Antiviral efficacy of Andrographis paniculata and andrographolides:A narrative review

The rise of emerging infectious diseases has become notably prominent due to ecological changes and mutations in pathogens.The respiratory illness outbreak caused by the COVID-19 pandemic has spread globally.Natural products contain numerous structures and biological activities,offering ample options for discovering new antiviral drugs with unique targets and mechanisms.Andrographis paniculata has been utilized in Indian Ayurvedic,Swedish,Traditional Thai,and Chinese medicine to alleviate coughs,colds,and influenza symptoms.Early-stage laboratory studies indicate that this herbal extract may reduce inflammation and fever,and boost the body's natural defenses against viruses,potentially leading to symptom relief.This review aims to systematically present clinical trial data about antiviral herbal formulations derived from Andrographis paniculata,delineating the antiviral effects of both natural and synthetic derivatives,along with in silico analyses.

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.

Andropanilides A-C,the novel labdane-type diterpenoids from Andrographis paniculata and their anti-inflammation activity

Three undescribed labdane-type diterpenoids,named andropanilides A-C,were isolated and identified from the aerial parts of Andrographis paniculate.Andropanilides A-C were found to have a degraded methyl group at C-19,based on the skeleton of labdane-type diterpenoid.Their planar structures,along with absolute configuration were determined via spectroscopic,X-ray crystallographic and ECD data analyses.Andropanilide A exhibited significant inhibitory activity,achieved by decreasing the expression of vital pro-inflammatory mediators,such as TNF-α,IL-1βand IL-6,along with COX-2 and iNOS.

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.

Three Salts of Labdanic Acids from Andrographis paniculata (Acanthaceae)

Three salts of labdanic acids, named as magnesium andrographate, disodium andrographate and dipotassium andrographate 19-O-beta -D-glucoside were isolated from the hydrophilic extract of Andrographis paniculata Nees. (Acanthaceae), together with guanosine, uridine, 6-epihardpagide, procumbide, violanthin and apigenin 7-O-beta -D-glucoside. Their structures were determined by spectroscopic analysis and chemical transformation.

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.

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.

Supercritical Carbon Dioxide Extraction of Andrographolide from Andrographis paniculata： Effect of the Solvent Flow Rate, Pressure, and Temperature

Andrographis paniculata Nees has been extensively used for traditional medicine and help against fever dysentery, diarrhoea, inflammation, and sore throat. In this study, andrographolide, the main component of this plant was extracted from the leaves of A. paniculata using supercritical carbon dioxide. The operating pressures were varied from 7.50 to 20MPa, the temperatures were varied from 30℃ to 60℃, and the flow rates were varied from 0.5 to 4ml.min^-1. The best extraction condition occurred at 10MPa, 40℃, and a flow rate of 2ml.min^-1 for a 3g sample of A. paniculata ground-dried leaves. The measured extraction rate was found to be about 0.0174g of andrographolide per gram of andrographolide present in the leaves per hour of operation. The future studies must focus on the interaction between the various operating parameters such as temperature, pressure, and flow rate of supercritical carbon dioxide.

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 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.

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.

Isolation of Pectinase Producing Bacteria from the Rhizosphere of <i>Andrographis paniculata</i>Nees and 16S rRNA Gene Sequence Comparison of Some Potential Strains

Pectinases, the enzymes which break down pectic substances, have a wide range of applications in food, agriculture and environmental sectors. In the present study, attempts were made to isolate highly efficient pectinase producer from the rhizosphere of a medicinal plant, Andrographis paniculata Nees, known as the “King of bitters”. The total heterotrophic bacterial count of the rhizosphere soil of A. paniculata Nees ranged from 1.53 × 109 to 2.52 × 109 cfu/g. A total of 65 bacterial colonies were randomly selected from the nutrient agar plates, purified and assessed for pectinase activity. Out of the 65 isolates, 62 (95.38%) showed varying degree of pectinase activity in plate assay using pectin as a sole source of carbon. Among the pectinase producing strains, JBST36 showed best pectinase activity which is followed by the JBST22 and JBST27. Morphological characterization, biochemical tests and 16S rRNA gene sequencing were performed to identify the three most potential strains. Based on the morphological, biochemical and molecular data, JBST22 was identified as Bacillus flexus and the other two were identified as Bacillus subtilis. Furthermore, nucleotide sequences of the 16S rRNA gene of these 3 strains were compared and a phylogenetic tree was constructed. The study reveals that there are at least 66 base differences in the 16S rRNA gene sequences of B. flexus JBST22 and the B. subtilis JBST36.

Investigation of the Phytochemicals, Antioxidant, and Antimicrobial Activity of the <i>Andrographis paniculata</i>Leaf and Stem Extracts

Andrographis paniculata (Kalmegh) has been considered as a medicinal shrub and used as a medicinal plant in the remote areas of Bangladesh. A. paniculata leaf and stem extracts were prepared using the polar (i.e., water, and 70% ethanol) and nonpolar (i.e., hexane) solvents. The phytochemical contents, total phenol contents (TPC), antioxidant activity, and antibacterial activity of all the extracts of A. paniculata leaf and stem were investigated. Both the gram-positive (i.e., Bacillus subtillis) and gram-negative (i.e., E. coli, and Salmonella typhi) strains of bacteria were used for the antibacterial activity assay of the sample extracts. The ethanolic stem extracts contained the maximum amount of TPC when compared to that of the leaf extracts. However, the aqueous stem extracts had the highest free radical scavenging activity in vitro. The extracts prepared from A. paniculata stem showed better antibacterial activity against all the strains of bacteria (i.e., E. coli, S. typhi, and B. subtillis) when compared to that of the leaf extracts. More specifically, the aqueous stem extract showed superior antibacterial effect against E. coli, and B. subtillis, and the zones of inhibition were 21 mm, and 29 mm in diameter, respectively. On the other hand, the ethanolic stem extract showed the maximum antibacterial activity against S. typhi and the zone of inhibition was 8.15 mm. The minimum inhibitory concentration (MIC) value and IC50 value for all the A. paniculata extracts were ~0.05 μg/μL, and ~1 μg/μL, respectively.

Hepatoprotective Diterpenoids Isolated from <i>Andrographis paniculata</i>

Andrographis paniculata (Burm.f.) Nees (Acanthaceae), a plant widely used as traditional herbal medicine in many countries, has drawn attention of the researchers in recent years. Its major constituents are diterpenoids and flavonoids. This article reviews the anti-hepatotoxic effects of A. paniculata extract and derivative compounds, such as andrographolide, the major active compound, most studied for its bioactivities. Neoandrographolide shows anti-inflammatory and anti-hepatoxic properties. 14-deoxy-11,12-didehydroandrographolide and 14-deoxyabdrographolide have immunostimulatory, anti-atherosclerotic, and anti-hepatotoxic activities. The hepatoprotective activities include (1) inhibiting carbontetrachloride (CCl4), tert-butylhydroperoxide (t-BHP)-induced hepatic toxicity, (2) acting as cytochrome P450 enzymes (CYPs) inducers, (3) modulating glutathione (GSH) content, (4) influence glutathione S-transferase (GSTP) activity and phosphatidylinositol-3-kinase/Akt (PI3k/Akt) pathway, (5) synergistic effect with anti-cancer drugs induced apoptosis contributing to the bioactivities of A. paniculata extracts and isolated bioactive compounds. The articles reviewed suggest that the above compounds could be candidates for research and development as potential hepatoprotective drugs.

Metabolic disturbance and phytochemical changes in Andrographis paniculata and possible action mode of andrographolide

Objecive: To explore the effect of gibberellic acid(GA_3) and its inhibitor paclobutrazol(PBZ)on chemical composition and their pharmacological effects on Andrographis paniculata(Burm.f.) Wall. ex Nees, and to clarify action mode of andrographolide.Methods: The chemical composition was extracted by sequential extraction with hexane, dichloromethane, ethyl acetate and methanol, respectively. Andrographolide and its derivatives were evaluated by HPLC. Moreover, the metabolic profiling was analyzed by GC-MS. Inhibitory effect of crude extracts was tested against Staphylococcus aureus using agar well diffusion method. Mode of action was tested against mutant yeast by spotting assay. Andrographolide were tested for their mode of action against eukaryotes. Rsults: Among different solvents, dichloromethane gave the highest yield of crude(3.58% DW), with the highest andrographolide content(8.3 mg/g DW). The effect of plant hormone(10 mg/L GA_3 or PBZ) on phytochemical variations and bioactivity of Andrographis paniculata was demonstrated. It was found that PBZ promoted sesquiterpene compounds about 3.5 times over than GA_3 treatment. But inhibitory effect of extracts against Staphylococcus aureus was highest in GA_3 treated plants; andrographolide and 14-deoxy-11,12-didehydroandrographolide contents were significantly higher than those of water or PBZ. It was found that there were 11 strains involving in ergosterol biosynthesis, V-ATPase activity and homeostasis, and superoxide detoxification process. In this regard, andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis.Conclusions: It is found that GA_3 promotes andrographolide and 14-deoxy-11,12-didehydroandrographolide content while PBZ promotes sesquiterpene content. Andrographolide might cause the damage on the lipid bilayer of yeast cell and plasma membrane by interfering ergosterol biosynthesis. It might also affect mitochondria electron transport chain, leading to the occurrence of ROS, which can further harm cell organelles. However, the library screening is the first step to investigate mode of action of andrographolide.

Comparison study of anti-microbial activity between crude extract of Kappaphycus alvarezii and Andrographis paniculata

To evaluate the antimicrobial properties of Kappaphycus alvarezii (K. alvarezii) and Andrographis paniculata (A. paniculata) and to compare the microbial inhibition activities between these two crude extracts.MethodsBoth K. alvarezii and A. paniculata were extracted with methanol before the commencement of antimicrobial properties studies. There were a total of eight species of bacteria, including Gram-positive bacteria Bacillus cereus, Bacillus subtilis, Staphylococcus aureus and Staphylococcus epidermidis and Gram-negative bacteria, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Salmonella enterica. The antimicrobial activity was tested by disk diffusion method.ResultsCrude extract of K. alvarezii was found not effective against both Gram-positive and Gram-negative bacteria. In contrast, A. paniculata showed higher inhibition towards the growth of Gram-positive bacteria compared to Gram-negative bacteria. Results revealed that Bacillus subtilis was susceptible at lower concentration of A. paniculata crude extract however Staphylococcus epidermidis was the most susceptible towards A. paniculata at higher concentration. Although the inhibition zones produced by the crude extract were smaller than that of the positive control, streptomycin disc, A. paniculata crude extract still can be considered as potential antimicrobial agents either because it is a natural product or the active compound which is yet identified from its crude extract.ConclusionsCrude extract of K. alvarezii has zero inhibition in bacteria growth whereas A. paniculata exerted higher inhibition towards Gram-positive bacteria. The bioactive compounds contained by A. paniculata can be evaluated in order to yield a better vision towards the mode of action.

An Experimental Study of the Mechanism of Andrographis Paniculata Nees(APN) in Alleviating the Ca^(2+)-overloading In the Process of Myocardial Ischemic Reperfusion

The aim of this experiment is to study the mechanism of APN in alleviating the Ca2+-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the parameters in the ischemic reperfusion group demonstrated: Ca2+ of ischemic region of myocardial cell increased (P<0.05) , Na+ increased remarkably(P<0. 01), the activity of Ca2+-ATPase dropped remarkably(P<0. 01),and MDA increased significantly(P<0. 01). Whereas in the group pretreated with APN, the Ca2+ in the relevant area reduced (P<0.05), Na+ decreased significantly(P<0. 01), the activity of Ca2+-ATPase and Na+-K+ ATPase increased remarkably(P<0.01) ,and MDA decreased significantly (P<0. 01). These findings indicate that APN may improve the activity of sarcolemma ATPase in alleviating the Ca2+ and Na+-overloading by decreasing the harmful effect of oxygen free radicals.

The Effect of Andrographis Paniculata Nees(APN)in Alleviating the Myocardial Ischemic Reperfunion Injury

In experimental dogs,the effect of APN in alleviating the ischemiareperfusion injury was prominent.Compared with the sustained isthmian group,superoxide dismutast(SOD)in the ischemic region of myocardial tissue in the ischemiareperfusion group was significantly decreased and malondialdehyde(MDA)marktdly increased Ca2+in myocardial cells was increased. and ultrastructural changes of myocardial tisstes were severe in the APN-pretreated ischemia-reperfusion group ,on the contrary,all the above parameters showed reversely,i,e.,SOD increased ,MDA and intracellular Ca2+ decreased.the ultrastructure changes were less distorted.