This study reported the profiling and the in-silico analysis of the therapeutic potential of proteins/peptides (for Alzheimer disease) isolated from Tinospora cordifolia, Evolvulus alsinoides, Centella asiatica and Convolvulus pluricaulis. The proteins/peptides were extracted by using four different pH based buffer solutions. The trypsin digested proteins/peptides were analyzed by LC-MS/MS based peptide mass fingerprinting which showed the presence of high number of proteins/peptides involved in regulating the oxidative stress. The sequential purification with 10 kDa and 3 kDa cut-off ultrafiltration membranes for buffer based extracted proteins/peptides was performed. The evaluation of crude and these filtrates revealed the highest antioxidant potential for 3 kDa cut-off filtrate of 0.1 M Tris HCl buffer (pH 8.0) from FRAP, DPPH, ABTS and NOS assays. The presence of peptides in 3 kDa cut-off filtrates was detected by HPLC, identified by MALDI-TOF MS and the fragmentation pattern was obtained by LC-MS/MS. The in-silico docking study revealed that the identified peptides showed the highest binding affinity against the Alzheimer targets (BACE1, nAChR, Aβ, AChE, GSK-3β, JNK). Thus, the findings of this study provided the preliminary evidence for the antioxidant and neuroprotective potential of the selected medicinal plants, by supporting their relevance in delaying the onset of neurodegeneration and highlighting their prospects for drug development.

Seagrass meadows, often referred to as the "lungs of the sea," are vital marine angiosperms in the coastal ecosystem. This study focuses on the metabolic profiling, mineral quantification, and antioxidant potential of five seagrass species from the Gulf of Mannar, India: Halodule uninervis, Thalassia hemprichii, Enhalus acoroides, Cymodocea serrulata, and Syringodium isoetifolium. FTIR and MRS confirmed the presence of sulfate esters and sulfate stretching. The GC-MS based metabolites identified common compounds were such as n-hexadecenoic acid, phytol, cyclic octa-atomic sulfur, and 3,7,11,15-Tetramethyl-2-hexadecen-1. The ICP-OES quantification revealed high amounts of essential elements like magnesium, calcium, and sulfur, which were further confirmed by EDAX and flame photometry. Among the solvent extracts, hexane extract demonstrated the highest antioxidant potential in S. isoetifolium, showing the most potent inhibition of 90.19 %, 96.09 %, 55.75 %, and 57.44 % in DPPH, ABTS, FRAP, and NOS assays, respectively.

Autophagy, a highly conserved and essential catabolic phenomenon transports cytoplasmic cargos to the lysosome for degradation. Dysfunctions of autophagy process are linked with several cancers. Significantly, UNC-51 like kinase 1 (ULK1) plays a major role in autophagy initiator. Over expression of ULK1 is found to be important in several cancers. Thus, inhibition of ULK1 may prevent variety of cancers. In this present study, Protein-protein interaction network analysis was carried out for ULK1. In this work, through network analysis, interactions of ULK1 with autophagy related functional proteins could be established which will be useful for attempts to target such interactions. E-pharmacophore models were generated and screened against chemical databases. Further, molecular docking, MD simulations and detailed trajectory analyses were carried out. Though all Leads are found with favourable binding, Lead 2 is ranked top based on protein directional motion analysis, interaction profiling with active site/hinge region, conformational stabilization and MMGBSA analysis. Also, in vitro experimental anticancer activity studies reveal that Lead 2 possess better inhibitory activity against MCF-7 and MDA-MB-231 cells, with IC50 values of 5 μM, 8 μM, respectively.

In the present study, three red algae samples, Acanthophora spicifera, Hypnea musciformis and Gelideilla acerosa, collected from Mandapam Coast, Gulf of Mannar, India, were extracted using polar solvents (Ethanol and Acetone) and non-polar solvents (Hexane and Chloroform). The crude extract of each alga was subjected to GCMS (Agilent 7890B; 5977A) analysis. A total of 288 compounds from all three red algae were identified. Of the 146 compounds identified in A. spicifera, 10 compounds have been commonly identified in all three solvents (hexane, ethanol and chloroform); another six compounds in ethanol and chloroform; five compounds in hexane and ethanol and another ten compounds in hexane and chloroform. Totally, 109 compounds have been identified in H. musciforms, only one compound, n-Hexadecanoic acid, was reported in all three solvents (hexane, ethanol and chloroform), and another 12 compounds have been commonly identified from ethanol and chloroform extracts. In G. acerosa, out of 151 compounds, seven compounds were identified commonly in ethanol and eleven in acetone and chloroform extracts. Overall the present study concludes that 32, 11, and 49 compounds identified were specific for hexane, ethanol and chloroform extracts of H. musciforms, respectively; 38, 27, and 42 compounds from ethanol, hexane and chloroform extracts of A. spicifera, respectively and exclusively 47, 35, and 35 different compounds in acetone, ethanol and chloroform extracts of G. acerosa, respectively. Therefore, the isolation of bioactive compounds is found to be polarity-specific. n-Hexadecanoic acid was the major constituent identified from A. spicifera in all three solvent extractions; in H. musciformis and in G. acerosa, only the acetone extract showed the highest peak area for n-Hexadecanoic acid. Seventy-one compounds identified through this study are yet to be reported in algae of India or elsewhere, and many of them have been found to have no report of biological activities. Therefore, these compounds would be evaluated, which will have a source for new drug candidates for communicable and non-communicable diseases. Further, the antimicrobial properties of crude extracts of all three red algae were tested using human pathogens (bacteria and fungi). The results revealed stronger antifungal activity against Candida sp. with hexane and chloroform extracts of H. musciformis and ethanol extracts of G. acerosa, whereas the antibacterial activity of H. musciformis extracts was stronger against all four human pathogenic bacteria than that of the other two red algae tested in this study. Therefore, the purification of compounds specific for antibacterial and antifungal properties from marine red algae may pave the way for new drug leads for the treatment of various human diseases.

Our group has previously reported on (E)-4-(1-(2-(5-(4-chlorophenyl)thiazol-2-yl)hydrazono)ethyl)phenol (3a) as an antiviral agent against DENV with an EC50 of 1.32 μM. In this study, we present the X-ray crystallographic structure and in vitro ADME profile of compound 3a. Additionally, to optimize 3a, we synthesized four derivatives (3b-3e) using an active analogue approach. The newly synthesized and characterized compounds were screened for antiviral activity against DENV via a virus reduction assay (RT-qPCR). Among them, compound 3c emerged as the most potent, with an EC50 of 0.01 μM and a selectivity index (SI) of 200. This compound was found to be 132 times more potent than 3a, although its toxicity was 63 times higher than that of 3a. Despite this, its selectivity index was twofold higher than that of compound 3a. In vitro permeability and metabolic stability studies showed that compound 3a exhibited permeability issues but demonstrated metabolic stability in both rat and human liver microsomes. In vivo pharmacokinetic studies in male rats revealed a bioavailability (F) of 6 % and a half-life (T1/2) of 1.75 h for compound 3a. The in vivo pharmacokinetic results for compound 3c suggest that it may require an appropriate formulation strategy to enhance its pharmacokinetic parameters.

In the crystal structure of the title chalcone derivative, C30H23NO2, the molecule adopts an s-cis conformation with respect to the C=O and C=C bonds. The triphenylamine moiety has a propeller-type shape, with dihedral angles between the mean planes of pairs of phenyl rings of 72.1 (6), 69.7 (1) and 65.6 (6)°. In the crystal, molecules are linked by C—H...O hydrogen bonds, forming chains extending parallel to [010]. In addition, weak C—H...π interactions consolidate the crystal packing. One of the phenyl rings of the triphenylamine moiety is disordered over two sets of sites.

Aerva lanata and Aerva javanica, belonging to the Amaranthaceae family, are significant and widely utilized plants because of their pharmacological and therapeutic properties, such as anti-inflammatory, antiasthmatic, anthelmintic, antidiabetic, anti-urolithiasis, etc. Thus, this study aimed to profile bioactive compounds, quantify minerals, and evaluate their bioactive properties from both plants. The FTIR and Raman spectra revealed characteristic functional groups like amines, alkyl halides, alcohols, and carboxylic acids. The XRD analysis demonstrated the crystallinity and phases of the minerals present in both plants. The mineral quantification by using EDAX, XRF, and ICP-OES revealed that A. lanata was found to be rich in calcium and magnesium minerals, while A. javanica contained high levels of potassium. The presence of thiazolidin-4-one, linoleic acid, barrigenol R1, lupeol, colchicine, etc. in A. lanata and vanillin lactoside, sinapic acid, oleic acid, ingol 12-acetate, etc. in A. javanica was identified by GC-MS analysis. The methanolic extract of A. lanata and A. javanica exhibited the strongest antioxidant activity in DPPH and ABTS assays. The xanthine oxidase (XO) inhibitor assay evaluated that the methanolic extracts contained potent XO inhibitor compounds. The in vitro anti-urolithiatic assay showed the diminished crystal size and growth of CaOx by inhibiting the kidney stone formation. Similarly, zeta potential analysis showed the reduction in the size of the crystal over different time intervals. Thus, this study highlighted A. lanata and A. javanica as valuable natural agents for renal lithiasis treatment, owing to their abundant mineral content, diverse bioactive compounds, strong antioxidant activity, and effective antiurolithiatic properties.

This study focuses on analyzing the rhizomes of two ginger varieties and four turmeric varieties to explore their phytochemical profiles using GC–MS analysis, determine minerals and mineral oxides content by XRD and ICP-OES, identify functional groups using FTIR, and evaluate antioxidant activities. Polarity-based organic solvents were employed to extract major metabolites from rhizomes. A total of 21 and 66 bioactive compounds were detected in ginger and turmeric varieties, respectively, in all three solvents used for extraction. The ICP-OES revealed 5.908 mg/kg of calcium in the rhizomes of black ginger (BG) and blue turmeric (BT) in mineral quantification. Flame photometer analysis indicated high sodium in the BG rhizome and higher potassium content in the BT rhizome. XRD analysis of black turmeric revealed the presence of ciclopirox olamine monohydrate, known for its antifungal activity, while BG showed the presence of a complex containing N-(4-Nitrophenyl)-3-(4-methoxyphenyl)-2-propenimine. FTIR reported the presence of alkyl halides and aromatic functional groups in BG and BT. Higher starch content was quantified in blue turmeric rhizomes. Furthermore, the methanolic extract of rhizomes exhibited the highest antioxidant activity among all assays tested, particularly in black ginger and blue turmeric varieties. Thus, diverse chemical and structural characteristics of rhizomes varieties provide valuable insights on stress-induced metabolite production in medicinal plants, emphasizing that stressors can amplify bioactive compounds synthesis and enhance therapeutic properties.

Fenugreek (Trigonella foenum-graecum) is an annual dicotyledonous plant belonging to the Fabaceae family. Germination of fenugreek seeds improves its nutritional profile, and it is traditionally consumed worldwide to regulate blood glucose levels, manage the menstrual cycle, and reduce body heat. However, the metabolite differences between germinated and ungerminated seeds remain underexplored. The primary objective of this study is to profile bioactive metabolites that are differentially expressed in raw fenugreek seeds, soaked seeds (12 h), and germinated seeds. Seeds were soaked for 12 h, consistent with traditional methods used in Indian households to sprout fenugreek for consumption. After soaking, seeds were germinated for 24 and 36 h, and freeze dried. The seeds were then ground into powder, and metabolites were extracted using hexane, dichloromethane, and methanol for gas chromatography-mass spectrometry (GC–MS) analysis. Proteins were also extracted from the seeds and analyzed by LC–MS/MS-based peptide mass fingerprinting following trypsin digestion. GC–MS analysis revealed several bioactive metabolites present in germinated seeds compared to ungerminated seeds. Molecular docking studies for selected compounds were performed against targets such as Human Aldose Reductase (ALR2), Cyclooxygenase-2 (COX-2), Cytochrome P450, Protein Kinase B, and the epidermal growth factor receptor to evaluate their antidiabetic, anti-inflammatory, antibacterial, anticancer, and antioxidant activities. The differentially expressed proteins were also profiled, revealing involvement in biological functions such as ion channel movement, translation, regulation of cell cycle progression, and signal transduction pathways. These proteins were found to be glycosylated, phosphorylated, and, in some cases, acetylated. These findings suggest that germinated fenugreek seeds are rich in nutraceutical compounds. Further research to identify peptides with potent biological activity could have significant implications for the nutraceutical industry.

In this study, five seagrass species Halodule uninervis, Thalassia hemprichii, Enhalus acoroides, Cymodocea serrulata, and Syringodium isoetifolium collected from the Mandapam coastal region of Rameswaram (Palk Bay region), Tamil Nadu, India, were selected to identify the antioxidant-rich proteins/peptides. The primary objective was to identify the proteins/peptides present in these seagrass filtrates extracted by using four different pH-based buffer extracts and to assess their antioxidant activity. Among the various buffer extracts, 0.1 M Citrate buffer (pH 5.5) exhibited the highest proteins/peptides recovery in all species. Of these, S. isoetifolium showed the highest recovery percentage (20.18 %) in the 10 kDa filtrate. Notably, the 3 kDa filtrate of S. isoetifolium demonstrated the highest antioxidant activity (83 %). The peptides sequences in all five seagrass samples were identified by MALDI - TOF MS analysis, Furthermore, in silico protein-peptide docking studies were conducted to assess the interaction of the identified peptides with key antioxidant-related targets, including superoxide dismutase, xanthine oxidase, inducible nitric oxide synthase, keap 1 protein, and myeloperoxidase. With all these targets, the peptide derived from S. isoetifolium exhibited better binding affinity. This study emphasized that the potential peptides identified from seagrass are the natural antioxidant sources that can be used to treat disorders linked to oxidative stress.

The ‘Severe Acute Respiratory Syndrome – Corona Virus -2’ (SARS-CoV2), identified first in China on 31st December 2019, immediately became a pandemic health concern. ‘Coronavirus Disease–2019’ (COVID-19) outbreak wasdeclared a global pandemic by the WHO in March 2020. More than 4,786,203 people died as a result of this illness, and about 233,908,734 people worldwide had been infected as of 1 st October 2021. Multi-organ involvement of COVID-19 often leads to death and other complications like cerebrovascular and various thyroid diseases. As SARS-CoV-2 has a level of resemblance with SARS-CoV, the antivirals used earlier have been attempted in the COVID-19 treatment. Proposing new antivirals is a lengthy process for SARSCoV2, and drug repurposing is also another route to reduce the number of deaths. SARS-CoV-2-infected patients who already have diseases like diabetes, hypertension, etc., are at more risk. Using phytocompounds as a control of SARS-CoV2 is also the need of the hour as the side effects of these are expected to be very less compared to the synthetic ones or vaccines. This review covers the above aspects in detail and reports the outcomes for the past few years period. The use of bioinformatics tools is also emphasized in this chapter.

Nutraceuticals can be utilized to improve wellness, reduce the rate of aging, avert chronic diseases, prolong life, andkeep the body in good shape. Because of their excellent nutritive, safety, as well as potential health benefits, nutraceuticals have lately received considerable interest. Supplementing the diet can help fulfill the increased nutritional requirements of one’s highly demanding lifestyle or health condition. Stress, health problems, and a vigorous lifestyle can all lead to an increased demand for very precise minerals or vitamins in the body. This article provides insight into various plant compounds that have therapeutic properties and that can be used as health supplements with nutraceutical activities.

The ancient Indian Siddha medicine system, practiced for thousands of years, is now receiving widespread recognition globally. "Siddha" system of medicine is one among the Indian traditional system of medicine that has its roots in Tamil culture. This study seeks to explore and document the diverse practices and medicinal remedies employed by Siddha practitioners. The Siddha formulations include oil-medicated herbal products and thailam, an oil formulation that contains drugs and raw extracts. Kuzhithailam is a specially prepared oil in the Siddha system by a destructive distillation process called the pudam process. Amukkara (Withania somnifera) and neem (Azadirachta indica) Kuzhithailams are two among the formulations. Neem, a popular herb for skin infections and general health because of its antibacterial, anti-inflammatory, and blood-purifying properties. Amukkara plant kizhangu helps mental health, boosts energy, and maintains hormonal balance. The current study investigates the metabolites of amukkara (AMKT) and neem Kuzhithailams (NMKT) by GC–MS and LC–MS/MS. Mass spectrometric analysis of AMKT and NMKT revealed the presence of metabolites belonging to different groups, including saturated and unsaturated fatty acids, phenolics, vitamins, terpenoids, and sterols. The alkaloid compounds, including withasomnine, pseudopelletierine, hygroline, and tigloidine, were detected in AMKT. Gedunin, nimbolide, 6-desacetylnimbin, 28-deoxonimbolide, azadiradione, nimbin, salannin, 2-monomyrsitin, and salannol were detected in NMKT. The Kuzhithailams possessed antioxidant activities, NMKT was observed to has a higher antioxidant capacity than AMKT. The bioactive compounds of neem Kuzhithailam have moieties like hydroxyl, ketone, conjugated double bonds, lactone etc. which stabilize the free radicals and contribute to higher antioxidant properties of NMKT compared to AMKT.

Psoriasis is a chronic immune-mediated inflammatory skin disease that involves dysregulated proliferation of keratinocytes. Psoriatic skin lesions are characterized by redness, thickness, and scaling. The interleukin axis of IL-23/IL-17 is critically involved in the development of human psoriasis. Imiquimod (IMQ), an agonist of TLR7 is known to induce psoriatic-like skin inflammation in mice. The topical application of IMQ induces systemic inflammation with increased proinflammatory cytokines in serum and secondary lymphoid organs. Further, matrix metalloproteases (MMPs) have been implicated in the pathophysiology of psoriatic-like skin inflammation. The increased MMP9 activity and gene expression of proinflammatory cytokines in IMQ-induced psoriatic skin is mediated by the activation of the MAPK pathway. Moreover, the increased expression of neutrophil-specific chemokines confirmed the infiltration of neutrophils at the site of psoriatic skin inflammation. In contrast, expression of IL-10, an anti-inflammatory cytokine gene expression is reduced in IMQ-treated mice skin. Topical application of unconjugated bilirubin (UCB) and its derivative dimethyl ester of bilirubin (BD1) on IMQ-induced psoriatic mice skin significantly mitigated the symptoms of psoriasis by inhibiting the activity of MMP9. Further, UCB and BD1 reduced neutrophil infiltration as evidenced by decreased myeloperoxidase (MPO) activity and reduced gene expression of proinflammatory cytokines, and neutrophil-specific chemokines. Apart from these modulations UCB and BD1 reduced MAPK phosphorylation and upregulated anti-inflammatory cytokines. To conclude, UCB and BD1 immunomodulated the psoriatic skin inflammation induced by IMQ in mice by inhibiting neutrophil mediated MMP9, decreased proinflammatory cytokines gene expression and modulating the MAPK pathway.

The goal of drug discovery is to locate lead compounds and novel compounds that have certain features and potential to be developed into drugs to treat diseases. The application of machine learning (ML), a branch of artificial intelligence (AI), has led to its widespread adoption as an essential component in modern computer applications in recent decades. The establishment of fresh models requires the development of new ML and AI algorithms. These tools are particularly useful in the area of quantitative structure–activity relationships (QSARs). One ML algorithm, random forest, was recently introduced to develop QSAR for predicting biological activity of compounds based on the description of the compounds' molecular structures. It also provides a variable that is of crucial importance to the measurement of the reduction wrapper algorithm. In this chapter, we focus on the various AI and ML algorithms that have been used in recent years of research, specifically on QSAR, to analyze the state of the art in the drug development process. These algorithms have also been used to model the molecular data and biological problems that are used in the drug discovery process. In addition, we have included in this chapter an overview of the fundamentals of QSAR in drug discovery as well as a discussion of the research tools that are now accessible.

In recent years, there has been a surge of interest in nutraceuticals, which offer health advantages and are alternatives to the existing treatment. Nutraceuticals can be extracted, incorporated as dietary supplements, and added to foods. Nutrients, herbs, and dietary supplements are the primary components of nutraceuticals that make them useful for preserving health, combating various diseases, and enhancing the quality of life. The booming expansion, research advancements, marketing fervor, quality control, and regulation will have a significant impact on their success or failure. The intention of this review is to evaluate the principal nutraceuticals that have an important function in the mitigation and cure of infectious as well as non-infectious illnesses.

Sphingosine kinases (SphKs) are a group of important enzymes that circulate at low micromolar concentrations in mammals and have received considerable attention due to the roles they play in a broad array of biological processes including apoptosis, mutagenesis, lymphocyte migration, radio- and chemo-sensitization, and angiogenesis. In the present study, we constructed three classification models by four machine learning (ML) algorithms including naive bayes (NB), support vector machine (SVM), logistic regression, and random forest from 395 compounds. The generated ML models were validated by fivefold cross validation. Five different scaffold hit fragments resulted from SVM model-based virtual screening and docking results indicate that all the five fragments exhibit common hydrogen bond interaction a catalytic residue of SphK1. Further, molecular dynamics (MD) simulations and binding free energy calculation had been carried out with the identified five fragment leads and three cocrystal inhibitors. The best 15 fragments were selected. Molecular dynamics (MD) simulations showed that among these compounds, 7 compounds have favorable binding energy compared with cocrystal inhibitors. Hence, the study showed that the present lead fragments could act as potential inhibitors against therapeutic target of cancers and neurodegenerative disorders.