Biological Evaluation and Binding Mechanism of 5-HT7 Specific Arylpiperazinyl-Alkyl Benzothiazolone: Radiobiology and Photo-physical Studies.

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.

Tobacco rattle virus-based virus-induced gene silencing (VIGS) as an aid for functional genomics in Saffron (Crocus sativus L.).

Several limitations in genetic engineering interventions in saffron exist, hindering the development of genetically modified varieties and the widespread application of genetic engineering in this crop. Lack of genome sequence information, the complexity of genetic makeup, and lack of well-established genetic transformation protocols limit its in planta functional validation of genes that would eventually lead toward crop optimization. In this study, we demonstrate agro infiltration in leaves of adult plants and whole corm before sprouting are suitable for transient gene silencing in saffron using Tobacco Rattle Virus (TRV) based virus-induced gene silencing (VIGS) targeting phytoene desaturase (PDS). Silencing of PDS resulted in bleached phenotype in leaves in both methods. TRV-mediated VIGS could be attained in saffron leaves and corms, providing an opportunity for functional genomics studies in this expensive spice crop. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01459-0.

CstPIF4 Integrates Temperature and Circadian Signals and Interacts with CstMYB16 to Repress Anthocyanins in Crocus.

Crocus sativus has emerged as an important crop because it is the only commercial source of saffron that contains unique apocarotenoids. Saffron is composed of dried stigmas of Crocus flower and constitutes the most priced spice of the world. Crocus floral organs are dominated by different classes of metabolites. While stigmas are characterized by the presence of apocarotenoids, tepals are rich in flavonoids and anthocyanins. Therefore, an intricate regulatory network might play a role in allowing different compounds to dominate in different organs. Work so far done on Crocus is focussed on apocarotenoid metabolism and its regulation. There are no reports describing the regulation of flavonoids and anthocyanins in Crocus tepals. In this context, we identified an R2R3 transcription factor, CstMYB16, which resembles subgroup 4 (SG4) repressors of Arabidopsis. CstMYB16 is nuclear localized and acts as a repressor. Overexpression of CstMYB16 in Crocus downregulated anthocyanin biosynthesis. The C2/EAR motif was responsible for the repressor activity of CstMYB16. CstMYB16 binds to the promoter of the anthocyanin biosynthetic pathway gene (LDOX) and reduces its expression. CstMYB16 also physically interacts with CstPIF4, which in turn is regulated by temperature and circadian clock. Thus, CstPIF4 integrates these signals and forms a repressor complex with CstMYB16, which is involved in the negative regulation of anthocyanin biosynthesis in Crocus. Independent of CstPIF4, CstMYB16 also represses CstPAP1 expression, which is a component of the MYB-bHLH-WD40 (MBW) complex and positively controls anthocyanin biosynthesis. This is the first report on identifying and describing regulators of anthocyanin biosynthesis in Crocus.

Morphological, phytochemical, and transcriptome analyses provide insights into the biosynthesis of monoterpenes in Monarda citriodora.

MAIN CONCLUSION: Morphological, phytochemical, and transcriptome analyses revealed candidate genes involved in the biosynthesis of volatile monoterpenes and development of glandular trichomes in Monarda citriodora. Monarda citriodora Cerv. ex Lag. is a valuable aromatic plant due to the presence of monoterpenes as major constituents in its essential oil (EO). Thus, it is of sheer importance to gain knowledge about the site of the biosynthesis of these terpenoid compounds in M. citriodora, as well as the genes involved in their biosynthesis. In this study, we studied different types of trichomes and their relative densities in three different developmental stages of leaves, early stage of leaf development (L1), mid-stage of leaf development (L2), and later stage of leaf development (L3) and the histochemistry of trichomes for the presence of lipid and terpenoid compounds. Further, the phytochemical analysis of this plant through GC-MS indicated a higher content of monoterpenes (thymol, thymoquinone, γ-terpinene, p-cymene, and carvacrol) in the L1 stage with a substantial decrease in the L3 stage of leaf development. This considerable decrease in the content of monoterpenes was attributed to the decrease in the trichome density from L1 to L3. Further, we developed a de novo transcriptome assembly by carrying out RNA sequencing of different plant parts of M. citriodora. The transcriptome data revealed several putative unigenes involved in the biosynthesis of specialized terpenoid compounds, as well as regulatory genes involved in glandular trichome development. The data generated in the present study build a strong foundation for further improvement of M. citriodora, in terms of quantity and quality of its essential oil, through genetic engineering.

Development and challenges in the discovery of 5-HT1A and 5-HT7 receptor ligands.

Serotonin (5-hydroxytryptamine) is a small molecule that acts both in the central and peripheral nervous system as a neurotransmitter and a hormone, respectively. Serotonin is synthesized via a multi-stage pathway beginning with l-tryptophan, which is converted by an enzyme called tryptophan hydroxylase into L-5-Hydroxytryptophan. It is well-known for its significance in the control of mood, anxiety, depression, and insomnia as well as in normal human functions such as sleep, sexual activity, and appetite. Thus, for medical chemists and pharmaceutical firms, serotonin is one of the most desirable targets. Among the seven different classes of serotonin receptors, the 5-HT1A was one of the first discovered serotonin receptors, and the 5-HT7 was the last addition to the serotonin receptor family. Both the classes were thoroughly examined. 5-HT1A neurotransmission-related dysfunctions are linked to many psychological conditions such as anxiety, depression, and movement disorders. 5-HT7 is a member of the cell surface receptor GPCR superfamily and is regulated by the serotonin neurotransmitter. It has been the focus of intensive research efforts since its discovery, which was prompted by its presence in functionally important regions of the brain. The thalamus and hypothalamus have the highest 5-HT7 receptor densities. They are also found in the hippocampus and cortex at higher densities. Thermoregulation, circadian rhythm, learning and memory, and sleep are all associated with the 5-HT7 receptor. It is also suspected that this receptor may be involved in the control of mood, indicating that it may be a beneficial target for depression treatment. Several differently structured molecules such as aminotetralins, ergolines, arylpiperazines, indolylalkylamines, aporphines, and aryloxyalkyl-amines are known to bind to 5-HT1A and 5-HT7 receptor sites. In brain serotonin receptors 5-HT1A and 5-HT7 are strongly co-expressed in regions involved in depression. However, their functional interaction has not been identified. An overview of the 5-HT1A and 5-HT7 receptor ligands belonging to different chemical groups is mentioned in this review.

The rose INFLORESCENCE DEFICIENT IN ABSCISSION-LIKE genes, RbIDL1 and RbIDL4, regulate abscission in an ethylene-responsive manner.

KEY MESSAGE: RbIDL1 and RbIDL4 are up-regulated in an ethylene-responsive manner during rose petal abscission and restored the Arabidopsis ida-2 mutant abscission defect suggesting functional conservation of the IDA pathway in rose. Abscission is an ethylene-regulated developmental process wherein plants shed unwanted organs in a controlled manner. The INFLORESCENCE DEFICIENT IN ABSCISSION family has been identified as a key regulator of abscission in Arabidopsis, encoding peptides that interact with receptor-like kinases to activate abscission. Loss of function ida mutants show abscission deficiency in Arabidopsis. Functional conservation of the IDA pathway in other plant abscission processes is a matter of interest given the discovery of these genes in several plants. We have identified four members of the INFLORESCENCE DEFICIENT IN ABSCISSION-LIKE family from the ethylene-sensitive, early-abscising fragrant rose, Rosa bourboniana. All four are conserved in sequence and possess well-defined PIP, mIDa and EPIP motifs. Three of these, RbIDL1, RbIDL2 and RbIDL4 show a three-fourfold increase in transcript levels in petal abscission zones (AZ) during ethylene-induced petal abscission as well as natural abscission. The genes are also expressed in other floral tissues but respond differently to ethylene in these tissues. RbIDL1 and RbIDL4, the more prominently expressed IDL genes in rose, can complement the abscission defect of the Arabidopsis ida-2 mutant; while, promoters of both genes can drive AZ-specific expression in an ethylene-responsive manner even in Arabidopsis silique AZs indicating recognition of AZ-specific and ethylene-responsive cis elements in their promoters by the abscission machinery of rose as well as Arabidopsis.

CstMYB1R1, a REVEILLE-8-like transcription factor, regulates diurnal clock-specific anthocyanin biosynthesis and response to abiotic stress in Crocus sativus L.

KEY MESSAGE: CstMYB1R1 acts as a positive regulator of Crocus anthocyanin biosynthesis and abiotic stress tolerance which was experimentally demonstrated through molecular analysis and over-expression studies in Crocus and Nicotiana. Regulatory mechanics of flavonoid/anthocyanin biosynthesis in Crocus floral tissues along the diurnal clock has not been studied to date. MYB proteins represent the most dominant, functionally diverse and versatile type of plant transcription factors which regulate key metabolic and physiological processes in planta. Transcriptome analysis revealed that MYB family is the most dominant transcription factor family in C. sativus. Considering this, a MYB-related REVEILLE-8 type transcription factor, CstMYB1R1, was explored for its possible role in regulating Crocus flavonoid and anthocyanin biosynthetic pathway. CstMYB1R1 was highly expressed in Crocus floral tissues, particularly tepals and its expression was shown to peak at dawn and dusk time points. Anthocyanin accumulation also peaked at dawn and dusk and was minimum at night. Moreover, the diurnal expression pattern of CstMYB1R1 was shown to highly correlate with Crocus ANS/LDOX gene expression among the late anthocyanin pathway genes. CstMYB1R1 was shown to be nuclear localized and transcriptionally active. CstMYB1R1 over-expression in Crocus tepals enhanced anthocyanin levels and upregulated transcripts of Crocus flavonoid and anthocyanin biosynthetic pathway genes. Yeast one hybrid (Y1H) and GUS reporter assay confirmed that CstMYB1R1 interacts with the promoter of Crocus LDOX gene to directly regulate its transcription. In addition, the expression of CstMYB1R1 in Nicotiana plants significantly enhanced flavonoid and anthocyanin levels and improved their abiotic stress tolerance. The present study, thus, confirmed positive role of CstMYB1R1 in regulating Crocus anthocyanin biosynthetic pathway in a diurnal clock-specific fashion together with its involvement in the regulation of abiotic stress response.

Evaluation of advanced, pathophysiologic new targets for imaging of CNS.

The inadequate information about the in vivo pathological, physiological, and neurological impairments, as well as the absence of in vivo tools for assessing brain penetrance and the efficiency of newly designed drugs, has hampered the development of new techniques for the treatment for variety of new central nervous system (CNS) diseases. The searching sites such as Science Direct and PubMed were used to find out the numerous distinct tracers across 16 CNS targets including tau, synaptic vesicle glycoprotein, the adenosine 2A receptor, the phosphodiesterase enzyme PDE10A, and the purinoceptor, among others. Among the most encouraging are [18 F]FIMX for mGluR imaging, [11 C]Martinostat for Histone deacetylase, [18 F]MNI-444 for adenosine 2A imaging, [11 C]ER176 for translocator protein, and [18 F]MK-6240 for tau imaging. We also reviewed the findings for each tracer's features and potential for application in CNS pathophysiology and therapeutic evaluation investigations, including target specificity, binding efficacy, and pharmacokinetic factors. This review aims to present a current evaluation of modern positron emission tomography tracers for CNS targets, with a focus on recent advances for targets that have newly emerged for imaging in humans.

Comprehensive analysis of codon usage pattern in Withania somnifera and its associated pathogens: Meloidogyne incognita and Alternaria alternata.

Meloidogyne incognita (Root-knot nematode) and Alternaria alternata (fungus) were among the dominant parasites of the medicinal plant Withania somnifera. Despite the fatal nature of their infection, a comprehensive study to explore their evolution and adaptation is lacking. The present study elucidates evolutionary and codon usage bias analysis of W. somnifera (host plant), M. incognita (root-knot nematode) and A. alternata (fungal parasite). The results of the present study revealed a weak codon usage bias prevalent in all the three organisms. Based on the nucleotide analysis, genome of W. somnifera and M. incognita was found to be A-T biased while A. alternata had GC biased genome. We found high similarity of CUB pattern between host and its nematode pathogen as compared to the fungal pathogen. Inclusively, both the evolutionary forces influenced the CUB in host and its associated pathogens. However, neutrality plot indicated the pervasiveness of natural selection on CUB of the host and its pathogens. Correspondence analysis revealed the dominant effect of mutation on CUB of W. somnifera and M. incognita while natural selection was the main force affecting CUB of A. alternata. Taken together the present study would provide some prolific insight into the role of codon usage bias in the adaptability of pathogens to the host's environment for establishing parasitic relationship.

Benzoxazolone-arylpiperazinyl scaffold-based PET ligand for 5-HT7 : Synthesis and biological evaluation.

Efforts are underway to improve the diagnosis and treatment for neurological disorders like depression, anxiety, epilepsy, and schizophrenia. The G-protein-coupled receptors (GPCRs) 5-HT7   receptor, the most recently identified member of 5-HT receptor family dysregulation has an association with various central nervous system (CNS) disorders and its ligands have an edge as potential therapeutics. Here, we report the synthesis, characterization, and biological evaluation of diversely substituted methoxy derivatives of 2-benzoxazolone arylpiperazine for targeting 5-HT7  receptors. Out of all derivatives, only C-2 substituted derivative, 3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)benzoxazol-2(3H)-one/ABO demonstrate a high affinity for human 5-HT7 receptors. [11 C]ABO was obtained by O-methylation of desmethyl-precursor using [11 C]CH3 OTf in the presence of NaOH giving a high radiochemical yield of 25 ± 12% (decay-corrected, n = 7) with stability up to 1.5 h postradiolabeling. In vitro autoradiography displays binding of [11 C]ABO in accordance with 5-HT7 distribution with a decrease of approximately 80% and 40% activity in the hippocampus and cerebellum brain region when administered with 10 µM cold ligand. Prefatory positron emission tomography scan results in Sprague-Dawley (SD) rat brain revealed fast and high radioactivity build-up in 5-HT7 receptor-rich regions, namely, the hippocampus (2.75 ± 0.16 SUV) and the cerebral cortex (2.27 ± 0.02 SUV) establishing selective targeting of [11 C]ABO. In summary, these pieces of data designate [11 C]ABO as a promising 5-HT7  receptor ligand that can have possible roles in clinics after its further optimization on different animal models.

Mechanical stress induces a scalable switch in cortical flow polarization during cytokinesis.

During animal development, cells need to sense and adapt to mechanical forces from their environment. Ultimately, these forces are transduced through the actomyosin cortex. How the cortex simultaneously responds to and creates forces during cytokinesis is not well understood. Here we show that, under mechanical stress, cortical actomyosin flow can switch polarization during cytokinesis in the C. elegans embryo. In unstressed embryos, longitudinal cortical flow contributes to contractile ring formation, while rotational cortical flow is additionally induced in uniaxially loaded embryos, i.e. embryos compressed between two plates. Rotational flow depends on astral microtubule signals and is required for the redistribution of the actomyosin cortex in loaded embryos. Rupture of longitudinally aligned cortical fibers during cortex rotation releases tension, initiates orthogonal longitudinal flow and, thereby, contributes to furrowing in loaded embryos. Moreover, actomyosin regulators involved in RhoA regulation, cortical polarity and chirality are all required for rotational flow, and become essential for cytokinesis under mechanical stress. In sum, our findings extend the current framework of mechanical stress response during cell division and show scaling of orthogonal cortical flows to the amount of mechanical stress.

Revisiting the role of TRAIL/TRAIL-R in cancer biology and therapy.

TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, can induce apoptosis in cancer cells, sparing normal cells when bound to its associated death receptors (DR4/DR5). This unique mechanism makes TRAIL a potential anticancer therapeutic agent. However, clinical trials of recombinant TRAIL protein and TRAIL receptor agonist monoclonal antibodies have shown disappointing results due to its short half-life, poor pharmacokinetics and the resistance of the cancer cells. This review summarizes TRAIL-induced apoptotic and survival pathways as well as mechanisms leading to apoptotic resistance. Recent development of methods to overcome cancer cell resistance to TRAIL-induced apoptosis, such as protein modification, combination therapy and TRAIL-based gene therapy, appear promising. We also discuss the challenges and opportunities in the development of TRAIL-based therapies for the treatment of human cancers.

Identification of tomato root growth regulatory genes and transcription factors through comparative transcriptomic profiling of different tissues.

Tomato is an economically important vegetable crop and a model for development and stress response studies. Although studied extensively for understanding fruit ripening and pathogen responses, its role as a model for root development remains less explored. In this study, an Illumina-based comparative differential transcriptomic analysis of tomato root with different aerial tissues was carried out to identify genes that are predominantly expressed during root growth. Sequential comparisons revealed ~ 15,000 commonly expressed genes and ~ 3000 genes of several classes that were mainly expressed or regulated in roots. These included 1069 transcription factors (TFs) of which 100 were differentially regulated. Prominent amongst these were members of families encoding Zn finger, MYB, ARM, bHLH, AP2/ERF, WRKY and NAC proteins. A large number of kinases, phosphatases and F-box proteins were also expressed in the root transcriptome. The major hormones regulating root growth were represented by the auxin, ethylene, JA, ABA and GA pathways with root-specific expression of certain components. Genes encoding carbon metabolism and photosynthetic components showed reduced expression while several protease inhibitors were amongst the most highly expressed. Overall, the study sheds light on genes governing root growth in tomato and provides a resource for manipulation of root growth for plant improvement. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12298-021-01015-0.

Expression of the tomato WRKY gene, SlWRKY23, alters root sensitivity to ethylene, auxin and JA and affects aerial architecture in transgenic Arabidopsis.

WRKY transcription factors (TFs) are a large plant-specific family of TFs that govern development and biotic/abiotic stress responses in plants. We have identified SlWRKY23 as a gene primarily expressed in roots. SlWRKY23 encodes a protein of 320 amino acids that functions as a transcriptional activator. It is transcriptionally up-regulated by ethylene, BAP and salicylic acid treatment but suppressed by IAA. Expression of SlWRKY23 in transgenic Arabidopsis affects sensitivity of roots to ethylene, JA and auxin with transgenic plants showing hypersensitivity to ethylene, JA and auxin-mediated primary root growth inhibition. This hypersensitivity is correlated with higher expression of ERF1 and ARF5 that mediate responses to these hormones. SlWRKY23 expression also affects aerial growth with transgenic plants showing greater number of leaves but smaller rosettes. Flowering time is reduced in transgenic lines and these plants also show a greater number of inflorescence branches, siliques and seeds. The siliques are longer and compactly packed with seeds but seeds are smaller in size. Root biomass shows a 25% decrease in transgenic SlWRKY23 Arabidopsis plants at harvest compared with controls. The studies show that SlWRKY23 regulates plant growth possibly through modulation of genes controlling hormone responses.

7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism.

Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anticancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant, which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in this study. Consistent with in vitro data, 7-HF caused substantial regression of tumour volume in a syngeneic mouse model of colon cancer. The molecule triggered extrinsic apoptotic pathway, which was evident as upregulation of DR4 and DR5 expression as well as induction of their downstream effector molecules (FADD, Caspase-8). Concurrent activation of intrinsic pathway was demonstrated with loss of ΔΨm to release pro-apoptotic cytochrome c from mitochondria and activation of downstream caspase cascades (Caspase -9, -3). Loss of p53 resulted in decreased sensitivity of cells towards pro-apoptotic effect of 7-HF with increased number of viable cells indicating p53-dependent arrest of cancer cell growth. This notion was further supported with 7-HF-mediated elevation of endogenous p53 level, decreased expression of MDM2 and transcriptional upregulation of p53 target genes in apoptotic pathway. However, 7-HF was equally effective in preventing progression of HCT116 p53+/+ and p53-/- cell derived xenografts in nude mice, which suggests that differences in p53 status may not influence its in vivo efficacy. Taken together, our results support 7-HF as a potential chemotherapeutic agent and provided a new mechanistic insight into its anticancer activity.

Trichoderma lixii (IIIM-B4), an endophyte of Bacopa monnieri L. producing peptaibols.

BACKGROUND: Exploration of microbes isolated from north western Himalayas for bioactive natural products. RESULTS: A strain of Trichoderma lixii (IIIM-B4) was isolated from Bacopa monnieri L. The ITS based rDNA gene sequence of strain IIIM-B4 displayed 99% sequence similarity with different Trichoderma harzianum species complex. The highest score was displayed for Hypocrea lixii strain FJ462763 followed by H. nigricans strain NBRC31285, Trichoderma lixii strain CBS 110080, T. afroharzianum strain CBS124620 and Trichoderma guizhouense BPI:GJS 08135 respectively. Position of T. lixii (IIIM-B4) in phylogenetic tree suggested separate identity of the strain. Microbial dynamics of T. lixii (IIIM-B4) was investigated for small peptides. Medium to long chain length peptaibols of 11 residue (Group A), 14 residue (Group B) and 17 residue (Group C) were identified using Matrix Assisted Laser Desorption/Ionization-Time of Flight (MALDI-TOF) mass spectrometer. Optimization is undeniably a desideratum for maximized production of desirable metabolites from microbial strain. Here optimization studies were carried out on T. lixii (IIIM-B4) using different growth media through Intact Cell Mass Spectrometry (ICMS). A multifold increase was obtained in production of 11 residue peptaibols using rose bengal medium. Out of these, one of them named as Tribacopin AV was isolated and sequenced through mass studied. It was found novel as having unique sequence Ac-Gly-Leu-Leu-Leu-Ala-Leu-Pro-Leu-Aib-Val-Gln-OH. It was found to have antifungal activity against Candida albicans (25 µg/mL MIC). CONCLUSION: In this study, we isolated a strain of T. lixii (IIIM-B4) producing medium and long chain peptaibols. One of them named as Tribacopin AV was found novel as having unique sequence Ac-Gly-Leu-Leu-Leu-Ala-Leu-Pro-Leu-Aib-Val-Gln-OH, which had antifungal properties.

Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition.

Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of ß amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD.

Phytofabricated silver nanoparticles of Phyllanthus emblica attenuated diethylnitrosamine-induced hepatic cancer via knock-down oxidative stress and inflammation.

Oxidative stress and inflammation play a pivotal role in the expansion and progression of hepatic cancer. Nanoparticle-based drug delivery can quickly enhance the restorative capability of hepatic cancer. Silver nanoparticles synthesized from plant source are of great importance due to their small size, economic, non-hazardous and different biomedical applications. In the current study, we have evaluated the impacts of oxidative stress and proinflammatory markers of biosynthesized silver nanoparticles of Phyllanthus emblica (PE) leaves against diethylnitrosamine-induced hepatocellular carcinoma (HCC) in wistar rats till 16 weeks with its underlying mechanism. The physico-chemical properties of biosynthesized silver nanoparticles were determined by ultra-visible spectroscopy, Fourier transform infrared spectroscopy, field emission scanning electron microscope, energy dispersive X-ray analysis, transmission electron microscopy and X-ray diffraction studies. Biofabricated silver nanoparticles (PEAgNPs) significantly enhanced the process of recovery from hepatic cancer in animal models, which was ascertained by increased body weight, reduced hepatic knobs on the outer surface of liver, downregulated serum biochemical parameters (ALT: 134.66 ± 2.60; AST: 120.33 ± 3.18; ALP: 153.33 ± 4.25; AFP: 167.33 ± 3.38), decreased hepatic lipid peroxidation (20.22 ± 1.74), increased membrane-bound enzymes (Na+/K+ATPase: 4.18 ± 0.20; Ca2+ATPase: 6.24 ± 0.12), increased antioxidants parameters (CAT: 64.89 ± 4.13; SOD: 6.01 ± 0.11; GPx: 8.55 ± 0.05), alteration in the level of proinflammatory cytokines (TNF-α: 90.15 ± 5.77; NF-κB: 173.29 ± 7.26; IL-6: 178.11 ± 3.16; IL-1ß: 48.26 ± 1.89) and histopathological studies. Our outcomes implicate successfully biofabrication of silver nanoparticles and exhibited a chemoprotective potential in the prevention and intervention of hepatocellular carcinoma.

Identification of Phytoconstituents in Leea indica (Burm. F.) Merr. Leaves by High Performance Liquid Chromatography Micro Time-of-Flight Mass Spectrometry.

Leea indica (Vitaceae) is a Southeast Asian medicinal plant. In this study, an ethyl acetate fraction of L. indica leaves was studied for its phytoconstituents using high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-microTOF-Q-MS/MS) analysis. A total of 31 compounds of different classes, including benzoic acid derivatives, phenolics, flavonoids, catechins, dihydrochalcones, coumarins, megastigmanes, and oxylipins were identified using LC-MS/MS. Among them, six compounds including gallic acid, methyl gallate, (-)-epigallocatechin-3-O-gallate, myricetin-3-O-rhamnoside, quercetin-3-O-rhamnoside, and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-ß-d-glucopyranoside were isolated and identified by NMR analysis. The LC-MS/MS analysis led to the tentative identification of three novel dihydrochalcones namely 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-rutinoside, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-glucosylpentoside and 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-(3″-O-galloyl)-ß-d-glucopyranoside. The structural identification of novel dihydrochalcones was based on the basic skeleton of the isolated dihydrochalcone, 4',6'-dihydroxy-4-methoxydihydrochalcone 2'-O-ß-d-glucopyranoside and characteristic LC-MS/MS fragmentation patterns. This is the first comprehensive analysis for the identification of compounds from L. indica using LC-MS. A total 24 compounds including three new dihydrochalcones were identified for the first time from the genus Leea.

Iodine-NH4OAc mediated regioselective synthesis of 2-aroyl-3-arylimidazo[1,2-a]pyridines from 1,3-diaryl-prop-2-en-1-ones.

The present protocol describes an efficient, metal-free regioselective synthesis of 2-aroyl-3-arylimidazo[1,2-a]pyridines from 1,3-diaryl-prop-2-en-1-ones and 2-aminopyridine. The iodine-NH4OAc promoted reaction offers a novel route in the synthesis of 2-aroyl-3-arylimidazo[1,2-a]pyridines. This protocol offers significant flexibility in accessing medicinally important 2-aroyl-3-arylimidazo[1,2-a]pyridines with various substitution patterns.