In silico antiplasmodial effects of phytocompounds derived from Andrographis paniculata on validated drug targets of different stages of Plasmodium falciparum

Background:Andrographis paniculata has been widely reported as an herbal plant for malaria treatment.The increasing rate of resistance to recommended antimalarial drugs has justified the need for a continuous search for new and more potent drugs that target all stages of the Plasmodium falciparum life cycle from natural plant sources.This study aimed to determine the antiplasmodial effect of phytocompounds derived from A.paniculata on the stages of plasmodium falciparum.Methods:Phytocompounds from A.paniculata were identified by Gas Chromatography-Mass Spectrophotometry(GCMS)analysis.The phytocompounds were screened for their druggability using Lipinski’s rule of five and subjected to Absorption,Distribution,Metabolism,Excretion,Toxicity(ADMET)and druglikeness analysis.The phytocompounds were docked against some validated drug targets at different stages of Plasmodium falciparum(hepatic,asexual,sexual,and vector targets)using PyRx software to analyze the inhibitory potential and protein-ligand interaction.Thereafter,the stability and flexibility of the best complexes were assessed through molecular dynamics simulations at 50ns using WebGRO.Result:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl exhibited a higher binding affinity and better stability throughout the simulation period with P.falciparum dihydrofolate reductase-thymidylate synthase and Plasmodium falciparum M1 alanyl aminopeptidase for asexual blood stage and gametocyte stage of Plasmodium falciparum,respectively than the existing drugs.Meanwhile,N-Ethyl-3-methoxy-4-methylphenethylamine was also found to have a higher binding affinity and more stability throughout the simulation period with P.falciparum purine nucleoside phosphorylase and Plasmodium falciparum gametocyte surface protein for Hepatic schizonts stage of Plasmodium falciparum and gametocyte transmission blocking stage,respectively,than the existing drugs.Conclusion:The 7a-Isopropenyl-4,5-dimethyloctahydroinden-4-yl and N-Ethyl-3-methoxy-4 methylphenethylamine from A.paniculata are predicted as an antimalarial drug candidate.Thus,it is recommended that in vitro and in vivo bioassays be conducted on these hit compounds to validate these predictions.

一种新的多金属超富集植物——圆锥南芥(Arabis paniculata L.)

野外调查和营养液培养试验表明,圆锥南芥(Arabis Paniculata L.)具有超量富集Pb/Zn/Cd的能力,是国内首次发现的Pb/Zn/Cd多金属超富集植物,它的出现填补了国内多金属超富集植物的空白,为重金属复合污染土壤的植物修复提供了新的种质资源。

镉在圆锥南芥(Arabis paniculata Franch.)中的亚细胞分布及其化学形态

通过水培的方式,采用差速离心技术和化学试剂逐步提取法研究了Cd在圆锥南芥(Arabis paniculata Franch.)叶片和根中的亚细胞分布和化学形态。研究结果表明,在Cd处理浓度为1.0mg·L-1时,圆锥南芥叶片中的Cd主要贮藏在细胞壁和细胞核中,而根系中Cd的分布顺序为:细胞壁>核糖体>细胞核>叶绿体>线粒体;10.0mg·L-1Cd处理时,叶片中的Cd主要集中在细胞壁以及细胞核中,根系中核糖体含量最高,占全量的53.92%。这说明圆锥南芥叶片富集的Cd主要贮存在细胞壁以及细胞核中,而根系富集的Cd主要分布在核糖体与细胞壁中。化学形态结果表明Cd处理水平的变化对圆锥南芥Cd的化学形态有明显的影响。1.0mg·L-1Cd处理时,圆锥南芥叶片中以水提取态Cd为主,根系中乙醇提取态Cd的含量最高;当Cd提高到10.0mg·L-1时,叶片和根系中Cd均以NaCl提取态含量最高,说明随着Cd浓度的增加,Cd与蛋白质、果胶酸等形态结合是圆锥南芥减轻Cd毒害的主要机制。

Investigation of hypoglycemic,hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark in diabetic rats

Objective:To investigate the hypoglycemic,hypolipidemic and antioxidant activities of aqueous extract of Terminalia paniculata bark(AETPB) in streptozotocin(STZ)-mduced diabetic rats.Methods:Acute toxicity was studied in rats after the oral administration of AETPB to determine the dose to assess hypoglycemic activity.In rats,diabetes was induced by injection of STZ(60 mg/kg,i.p.) and diabetes was confirmed 72 h after induction,and then allowed for 14 days to stabilize blood glucose level.In diabetic rats,AETPB was orally given for 28 days and its effect on blood glucose and body weight was determined on a weekly basis.At the end of the experimental day,fasting blood sample was collected to estimate the haemoglobin(Hb),glycosylated haemoglobin(HbA1c),serum creatinine,urea,serum glutamate-pyruvate transaminase(SGPT),serum glutamate-oxaloacetate transaminase(SGOT) and insulin levels. The liver and kidney were collected to determine antioxidants levels in diabetic rats.Results: Oral administration of AETPB did not exhibit toxicity and death at a dose of 2000 mg/kg.AETPB treated diabetic rats significantly(P<0.001,P<0.01 and P<0.05) reduced elevated blood glucose, HbAlc,creatinine,urea,SGPT and SGOT levels when compared with diabetic control rats.The body weight,Hb,insulin and total protein levels were significantly(P<0.001,P<0.01 and P<0.05) increased in diabetic rats treated with AETPB compared to diabetic control rats.In diabetic rats, AETPB treatment significantly reversed abnormal status of antioxidants and lipid profile levels towards near normal levels compared to diabetic control rats.Conclusions:Present study results confirm that AETPB possesses significant hypoglycemic,hypolipidemic and antioxidant activities in diabetic condition.

Heavy metal accumulation by panicled goldenrain tree(Koelreuteria paniculata) and common elaeocarpus(Elaeocarpus decipens) in abandoned mine soils in southern China

Phytoremediation can be used as a sustainable technology for mine spoil remediation to remove heavy metals. This study investigated the concentration of 7 heavy metal contamination in soil and plant samples at an abandoned mine site. We found that, after vegetation remediation at the abandoned mine site, the reduction rates for 7 heavy metals were in the range of 4.2%-86%, where reduction rates over 50% were achieved for four heavy metals （Zn, Mn, Cd, Ni）. Transfer coefficients of the panicled goldenrain tree （Koelreuteria paniculata Laxm） and the common elaeocarpus （Elaeocarpus decipens） for Zn, Mn, Ni, and Co were more than 1. Enrichment coefficients of both trees for Mn were higher than 1. Our results suggest that the panicled goldenrain tree and the common elaeocarpus tree may act as accumulators in remediation. Moreover, the woody vegetation remediation in abandoned mining areas play an important role in improving scenery besides removing heavy metal from contaminated soil.

Evaluation of Andrographis paniculata Burm.f.(Family.Acanthaceae) extracts against Culex quinquefasciatus(Say.) and Aedes aegypti(Linn.)(Diptera:Culicidae)

Objective:To investigate the larvicidal and ovicidal efficacy of different extracts of Andrographis paniculata（A.paniculata） against Culex quinquefasciatus（Cx.quinquefasciatus） Say and Aedes aegypti（Ae.aegypti ） L（Diptera:Culicidae）.Methods:Larvicidal efficacy of the crude leaf extracts of A.paniculata with five different solvents like benzene,hexane,ethyl acetate, methanol and chloroform was tested against the early third instar larvae of Cx.quinquefasciatus and Ae.aegypti.The ovicidal activity was determined against two mosquito species to various concentrations ranging from 50-300 ppm under the laboratory conditions.Results:The benzene, hexane,ethyl acetate,methanol and chloroform leaf extract of A.paniculata was found to be more effective against Cx.quinquefasciatus than Ae.aegypti.The LC50 values were 112.19,137.48, 118.67,102.05,91.20 ppm and 119.58,146.34,124.24,110.12,99.54 ppm respectively.Among five tested solvent,methanol and ethyl acetate crude extract was found to be most effective for ovicidal activity against two mosquito species.The extract of methanol and ethyl acetate exerted 100%mortality at 200 ppm against Cx.quinquefasciatus and at 250 ppm against Ae.aegypti. Conclusions:From the results it can be concluded the crude extract of A.paniculata was a potential for controlling Cx.quinquefasciatus and Ae.aegypti mosquitoes.

Hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatocellular damage in Wistar albino rats

Objective:To evaluate the hepatoprotective activity of Terminalia paniculata against paracetamol induced hepatic damage in rats.Methods:The plant material was shade dried, powdered and extracted with ethanol.Liv 52 and silymarin were used as standard drugs and 2%gum acacia as a control(vehicle).Alteration in the levels of biochemical markers of hepatic damage like AST,ALT,ALP and lipid peroxides were tested,and phytochemical tests were also performed.Results:Paracetamol(2 g/kg) increased the serum levels of alanine aminotransfer (ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP) and the lipid peroxides. Treatment of Liv 52,silymarin and ethanolic extract of Terminalia paniculata(200 mg/kg) altered levels of biochemical marker and showed significant hepatoprotective activity.Ethanolic extract revealed the presence of phenolic compound and flavanoids.Our findings suggested that ethanolic bark extract of Terminalia paniculata possessed hepatoprotective activity in a dose dependent manner.Conclusions:Terminalia paniculata possesses hepatoprotective activity.It could be an effective and promising preventive agent against PCT induced hepatotoxicity.

Effects of Atmospheric Pressure Air Plasma Pretreatment on the Seed Germination and Early Growth of Andrographis paniculata

The objective of this paper is to demonstrate whether air plasma can change the seed germination characteristics, seedling emergence, as well as biochemical reactivity, in Andrographis paniculata （A. paniculata） seedlings by modifying the seed coat and finding a beneficial treatment dose. Eight treatment doses and one control were used to conduct electrical conductivity determination, a germination test, a seedling emergence test and a biochemical assay. The results showed that after being treated with air plasma excited at 5950 V for 10 s, the perme- ability of the seeds was improved significantly, resulting in the acceleration of seed germination and seedling emergence. In the meantime, the catalase activity and catalase isoenzyme expression were also improved, while the malondialdehyde content in the seedlings was decreased （which means greater counteraction with environmental stress）. After being treated with 4250 V for 10 s and 5950 V for 20 s, the seed germination was enhanced, but without an obvious change in seedUng emergence. However, after treatment with 3400 V for 20 s and 5100 V for 10 s, the permeability of the seeds was decreased, resulting in a delay in seedling emergence. These results indicate that air plasma can change the physiological and biochemical characteristics of Andrographis paniculata seeds by modifying the seed coat, combined with the effects of the active plasma species, and that different treating doses have different effects.

环境因子对千里香(Murraya paniculata)蒸腾强度的影响

蒸腾作用是植物水分关系中的一个重要部分,它基本上是蒸发的物理过程,因此受环境因子的影响,同时它也是受植物体本身结构特点影响的生理过程。对植物的蒸腾强度测定,有利于了解植物与环境之间的关系。千里香[Murraya paniculata(L.)Jack]是一种主要生长于石灰岩地区的具有重要药理作用的植物。其生长地的土壤浅薄,而基岩本身又易透水,故石灰岩地区蓄水保水能力较差,土壤常较干燥,测定千里香植物的蒸腾强度,有利于了解石灰岩地区植物的某些特点。

Mechanism of antagonistic effects of Andrographis paniculata methanolic extract against Staphylococcus aureus

Objective: To investigate the effects of Andrographis paniculata(Burm.f.) Wall. Ex Nees(A. paniculata) on expressions and activities of catalase, superoxide dismutase and alkylhydroperoxide reductase C in Staphylococcus aureus(S. aureus) with respect to its survival in vitro. Methods: Antioxidative property of methanolic leaves extract of A. paniculata(0.06 mg/m L). Minimum inhibitory concentration(MIC) was determined by its ability to reduce hydrogen peroxide(H_2O_2) toxicity against S. aureus ATCC 25923(3.8×10~8 cfu/m L). Effects of the extract on expressions of kat A(encoding catalase), sod A and sod M [encoding superoxide dismutases(SODs)], and ahp C [encoding alkylhydroperoxide reductase C(AhpC)] in S. aureuswere determined by RT-q PCR and corresponding enzyme activity assays were performed. Nitroblue tetrazolium reduction(NBT) assay was performed to determine effects of the extract on intracellular and extracellular levels of O_2-in S. aureus. Results: Cells challenged with 7.5 mmol/L H_2O_2 showed 0% survival in 30 min whereas 25% survived after treatment with the extract and H_2O_2. Cells that were treated with the extract alone had 43% survival in the same exposure period. Expressions of sod A and sod M genes in extract-treated cells were lowered 0.8-fold and 0.7-fold, respectively with decrease in total SOD activity of 26.8 U compared to untreated cells, 32.4 U(P<0.05). In contrast, extract-treated S. aureus cells showed 3.3-fold increase in kat A expression with corresponding increase in catalase activity of 1.828 U compared to untreated cells which was 1.248 U,(P<0.05). More profoundly, ahp C expression was increased 61-fold in extract-treated cells,(P<0.05) with corresponding increase in Ahp C activity of 0.018 U compared to untreated cells, 0.012U,(P<0.05). Extract-treated cells had significantly lower intra-and extracellular O_2-levels with absorbance readings(A_(575nm)) of 0.340 and 0.524 compared to untreated cells which were 0.516 and 0.928(P<0.05), respectively. Conclusions: Taken together these results suggest that the low MIC of A. paniculatamethanolic leaves extract(0.06 mg/m L) reduce H_2O_2 toxicity and more importantly, was in itself effectively inhibitory against S. aureus. Further, our observations suggest that a probable mode of its inhibitory mechanism against S. aureus is by reducing total SOD activity through downregulation of sod A and sod M expressions.

发根农杆菌(Agrobacterium rhizogenes) Ri T-DNA遗传转化丝石竹(Gypsophila paniculata)的研究

近年来,已发展出遗传转化高等植物的一些新技术,其中有些技术如脂质体融合,微注射技术和电击导入都是基于动物细胞培养方面的工作,而另一些技术是来自于植物界独特的天然转化系统,其中包括已知能遗传转化高等植物的农杆菌(Agrobacterium)的二个种,即致瘤农杆菌(A.tumefaciens)和发根农杆菌(A.rhizogenes),这二个种都能够将其致病质粒Ti或Ri所携带的DNA序列(T-DNA)插入到双子叶植物细胞核基因组中。pTi诱发寄主产生根基肿瘤,pRi诱发寄主产生毛状根。二者的差别可能是毛状根可以从毛状根培养物获得具有完整的T-DNA序列的有生育能力的再生植株,而从致病农杆菌(A.tumefaciens)菌株所诱发的肿瘤很难获得再生植株。因此,利用发根农杆菌(A.rhizogenes)pRi作为遗传转化高等植物的基因克隆载体的研究和应用日益受到重视。

A new ent-labdane diterpenoid lactone from Andrographis paniculata

A new ent-labdane diterpenoid lactone was isolated from Andrographis paniculata.Its structure was identified on the basis of spectral data including 2D NMR.

Studies on antioxidative activities of methanol extract from Murraya paniculata

Murraya paniculata(L.),a well-known medical plant,has widely been used to treat inflammation,stomach ache,internal and external injuries,and for other purposes.In this study,we determined the reducing,lipid peroxidation inhibition,1,1-diphenyl-2-picryl-hydrazil radical(DPPH•)scavenging,superoxide anion radical(O2−•)scavenging,hydroxyl radical(HO•)scavenging and hydrogen peroxide(H2O2)scavenging activities of the methanolic extract of M.paniculata(MPE)by UV–vis spectrophotometer.The results showed that M.paniculata was rich in flavonoids(375 mg RE/g of extract).Reducing,lipid peroxidation inhibition and HO•scavenging activities of the extract were 0.26 mg/mL,0.023 mg/mL and 0.302 mg/mL,respectively,these activities were significantly higher than those of trolox.Other antioxidative behavior indicators,i.e.,DPPH•scavenging,O2−•scavenging and H2O2 scavenging activities of MPE were 0.93 mg/mL,0.581 mg/mL and 0.47 mg/mL,respectively,and were comparable to those exhibited by trolox.These results indicate that the methanolic extract of M.paniculata exhibited strong antioxidative and radical scavenging activities.

Investigation of antioxidant and anti-inflammatory activity of leaves of Dalbergia paniculata(Roxb)

Objective:To investigate the antioxidant and anti-inflammatory activity of orally administered methanolic leaf extract of Dalbergia paniculala(D.paniculata) in Carrageenan induced inflammation in rats.Methods:In vitro antioxidant activity was evaluated for superoxide radical, Hydroxyl radical and DPPH radical scavenging activity.Three doses 200 mg/kg,400 mg/kg and 800 mg/kg of D.paniculala were tested for anti-inflammatory activity in Carrageenan induced rat paw edema model and paw thickness was measured every one hour up to 6 h. Results:The melhanolic leaf extract of D.paniculala produced dose dependent inhibition of Superoxide radical,Hydroxyl radical and OPPH radicals.In Carrageenan induced inflammation model,all three doses produced significant percentage inhibition of rat paw edema and 800 mg/kg dose produced maximum percent inhibition of rat paw edema(47.83%) at 3h compared to control group.Conclusions:In the present study we found that methanolic leaf extract of D.paniculata showed good in vitro antioxidant activity and in vivo anti-inflammatory activity in rats.

Studies on effects of Andrographis paniculata(Burm.f.) and Andrographis lineata nees(Family:Acanthaceae) extracts against two mosquitoes Culex quinquefasciatus(Say.) and Aedes aegypti(Linn.)

Objective:To investigate the studies on effects of Andrographis paniculata(A.paniculata) (Burm.f.) and Andrographis lineata(A.lineata) nees(Family:Acanthaeeae)extracts against two mosquitoes Culex quinquefasciatus(Cx.quinquefasciatus)(Say.) and Aedes aegypti(Ae.aegypti) (Linn.).Methods:The aqueous and petroleum ether extracts of two plant species.A.paniculata and A.lineate were examined against the larvae of,4.aegypti(L.) and Cx.quinquefasciatus with gradually increasing concenlration ie.from 50 to 200 ppm of solvent extracts and to test their activity in combination with each other.Results:In a 24 h bioassay experiment with plant extracts,highest mortalities were recorded at 200 ppm of concentrations for leaves of 4.lineta and A.paniculata individually.For combination effect,only 150 ppm of the mixture of solvent extracts of petroleum ether:aqueous(1:1) extracts showed 100%mortality after 24 h of exposure. Conclusions:The results show that,insecticides of plant combination is ecofriend and has better larvicidal activity compared to individual extracts.

Dengue virus infections and anti-dengue virus activities of Andrographis paniculata

Dengue is a debilitating disease that poses a perpetual threat to human health and increases the global economic burden every year.Despite advances in medical sciences,dengue virus(DENV)infects approximately 200 million people every year.To date,no effective antiviral is valiable to treat DENV in individuals despite great efforts in accomplishing these goals.Numerous approaches have been used in the search for dengue antiviral like screening of combinatorial compounds against DENV enzymes and structurebased computational discovery.In recent years,investigators have turned their focus into medicinal plants,trying to identify compounds that can be used as dengue antiviral.Nature represents a great reservoir of potential substances that can be explored with the aim of discovering new drugs that can be either used directly as pharmaceuticals or can provide drug leads,which can be scrutinized further for the development of new anti-dengue natural product.Many previous investigations have dealt with numerous plant extracts or bioactive principles for their antiviral property as they normally considered being safer when compared to synthetic drugs.Andrographis paniculata belongs to family Acanthaceae and is generally known as‘king of bitters’.Diverse bioactive compounds from this plant such as diterpenes,flavonoids,xanthones,noriridoides and other miscellaneous compounds have exhibited their potential as therapeutics for various chronic as well as infectious diseases.This review is based on literature review on scientific journals,books and electronic sources,which highlights the pathogenesis of DENV and describe an assortment of bioactive principles that have been possessing antiviral potential,which include dengue and discuss the therapeutic efficacy and mechanism of action of Andrographis paniculata.However,a detailed and more comprehensive clinical trial on mammalian tissues and organs is needed in future studies.

Genome-wide identification of WRKY gene family and expression analysis under abiotic stresses in Andrographis paniculata

Andrographis paniculata(A.paniculata)is a Chinese herbal medicine that clears away heat,reduces inflammation,protects the liver,and promotes choleretics.The WRKYs of A.paniculata are still not well characterized,although many WRKYs have been identified in various plant species.In the present study,59 A.paniculata WRKY(ApWRKY)genes were identified and renamed on the basis of their respective chromosome distribution.These ApWRKYs were divided into three groups via phylogenetic analysis according to their WRKY domains and combined with WRKY of Arabidopsis.The 59 identified ApWRKY transcription factors were nonuniformity distributed on 23 chromosomes of A.paniculata.From the structural analysis of the conserved motifs,different ApWRKYs structures showed different biological functions,and the ApWRKY transcription factor had certain species-specificity in the evolutionary process.The expression patterns of the 41 ApWRKYs were examined through quantitative real-time PCR(qRT-PCR)in various tissues and under abiotic stresses(salt).The results showed that most of the ApWRKY had different reactions to salt treatment.In addition,the content of the four main secondary metabolites in A.paniculata leaves was determined under salt stress.The results show that under a low concentration of salt treatment,the synthesis of andrographolide can be improved.

In vitro anti oxidant activity and acute oral toxicity of Terminalia paniculata bark ethanolic extract on Sprague Dawley rats

Objective:To ensure the safety and evaluate the anti oxidant activity of Terminalia paniculata(T.paniculata)ethanolic extract in Sprague Dawley rats.Methods:The solvent extracts(hexane,ethyl acetate and ethanol)of T.paniculata were subjected to phytochemical analysis and their DPPH radical scavenging activity was assayed.The oral acute toxicity was evaluated using ethanolic extract of T.paniculata.Results:Ethyl acetate and elhanolic extracts showed more phytochemicals,whereas highest DPPH scavenging activity was found in ethanolic extract.In an acute toxicity study,T.paniculata ethanolic extract was orally administered(1000 mg/kg body weight)to rats and observed for72 h for any toxic symptoms and the dose was continued up to 14 d.On the 15th day rats were sacrificed and blood samples were collected from control and test animals and analyzed for some biochemical parameters.We did not observe any behavioral changes in test groups in comparison with their controls.Also,there were no significant alterations in biochemical,hematological(hemoglobin content and blood cells count)and liver function parameters such as serum glutamate pyruvate transaminase,serum glutamate oxaloacetate transaminase,alkaline phosphatase,total proteins,albumin and bilirubin levels between T.paniculata ethanolic extract treated and normal control groups.Conclusions:Together our results demonstrated that T.paniculala ethanolic possessed potent antioxidant activity and it was safer and non toxic to rats even at higher doses and therefore could be well considered for further investigation for its medicinal and therapeutic efficacy.

A new ent-labdane eiterpenoid lactone from Andrographis paniculata

A new ent-labdane diterpenoid lactone with a new natural product was isolated from Andrographis paniculata. Their structures were elucidated on the basis of spectral evidences including 2D NMR.

Antidiabetic effect of combination of fractionated-extracts of Andrographis paniculata and Centella asiatica: In vitro study

Objective: To examine the effect of combination of Andrographis paniculata herb fraction(AHF) and Centella asiatica herb fraction(CHF) on PPAR γ and GLUT4 mRNA expression in 3 T3-L1 adipocyte, and its effect on insulin-stimulated glucose uptake. Methods: 3 T3 L1 adipocyte cells were used to investigate gene expression of PPARy reverse transcription-polymerase chain reaction method. The γ and GLUT4 protein b adipocyte cells were differentiated by using insulin, dexamethasone and 3-isobutyl-1-methylxanthine from 3 T3-L1 cells. Pioglitazone, AHF, CHF and the combination of both herbs were evaluated on glucose uptake activity, PPAR γ and GLUT4 mRNA expressions in 3 T3-L1 adipocyte. Results: The results showed that combination of AHF at 30 μg/mL and CHF at 10 μg/mL could enhance insulin-stimulated glucose uptake. The combination also increased PPAR γ and GLUT4 mR NA expressions significantly in comparison to those of negative control(DMSO). These effects were equal in comparison to those of pioglitazone(0.02 μM) and its single extracts Conclusions: The combination of AHF and CHF can increase glucose uptake and insulin sensitivity through up-regulation of PPAR γ and GLUT4 mRNA expressions in 3 T3-L1 adipocyte.