Pharmacokinetics, dynamics, toxicology and molecular docking of bioactive alkaloid vasicine from Adhatoda vasica: a promising toxin binder against aflatoxin B1 and ochratoxin A.

Vasicine from Adhatoda vasica was investigated in the management of aflatoxicosis and ochratoxicosis by in silico molecular docking approach. The computational analysis was carried out using Discovery Studio Autodock 4.5 tool. Absorption, distribution, metabolism, and excretion (ADME), pharmacodynamics and toxicity studies were also carried out using Swiss ADME and PASS online server, respectively. The standard drug compound used was silymarin and the structure were retrieved from the protein data bank for both the test compound vasicine and the standard drug. Vasicine interacted with aflatoxin B1 at 10 different poses and the maximum dock score was found to be 83.04 and the binding energy was -37.54 kcal/mol. Silymarin interacted with aflatoxin B1 at 10 different poses and the maximum dock score was found to be 143.578 and the binding energy was -67.32 kcal/mol. Vasicine interacted with ochratoxin A at 10 different poses and the maximum dock score was found to be 73.75 and the binding energy was -56.20 kcal/mol. Silymarin interacted with ochratoxin A at 10 different poses and the maximum dock score was found to be 89.23 and the binding energy was -98.86 kcal/mol. The compounds possess good gastro intestinal absorption with antioxidant property and exhibits minimum adverse effects. The obtained results support the toxin mitigating potential of the test compound with minimum adverse effects and hence vasicine can be regarded as a potential toxin binder of aflatoxin B1 and ochratoxin A, wherein it can be implemented for alleviating aflatoxicosis and ochratoxicosis.

Justicia carnea extracts ameliorated hepatocellular damage in streptozotocin-induced type 1 diabetic male rats via decrease in oxidative stress, inflammation and increasing other risk markers.

IntroductionDiabetes mellitus is still a raging disease not fully subdued globally, especially in Africa. Our study aims to evaluate the anti-diabetic potentials of Justicia carnea extracts [crude (JCC), free (JFP) and bound phenol (JBP) fractions], in streptozotocin (STZ)-induced type-1 diabetes in male albino rats.Materials and MethodsAbout thirty (30) animals were induced for type 1 diabetes with STZ; thereafter, treatment began for 14 days, after which the animals were euthanized, blood/serum was collected, the liver was removed and divided into two portions, for biochemical and histopathological analyses. Standard procedures were used to evaluate the liver biomarkers, like alanine transaminase (ALT), fructose-1,6-bisphosphatase, glucose-6- phosphatase, hexokinase activities, albumin, bilirubin, hepatic glucose concentrations; antioxidant status and pro- and anti-inflammatory cytokines were similarly assessed.ResultsThese results revealed that the extracts ameliorated the harmful effects of STZ-induced diabetes in the liver by enhancing the activities of liver-based biomarkers, reducing the concentrations of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine.DiscussionThe results agreed with previous research, and the free phenol fraction showed excellent results compared to othersConclusionThese suggested that J. carnea could serve as an alternative remedy in ameliorating liver complications linked to oxidative damage and inflammation in STZ-induced type-1 diabetes.

Potential of pyrroquinazoline alkaloids from Adhatoda vasica Nees. as inhibitors of 5-LOX - a computational and an in-vitro study.

Inflammation plays a major role in the onset and progression of many diseases related to the respiratory system. Cysteinyl leukotrienes, the products of 5-LOX are a potent bronchoconstrictor. Vasicine, vasicinone and deoxyvasicine are the pyrroquinazoline alkaloids of Adhatoda vasica that are well known for their bronchodilatory activity. The current investigation evaluates the 5-LOX inhibitory potential of these alkaloids. Molecular docking results indicated that these alkaloids have similar binding energy as that of Zileuton, a commercial drug. Analysis of the molecular dynamics simulations, the binding free energy derived from MM-PBSA and interaction entropy indicated that vasicinone (-8.33 kcal/mol) exhibited a binding free energy comparable to that of Zileuton (-8.52 kcal/mol). The in-vitro results indicate the potential of vasicinone as a competitive inhibitor, while the in-silico results highlighted the potential of vasicine and deoxyvasicine as allosteric inhibitors. A possible mechanism behind the activity exhibited by the plant was also determined, which emphasized the potential of these alkaloids as leads for the design of novel 5-LOX inhibitors.

Alkaloids of Adhatoda vasica Nees. as potential inhibitors of cyclooxygenases - an in-silico study.

Eicosanoid pathways play a crucial role in the progression and resolution of inflammation. NSAIDs act as anti-inflammatory agents by inhibiting both the isoforms of cyclooxygenases (COXs) whereas, COXIBs act as specific COX-2 inhibitors. Excessive usage of the same is linked with gastrointestinal bleeding and increased cardiovascular risk, respectively. The current in-silico study was aimed at evaluating the potential of major alkaloids of A. vasica (vasicine (VAS), vasicinone (VAE), and Deoxyvasicine (DOV)) as inhibitors of COXs. The results of the computed binding energy (ΔG) indicate that Celecoxib (CEL), DOV, and VAS have a higher affinity to COX-2, while VAE has a higher affinity to COX-1, and Mefenamic acid (MEF) was not selective. Among the alkaloids, VAE exhibited the best ΔG (of -8.2 kcal/mol) with COX-1, while VAS exhibited the best ΔG (of -8.2 kcal/mol) with COX-2. This was comparable to the ΔG exhibited by Mefenamic acid (-8.7 kcal/mol with both the COXs). With their potential to remain gastroprotective while having the ability to inhibit enzymes of both the prostaglandin and leukotriene pathways, the alkaloids of A. vasica could be promising leads for the design of Eicosanoid pathway modulators/inhibitors.Communicated by Ramaswamy H. Sarma.

Floral morphs of Justicia adhatoda L. differ in fruit and seed, but not floral, traits or pollinator visitation.

Pigment patterns in corollas are common, and act as nectar guides for pollinators. We discovered multiple floral morphs of Justicia adhatoda L. (Acanthaceae) with variable extents of corolla vein pigmentation in a population in Sariska, Rajasthan. Two floral morphs, one completely white and the other white with dark purple vein pigmentation, were compared in order to investigate any possible differences relating to: (a) corolla surface structure, (b) pollinator visitation, (c) reward for the pollinator, and (d) fitness parameters in the morphs. Both morphs showed similar UV reflectance, had distally located conical cells in petals, indicated similar pollinator visitation and had similar nectar content. Contrastingly, seed germination and seed weight were significantly higher in the purple-veined morph, while fruit set and seed set were higher in the white morph which also showed higher amounts of saturated fatty acids in the seeds. The results about aborted seeds differed inconsistently. Thus, variation in corolla pigmentation in J. adhatoda suggests fitness trade-off between the morphs with higher fruit and seed set, but lower seed germination and seed weight in the white morph compared to the purple-veined. We are led to the possibility of different selective pressures acting on the morphs and resulting in adaptive polymorphism.

Ultraviolet-B mediated biochemical and metabolic responses of a medicinal plant Adhatoda vasica Nees. at different growth stages.

In the present study, the effects of elevated UV-B (eUVB; ambient ± 7.2 kJ m-2 day-1) were evaluated on the biochemical and metabolic profile of Adhatoda vasica Nees. (an indigenous medicinal plant) at different growth stages. The results showed reduction in superoxide radical production rate, whereas increase in the content of hydrogen peroxide which was also substantiated by the histochemical localization. Malondialdehyde content, which is a measure of oxidative stress, did not show significant changes at any of the growth stages however photosynthetic rate and chlorophyll content showed reduction at all growth stages under eUV-B exposure. Increased activities of the enzymatic and non-enzymatic antioxidants were noticed except ascorbic acid, which was reduced under eUV-B exposure. The metabolic profile of A. vasica revealed 43 major compounds (assigned under different classes) at different growth stages. Triterpenes, phytosterols, unsaturated fatty acids, diterpenes, tocopherols, and alkaloids showed increment, whereas reduction in saturated fatty acids and sesquiterpenes were observed under eUV-B treatment. Vasicinone and vasicoline, the two important alkaloids of A. vasica, showed significant induction under eUV-B exposure as compared to control. Treatment of eUV-B leads to the synthesis of some new compounds, such as oridonin oxide (diterpene) and α-Bisabolol oxide-B (sesquiterpene), which possess potent anti-inflammatory and anticancerous activities. The study displayed that differential crosstalk between antioxidants and secondary metabolites at different growth stages, were responsible for providing protection to A. vasica against eUV-B induced oxidative stress and enhancing its medicinal properties.

Ionic liquid functionalized biogenic synthesis of AgAu bimetal doped CeO2 nanoparticles from Justicia adhatoda for pharmaceutical applications: Antibacterial and anti-cancer activities.

The noble metal such as Ag and Au doped CeO2 nanoparticles was successfully prepared by ionic liquid assisted hydrothermal method in the presence of Justicia adhatoda leaves extract and were used as an antibacterial and anticancer agent. The FT-IR and Raman spectrum exhibit the peaks at 460 and 464 cm-1 assigned to CeO stretching vibrations of NPs. The electron microscopic micrographs confirmed the spherical shaped morphology of prepared NPs. The insertion of Ag and Au ions into the CeO2 surface creates lattice defects the leads to reduce the band gap energy of Ag-Au/CeO2 at 3.15 eV. The XRD results suggested the average crystalline size of the silver­gold loaded CeO2 was 28 nm. From the elemental mapping images, we have visualized that existence and uniform distribution of Ag, Au, Ce, and O in the prepared nanomaterials. The antibacterial activity of unloaded and bimetal loaded CeO2 NPs was evaluated with Gram-positive and Gram-negative bacteria using disc diffusion assay. The AgAu loaded CeO2 NPs exhibited the highest zone of inhibition against E. coli and S. aureus strains when compared with pristine CeO2, Ag loaded CeO2, and Au loaded CeO2 NPs. In addition, the 100 µg mL-1 of CeO2, Ag/CeO2, Au/CeO2 and Ag-Au/CeO2 NPs exposed the 50, 51, 52 and 56% of anticancer activity against the HeLa cells respectively. Overall, this study concludes that the ionic liquid functionalized green synthesized bimetal loaded cerium oxide NPs showed potent antibacterial and anticancer activities.

Investigation of anti-inflammatory and anti-cancer activity of Justicia adathoda metabolites.

To analyse metabolic compounds of Justicia adathoda to evaluate against pathogens, inflammation and cervical cancer. The investigation exposed that the extracts of Justicia adathoda have potent metabolic to eradicate the human diseases. The antibacterial, tumorolytic and anti-inflammatory activity of ethyl acetate and aqueous extracts of Justicia adathoda (leaves) were assessed. In vitro anti-inflammatory activity was assessed by standard procedures. Justicia adathoda metabolic exhibit anticancer activity in human cervical cancer cell line (HeLa) (in vitro) analysis. Flavonoids, saponins, alkaloids, amino acids, tannins and terpenoids were present in both the extracts. The active components present in the extracts were found to be amino acids, alkaloids, lipids and triterpenoids which have antibacterial activity shows inhibition against Salmonella and Escherichia coli. Justicia adathoda possesses significant anti-inflammatory activity and it was confirmed by in-vitro analysis. The anticancer activity was found effective in human cervical cancer cell line (HeLa) (in-vitro) analysis. From the investigation could conclude that the metabolic compounds Justicia adathoda is effective against Anti-inflammation and ethyl acetate extract of Justicia adathoda are effective for Cancer.

Tocolytic activity assessment of the methanol leaf extract of Justicia flava Vahl (Acanthaceae) on mouse myometrial contractility and preliminary mass spectrometric determination of secondary metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Justicia flava are traditionally used in the South of Nigeria to prevent preterm births. AIM OF THE STUDY: In this study, the activity of the methanol leaf extract of J. flava (JF) was investigated on uterine contractility in non-pregnant and pregnant isolated mouse tissues. MATERIAL AND METHODS: The effects on spontaneous, oxytocin, and KCl-induced contractions were determined. The effects in calcium-free media were also determined. Possible mechanisms of activity were investigated using receptor and channel modulators. Mass spectrometric analysis was additionally performed on the leaf extract to identify secondary metabolites. RESULTS: JF was observed to inhibit spontaneous, oxytocin and high KCl-induced uterine contractility. JF also inhibited contractions in Ca2+-free media. JF was found to exert its inhibitory effect via interaction with inositol triphosphate and ryanodine receptors and also through modulation of K+- channels. Lignans and alkaloids were identified with the lignans being the most abundant in JF. CONCLUSION: JF has been shown to potently inhibit uterine contractions in non-pregnant and pregnant isolated mouse uterus. The inhibitory activity of JF has been shown to occur via blockade of extracellular and intracellular calcium entry and these effects may be due to the lignans identified in - JF. JF has therefore been shown in this study to be a lead plant in the discovery of new drugs with uterine inhibitory activity.

Ionic liquid - A greener templating agent with Justicia adhatoda plant extract assisted green synthesis of morphologically improved Ag-Au/ZnO nanostructure and it's antibacterial and anticancer activities.

Metal and metal oxide nanoparticles (NPs) possess significant properties that are promising materials for biological applications. In this research work, we prepared ionic liquid assisted Ag-Au/ZnO NPs, using J.adhatoda leaves extract by hydrothermal method. Ionic liquids performed as a stabilizing and templating agent to improve the surface morphology of the synthesized Ag and Au doped ZnO NPs. The prepared ZnO, Ag-doped ZnO, Au doped ZnO, and AgAu doped ZnO NPs exhibit the average crystalline size of 36, 34, 32, and 25 nm and their band gap energy values are 3.36, 3.29, 3.17, and 2.98 eV respectively. The XRD and UV-DRS result shows that after doping of Au and Ag the ZnO crystalline size and band gap energy was decreased, which leads to enhanced the biomedical (antibacterial and anticancer) properties of AgAu doped ZnO NPs. The Raman active mode of A1 (LO) and A1 (TO) showed that the formation of lattice defects due to the Ag and Au doping in the ZnO crystalline plane to improve the Ag-Au/ZnO properties. SEM and TEM images revealed that the prepared AgAu doped ZnO NPs exhibits nano stick shape with particle size range from 20 to 25 nm. The EDX spectrum and elemental mapping results confirmed that Ag and Au atoms are doped and spread over the ZnO NPs. The corresponding SAED pattern also confirms the crystallinity of Ag-Au/ZnO NPs. Furthermore, the synthesized Ag-Au/ZnO NPs has been explored for its antibacterial and anticancer activities. It shows good antibacterial activity against E.coli and S.aureus bacteria. Additionally, the Ag-Au/ZnO NPs show excellent anticancer activity against the HeLa cancer cells. The excellent antibacterial and anticancer results prove that the bi-metal (Ag and Au) doping can enhance the biomedical properties of ZnO NPs. It will be a promising material in the biomedical field.

Silver nanoparticles from Justicia spicigera and their antimicrobial potentialities in the biocontrol of foodborne bacteria and phytopathogenic fungi.

In the present work, the biosynthesis of silver-nanoparticles (AgNP) was evaluated using the aqueous extract from Justicia spicigera. The obtained silver nanoparticles were characterized using UV-visible spectroscopic techniques, energy dispersive X-ray spectrometers (EDS), zeta potential and dynamic light scattering. The antimicrobial activity of biosynthesized AgNP was tested against foodborne bacteria (Bacillus cereus, Klebsiella pneumoniae and Enterobacter aerogenes) and phytopathogenic fungi (Colletotrichum sp., Fusarium solani, Alternaria alternata and Macrophomina phaseolina). The elemental profile of synthesized nanoparticles using J. spicigera shows higher counts at 3keV due to silver, confirming the formation of silver nanoparticles. Scanning electron microscopy (SEM) analysis showed a particle size between 86 and 100nm with spherical morphology. AgNP showed effective antibacterial and antifungal activity against the tested organisms principally with B. cereus, K. pneumoniae, E. aerogenes, A. alternata and M. phaseolina. Therefore, further studies are needed to confirm the potential of AgNP from J. spicigera in the control of indicator organisms under field conditions.

Facile biological synthetic strategy to morphologically aligned CeO2/ZrO2 core nanoparticles using Justicia adhatoda extract and ionic liquid: Enhancement of its bio-medical properties.

In this study, a typical green synthesis route has approached for CeO2/ZrO2 core metal oxide nanoparticles using ionic liquid mediated Justicia adhatoda extract. This synthesis method is carried out at simple room temperature condition to obtain the core metal oxide nanoparticles. XRD, SEM and TEM studies employed to study the crystalline and surface morphological properties under nucleation, growth, and aggregation processes. CeO2/ZrO2 core metal oxides display agglomerated nano stick-like structure with 20-45nm size. GC-MS spectroscopy confirms the presence of vasicinone and N,N-Dimethylglycine present in the plant extract, which are capable of converting the corresponding metal ion precursor to CeO2/ZrO2 core metal oxide nanoparticles. In FTIR, the corresponding stretching for Ce-O and Zr-O bands indicated at 498 and 416cm-1 and Raman spectroscopy also supports typical stretching frequencies at 463 and 160cm-1. Band gap energy of the CeO2/ZrO2 core metal oxide is 3.37eV calculated from UV- DRS spectroscopy. The anti-bacterial studies performed against a set of bacterial strains the result showed that core metal oxide nanoparticles more susceptible to gram-positive (G+) bacteria than gram-negative (G-) bacteria. A unique feature of the antioxidant behaviors core metal oxides reduces the concentration of DPPH radical up to 89%. The CeO2/ZrO2 core metal oxide nanoparticles control the S. marcescent bio-film formation and restrict the quorum sensing. The toxicology behavior of CeO2/ZrO2 core metal oxide NPs is found due to the high oxygen site vacancies, ROS formation, smallest particle size and higher surface area. This type of green synthesis route may efficient and the core metal oxide nanoparticles will possess a good bio-medical agent in future.