Cytotoxic Lignan from the Non-Transformed Root Culture of Phyllanthus amarus.
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ABSTRACT:
SUBMITTER: Sparzak B
PROVIDER: S-EPMC6272180 | biostudies-literature | 2015 Apr
REPOSITORIES: biostudies-literature
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Project description:Two new (1 and 2) and four known arylnaphthalene lignan lactones (3-6) were isolated from different plant parts of Phyllanthus poilanei collected in Vietnam, with two further known analogues (7 and 8) being prepared from phyllanthusmin C (4). The structures of the new compounds were determined by interpretation of their spectroscopic data and by chemical methods, and the structure of phyllanthusmin D (1) was confirmed by single-crystal X-ray diffraction analysis. Several of these arylnaphthalene lignan lactones were cytotoxic toward HT-29 human colon cancer cells, with compounds 1 and 7-O-[(2,3,4-tri-O-acetyl)-?-L-arabinopyranosyl)]diphyllin (7) found to be the most potent, exhibiting IC50 values of 170 and 110 nM, respectively. Compound 1 showed activity when tested in an in vivo hollow fiber assay using HT-29 cells implanted in immunodeficient NCr nu/nu mice. Mechanistic studies showed that this compound mediated its cytotoxic effects by inducing tumor cell apoptosis through activation of caspase-3, but it did not inhibit DNA topoisomerase II? activity.
| S-EPMC4073661 | biostudies-literature
Project description:Phyllanthus amarus is widely grown in this sub-continent and used traditionally to treat many common ailments. In the present study, lignan rich fraction of P. amarus extract was used on cervical cancer cell lines (HeLa, SiHa and C33A) to study it's mechanism of cell death induction. As the cells were treated with IC50 doses of LRF, characteristic apoptotic features were observed. Increased sub G0 population were observed both in Hela and C33 cells, while G1/S arrest was observed in SiHa cells than their untreated counterparts. Increased production of ROS and change in MMP were also detected in the treated cells. Presence of ?H2AX, was observed by immunofluorescence. Reduced expression of HPV (16/18) as well as ET-1, an autocrine growth substance, were observed in the treated cells. Immunoblotting as well as ICFC studies showed enhanced expressions of BAX, Caspase 3 and PARP (cleaved) in the treated cells. A major lignan, phyllanthin was isolated from the chloroform fraction and showed strong irreversible affinities for viral E6 and MDM2 in in silico analysis. The study conclusively indicates that LRF has the potential to induce apoptotic cell death in cervical cancer cells by activation of p53 and p21 against DNA damage.
| S-EPMC6802087 | biostudies-literature
Project description:The present study was aimed to evaluate adaptive mechanism in terms of seed characters of Phyllanthus amarus collected from ten different locations of Tamil Nadu, India. The adaptive variations among the collected populations were assessed based on the sink and float percentages of the seeds in water, the percentage of seed germination, total protein, carbohydrates and their seedling's growth ability such as shoot and root lengths. From this, we observed that the population had a significantly higher germination percentage of sinking seeds that were attributed to its relatively higher carbohydrate and protein contents than the floating seeds. A comparison of the seed population by cluster analysis and principal coordinate analysis showed that the Chennai population constituted a single clade that was very distinct from the other nine populations, which were further grouped into two sub-clusters. They exhibited a trend consistent with their geographical proximity. Standardised Mantel's t tests had revealed that the adaptive diversity of the P. amarus population was significantly affected by the geographic distance (r = 0.78, t = 2.68, P > 0.001), altitude (r = 0.35, t = 21.53, P > 0.05), minimum temperature (r = 0.43, t = 1.49, P > 0.01) and maximum temperature (r = 0.49, t = 1.67, P > 0.001). Seed's characteristics and geographical conditions were correlated along with 19 bioclimatic variables. In dry season, the seedling's rooting ability showed positive correlation, while its protein content exhibited a negative correlation. It is clearly evident from this study that the geographical variables significantly influence the adaptive ability of the P. amarus.
| S-EPMC5893483 | biostudies-literature
Project description:This is the first report on identification and quantification of important hepatoprotective and anticancer polyphenolic lignans such as phyllanthin (PH), hypophyllanthin (HPH), niranthin (NH) and phyltetralin (PT) in natural plant and in vitro cultures of Phyllanthus tenellus Roxb. The identification of lignans was carried out by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS) and quantified using High-Performance Liquid Chromatography (HPLC). In addition, an efficient protocol has been developed for multiple shoot induction in nodal explants of in vitro derived shoots of P. tenellus. Maximum number of shoot regeneration (7.83 ± 0.15) was achieved on medium incorporated with 1.0 mg/l 6-Benzylaminopurine (BAP). The medium containing Indole-3-acetic acid (IAA) 2 mg/l was superior for induction of rooting in in vitro raised shoots. The plantlets were acclimatized to the field condition with 100% survival. The quantitative HPLC analysis showed that the lignan content was variable with the auxins and cytokinins incorporated in the medium. The lignan content was higher in callus grown on Murashige and Skoog (MS) medium + 2.0 mg/l Naphthaleneacetic acid (NAA). The reported protocol can be used for mass propagation and application of biotechnological approaches for improvement of P. tenellus. The results indicate intriguing possibilities for the utilization of P. tenellus plant parts as an alternative source and of callus culture to scale up bioactive lignan production for pharmaceutical applications.
| S-EPMC7327055 | biostudies-literature
Project description:Despite modern medicine, there is an increasing trend for cases of the bacterial infection leptospirosis, and this has led to the exploration of alternative medicines from various sources including plants. The aim of this study was to investigate the in vitro anti-leptospiral activity of Phyllanthus amarus extracts alone and combined with penicillin G, ceftriaxone, and doxycycline. Antimicrobial susceptibility testing was performed using the microdilution broth technique upon methanol extract (ME), aqueous extract (AE), and antibiotics against the Leptospira interrogans serovars Australis, Bataviae, Canicola, and Javanica, to determine minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). The results were analyzed using an ELISA microplate reader combined with microscopic analysis. Synergy testing using a checkerboard assay was performed to determine the fractional inhibitory concentration index values of extracts combined with antibiotics against leptospires. Scanning electron microscopy (SEM) was used to investigate morphological changes of leptospires caused by potential anti-leptospiral agents alone and combined with antibiotics. The MICs and MBCs for P. amarus extracts ranged from 100 to 400 µg/mL for AEs and from 400 to 800 µg/mL for MEs. Penicillin G was the most effective anti-leptospiral drug, with MICs and MBCs ranging from <0.01 to 0.78 and <0.01 to 3.13 µg/mL, respectively, followed by ceftriaxone, with both MICs and MBCs ranging from 0.05 to 0.78 µg/mL, and doxycycline, with MICs and MBCs ranging from 0.39 to 3.13 µg/mL and 12.5 to 25 µg/mL, respectively. Combinations of P. amarus extracts and antibiotics did not show synergistic effects on all tested Leptospira serovars, with some combinations demonstrating antagonistic effects. SEM analysis, however, showed distorted Leptospira surfaces. P. amarus AE performed better anti-leptospiral activity than P. amarus ME. The morphological effects of P. amarus extract alone and its combination with antibiotic on Leptospira cells revealed promising anti-leptospiral properties.
| S-EPMC7998951 | biostudies-literature
Project description:Phyllanthus amarus Schum. and Thonn., a globally distributed herb is known for its several therapeutic potentials. P. amarus has a long history of use in the traditional system of medicine for over 2000 years owing to its wide array of secondary metabolites that confer significant medicinal attributes. Research on various aspects including ethnobotany, phytochemistry to bioactivity, or pharmacological studies has been conducted over the past several decades on this potent herb. P. amarus extracts have shown a broad range of pharmacological activities like hepatoprotective, antioxidant, antiviral, antimicrobial, antidiabetic, anti-inflammatory, anticancer, antimalarial, nephroprotective, diuretic, and several other properties. The present review compiles and covers literature and research of several groups across past decades to date and focuses on how the therapeutic significance of this plant can be further explored for future research either as herbal formulations, alternative medicine, or in the pharmaceutical industry.Supplementary informationThe online version contains supplementary material available at 10.1007/s13237-022-00409-z.
| S-EPMC9660160 | biostudies-literature
Project description:Phyllanthus amarus (Schum & Thonn), a plant belonging to the family of Euphorbiaceae is used in Ivorian traditional medicine to treat cardiovascular disorders such as hypertension. However, although this plant has been described as a diuretic agent, the underlying mechanism remains unclear. Therefore, the aim of the present study was to investigate the mechanism action of diuretic effects of an ethanolic fraction of Phyllanthus amarus (EFPA) in rats.Effects of EFPA on urinary excretion were carried out for doses ranging from 5 to 80 mg/kg given by intraperitoneal injection (i.p.) and compared with that induced by furosemide (5 mg/kg) after 8 h. Thereafter, the diuretic activity of EFPA was also evaluated in the presence of indomethacin (5 mg/kg, i.p.) in order to determine the involvement of prostaglandins, after 24 h.Between 5 and 80 mg/kg, EFPA induced a significant urinary excretion. The profile of urinary excretion showed that after 2 h, the highest dose of 80 mg/kg induced a urinary volumetric excretion (UVE), which was similar to that induced by furosemide. After 24 h, EFPA at 10 mg/kg increased significantly UVE, Na+ (43 mEq) and Cl¯ (97 mEq) urinary excretions without promoting kaliuresis. In rats pretreated with indomethacin, the urinary excretion and the natriuretic response of EFPA were significantly reduced.Altogether, this study has shown that EFPA promotes a significant urinary excretion of water and Na+, confirming its diuretic activity. Moreover, the increased diuresis could be attributed, at least in part, to the involvement of prostaglandins.
| S-EPMC5856278 | biostudies-literature
Project description:Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.
| S-EPMC7865555 | biostudies-literature
Project description:Background: Phyllanthus amarus (PA) is widely studied for its hepatoprotective properties but has recently received increasing attention due to its diverse anti-inflammatory effects. However, the effects of PA in modulating immune responses in the central nervous system leading to protection against functional changes remain unexplored. Therefore, we sought to examine the protective effects of 80% v/v ethanol extract of PA on lipopolysaccharide (LPS)-induced non-spatial memory impairment and neuroinflammation. Methods: Selected major phytoconstituents of PA extract were identified and quantified using high-performance liquid chromatography. Subchronic neurotoxicity was performed in male Wistar rats given daily oral administration of 100, 200, and 400 mg/kg of the PA extract. Their neurobehavioral activities (functional observation battery and locomotor activity) were scored, and the extracted brains were examined for neuropathological changes. Rats were treated orally with vehicle (5% Tween 20), PA extract (100, 200, and 400 mg/kg), or ibuprofen (IBF; 40 mg/kg) for 14 and 28 days before being subjected to novel object discrimination test. All groups were challenged with LPS (1 mg/kg) given intraperitoneally a day prior to the behavioral tests except for the negative control group. At the end of the behavioral tests, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, nitric oxide (NO), inducible nitric oxide synthase (iNOS), CD11b/c integrin expression, and synaptophysin immunoreactivity were determined in the brain tissues. Results: Gallic acid, ellagic acid, corilagin, geraniin, niranthin, phyllanthin, hypophyllanthin, phyltetralin, and isonirtetralin were identified in the PA extract. Subchronic administration of PA extract (100, 200, and 400 mg/kg) showed no abnormalities in neurobehavior and brain histology. PA extract administered at 200 and 400 mg/kg for 14 and 28 days effectively protected the rodents from LPS-induced memory impairment. Similar doses significantly (p < 0.05) decreased the release of proteins like TNF-α, IL-1β, and iNOS in the brain tissue. NO levels, CD11b/c integrin expression, and synaptophysin immunoreactivity were also reduced as compared with those in the LPS-challenged group. Conclusion: Pre-treatment with PA extract for 14 and 28 days was comparable with pre-treatment with IBF in prevention of memory impairment and alleviation of neuroinflammatory responses induced by LPS. Further studies are essential to identify the bioactive phytochemicals and the precise underlying mechanisms.
| S-EPMC6558432 | biostudies-literature
Project description:Phyllanthus amarus, also known as Bhui Korma in India, is well known for its medicinal properties and is used to treat several diseases worldwide. This study aims to identify phytochemicals from P. amarus and assess their anti-viral activity through in silico methods against the main protease (3CLPro/MPro) enzyme of the novel coronavirus. 190 compounds were obtained from literature and docked against 3CLPro and 16 compounds showed higher binding affinity with 3CLPro with their values lying between -8.9 kcal/mol to -9.6 kcal/mol. The top two compounds, Myricitrin (CID: 5352000) and Quercetin-3-O-glucuronide (CID: 12004528) gave high binding affinity values of -9.6 kcal/mol and -9.4 kcal/mol respectively and also display favourable binding interactions with the 3CLPro. Both the compounds were further subjected to molecular dynamics simulation and MM-PBSA based binding free energy calculations. ADMET and drug-likeness properties were studied to assess the pharmacokinetic properties of the compounds. Favourable pharmacokinetic results reinforced the applicability of the compounds assessed. Along with continuous studies being carried out with chemical compounds, research needs to expand into all areas, including the use of natural compounds as drug compounds. The identified hits from this study can be taken further for in vitro and in vivo studies to examine their efficacy against COVID-19. Graphical abstract Image 1
| S-EPMC8364217 | biostudies-literature