities could be attributed to phyllanthin and hypophyllanthin.
• The hepatoprotective and antioxidant activities of P. indofischeri are demonstrated for the first time in literature. The study also confirms the hepatoprotective and antioxidant activities of leaves of P. emblica and P. polyphyllus. The molecule(s) responsible for the activities is being investigated.
• Tseng, Hsu-Hung & Chen, Pei-Ni & Kuo, Wu-Hsien & Wang, Jhih-Wei & Chu, Shu-Chen & Hsieh, Yih-Shou. (2012). Antimetastatic Potentials of Phyllanthus urinaria L on A549 and Lewis Lung Carcinoma Cells via Repression of Matrix-Degrading Proteases. Integrative cancer therapies. 11. 267- 78. 10. 1177/ 1534735- 411417128. Tumor metastasis is the most important cause of cancer death and various treatment strategies have targeted at preventing the occurrence of metastasis. Phyllanthus urinaria L is a popular folk medicine and has several proven biological properties, including antioxidant, antihypertension, and anti-inflammatory. This study provides molecular evidence associated with the antimetastatic effects of P urinaria L extracts (PUE), which contained polyphenols including gallic acid, methyl gallate, epicatechin, epigallocatechin- 3- gallate, gallocatechin- 3- gallate, rutin, epicatechin- 3- gallate, and naringin, by showing a marked inhibition on the invasion (P < .001) and migration (P < .001) of highly metastatic A549 and Lewis lung carcinoma (LLC) cells. To further investigate the precise involvement of PUE in tumor metastasis, A549 and LLC cells were treated with PUE at various concentrations and results from zymography and Western blotting showed that a PUE treatment may decrease the expressions of matrix metalloproteinase-2 (MMP- 2; P < .001), MMP-9 (P < .001), urokinase plasminogen activator (P < .001), and their endogenous inhibitors, that is, tissue inhibitor of metalloproteinase- 2 and plasminogen activator inhibitor- 1, in a concentration-dependent manner. Reverse transcription- polymerase chain reaction and MMP- 2 promoter luciferase analysis (P < .001) revealed that PUE inhibits the transcription of MMP- 2 mRNA. PUE also exerted an inhibitory effect on the DNA-binding activity and the nuclear translocation of NF- κB and AP-1. Furthermore, the inhibitory effects of PUE on the metastasis and growth of LLC cells in vivo were proven. These results indicate that PUE could be applied to be a potential antimetastatic agent.
• Deshpande, Mangirish & Balekar, Neelam. (2018). Evaluation of anti-ulcer activity of the ethanolic extract of phyllanthus urinaria in experimental animals. Asian Journal of Pharmaceutical and Clinical Research. 11. 197. 10. 22159/ ajpcr. 2018. v11i12. 28235. Objective: The objective of this study is to investigate the antiulcer activity of the ethanolic extract of Phyllanthus urinaria (EEPU). Methods: In vivo, the anti-ulcer activity of EEPU was evaluated in the present study at 500 mg/ kg body weight by pyloric ligation, ethanol-induced ulcer, aspirin-induced ulcer, and cold restraint-induced ulcer model. The anti-ulcer activity was assessed by determining and comparing the gastric volume, pH, free and total acidity, ulcer number and its inhibition, and ulcer severity. Result EEPU at 500 mg/ kg body weight dose showed significant antiulcer activity by decreasing ulcer index, gastric volume, pH, and free and total acidity. The gastroprotective effect of EEPU was substantiated by histopathological studies of the stomach in ulcer and treated groups. Conclusion It can be concluded from the results that EEPU has potential antiulcer activity.
• J R, Anusha & Remya, R.V. & Premila, J.M. & Fleming, A. T. (2014). Antioxidant and anticandidal activity studies on phyllanthin compounds from Phyllanthus niruri. International Journal of Pharmacy and Pharmaceutical Sciences. 6. 323- 326. Objective: The present study was to investigate the phyllanthin present in Phyllanthus niruri which belongs to the family, Euphorbiaceae. The vital aim was to evaluate the antioxidants and to determine the anticandidal efficacies against Candida albicans. Methods: Phyllanthin, is one of the active lignans that was isolated from Phyllanthus niruri by silica gel column chromatography employing gradient elution with hexane-ethyl acetate solvent mixture. The eluted samples were further identified and estimated using HPTLC. The free radical scavenging activity of phyllanthin was examined using a DPPH assay. Anticandidal activity was studied by analyzing the growth inhibition and Minimum Fungicidal Concentration (MFC) rate. Results: The retention time of phyllanthin is 23.4 and its total run time was 45 min. Phyllanthin exhibited very high antioxidative properties by its low IC50=7.5 μmol/mL. The isolated phyllanthin alters the growth of C. albicans and shows significant results in vitro. Among the various concentrations of phyllanthin, 250 μl/ L concentration revealed a high rate of inhibition. Conclusion: The phyllanthin compound from the medicinal plant, Phyllanthus niruri is confirmed as an effective antifungal agent to prevent candidiasis and the secondary infections caused by various diseases.

Recent Research on Phyllanthus niruri

• Wahyuni, Tutik & Azmi, Dzul & Permanasari, Adita & Adianti, Myrna & Tumewu, Lidya & Widiandani, Tri & Chie, Utsubo & Widyawaruyanti, Aty & Fuad, Achmad & Hotta, Hak. (2019). ANTI-VIRAL ACTIVITY OF Phyllanthus niruri AGAINST HEPATITIS C VIRUS. Malaysian Applied Biology. 48. 105- 111. Hepatitis C virus (HCV) infection is a global problem that causes liver disease and hepatocellular carcinoma. Although the current standard treatment provided a significant improvement in response rate with sustained virology response of more than 90%, however, the high cost was limited access to this therapy, resistance emergence, and serious side effects which provide the necessities to find the new anti-HCV agents. In the current study, we evaluated the ethanol extract of Phyllanthus niruri for its anti-HCV activities. Anti-HCV activity was determined by in vitro culture cells of Huh 7it. Anti-HCV activity of P. niruri extract revealed strong inhibition against HCV with IC 50 values of 4.14 µg/ mL and yielded stronger activity in the entry step of the HCV life cycle. Moreover, the P. niruri extract enhanced the anti-HCV activity of simeprevir (NS3 protease inhibitor) with an increase in the activity up to 4-fold compared to a single treatment of simeprevir. Docking analysis was performed to predict the interaction of phyllanthin and hypophyllantin, known compounds of P. niruri against HCV receptors. Both phyllantin and hypophyllantin were mediated a strong interaction with 4GAG, a protein that is involved in the entry step of HCV. These results suggested that the ethanol extract of P. niruri may be a good candidate for the development of anti-HCV drugs.
• Asare, George & Addo, Phyllis & Bugyei, Kwasi & Gyan, Ben & Adjei, Samuel & Otu-Nyarko, Lydia & Wiredu, Edwin & Nyarko, Alexander. (2011). Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri. Interdisciplinary toxicology. 4. 206- 10. 10. 2478/ v10102- 011- 0031- 9. Acute toxicity studies of aqueous leaf extract of Phyllanthus niruri Phyllanthus niruri is a plant with medicinal properties. It is often used to treat mild malaria and the elimination of renal stones. However, studies on its toxicity are scarce. The study was carried out to determine if the aqueous leaf extract of P. niruri administered to female Sprague-Dawley rats would illicit evidence of toxicity. Fifteen female rats weighing 150- 200 g were divided into 3 groups. Rats in Group 1 were given a single low dose (LD) of 2000 mg/ kg b. w. of the extract by oral gavage within 24 hrs. Rats in Group 2 were given a single high dose (HD) of 5 000 mg/ kg b. w. of the extract by oral gavage within 24 hrs. Rats in Group 3 were not given any extract but drinking water and served as the control group (C). All the rats were observed for signs of toxidromes for 14 days. On the 15^th  day, all the rats were sacrificed. Body organs were harvested for macroscopic examination. Urine and blood samples were drawn and analyzed. Hematological tests performed included full blood count and hemoglobin. Biochemical examinations included bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatase (ALP), γ- glutamyl- transpeptidase (GGT), urea, and creatinine. The results of the three groups were not significantly different. Examination of the various body organs did not show any abnormality. Thus, no toxicity was observed at the levels administered. The LD 50 of the aqueous extract is > 5,000 mg/kg. b. w.
• Manonmani, Pandian & Ramar, Marimuthu & Geetha, Natesan & Valan Arasu, Mariadhas & Erusan, Raskin & Sowmiya, Justin. (2015). Hepatoprotective activity of aqueous extract of Phyllanthus niruri in CCl₄ induced liver toxicity-in vivo study. Research Journal of Biotechnology. 10. 11- 17. In rural India, Phyllanthus niruri is mainly used as the traditional medicine for the treatment of liver disorders. The present study aimed to evaluate the efficacy of Phyllanthus niruri on the induction of oxidative hepatic damage by carbon tetrachloride CCl₄ in male Swiss albino mice. A single dose of 0.2 ml/ kg of CCl₄ along with vehicle alternatively for 15 days and 100 mg/kg of Phyllanthus niruri plant extract was orally administered for 20 days. Liver damage was assessed by the estimation of serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Results indicated a significant increase in the level of liver enzymes like ALT, AST, ALP and bilirubin content 273.6 ± 2.40, 98.60 ± 2.13, 248.6 ± 4.87 U/ L and 6.5 ± 0.16 μmol/ L in CCl₄ intoxicated animals when compared with that of the control group of mice 120.8 ± 2.87, 42.73 ± 1.98, 173.5 ± 3.24 U/L and 0.6 ± 0.02 μmol/ L respectively. Hematological investigations (RBC count, PVC, Hb, WBC count, and Platelet count) did not reveal any significant changes among the different groups whereas histological examination confirmed that the liver hepatocytes arranged in one cell thickness indicated the curative effect of cystic fibrosis, a mild inflammatory change and greater area of regeneration. The reduction in body weight was minimal and liver enlargement was also less compared to the animals in the toxic control group. Overall results indicated that the aqueous extract of P. niruri possesses hepatoprotective effects which can be used in the treatment of liver diseases.
• Aarthi, C. & Ramesh Babu, Polani. (2016). Antimicrobial and antioxidant activity of phyllanthus niruri. 8. 14701- 14707. Medicinal plants have been used as remedies for human diseases for centuries. The reason for using them as medicine lies in the fact that they contain chemical components of therapeutic value. Knowledge about plants that were found to be most effective against particular ailments was passed down to succeeding generations. The development of resistance in microorganisms due to the excessive use of conventional antibiotics and the increase in the emergence of infectious diseases has led to the search for new antimicrobial compounds with increased efficiency in terms of their mechanisms of action. Antioxidants are also of interest to biologists and clinicians because they help to protect the human body against damage caused by reactive oxygen species (ROS). Compounds from natural sources capable of protecting against ROS-mediated damage may have potential applications in the prevention and/or curing of diseases. In the present study, the antimicrobial and antioxidant potential of Phyllanthus niruri Linn belongs to the family Euphorbiaceae, commonly known as Stonebreaker, was studied in ethanol, methanol, and aqueous extracts. Results revealed that the plant selected has good antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Salmonella typhi, and higher activity was observed in methanolic extract than ethanolic and aqueous extracts. Antioxidant activities of Phyllanthus niruri Linn in methanolic, ethanolic, and aqueous extracts were 83.63 %, 76.36 %, and 70.90 % respectively. 
• Udupa, A. (2010). Diuretic activity of Phyllanthus niruri (Linn.) in rats. Health. 02. 511- 512. 10. 4236/ health. 2010. 25076. Aqueous extract of Phyllanthus niruri (200 mg/ kg and 400 mg/ kg. p.o. single dose) was tested for its diuretic activity and compared with the standard drug hydrochlorothiazide (10 mg/ kg p.o. single dose). A significant increase in the volume of urine and excretion of sodium, potassium, and chloride was recorded when an aqueous extract of Phyllanthus niruri was administered to hydrated albino rats.
• Basappa biradar, biradar kalyani & Payghan, Santosh & Ramchandra, Setty. (2010). Evaluation of Diuretic Activity of Phyllanthus fraternus Web Arial Parts On Albino Rats. International Journal of Pharmaceutical & Biological Archives. 1. 389. The study was designed to evaluate the diuretic activity of Phyllanthus fraternus web (Euphorbiaceae). The 70 % methanolic extract of aerial parts of Phyllanthus fraternus was tested by using Wister albino rats. The animals were grouped into 4 groups containing 6 animals in each. All animals were hydrated with normal saline at a dose of 25 ml/kg orally 30sec before treatment. Group I served as control, and groups II & III were treated with 100mg/kg and 200mg/kg of 70 % methanolic extract respectively. Group IV was treated with the standard frusemide 20mg/kg. The volume of urine was measured at the end of 6 hrs. The Na +, K + & Cl -ion concentrations in the urine samples were determined. The volume of urine (7.38 ± 0.18 & 9.11 ± 0.14) and urinary Na +, K + & Cl -ionic concentrations (3.15 ± 0.15 & 6.15 ± 0.24, 2.50 ± 0.10 & 3.57± 0.10) and 5.60 ± 0.13 & 7.39 ± 0.13) were found to rise in test group II and III.
• Ahm, Thippeswamy & Shirodkar, Akshay & Koti, Basavaraj & Sadiq, A & Praveen, D & Swamy, A & Patil, Mahesh. (2011). Protective role of Phyllantus niruri extract in doxorubicin-induced myocardial toxicity in rats. Indian journal of pharmacology. 43. 31- 5. 10. 4103/ 0253- 7613. 75663. To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq. E. PN) against doxorubicin (Dox)-induced myocardial toxicity in rats. Cardiotoxicity was produced by Dox administration (15 mg/ kg for 2 weeks). Aq. E PN (200 mg/ kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose. Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST, and ALT to normal levels. Aq. E PN increased the GSH, SOD, and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency. These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.
• Kumar, Anuj & Rana, Akhilesh & Singh, Amit & Singh, Alok. (2019). Effect of Methanolic Extract of Phyllanthus niruri on Leptin Level in Animal Model of Diabetes Mellitus. Biomedical and Pharmacology Journal. 11. 57- 63. 10. 13005/ bpj/ 1613. To study the effect of methanolic extract of Phyllanthus niruri on an animal model of Diabetes Mellitus. Diabetes Mellitus was induced in rats by injecting Streptozotocin (60mg/ kg) intraperitoneally. Blood glucose was measured on day 3 by GOD- POD method. Rats having fasting blood glucose > 250 mg/dl were further selected for study. Four groups were created i.e., Control, Control+ Streptozotocin, Streptozotocin+ Metformin (75 mg/  kg), and Streptozotocin+ extract of P. niruri (250 mg/ kg). Each group consisted of 6 rats of either sex. Metformin and experimental extract were administered for 21 days. Blood Glucose was measured on days 7 and 21. Triglyceride, Cholesterol, and Leptin levels were also measured by commercially available kits. Antioxidant potential was assessed by estimating the extent of Lipid peroxidation (LPO) by Malondialdehyde (MDA), Nitric oxide (NO), Superoxide dismutase (SOD), and Glutathione (GSH) in four different tissues i.e. Liver, Kidney, Pancreas, Muscle on day 21. Unpaired and paired student t-tests were applied for statistical analysis using SPSS Software. The extract of P. niruri showed a significant decrease in blood glucose levels on day 21 (p-0.04). The treatment didn’t show a significant lowering of Leptin and Cholesterol levels however Triglyceride level was significantly reduced (p-0.05). The treatment group showed improvement in oxidative stress by increasing SOD and GSH and decreasing LPO and NO activity. The study showed anti-hyperglycemic and anti-oxidative properties of methanolic extract of P.niruri.
• Khare, P. & Mishra, V.K. & Arun, K. & Bais, N. & Singh, R. (2014). Study on in vitro anti-lithiatic activity of Phyllanthus niruri linn. Leaves by homogenous precipitation and turbidity method. International Journal of Pharmacy and Pharmaceutical Sciences. 6. 124- 127. Objective: Kidney stone is one of the most prevalent diseases worldwide and calcium oxalate is the main component of the majority of stones formed in the urinary system of the patients. Traditional knowledge on the use of medicinal plants for curing chronic diseases is proving its worth to modern society too. In this regard, the study was conducted to find out the role of Phyllanthus niruri Linn. leaves extracts in inhibiting stone formation and dissolution of already exiting stone in the renal system using in vitro methods in the laboratory Methods: Leaves powder was serially extracted in petroleum ether, ethyl acetate, methanol and water. An in vitro study was conducted to assess the antiurolithiatic effect of plants for all the extracts with two standard drugs namely, Neeri and Cystone as control. Two methods, the turbidity method and calcium oxalate dissolution methods were practiced to access the inhibition of stone formation and dissolution of stone crystals respectively. A microscopic study was done for the comparative evaluation of crystal density and size in each treatment in the turbidity method. Results: Water extract from plant leaves proved its potential statistically equal to the standard drug, cystone in dissolving the existing calcium oxalate crystals. Water extract could dissolve 56.8 % of crystals while cystone dissolved 58.4 % of crystals in an in vitro study and was found statistically at par. Water extract also could inhibit up to 53.09 % aggregation of calcium oxalate crystals as compared to the cystone with 76.54 %. Among other extracts, methanol extract got second position in anti-lithiatic activity. Conclusion: Common medical practice recommends the use of cystone as an effective medicine for preventing as well as treating renal stone which is found at par with the water extract of plant leaves to inhibit the stone formation even in its crude form. Results guide us for the further detailed investigation and development of new drugs from this medicinal plant.
• Abdulla, Mahmood & Khaled, Abdul-Aziz & Ahmed, & Hussain, Fouad & Al-Bayaty, Fouad & Masood, Yaghma. (2010). Gastroprotective effect of Phyllanthus niruri leaf extract against ethanol-induced gastric mucosal injury in rats. African Journal of Pharmacy and Pharmacology. 4. The main objective of this study is to evaluate the gastroprotective activity of the Phyllanthus niruri leaf extract against ethanol-induced gastric mucosal injury in rats. Six groups of Wistar rats were pre-treated, respectively, with distilled water; omeprazole 20 mg/ kg; and 250, 500, 750, and 1000 mg/ kg P. niruri leaf extract 30 min before oral administration of absolute ethanol to generate gastric mucosal injury. One hour later, the rats were sacrificed, and the ulcer areas of the gastric walls were determined. Gross evaluation has revealed that the negative control rats exhibited severe mucosal injury, whereas pre-treatment with P. niruri leaf extract resulted in significantly less gastric mucosal injury and flattening of the mucosal folds. Histological studies of the gastric wall revealed that negative control rats suffered very severe damage of gastric mucosa, along with edema and leucocyte infiltration of the submucosal layer compared to rats pre-treated with P. niruri leaf extract where there was marked gastric protection along with reduction or inhibition of edema and leucocytes infiltration of the submucosa. The present finding suggests that P. niruri leaf extract promotes ulcer protection as ascertained by the comparative decreases in ulcer areas, inhibition or reduction of edema, and leukocyte infiltration of the submucosa.
• Rahman, Md. Sohanur & Begum, Mst Marium & Begum, Rayhana. (2017). Evaluation of the anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats. BMC Complementary and Alternative Medicine. 17. 2- 10. 10. 1186/ s12906-017- 1771- 7. The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analog in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcers and inflammation. In this project, we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at doses of 100, 200, and 400 mg/ kg, p. o. while using ibuprofen (20 mg/ kg, p. o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1 % w/ v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, the antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200, and 400 mg/ kg, p. o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats – keeping omeprazole (20 mg/ kg, p. o.) as reference. The rats were dissected, and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80 %, 55.32 %, and 69.14 % at doses of 100, 200 and 400 mg/ kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed a good protective effect against ethanol-acid-induced gastric mucosal injury in the rats. Administration of the extract’s doses (100, 200, and 400 mg/ kg) demonstrated a significant (p < 0.01) reduction in the ethanol-acid-induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid-induced gastric ulcer as compared to omeprazole (20 mg/ kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration, and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of the mucosal layer and significantly prevented the formation of hemorrhage and edema. The investigation suggests that the methanolic extract of P. niruri leaf possesses anti-inflammatory activity and promotes ulcer protection as ascertained by the regeneration of the mucosal layer and substantial prevention of the formation of hemorrhage and edema.
• Porto, Cínthia & Soares, Luiz & Souza, Tatiane & Petrovick, Pedro & Lyra, Ibson & Junior, Raimundo & Langassner, Silvana Maria & Araújo, Aurigena & Guerra, Gerlane. (2013). Anti-inflammatory and antinociceptive activities of Phyllanthus niruri spray-dried standardized extract. Revista Brasileira de Farmacognosia. 23. 138- 144. 10. 1590/ S0102- 695X- 2013005000004. Phyllanthus niruri L., Euphorbiaceae, spray-dried standardized extract was studied for its anti-inflammatory and antinociceptive activities in adult albino rats and mice. The anti-inflammatory effect of the spray-dried standardized extract was observed in carrageenan-induced paw edema and thioglycolate-induced leukocyte migration, while antinociceptive effects were observed using Randall & Selitto, tail flick, and hot plate tests. This study showed that intraperitoneal spray-dried standardized extract at 100, 200, 800, or 1600 mg/kg reduced the vascular response in the inflammatory process of paw edema induced by 1 % carrageenan. Oral spray-dried standardized extract at 100 or 200 mg/kg inhibited leukocyte migration to the site of inflammation induced by 3 % thioglycolate. In rats, at 100 and 200 mg/kg intraperitoneally, the extract exhibited a marked peripheral analgesic effect in a Randall & Selitto assay and showed significant central analgesic activity in a hot plate and tail flick assay. In conclusion, this study suggested that Phyllanthus niruri spray-dried standardized extract has potent inflammatory and antinociceptive activities and that these activities are not modified by the standard drying process, making it feasible to use the dry extract standardized to obtain a phytotherapic preparation and thus validating its use for the treatment of pain and inflammation disorders.
• Sharma, Priyanka & Parmar, Jyoti & Verma, Preeti & Goyal, P. (2009). Anti-tumor activity of Phyllanthus niruri (a medicinal plant) on chemical-induced skin carcinogenesis in mice. Asian Pacific journal of cancer prevention: APJCP. 10. 1089- 94. Chemoprevention is an important strategy to control the process of carcinogenesis. The potential of using medicinal herbs such as cancer chemopreventive nutraceuticals and functional food is promising. Thus, there is a need for exploring drugs/agents that act as chemo-preventive agents. Phyllanthus niruri is a well-known medicinal plant that has been used in Ayurvedic medicine as hepatoprotective, antiviral, antibacterial, analgesic, antispasmodic, and antidiabetic. The present study was carried out to evaluate the anti-tumor activity of a hydro-alcoholic extract of the whole plant, in 7-9 week-old male Swiss albino mice, on the two-stage process of skin carcinogenesis induced by a single topical application of 7, 12- dimethylbenz anthracene (100 microg/ 100 micro- acetone) and two weeks later promoted by repeated application of croton oil (1% in acetone/three times a week) till the end of the experiment (16 weeks). The oral administration of P. niruri at a dose of 1000 mg/ kg/ b.wt. At peri-i.e.,e. 7 days before and 7 days after DMBA application) and post- (i.e. starting from the Croton oil application) initiation phase of papillomagenesis caused a significant reduction in tumor incidence, tumor yield, tumor burden, and cumulative number of papilloma as compared to carcinogen-treated controls. Furthermore, the average latent period was significantly increased in the PNE-treated group. The results thus suggest that P. niruri extract exhibits significant anti-tumor activity, which supports the traditional medicinal utilization of this plant.
• Begum, Rayhana. (2017). Evaluation of the anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats. 17. 267. Background: The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analog in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcers and inflammation. In this project, we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. Methods: The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200, and 400 mg/  kg, p.o. while using ibuprofen (20 mg/ kg, p. o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, the antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200, and 400 mg/ kg, p. o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats – keeping omeprazole (20 mg/ kg, p. o.) as reference. The rats were dissected, and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. Results: P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46. 80 %, 55.32 %, and 69.14 % at doses of 100, 200, and 400 mg/ kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed a good protective effect against ethanol-acid-induced gastric mucosal injury in the rats. Administration of the extract’s doses (100, 200, and 400 mg/ kg) demonstrated a significant (p < 0.01) reduction in the ethanol-acid-induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/ kg) resulted in better inhibition of ethanol-acid-induced gastric ulcer as compared to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration, and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of the mucosal layer and significantly prevented the formation of hemorrhage and edema. Conclusions: The investigation suggests that the methanolic extract of P. niruri leaf possesses anti-inflammatory activity and promotes ulcer protection as ascertained by the regeneration of the mucosal layer and substantial prevention of the formation of hemorrhage and edema.
• Sathisha, A. & Udupa, L. & Rathnakar, U.P. & Pal, P.G. & Acharya, Sahana & Shastry, Rajeshwari. (2009). Anti-inflammatory and analgesic activity of Phyllanthus niruri in rodent models. Indian Drugs. 46. 50- 53. This study was an attempt to explore the anti-inflammatory and analgesic activity of aqueous extract of Phyllanthus niruri in rodents. The analgesic activity of the aqueous extract (400 mg/ kg and 800 mg/ kg) was investigated in the hot-plate model, the tail-flick method in rats, and the writhing model of the mice. The acute anti-inflammatory activity of Phyllanthus niruri was studied in rats by carrageenan-induced paw edema. Cotton pellets were implanted in rats to study the effect on chronic granuloma. The aqueous extract revealed significant anti-inflammatory activity in the carrageenan model (p< 0.001) and chronic granuloma models (p< 0.001); and analgesic activity by both central (p< 0.001) and peripheral (p< 0.001) mechanisms in this study. These results suggest that the aqueous extracts of Phyllanthus niruri possess analgesic and anti-inflammatory activity.
• Okoli, Charles & Obidike Ezenyi, Ifeoma & Ezike, Adaobi & Akah, Peter & Salawu, O.A. (2011). Studies on the possible mechanisms of antidiabetic activity of extracting aerial parts of Phyllanthus niruri. Pharmaceutical biology. 49. 248- 255. 10. 3109/ 13880209. 2010. 501456. CONTEXT/ OBJECTIVES: The effects of methanol extract of aerial parts of Phyllanthus niruri L. (Euphorbiaceae), an antidiabetic herb, on glucose absorption and storage in diabetes were studied to elucidate the mechanisms of blood glucose lowering and glycemic control in diabetes. The effect of chronic oral administration of the extract on glycemic control was evaluated in alloxan diabetic rats using blood glucose lowering and post-prandial glucose suppression activities as well as effects on hemoglobin glycation and body weight. Effects on glucose mobilization and storage were assessed using the weight and glycogen content of liver isolated from treated diabetic rats, while in vitro inhibition of α-amylase and α-glucosidase enzyme activities were used as indices of effect on glucose absorption. Results showed that the extract lowered blood glucose, suppressed postprandial rise in blood glucose following a glucose meal, reduced hemoglobin glycation, and increased absolute and relative weights as well as glycogen content of the liver in diabetic rats. Treatment with the extract also ameliorated the decrease in body weight caused by the diabetic disease. In vitro, the extract inhibited α-amylase (IC₅₀: 2.15 ± 0.1 mg/ mL) and α-glucosidase (IC₅₀: 0.2 ± 0.02 mg/ mL) activities. These findings suggest that aerial parts of P. niruri may owe their blood glucose-lowering properties to the inhibition of glucose absorption and enhancement of glucose storage.
• Najari Beidokhti, Maliheh & Andersen, Mia & Eid, Hoda & Sánchez-Villavicencio, Mayra & Staerk, Dan & Haddad, Pierre & Jäger, Anna. (2017). Investigation of antidiabetic potential of Phyllanthus niruri L. using assays for α-glucosidase, muscle glucose transport, liver glucose production, and adipogenesis. Biochemical and Biophysical Research Communications. 493. 10. 1016/ j. bbrc. 2017. 09. 080. Phyllanthus niruri is used in herbal medicine for the treatment of diabetes. The objective of this study was to investigate the antidiabetic potential of P. niruri, using assays for α-glucosidase, muscle glucose transport, liver glucose production, and adipogenesis. α-Glucosidase inhibitory activity was performed on aqueous and ethanolic extract of aerial parts of P. niruri. The aqueous and ethanolic extract of P. niruri showed α-glucosidase inhibitory activity with IC50 values of 3.7 ± 1.1 and 6.3 ± 4.8 μg/mL, respectively. HR-bioassay/HPLC-HRMS and NMR analysis were used for the identification of compounds. Corilagin (1) and repandusinic acid A (2) were identified as α-glucosidase inhibitors in the water extract of P. niruri with IC50 values of 0.9 ± 0.1 and 1.9 ± 0.02 μM, respectively. In in vitro cell-based bioassays, cells were treated for 18 h with maximal non-toxic concentrations of the ethanolic extract of P. niruri, which were determined by the lactate dehydrogenase cytotoxicity assay. The ethanolic extract of P. niruri was not able to reduce glucose- 6- phosphatase activity. However, the extract increased deoxyglucose uptake in C2C12 muscle cells and enhanced adipogenesis in 3T3- L1 fat cells which has been reported for the first time. The present study demonstrated that P. niruri may thus have potential application for the treatment and/or management of type 2 diabetes.
• Singh, Tanuja & x, Ruchi & Singh, Anjali & Kumar, Ravish & Singh, Jitendra. (2015). Acute toxicity study of Phyllanthus niruri and its effect on the cytoarchitectural structure of nephrocytes in Swiss albino mice Mus-musculus. Pharmacognosy Journal. 8. 77- 80. 10. 5530/ pj. 2016. 1. 17. Background: In the era of the herbal renaissance, the world is moving towards the medicinal plant that repairs and strengthens the body system without any toxic side effects. Popular medicinal plant Phyllanthus niruri contains various bioactive molecules, the present study aimed to observe the biochemical and cytoarchitectural alterations in the kidney associated with acute oral toxicity (LD50) of aqueous extract of P.niruri in Swiss albino mice. However, limited data is available about the toxicity of herbal remedies used for medication, which is a critical constraint. Materials and Methods: For the acute oral toxicity study, the animals were divided into six groups of 6 mice each. Group I was named the control group and the treatment groups administered aqueous leaf extract of P. niruri orally at different doses of 500 mg/ Kg bw (Group II), 1000 mg/ Kg bw (Group III), 2000 mg/ Kg bw (Group- IV), 2500 mg/ Kg bw (Group- V) and 3000 mg/ Kg bw (Group-VI) for 7 consecutive days. The mice were sacrificed, and serum was collected for biochemical analysis. The kidney was dissected and processed for histological analysis. Results: The LD50 dose of P. niruri was found to be 2590.984 mg/ Kg bw in the Swiss albino mice model in laboratory conditions. The result showed the elevated serum level of urea in treated groups of mice at higher doses which was found to be statistically significant as compared to the control (Group-I). There was not any significant increase in serum creatinine has been observed. Histological alterations were observed at higher doses of more than 2500 mg/Kg bw (Group-VI). Conclusion: It is evident from our study that P. niruri may have a toxic effect on high doses. Therefore, it should be ingested with precautions.
• Veeramaneni, Alekhya & Thiyagarajan, Deepan & Reddy, Sandhya & Mattateja, Mookambika & Nerella, V N & Dhanaraju, Magharla Dasaratha. (2024). ACUTE TOXICITY AND ANTIDIABETIC ACTIVITY OF PHYLLANTHUS NIRURI USING ZEBRA FISH. Journal of Biological Research and Reviews. 1. 10. 5455/ JBRR. 2024080- 1045925. This study was designed to assess the acute toxicity and antidiabetic activity of the Ethanolic extract of Phyllanthus niruri (EEPN). Several in vivo studies have demonstrated that extracts of Phyllanthus niruri have significantly lowered blood glucose levels and lowered the complications associated with Type 2 diabetes in rodents, but to date, no studies have been reported using the zebrafish model for antidiabetic activity using Phyllanthus niruri. In the present study, zebrafish are divided into six groups and given doses of 6, 12, 25, 50, 100, 200, and 400 mg/ L of EEPN for extraction. These fish are then examined at intervals of 6, 24, 48, and 72 hours. 30 zebra fish were divided into control and treatment groups to evaluate their anti-diabetic activity. For 30 days, a high-glucose diet was used to induce diabetes in all zebrafish. The test groups are treated with concentrations of the extracts 25mg/L & 50mg/L and standard with 20mM metformin. The blood glucose levels were estimated on alternative days for seven days and on the seventh day fish were studied histopathologically. Acute toxicity study of EEPN does not show any mortality, morbidity, or behavioral changes even after 96 hrs at a maximum concentration of 400 mg/ L. The extract showed a significant lowering of blood glucose levels in diabetic zebra models. Extensive studies can be done on the extract to study the natural lead compounds from this plant which are responsible for antidiabetic activity.
• Mukherjee, Mithun & Gupta, Sharmistha. (2018). Evaluation of acute toxicity and anti-asthmatic activity of Phyllanthus niruri L. leaves extracts. Asian Journal of Pharmacy and Pharmacology. 4. 615- 619. 10. 31024/ app. 2018. 4. 5. 11.
• Raja, Wasim & Dubey, Amit & Patel, Mahesh. (2019). Anti-tumour Activity of Phyllanthus Niruri Root Extract Against 7, 12- Dimethylbenz (A) Anthracene Induced Mouse Skin Carcinogenesis. European Journal of Pharmaceutical Sciences. 4. 471- 477. Chemoprevention is an important strategy to control the process of carcinogenesis. The potential of using medicinal herbs as cancer chemo-preventive nutraceuticals and functional food is promising. Thus, there is a need for exploring drugs/agents that act as chemo-preventive agents. Phyllanthus niruri is a well-known medicinal plant that has been used in Ayurvedic medicine as hepatoprotective, antiviral, antibacterial, analgesic, antispasmodic, and antidiabetic. In the present investigation, the anticancer activity of Phyllanthus niruri root extract was evaluated using two-stage skin carcinogenesis in Swiss albino mice, induced by a single application of 7, 12- dimethyadenz- anthracene (104 μg/ 100 μl acetone) and one week later, promoted by repeated application of croton oil (1 % in acetone/thrice a week) till the end of the experiment (16 weeks). The tumor incidence, tumor yield, tumor Burden, and cumulative number of papillomae were found to be higher in control (without Phyllanthus niruri treatment) as compared to experimental animals (Phyllanthus niruri treated). The difference in the values of the results of the experimental group was statistically analyzed and found to be significant in comparison to the control group (p< 0.05). The results thus suggest that P. niruri extract exhibits significant anti-tumor activity, which supports the traditional medicinal utilization of this plant. In conclusion, the present study demonstrates the chemopreventive of Phyllanthus niruri root extract on DMBA-induced skin tumorigenesis in Swiss albino mice.

Recent Research on Phyllanthus amarus

• Pramyothin, Pornpen & Ngamtin, Chanon & Poungshompoo, Somlak & Chaichantipayuth, Chaiyo. (2007). Hepatoprotective activity of Phyllanthus amarus Schum. Et. Thonn. Extract in ethanol-treated rats: In vitro and in vivo studies. Journal of Ethnopharmacology. 114. 169- 73. 10. 1016/ j. jep. 2007. 07. 037. The present study was undertaken to investigate the protective effect and possible mechanism of aqueous extract from Phyllanthus amarus Schum. Et. Thonn. (PA) on ethanol-induced rat hepatic injury. In the in vitro study, PA (1- 4 mg/ ml) increased % MTT reduction assay and decreased the release of transaminases (AST and ALT) in rat primary cultured hepatocytes being treated with ethanol. Hepatotoxic parameters studied in vivo included serum transaminases (AST and ALT), serum triglyceride (STG), hepatic triglyceride (HTG), tumor necrosis factor-alpha (TNF- alpha), interleukin 1 beta (IL- 1 beta), together with histopathological examination. In an acute toxicity study, a single dose of PA (25, 50, and 75 mg/ kg, p.o.) or SL (silymarin, a reference hepatoprotective agent, 5 mg/ kg), 24h before ethanol (5 g/ kg, p.o.) lowered the ethanol-induced levels of transaminases (AST and or ALT). The 75 mg/ kg PA dose gave the best result similar to SL. Treatment of rats with PA (75 mg/ (kg day), p.o.) or SL (5 g/ (kg day), p.o.) for 7 days after 21 days with ethanol (4 g/ (kg day), p.o.) enhanced liver cell recovery by bringing the levels of AST, ALT, HTG and TNF- alpha back to normal. Histopathological observations confirmed the beneficial roles of PA and SL against ethanol-induced liver injury in rats. Possible mechanisms may involve their antioxidant activity.
• P., Saranraj. (2012). Screening of Antibacterial Activity of the Medicinal Plant Phyllanthus amarus Against Urinary Tract Infection Causing Bacterial Pathogens. Applied Journal of Hygiene. 1. Urinary tract infections (UTI) are one of the most commonly occurring infections in hospitals. However, microorganisms causing UTIs vary in their susceptibility from place to place and from time to time. In this present study, the herbal plant Phyllanthus amarus was tested for its antibacterial activity against urinary tract infection-causing bacterial isolates viz., Staphylococcus aureus, Serratia marcescens, Escherichia coli, Enterobacter sp., Streptococcus fecalis, Klebsiella pneumoniae, Proteus mirabilis and Pseudomonas aeruginosa. The Phyllanthus amarus was shade-dried and extracted with methanol, acetone, chloroform, petroleum ether, and hexane. The antibacterial activity of Phyllanthus amarus was determined by the agar well diffusion method. It was found that the methanol extract of Phyllanthus amarus showed the highest inhibitory activity against UTI-causing bacterial pathogens when compared to other solvent extracts. From this, it was concluded that the solvent methanol can leach out antimicrobial principles more effectively from the plant than the other solvents. Phytochemical analysis showed the presence of alkaloids, flavonoids, phenols, and triterpenes.
• Lira, Dilshad & Uddin, Aftab & Uddin, Mohi & Rouf, Abu. (2014). Assessment of cytotoxic activities of Phyllanthus amarus and Monstera deliciosa. Journal of Applied Pharmaceutical Science. 4. 110 – 113. 10. 7324/ JAPS. 2014. 40719. Medicinal plants constitute an important component of flora and are widely distributed in Bangladesh. The pharmacological evaluation of substances from plants is an established method for the identification of lead compounds which shows the way to the development of novel and safe medicinal agents. Based on ethnopharmacological literature two widely used medicinal plants Phyllanthus amarus and Monstera deliciosa were chosen to investigate their cytotoxicity through brine shrimp lethality bioassay which is a simple, reliable, and convenient method for assessment of the bioactivity of medicinal plants. The plants were collected from their natural habitat, dried under shade, and extracted with ethyl acetate. In this study, ethyl acetate extract of Phyllanthus amarus exhibited potent cytotoxicity with LC50 values of 9.15 μg/ ml and 20.16 μg/ ml of leaves and the whole plant respectively. Monstera deliciosa exhibited cytotoxicity with LC50 values of 36.60 μg/ ml and 300.4 μg/ ml of leaves and branches respectively. From the result, it can be predicted that extractives of Phyllanthus amarus possess cytotoxic principles and showed significantly more potency in leaves rather than whole plants. In the case of Monstera deliciosa the extractives of leaves exhibited very mild mortality while the extractives of branches did not show considerable cytotoxicity.
• Pathak, Manish & Singh, U & Upadhyay, Gaurav. (2017). ANTIBACTERIAL ACTIVITY OF PHYLLANTHUS AMARUS PLANT EXTRACT AGAINST RESISTANT PATHOGENIC BACTERIAL STRAINS: AN ETHANOMEDICINAL PLANT. Objective: To evaluate the antimicrobial activity of Phyllanthus amarus plant extract against resistant pathogenic bacterial strains. Methods: Aqueous and acetone extract of Phyllanthus amarus (Family: Euphorbiaceae) was studied against resistant pathogenic bacterial strains (Bacillus subtilis, Staphylococcus aureus, Enterococcus fecalis, Salmonella typhi, Salmonella paratyphi B, Proteus vulgaris and Serratia marsescens by disc diffusion method comparable to that of a standard antibacterial Lomefloxacin. Result: Aqueous extract showed 57 % efficiency in inhibiting the pathogenic isolates while acetone extract showed 29 % efficiency. Conclusion: Phyllanthus amarus aqueous extract was found to be anti-microbially more effective than the acetone extract.
• Lim, Yau & Murtijaya, J. (2007). Antioxidant properties of Phyllanthus amarus extracts as affected by different drying methods. LWT – Food Science and Technology. 40. 1664- 1669. 10. 1016/ j. lwt. 2006. 12. 013. The total phenolic content (TPC) and antioxidant activity of fresh and dried Phyllanthus amarus plant materials were evaluated using the Folin-Ciocalteau method, 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) free radical scavenging activity and ferric reducing antioxidant power (FRAP) assays. Different drying treatments led to a significant reduction (P< 0.05) in the antioxidant properties of P. amarus methanolic extracts, with microwave drying causing the highest decrease in TPC and antioxidant activity exhibited by the reduction in both radical scavenging activity and FRAP. On the other hand, boiling water extracts appeared to exhibit significantly stronger antioxidant potentials (P< 0.05) even in dried plant materials due to greater solubility of compounds, breakdown of cellular constituents as well as hydrolysis of tannins. Its strong free radical scavenging activity suggests that it has great potential in the food industry as a functional food ingredient.
• Sen, A. & Batra, A. (2013). The study of in vitro and in vivo antioxidant activity and total phenolic content of Phyllanthus amarus Schum. & Thonn.: A medicinally important plant. International Journal of Pharmacy and Pharmaceutical Sciences. 5. 942- 947. The presence of natural antioxidant activity in plants has been well-acknowledged worldwide. There is an increasing demand for natural antioxidants to replace synthetic additives in the food and Pharmacological industries. Phyllanthus amarus Schum. & Thonn., commonly known as Buhi amla, is also one of the traditionally used medicinal plants. The main goal of this study is to determine the free radical scavenging properties screened for different in vivo and in vitro plant extraction of Phyllanthus amarus Schum. & Thonn. Free radical scavenging activity was evaluated using the 1, 1- diphenyl- 2-picrylhydrazyl (DPPH) method. In vitro, callus was induced using internodal explant on MS medium fortified with 2, 4-D (0.6 mg/ l). The analysis was carried out for in vivo plant and in vitro callus to determine the quantitative phenolic content along with the antioxidant activity of different plant extracts. The result of the present study showed that the methanol extract of Phyllanthus amarus Schum. & Thonn. Contains the highest number of phenolic compounds and exhibits the greatest antioxidant activity in comparison to other extracts. It has been observed that the vitro plant extract shows more Phenolic contents and reveals better antioxidant activity as compared to in vivo plant extraction.
• Abankwa, Joseph & Eunice, Dotse & Appiah-Opong, Regina & Nyarko, Alexander. (2020). Antioxidant and anti-prostate cancer activities of Moringa oleifera, Phyllanthus amarus, and Carica papaya. Health Sciences Investigations Journal. 24- 30. 10. 46829/ hsijournal. 2020. 6. 1. 1. 24- 30. Background: Globally, interest in herbal medicines is increasing. In Ghana, most herbalist use herbal medicines for the treatment of various ailments including prostate cancer, although no empirical evidence on their efficacies exists. Objective: The present study aimed to test the antioxidant and anti-prostate cancer activities of Moringa oleifera, Phyllanthus amarus, and Carica papaya. Methods: Plants parts used were air-dried, ground, and sequentially extracted using solvents with increasing order of polarity (petroleum ether, dichloromethane, ethyl acetate, ethanol, and aqueous). The 2, 2- diphenyl- 1- picryl- hydrazyl assay, Folin Ciocalteu method, and tetrazolium-based calorimetric assay were used to determine total antioxidant capacities, total phenolic content of extracts and cytotoxicity of the LNCaP and PC3 prostate cancer cells, respectively. Results: The ethanolic extract of P. amarus possessed the highest phenolic content while its aqueous extract showed the strongest antioxidant activity (EC50= 19.32 ± 1.13 μg/ mL). Aqueous extract of C. papaya exhibited anti-prostate cancer activity with good selectivity towards PC3 cells [IC50= 45.68 ±1.16 μg/ mL, selectivity index (SI) =18], whereas dichloromethane extract of P. amarus showed the strongest anticancer activity against LNCaP cells (IC50= 43.97±1.14 μg/ mL). Conclusion: These findings lend pharmacological credence to the anecdotal evidence of the anti-prostate cancer properties of the plants. Further studies must be performed to identify the active principles in the bioactive plant components.
• Nagarajan, Srividya & Sushma, Periwal. (1995). Diuretic, hypotensive, and hypoglycaemic effects of Phyllanthus amarus. Indian journal of experimental biology. 33. 861- 864. Diuretic, hypotensive, and hypoglycaemic effects of Phyllanthus amarus (syn. Phyllanthus niruri) on human subjects were assessed. Nine mild hypertensives (four of them also suffering from diabetes mellitus) were treated with a preparation of the whole plant of P. amarus for 10 days. Suitable parameters were studied in the blood and urine samples of the subjects, along with physiological profiles and dietary patterns before and after the treatment period. A significant increase in 24 hr urine volume, urine, and serum Na levels was observed. A significant reduction in systolic blood pressure in non-diabetic hypertensives and female subjects was noted. Blood glucose was also significantly reduced in the treated group. Clinical observations revealed no harmful side effects.
• Yao, Alain & Kamagate, Mamadou & Amonkan, Augustin & Camille, Koffi & N, Mathieu & Kouame, Goran & Die- Kakou, Henri & Kpahe, Fidele & Mathieu, Kouame. (2016). Comparative effects of aqueous extract of Phyllanthus amarus and its fractions on urinary excretion in rat. The Journal of Phytopharmacology. 5. 182- 184. 10. 31254/ phyto. 2016. 5503. The present study aimed to compare the effect of Phyllanthus amarus extracts and their fractions on urinary excretion. The aqueous extract of Phyllanthus amarus was prepared by a decoction of the whole plant and lyophilized. Ethanolic fraction and chloroformic fraction of Phyllanthus amarus were obtained from aqueous extract. Animals were divided into 5 groups of 6 rats and placed individually in metabolic cages. The control group received normal water. A positive control group received furosemide (5 mg/ kg, i.p.), used as a reference loop diuretic drug. Three other groups were treated with aqueous extract or ethanolic fraction or chloroformic fraction of Phyllanthus amarus by intraperitoneal injection at the same dose of 40 mg/  kg. Urine volumes were collected each 2 h during an 8 h period. The diuretic action was obtained by a ratio of urinary excretion of the treated group and that of the control group. Phyllanthus amarus extracts increased urinary excretion. This effect was time-dependent and significant, compared to the control group (p <  0.001). During all experiments, ethanolic fraction increased urinary excretion, more than other extracts. After 8-hour periods, it had eliminated about 2.44 ± 0.27 mL, however, this value remained less than that of furosemide (3.01 ± 0.17 mL). The urinary excretion induced by furosemide was significantly high (p < 0.05), compared to ethanolic fraction, but the ratio was similar. This study showed that, like furosemide, ethanolic fraction seemed to be the most potent extract for diuresis. Further studies might be carried out to identify the active molecules and their mechanisms.
• Mbagwu, Herbert & Jackson, Clement & Jackson, Idongesit & Ekpe, Godwin & Eyakekop, Udeme. (2011). Evaluation of the hypoglycemic effect of aqueous extract of Phyllanthus amarus in alloxan-induced diabetic albino rats. Journal of Pharmaceutical and Biomedical Research. 2. The hypoglycemic potential of aqueous extract of Phyllanthus amarus Schum was investigated in alloxan-induced diabetic albino rats. The extract at a dose of 260 mg/ kg produced a significant (P< 0.05) reduction in blood glucose level by 112 % at 24 h of oral administration. At 390 mg/  kg, a significant reduction (P< 0.05) in blood glucose levels of 102 % (6 h) and 82% (24 h) was observed. A significant reduction (P< 0.01) in blood glucose levels of 81% and 61% (day 7) at doses of 130 and 260 mg/kg of extract respectively were observed. The extract also a highly significant (P< 0.001) decrease in blood glucose levels of 38% and 30% (day 14) at doses of 130 and 260 mg/ kg respectively. On the administration of a 390 mg/kg dose of extract, a significant reduction (P< 0.001) in blood glucose levels of 41 % on day 7 and 16 % on day 14 was observed. The above results indicate the presence of hypoglycemic constituents in the plant, Phyllanthus amarus Schum.
• Bolanle, Iranloye & Owoyele, Bamidele & Kelani, O & Olaleye, Samuel. (2011). Analgesic activity of aqueous leaf extract of Phyllanthus amarus. African journal of medicine and medical sciences. 40. 47- 50. Various doses of the aqueous extract of Phyllanthus amarus (AEPA) were investigated for analgesic and anti-inflammatory activities using both thermal and chemical models of pain assessment in rats. The extract caused a significant (P < 0.05) dose-related increase in inhibition of the carrageenan-induced paw edema in the rats. The inhibition produced by 200 mg/kg AEPA (70.20 %) was significantly higher than that of the reference drug (Acetylsalicylic acid). The extract produced a marked analgesic activity by inhibiting both early and late phases of pain stimulus in Formalin-induced paw-licking rats and also a significant and dose-related increase in inhibiting the mean tail immersion duration (MITD) at varying water bath temperature (50 degrees C, 55 degrees C, and 60 degrees C). This study thus established the anti-inflammatory and analgesic activities of Phyllanthus amarus.
• Shokunbi, Olutayo & Odetola, A. (2008). Gastroprotective and antioxidant activities of Phyllanthus amarus extract absolute ethanol-induced ulcer in albino rats. Journal of Medicinal Plants Research. 2. 261- 267. This study was designed to evaluate the gastroprotective and antioxidant effects of aqueous and acetone extracts of Phyllanthus amarus leaves in albino rats. P. amarus extracts (500 and 1000 mg/ Kg), as well as cimetidine (100 mg/Kg), were administered orally once a day for two weeks before challenge with absolute ethanol (1 ml/ 200 g body weight). Pretreatment with P. amarus aqueous extract (500 mg/ Kg) and cimetidine inhibited the ulceration damage of absolute ethanol by 59.3 and 41.2 % and decreased the serum alanine aminotransferase (ALT) by 35 %, 24 % and aspartate aminotransferase (AST) by 7 and 6 % respectively. The acetone extract (1000 mg/ Kg) also significantly increased (P < 0.01) the absolute ethanol-mediated decrease in the activities of gastric mucosal catalase (CAT), superoxide dismutase (SOD), and glutathione-s-transferase (GST) by 53, 8 and 33% respectively. Cimetidine respectively caused 52, 14, and 38 % significant (P< 0.01) increases in the absolute ethanol-induced decrease in the activities of CAT, SOD, and GST. Furthermore, P. amarus aqueous extract (500 mg/ Kg) and cimetidine were noted to increase the activities of liver CAT by 18 and 20 %, SOD by 25 and 19 %, and GST by 122 and 54 % respectively. However, the liver thiobarbituric acid reacting substances (TBARS) values of all the groups pretreated with P. amarus extracts and cimetidine were not significantly different (P < 0.05) from the ethanol group. In this study, P. amarus extracts appear to act as an in vivo natural antioxidant and an effective gastroprotective agent that is as effective as cimetidine. P. amarus may also offer protection against the toxic effects of alcohol on the liver.
• Pingale, S. S. & Shewale, S. S. (2011). Acute toxicity study of Phyllanthus amarus. International Journal of Pharmaceutical Sciences Review and Research. 9. 81-84. The study was designed to examine the acute toxicity of Phyllanthus amarus. Aerial parts of Phyllanthus amarus were collected from Avsari Forest Park, and the fresh juice of aerial parts was prepared and used for study. The acute toxicity study is carried out as per OECD guidelines in Swiss mice weighing 35 to 50 gm. The dose of 2, 4, 6, and 8gm/kg body weight plant material was administered orally in the form of aqueous slurry. The groups were almost continuously observed for mortality and behavioral changes firstly for 24 hrs and then for daily fortnight. The observations of changes in body weight, food and water intake as well as cage side observations were reported. There was no abnormality observed in any of these three groups. The results provide evidence that Phyllanthus amarus plant material was found to be nontoxic.
• Ranjita, (2020). Acute toxicity study and phytochemical screening of Phyllanthus amarus ethanolic extract on Wistar albino rats. IP International Journal of Comprehensive and Advanced Pharmacology. 5. 84-86. 10.18231/j.ijcaap.2020.018.
• Noor, Nur & Nafiah, Mohd & Hasnan, Muhammad Hafiz Husna & Tan, Siow-Ping & Yee, Liew. (2019). Anticancer Effect of Hypophyllanthin, Niranthin, and Lintetralin from Phyllanthus amarus on HeLa Cells And NIH/ 3T3 Cells. International Journal of Engineering and Technology. 8. 106- 110. 10. 35940/ ijrte. B1024. 0782S719. Phyllanthus amarus which is locally known as Dukung Anak was one of the herbs used in traditional medicine and research on P. amarus in Malaysia was not widely reported. This present research has isolated three chemical compounds, and their anticancer effect on this species has been determined. Three lignans, namely hypophyllanthin were afforded from hexane crude while niranthin and lintetralin were afforded from ethanol crude. Anticancer test against HeLa cells and NIH/ 3T3 cells by MTT assays was tested for its anticancer effect. The result shows that hypophyllanthin was considered to possess an active anticancer effect on HeLa cells than NIH/ 3T3 cells compared to niranthin and lintetralin.
• Ezedom, Theresa & Onyesom, I. & Awhin, Prosper & Elu, Chinwendu & Acha, Joy. (2023). PROFILING OF PHYLLANTHUS AMARUS PHYTOCHEMICAL CONSTITUENTS AND EVALUATION OF ASSOCIATED ANTIMALARIAL ACTIVITY AND ANTIOXIDANT POTENTIAL IN EXPERIMENTAL MICE. EPH – International Journal of Biological & Pharmaceutical Science. 9. 4- 12. 10. 53555/ eijbps. v9i1. 40. The failing curative ability of antimalarials has prompted an open discussion about the use of antioxidants in combination with antimalarials for effective chemotherapy. This study profiled the phytochemical constituents of Phyllanthus amarus and evaluated their antimalarial and antioxidant activities. Phytochemical screening, antimalarial, and acute oral toxicity were determined according to standard procedures. Blood antioxidant activity was assessed by measuring antioxidant enzymes and nitric oxide (NO), concentrations of malarial-infected mice treated with P. amarus phytochemicals. Alkaloids, the most abundant phytochemical, demonstrated the highest malarial parasite chemosuppression and greatly improved NO concentration in infected mice. However, flavonoid extract demonstrated the highest antioxidant potential with the most significant impact on catalase and malondialdehyde activity. Alkaloids may function as antimalarial agents by inhibiting haem polymerization to hemozoin as judged by its increased effect on NO concentration which bears a reverse relationship with hemozoin.
• Pammi, S. & Giri, Archana. (2021). In vitro cytotoxic activity of Phyllanthus amarus Schum. & Thonn. World Journal of Biology Pharmacy and Health Sciences. 6. 034- 042. 10.30574/wjbphs.2021.6.2.0050. Some bioactive compounds from plants are excellent sources of anticancer drugs. These natural phytochemicals are used in active research for cancer prevention and treatment. In our present study, invitro anticancer activity was evaluated using dimethylformamide leaf extract of Phyllanthus amarus as its GC- MS analysis revealed many active principles that exhibited good antimicrobial and antioxidant properties. There were reports that anti-proliferative activity is always coupled with antioxidant activity. Anti-cancer activity of the P. amarus leaf extract was tested against HCT 15 and T47D cell lines and the inhibitory effect on the HCT 15 cell line was found to be greater than the T47D cell line. With the increasing concentration of extract, the percentage of viability of cell lines was found to decrease for both cell lines. The anticancer activity of the leaf extract of P. amarus is comparable to the positive control drug doxorubicin. N- Hexadecanoic acid, lignans, and polyphenol compounds in leaf extract may be responsible for the anticancer activity. These phytochemicals block cancer cell propagation by controlling cancer stem cells and can influence all the stages of cancer development effectively.