Phyllanthus amarus: ethnomedicinal uses, phytochemistry and pharmacology: a review

Ethnopharmacological relevance

Phyllanthus amarus Schum. &; Thonn. belongs to the family Euphorbiaceae is a small herb well known for its medicinal properties and widely used worldwide. P. amarus is an important plant of Indian Ayurvedic system of medicine which is used in the problems of stomach, genitourinary system, liver, kidney and spleen. It is bitter, astringent, stomachic, diuretic, febrifuge and antiseptic. The whole plant is used in gonorrhea, menorrhagia and other genital affections. It is useful in gastropathy, diarrhoea, dysentery, intermittent fevers, ophthalmopathy, scabies, ulcers and wounds.

Materials and methods

The present review covers a literature across from 1980 to 2011. Some information collected from traditional Ayurvedic texts and published literature on ethanomedicinal uses of Phyllanthus amarus in different countries worldwide.

Results

Phytochemical studies have shown the presence of many valuable compounds such as lignans, flavonoids, hydrolysable tannins (ellagitannins), polyphenols, triterpenes, sterols and alkaloids. The extracts and the compounds isolated from P. amarus show a wide spectrum of pharmacological activities including antiviral, antibacterial, antiplasmodial, anti-inflammatory, antimalarial, antimicrobial, anticancer, antidiabetic, hypolipidemic, antioxidant, hepatoprotective nephroprotective and diurectic properties.

Conclusion

The present review summarizes information concerning the morphology, ecology, ethnopharmacology, phytochemistry, biological activities, clinical applications and toxicological reports of P. amarus. This review aims at gathering the research work undertaken till date on this plant in order to provide sufficient baseline information for future works and commercial exploitation.     

Evidence that the repair deficient mei-9a female in drosophila melanogaster is a strong potentiator of chromosome loss induced in the paternal genome by dimethyinitrosamine

From matings of X^c2/B^sYy⁺ males treated or not with 2.5 mM DMN (dimethylnitrosamine) with repair-deficient mei-9^a females or with ordinary females, induced frequencies of observed (recovered) chromosome loss were 3.69% and 0.65% and inferred (non-recovered) ring-X loss based on shifts in sex ratio (♀♀/♂♂) was 47.9% and 9.4%, respectively. Results indicate that the mei-9^a female is a strong potentiator of DMN-induced chromosome damage in sperm and suggest that DMN-induced chromosome lesions are produced in substantially higher frequency in treated sperm than deducible after crosses with repair-efficient females.     

Axon reaction in hypoglossal and dorsal motor vagal neurons of adult rat: Incorporation of [3H]leucine

Pairs of adult rats received [³H]leucine (i.p., 5 μCi/g body weight) 0.25, 1, and 16 h before killing and zero (unoperated control animals) and 1 to 164 days after unilateral cervical vagotomy and hypoglossal neurotomy. Grain counts and morphometric measurements were made on axotomized and uninjured neurons in histoautoradiographs of the medullary nuclei. Axotomized hypoglossal neurons, which largely survive the injury, both enlarged and incorporated increased amounts of tritiated leucine at each labeling interval, 3 through 28 days postoperatively. In the vagal dorsal motor nucleus (DMN), axotomized cells, which frequently die after neurotomy, enlarged slightly through 28 days postoperatively, then atrophied; DMN neurons increased amino acid uptake for a shorter period (days 7 through 14) than hypoglossal neurons. This increase achieved statistical significance only when the labeling intervals were 0.25 or 1.0 h. Neurons of the DMN contralateral to vagotomy also enlarged. Axotomized DMN neurons did not sustain increased protein synthesis as long as their hypoglossal counterparts and seemed to fail to increase synthesis of structural protein with long half-lives (16-h labeling interval). The frequently necrobiotic response of axotomized DMN neurons may relate to these phenomena. From these and earlier results, we conclude that axon reaction appears to differ fundamentally in peripheral and central neurons. This difference may have significance for research on regeneration in the central nervous system.     

Differential effect of chronic ethanol consumption by the rat on microsomal oxidation of hepatocarcinogens and their activation to mutagens

The effect of chronic ethanol consumption by rats on hepatic microsomal activation of the hepatocarcinogens dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF) was investigated. There was a marked increase in the rate of the oxidative demethylation of DMN and its activation to a mutagen by microsomes following ethanol intake. N- and C-hydroxylation of 2-AAF were measured at substrate concentrations ranging from 2 to 70 microM. The ratio of formation of N-hydroxy-2-acetylaminofluorene to C-hydroxy-2-acetylaminofluorenes increased with decreasing substrate concentration, suggesting enhanced carcinogenic potential of 2-AAF with diminishing levels of carcinogen. Kinetic analysis indicated that N-hydroxylation as well as 7-, 5- and 3-hydroxylation of 2-AAF do not follow Michaelis-Menten kinetics. In contrast to the marked inductive effect of ethanol consumption on the metabolic activation of DMN, only a minimal random effect on the N-hydroxylation of 2-AAF was demonstrable in two separate experiments. Furthermore, N-hydroxylation of 2-AAF by microsomes from control and ethanol-treated rats followed similar kinetics. While ethanol consumption enhanced the mutagenic activation of DMN by hepatic microsomes, no such effect of ethanol consumption on the conversion of 2-AAF to a mutagen was observed. The data indicate that chronic ethanol consumption does not have a general inductive effect on the microsomal activation of hepatocarcinogens.     

Factors influencing the microsome- and mitochondria-catalyzed in vitro binding of diethylnitrosamine and N-nitrosopiperidine to deoxyribonucleic acid.

[¹⁴C]Diethylnitrosamine ([¹⁴C]DEN) and [¹⁴C]N-nitrosopiperidine ([¹⁴]NPiP) bind covalently to calf thymus DNA in an in vitro incubation system containing rat liver microsomes. The reaction is NADPH-dependent. Pretreatment of the animals with phenobarbital (PB) enchances the binding of both DEN and NPiP to DNA, whereas the binding of DEN to DNA decreases after 3-methylcholanthrene pretreatment. The PB effect, as observed from the binding of DEN to DNA. is more pronounced in young rats than in the older animals. Addition of cytosol to the incubation system enhances the binding of DEN 3- to 4-fold and the binding of NPiP 2- to 3-fold. Addition of mitochondria to the incubation system increases the binding of [¹⁴C]DEN only slighty. but increases the binding of NPiP more than 5-fold. Addition of mitochondria has no effect on the binding of [¹⁴C]dimethylnitrosamine ([¹⁴C]DMN). Mitochondria alone markedly catalyze the binding of NPiP to DNA. Addition of benzylamine. which is a substrate of mitochondrial monoamine oxidase as well as an inhibitor of DMN-demethylase, inhibits the binding of NPiP catalyzed by microsomes and microsomes plus mitochondria.     

Brain connectivity and high functioning autism: a promising path of research that needs refined models, methodological convergence, and stronger behavioral links

Here we review findings from studies investigating functional and structural brain connectivity in high functioning individuals with autism spectrum disorders (ASDs). The dominant theory regarding brain connectivity in people with ASD is that there is long distance under-connectivity and local over-connectivity of the frontal cortex. Consistent with this theory, long-range cortico-cortical functional and structural connectivity appears to be weaker in people with ASD than in controls. However, in contrast to the theory, there is less evidence for local over-connectivity of the frontal cortex. Moreover, some patterns of abnormal functional connectivity in ASD are not captured by current theoretical models. Taken together, empirical findings measuring different forms of connectivity demonstrate complex patterns of abnormal connectivity in people with ASD. The frequently suggested pattern of long-range under-connectivity and local over-connectivity is in need of refinement.     

Detection of DNA damage in peripheral lymphocytes by 7 compounds using comet assay

目的：检测过氧化氢（Ｈ２Ｏ２）、甲磺酸乙酯（ＥＭＳ）、丝裂霉素Ｃ（ＭＭＣ）、二甲基亚硝胺（ＤＭＮＡ）、苯并（ａ）芘（ＢａＰ）、２氨基芴（２ＡＦ）和环磷酰胺（ＣＰ）诱发小鼠、大鼠及人外周血淋巴细胞ＤＮＡ单链断裂．方法：体外单细胞微量凝胶碱性电泳试验（慧星试验）．结果：除ＥＭＳ０９７ｍｍｏｌ·Ｌ－１在小鼠淋巴细胞，ＭＭＣ３０μｍｏｌ·Ｌ－１在小鼠、人淋巴细胞中呈阴性外，其余均为阳性．最低可检测浓度分别为Ｈ２Ｏ２１μｍｏｌ·Ｌ－１，ＥＭＳ０４８ｍｍｏｌ·Ｌ－１，ＢａＰ５０μｍｏｌ·Ｌ－１，ＣＰ２０ｍｍｏｌ·Ｌ－１，ＭＭＣ１０μｍｏｌ·Ｌ－１，ＤＭＮＡ２７３ｍｍｏｌ·Ｌ－１，２ＡＦ６２５μｍｏｌ·Ｌ－１．ＣＰ、ＢａＰ、２ＡＦ需经Ｓ９Ｍｉｘ代谢活化才显示毒性．结论：彗星试验检测出ＭＭＣ诱导大鼠，ＥＭＳ诱导大鼠和人，以及Ｈ２Ｏ２、ＤＭＮＡ、ＢａＰ、ＣＰ和２ＡＦ诱导小鼠、大鼠和人外周血淋巴细胞ＤＮＡ单链断裂损伤．     

Alterations in mitochondrial respiratory functions, redox metabolism and apoptosis by oxidant 4-hydroxynonenal and antioxidants curcumin and melatonin in PC12 cells

Cellular oxidative stress and alterations in redox metabolisms have been implicated in the etiology and pathology of many diseases including cancer. Antioxidant treatments have been proven beneficial in controlling these diseases. We have recently shown that 4-hydroxynonenal (4-HNE), a by-product of lipid peroxidation, induces oxidative stress in PC12 cells by compromising the mitochondrial redox metabolism. In this study, we have further investigated the deleterious effects of 4-HNE on mitochondrial respiratory functions and apoptosis using the same cell line. In addition, we have also compared the effects of two antioxidants, curcumin and melatonin, used as chemopreventive agents, on mitochondrial redox metabolism and respiratory functions in these cells. 4-HNE treatment has been shown to cause a reduction in glutathione (GSH) pool, an increase in reactive oxygen species (ROS), protein carbonylation and apoptosis. A marked inhibition in the activities of the mitochondrial respiratory enzymes, cytochrome c oxidase and aconitase was observed after 4-HNE treatment. Increased nuclear translocation of NF-kB/p65 protein was also observed after 4-HNE treatment. Curcumin and melatonin treatments, on the other hand, maintained the mitochondrial redox and respiratory functions without a marked effect on ROS production and cell viability. These results suggest that 4-HNE-induced cytotoxicity may be associated, at least in part, with the altered mitochondrial redox and respiratory functions. The alterations in mitochondrial energy metabolism and redox functions may therefore be critical in determining the difference between cell death and survival.     

静息态功能磁共振研究未治疗首次发作重症抑郁症患者默认网络功能连接

目的 探讨静息态功能磁共振（rs-fMRI）技术和种子点功能连接的方法对未治疗首次发作重症抑郁症(MDD)患者默认网络(DMN)的功能连接改变。方法 选取2016年6月～2018年1月重庆医科大学附属第一医院收治的16例MDD患者为观察组,并同时选取19例年龄、性别和受教育年限相匹配的健康志愿者为照组,均行rs-fMRI扫描,运用基于种子点的功能连接方法,提取脑DMN相关脑区,选择功能连接显著差异脑区(P＜0.01)作为感兴趣区（ROI）,并行ROI脑区功能连接强度与其汉密尔顿抑郁量表评分及发作时间做直线相关分析。结果 观察组DMN相关的脑区分布于双侧楔前叶、左侧内侧和旁扣带回、右侧内侧额上回、左侧背外侧额上回、右侧额中回、右侧颞上回;而对照组DMN相关的脑区分布于双侧楔前叶、右侧角回、双侧额中回、双侧颞中回;与对照组相比,观察组DMN在左内侧额上回脑区功能连接强度值显著减低(P＜0.01)。观察组左内侧额上回功能连接强度值与其汉密尔顿抑郁量表评分(r=0.084,P=0.756)、发作持续时间(r= 0.116,P=0.670)不相关。结论 未治疗首次发作重症抑郁症患者存在默认网络功能连接异常,但未发现其与患者抑郁严重程度和发作持续时间有相关性。