Carbon dot unravels accumulation of triterpenoid in Evolvulus alsinoides hairy roots culture by stimulating growth, redox reactions and ANN machine learning model prediction of metabolic stress response.

Evolvulus alsinoides, a therapeutically valuable shrub can provide consistent supply of secondary metabolites (SM) with pharmaceutical significance. Nonetheless, because of its short life cycle, fresh plant material for research and medicinal diagnostics is severely scarce throughout the year. The effects of exogenous carbon quantum dot (CD) application on metabolic profiles, machine learning (ML) prediction of metabolic stress response, and SM yields in hairy root cultures of E. alsinoides were investigated and quantified. The range of the particle size distribution of the CDs was between 3 and 7 nm. The CDs EPR signal and spin trapping experiments demonstrated the formation of O2-•spin-adducts at (g = 2.0023). Carbon dot treatment increased the levels of hydrogen peroxide and malondialdehyde concentrations as well as increased antioxidant enzyme activity. CD treatments (6 µg mL-1) significantly enhanced the accumulation of squalene and stigmasterol (7 and 5-fold respectively). The multilayer perceptron (MLP) algorithm demonstrated remarkable prediction accuracy (MSE value = 1.99E-03 and R2 = 0.99939) in both the training and testing sets for modelling. Based on the prediction, the maximum oxidative stress index and enzymatic activities were highest in the medium supplemented with 10 µg mL-1 CDs. The outcome of this study indicated that, for the first time, using CD could serve as a novel elicitor for the production of valuable SM. MLP may also be used as a forward-thinking tool to optimize and predict SM with high pharmaceutical significance. This study would be a touchstone for understanding the use of ML and luminescent nanomaterials in the production and commercialization of important SM.

Deciphering the Anticancer Arsenal of Piper longum: Network Pharmacology and Molecular Docking Unveil Phytochemical Targets Against Lung Cancer.

Introduction: Lung cancer, characterized by uncontrolled cellular proliferation within the lung tissues, is the predominant cause of cancer-related fatalities worldwide. The traditional medicinal herb Piper longum has emerged as a significant contender in oncological research because of its documented anticancer attributes, suggesting its potential for novel therapeutic development. Methods: This study adopted network pharmacology and omics methodology to elucidate the anti-lung cancer potential of P. longum by identifying its bioactive constituents and their corresponding molecular targets. Results: Through a comprehensive literature review and the Integrated Medicinal Plant Phytochemistry and Therapeutics database (IMPPAT), we identified 33 bioactive molecules from P. longum. Subsequent analyses employing tools such as SwissTargetPrediction, SuperPred, and DIGEP-Pred facilitated the isolation of 676 potential targets, among which 72 intersected with 666 lung cancer-associated genetic markers identified through databases including the Therapeutic Target Database (TTD), Online Mendelian Inheritance in Man (OMIM), and GeneCards. Further validation through protein-protein interaction (PPI) networks, gene ontology, pathway analyses, boxplots, and overall survival metrics underscored the therapeutic potential of compounds such as 7-epi-eudesm-4(15)-ene-1ß, demethoxypiplartine, methyl 3,4,5-trimethoxycinnamate, 6-alpha-diol, and aristolodione. Notably, our findings reaffirm the relevance of lung cancer genes, such as CTNNB1, STAT3, HIF1A, HSP90AA1, and ERBB2, integral to various cellular processes and pivotal in cancer genesis and advancement. Molecular docking assessments revealed pronounced affinity between 6-alpha-diol and HIF1A, underscoring their potential as therapeutic agents for lung cancer. Conclusion: This study not only highlights the bioactive compounds of P. longum but also reinforces the molecular underpinnings of its anticancer mechanism, paving the way for future lung cancer therapeutics.

Network pharmacology: an efficient but underutilized approach in oral, head and neck cancer therapy-a review.

The application of network pharmacology (NP) has advanced our understanding of the complex molecular mechanisms underlying diseases, including neck, head, and oral cancers, as well as thyroid carcinoma. This review aimed to explore the therapeutic potential of natural network pharmacology using compounds and traditional Chinese medicines for combating these malignancies. NP serves as a pivotal tool that provides a comprehensive view of the interactions among compounds, genes, and diseases, thereby contributing to the advancement of disease treatment and management. In parallel, this review discusses the significance of publicly accessible databases in the identification of oral, head, and neck cancer-specific genes. These databases, including those for head and neck oral cancer, head and neck cancer, oral cancer, and genomic variants of oral cancer, offer valuable insights into the genes, miRNAs, drugs, and genetic variations associated with these cancers. They serve as indispensable resources for researchers, clinicians, and drug developers, contributing to the pursuit of precision medicine and improved treatment of these challenging malignancies. In summary, advancements in NP could improve the globalization and modernization of traditional medicines and prognostic targets as well as aid in the development of innovative drugs. Furthermore, this review will be an eye-opener for researchers working on drug development from traditional medicines by applying NP approaches.

Comprehensive in vitro and in vivo evaluation of therapeutic potential of Bacopa-derived asiatic acid against a human oral pathogen Streptococcus mutans.

Dental caries is a common human oral disease worldwide, caused by an acid-producing bacteria Streptococcus mutans. The use of synthetic drugs and antibiotics to prevent dental caries has been increasing, but this can lead to severe side effects. To solve this issue, developing and developed countries have resorted to herbal medicines as an alternative to synthetic drugs for the treatment and prevention of dental caries. Therefore, there is an urgent need for plant-derived products to treat such diseases. Bacopa monnieri, a well-documented medicinal plant, contains 52 phytocompounds, including the pentacyclic triterpenoid metabolite known as asiatic acid (ASTA). Hence, this study aimed to demonstrate, for the first time, the antibacterial activity of phytocompound ASTA against S. mutans. The findings revealed that ASTA significantly inhibited the growth of S. mutans and the production of virulence factors such as acidurity, acidogenicity, and eDNA synthesis. Molecular docking analysis evaluated the potential activity of ASTA against S. mutans virulence genes, including VicR and GtfC. Furthermore, toxicity assessment of ASTA in human buccal epithelial cells was performed, and no morphological changes were observed. An in vivo analysis using Danio rerio (zebrafish) confirmed that the ASTA treatment significantly increased the survival rates of infected fish by hindering the intestinal colonization of S. mutans. Furthermore, the disease protection potential of ASTA against the pathognomonic symptom of S. mutans infection was proven by the histopathological examination of the gills, gut, and kidney. Overall, these findings suggest that ASTA may be a promising therapeutic and alternative drug for the treatment and prevention of oral infection imposed by S. mutans.

Physiological and metabolic analyses reveal the proline-mediated flowering delay mechanism in Prunus persica.

Peaches are susceptible to various environmental stresses. Particularly in late spring, freezing temperatures can damage peaches and consequently, affect their productivity. Therefore, flowering delay is a prominent strategy for avoiding spring frost damage. Our previous study confirmed that treatment with 5% sodium alginate and 100 mM CaCl2 (5AG) to avoid frost damage during the blooming stage delays flowering. To reveal the flowering delay mechanism of peaches, this study systematically analyzed the modification of amino acid profiles in control and 5AG-treated peach plants at different day intervals. Our findings indicate that arginine (Arg), glutamate (Glu), and proline (Pro) levels differed between the control and 5AG-treated peach shoots throughout the phenological development of flower buds. Furthermore, two amino acids (Arg and Glu) are involved in the Pro pathway. Thus, using a computational metabolomics method, Pro biosynthesis and its characteristics, gene ontology, gene synteny, cis-regulatory elements, and gene organizations were examined to decipher the involvement of Pro metabolism in peach flowering delay. In addition, qRT-PCR analysis revealed the transcriptional regulation of Pro-related and flowering-responsive genes and their role in flowering delay. Overall, this pilot study provides new insights into the role of Pro in the flowering delay mechanisms in Prunus persica through 5AG treatment.

Cloning of CAT genes in Satsuma mandarin and their expression characteristics in response to environmental stress and arbuscular mycorrhizal fungi.

KEY MESSAGE: CitCAT1 and CitCAT2 were cloned and highly expressed in mature leaves. High temperatures up-regulated CitCAT1 expression, while low temperatures and Diversispora versiformis up-regulated CitCAT2 expression, maintaining a low oxidative damage. Catalase (CAT), a tetrameric heme-containing enzyme, removes hydrogen peroxide (H2O2) to maintain low oxidative damage in plants exposed to environmental stress. This study aimed to clone CAT genes from Citrus sinensis cv. "Oita 4" and analyze their expression patterns in response to environmental stress, exogenous abscisic acid (ABA), and arbuscular mycorrhizal fungal inoculation. Two CAT genes, CitCAT1 (NCBI accession: PP067858) and CitCAT2 (NCBI accession: PP061394) were cloned, and the open reading frames of their proteins were 1479 bp and 1539 bp, respectively, each encoding 492 and 512 amino acids predicted to be localized in the peroxisome, with CitCAT1 being a stable hydrophilic protein and CitCAT2 being an unstable hydrophilic protein. The similarity of their amino acid sequences reached 83.24%, and the two genes were distantly related. Both genes were expressed in stems, leaves, flowers, and fruits, accompanied by the highest expression in mature leaves. In addition, CitCAT1 expression was mainly up-regulated by high temperatures (37 °C), exogenous ABA, and PEG stress within a short period of time, whereas CitCAT2 expression was up-regulated by exogenous ABA and low-temperature (4 °C) stress. Low temperatures (0 °C) for 12 h just up-regulated CitCAT2 expression in Diversispora versiformis-inoculated plants, and D. versiformis inoculation up-regulated CitCAT2 expression, along with lower hydrogen peroxide and malondialdehyde levels in mycorrhizal plants at low temperatures. It is concluded that CitCAT2 has an important role in resistance to low temperatures as well as mycorrhizal enhancement of host resistance to low temperatures.

Untargeted metabolomics uncovers prime pathways linked to antibacterial action of citral against bacterial vaginosis-causing Gardnerella vaginalis: An in vitro and in vivo study.

Global increase in recurrence of bacterial vaginosis (BV) and worrisome rise in antimicrobial resistance pose an urgent call for new/novel antibacterial agents. In light of the circumstance, the present study demonstrates the in vitro and in vivo antibacterial activity of a phytochemical citral, with a particular emphasis to elucidate its mechanistic action against Gardnerella vaginalis -a potential cause of BV. Out of 21 phytochemicals screened initially against G. vaginalis, citral was envisaged to be a phenomenal antibacterial agent showing MIC and MBC at 128 µg/mL. Citral's rapid killing ability was revealed by a time-killing kinetics assay supported by CFU, signifying that it completely killed the given inoculum of planktonic G. vaginalis cells within 60 min. Further, citral was found to exhibit 1 min contact-killing efficacy together with mature-biofilm disintegrating ability at increasing MICs. To further understand the molecular action of citral, in vitro investigations such as ROS estimation, PI staining and intracellular protein release assay were performed, which demonstrated that citral deteriorated the membrane integrity of G. vaginalis. Galleria mellonella, a simple invertebrate model used to evaluate citral's non-toxic and antibacterial activity in vivo, demonstrates that citral completely restored the larvae from G. vaginalis infection. The metabolite level investigation using LC-MS revealed that citral had negative impact on biotin metabolism (via., biotin), spermidine metabolism (via., 5'-methylthioadenosine and spermidine) and nucleotide metabolism (via., guanine, adenine and uridine). Since that biotin is associated with seven different metabolic pathways, it is conceivable that citral could target biotin biosynthesis or its metabolism and as a result, disrupt other metabolic pathways, such as lipid and fatty acid synthesis, which is essential for the creation of cell membranes. Thus, the current study is the first of its kind to delineate the promising in vitro and in vivo antibacterial efficacy of citral and decipher its plausible antibacterial action mechanism through metabolomic approach, which concomitantly emphasizes citral as a viable natural therapeutic alternative to manage and control BV.

Tumor-targeted delivery of lnc antisense RNA against RCAS1 by live-attenuated tryptophan-auxotrophic Salmonella inhibited 4T1 breast tumors and metastasis in mice.

Emerging chemo- and radiotherapy resistance exacerbated the cancer risk and necessitated novel treatment strategies. Although RNA therapeutics against pro-oncogenic genes are highly effective, tumor-specific delivery remains a barrier to the implementation of this valuable tool. In this study, we report a tryptophan-auxotrophic Salmonella typhimurium strain as an onco-therapeutic delivery system with tumor-targeting ability using 4T1 mice breast-cancer model. The receptor-binding cancer antigen expressed on SiSo cell (RCAS1) is a cancer-specific protein that induces the apoptosis of peripheral lymphocytes and confers tumor immune evasion. We designed a long non-coding antisense-RNA against RCAS1 (asRCAS1) and delivered by Salmonella using a non-antibiotic, auxotrophic-selective, eukaryotic expression plasmid, pJHL204. After in vivo tumor-to-tumor passaging, the JOL2888 (ΔtrpA, ΔtrpE, Δasd + asRCAS1) strain exhibited high sustainability in tumors, but did not last in healthy organs, thereby demonstrating tumor specificity and safety. RCAS1 inhibition in the tumor was confirmed by western blotting and qPCR. In mice, JOL2888 treatment reduced tumor-associated macrophages, improved the T cell population, elicited cell-mediated immunity, and suppressed cancer-promoting genes. Consequently, the JOL2888 treatment significantly decreased the tumor volume by 80%, decreased splenomegaly by 30%, and completely arrested lung metastasis. These findings highlight the intrinsic tumor-targeting ability of tryptophan-auxotrophic Salmonella for delivering onco-therapeutic macromolecules.

Molecular Insights into Abiotic Stresses in Mango.

Mango (Mangifera indica L.) is one of the most economically important fruit crops across the world, mainly in the tropics and subtropics of Asia, Africa, and Central and South America. Abiotic stresses are the prominent hindrance that can adversely affect the growth, development, and significant yield loss of mango trees. Understanding the molecular physiological mechanisms underlying abiotic stress responses in mango is highly intricate. Therefore, to gain insights into the molecular basis and to alleviate the abiotic stress responses to enhance the yield in the mere future, the use of high-throughput frontier approaches should be tied along with the baseline investigations. Taking these gaps into account, this comprehensive review mainly speculates to provide detailed mechanisms and impacts on physiological and biochemical alterations in mango under abiotic stress responses. In addition, the review emphasizes the promising omics approaches in unraveling the candidate genes and transcription factors (TFs) responsible for abiotic stresses. Furthermore, this review also summarizes the role of different types of biostimulants in improving the abiotic stress responses in mango. These studies can be undertaken to recognize the roadblocks and avenues for enhancing abiotic stress tolerance in mango cultivars. Potential investigations pointed out the implementation of powerful and essential tools to uncover novel insights and approaches to integrate the existing literature and advancements to decipher the abiotic stress mechanisms in mango. Furthermore, this review serves as a notable pioneer for researchers working on mango stress physiology using integrative approaches.

Methyl jasmonate and salicylic acid as powerful elicitors for enhancing the production of secondary metabolites in medicinal plants: an updated review.

Plant secondary metabolites are bioactive scaffolds that are crucial for plant survival in the environment and to maintain a defense mechanism from predators. These compounds are generally present in plants at a minimal level and interestingly, they are found to have a wide variety of therapeutic values for humans. Several medicinal plants are used for pharmaceutical purposes due to their affordability, fewer adverse effects, and vital role in traditional remedies. Owing to this reason, these plants are exploited at a high range worldwide and therefore many medicinal plants are on the threatened list. There is a need of the hour to tackle this major problem, one effective approach called elicitation can be used to enhance the level of existing and novel plant bioactive compounds using different types of elicitors namely biotic and abiotic. This process can be generally achieved by in vitro and in vivo experiments. The current comprehensive review provides an overview of biotic and abiotic elicitation strategies used in medicinal plants, as well as their effects on secondary metabolites enhancement. Further, this review mainly deals with the enhancement of biomass and biosynthesis of different bioactive compounds by methyl jasmonate (MeJA) and salicylic acid (SA) as elicitors of wide medicinal plants in in vitro by using different cultures. The present review was suggested as a significant groundwork for peers working with medicinal plants by applying elicitation strategies along with advanced biotechnological approaches.

Understanding Mutations in Human SARS-CoV-2 Spike Glycoprotein: A Systematic Review & Meta-Analysis.

Genetic variant(s) of concern (VoC) of SARS-CoV-2 have been emerging worldwide due to mutations in the gene encoding spike glycoprotein. We performed comprehensive analyses of spike protein mutations in the significant variant clade of SARS-CoV-2, using the data available on the Nextstrain server. We selected various mutations, namely, A222V, N439K, N501Y, L452R, Y453F, E484K, K417N, T478K, L981F, L212I, N856K, T547K, G496S, and Y369C for this study. These mutations were chosen based on their global entropic score, emergence, spread, transmission, and their location in the spike receptor binding domain (RBD). The relative abundance of these mutations was mapped with global mutation D614G as a reference. Our analyses suggest the rapid emergence of newer global mutations alongside D614G, as reported during the recent waves of COVID-19 in various parts of the world. These mutations could be instrumentally imperative for the transmission, infectivity, virulence, and host immune system's evasion of SARS-CoV-2. The probable impact of these mutations on vaccine effectiveness, antigenic diversity, antibody interactions, protein stability, RBD flexibility, and accessibility to human cell receptor ACE2 was studied in silico. Overall, the present study can help researchers to design the next generation of vaccines and biotherapeutics to combat COVID-19 infection.

A Recent Update on the Impact of Nano-Selenium on Plant Growth, Metabolism, and Stress Tolerance.

Selenium (Se) is a microelement that plays an important nutrient role by influencing various physiological and biochemical traits in plants. It has been shown to stimulate plant metabolism, enhancing secondary metabolites and lowering abiotic and biotic stress in plants. Globally, the enormous applications of nanotechnology in the food and agricultural sectors have vastly expanded. Nanoselenium is more active than bulk materials, and various routes of synthesis of Se nanoparticles (Se-NPs) have been reported in which green synthesis using plants is more attractive due to a reduction in ecological issues and an increase in biological activities. The Se-NP-based biofortification is more significant because it increases plant stress tolerance and positively impacts their metabolism. Se-NPs can enhance plant resistance to various oxidative stresses, promote growth, enhance soil nutrient status, enhance plant antioxidant levels, and participate in the transpiration process. Additionally, they use a readily available, biodegradable reducing agent and are ecologically friendly. This review concentrates on notable information on the different modes of Se-NPs' synthesis and characterization, their applications in plant growth, yield, and stress tolerance, and their influence on the metabolic process.

Integrated omics profiling and network pharmacology uncovers the prognostic genes and multi-targeted therapeutic bioactives to combat lung cancer.

Non-small cell lung cancer (NSCLC) is the frequent subtype of lung cancer and the currently used treatment methods, diagnosis, and chemoresistance are relatively ineffective. Determining the pharmacological targets from active biomolecules of medicinal plants has become a frontiers era for biomedical research to develop novel therapies. In view of these scenarios, this pilot study, network pharmacology, cheminformatics, integrative omics, molecular docking and in vitro anti-cancer analysis were performed to unveil the multi-targeted treatment mechanisms of novel plant bioactives to treat lung cancer. Bioactive molecules from medicinal plants were compiled from PubChem. Network pharmacology approach revealed that 29 compounds efficiently target the 390 human and lung cancer associated genes. In addition, comparative analysis was performed and identified the 7 bioactive molecules significantly targeting 8 lung cancer genes. The integrative omics analysis discovered unique genes between the lung cancer and normal lung tissues. These genes were further validated through protein-protein interaction, gene ontology, gene functional and pathway enrichment, boxplot and overall survival analyses to understand the function of unique genes and their involvement in cancer signaling pathways. Survival heatmap analyses identified the significant prognostic genes. Docking results revealed that, lupeol and p-coumaric acid displayed high binding affinities with MIF, CCNB1, FABP4. Hence, we selected these two bioactives for in vitro analysis. Furthermore, these selected bioactives were showed concentration dependent cytotoxicity against the lung adenocarcinoma cells (A549). This holistic study has opened up novel avenues and unravels the cancer prognostic genes which could serve as druggable target and bioactives with anti-cancerous efficacy. Further functional validations are prerequisites to deciphering these bioactives as commercial drug candidates.

Understanding Macroalgae: A Comprehensive Exploration of Nutraceutical, Pharmaceutical, and Omics Dimensions.

Driven by a surge in global interest in natural products, macroalgae or seaweed, has emerged as a prime source for nutraceuticals and pharmaceutical applications. Characterized by remarkable genetic diversity and a crucial role in marine ecosystems, these organisms offer not only substantial nutritional value in proteins, fibers, vitamins, and minerals, but also a diverse array of bioactive molecules with promising pharmaceutical properties. Furthermore, macroalgae produce approximately 80% of the oxygen in the atmosphere, highlighting their ecological significance. The unique combination of nutritional and bioactive attributes positions macroalgae as an ideal resource for food and medicine in various regions worldwide. This comprehensive review consolidates the latest advancements in the field, elucidating the potential applications of macroalgae in developing nutraceuticals and therapeutics. The review emphasizes the pivotal role of omics approaches in deepening our understanding of macroalgae's physiological and molecular characteristics. By highlighting the importance of omics, this review also advocates for continued exploration and utilization of these extraordinary marine organisms in diverse domains, including drug discovery, functional foods, and other industrial applications. The multifaceted potential of macroalgae warrants further research and development to unlock their full benefits and contribute to advancing global health and sustainable industries.

Unlocking Prognostic Genes and Multi-Targeted Therapeutic Bioactives from Herbal Medicines to Combat Cancer-Associated Cachexia: A Transcriptomics and Network Pharmacology Approach.

Cachexia is a devastating fat tissue and muscle wasting syndrome associated with every major chronic illness, including cancer, chronic obstructive pulmonary disease, kidney disease, AIDS, and heart failure. Despite two decades of intense research, cachexia remains under-recognized by oncologists. While numerous drug candidates have been proposed for cachexia treatment, none have achieved clinical success. Only a few drugs are approved by the FDA for cachexia therapy, but a very low success rate is observed among patients. Currently, the identification of drugs from herbal medicines is a frontier research area for many diseases. In this milieu, network pharmacology, transcriptomics, cheminformatics, and molecular docking approaches were used to identify potential bioactive compounds from herbal medicines for the treatment of cancer-related cachexia. The network pharmacology approach is used to select the 32 unique genes from 238 genes involved in cachexia-related pathways, which are targeted by 34 phytocompounds identified from 12 different herbal medicines used for the treatment of muscle wasting in many countries. Gene expression profiling and functional enrichment analysis are applied to decipher the role of unique genes in cancer-associated cachexia pathways. In addition, the pharmacological properties and molecular interactions of the phytocompounds were analyzed to find the target compounds for cachexia therapy. Altogether, combined omics and network pharmacology approaches were used in the current study to untangle the complex prognostic genes involved in cachexia and phytocompounds with anti-cachectic efficacy. However, further functional and experimental validations are required to confirm the efficacy of these phytocompounds as commercial drug candidates for cancer-associated cachexia.

Mycorrhizal Effects on Growth and Expressions of Stress-Responsive Genes (aquaporins and SOSs) of Tomato under Salt Stress.

Environmentally friendly arbuscular mycorrhizal fungi (AMF) in the soil can alleviate host damage from abiotic stresses, but the underlying mechanisms are unclear. The objective of this study was to analyze the effects of an arbuscular mycorrhizal fungus, Paraglomus occultum, on plant growth, nitrogen balance index, and expressions of salt overly sensitive genes (SOSs), plasma membrane intrinsic protein genes (PIPs), and tonoplast intrinsic protein genes (TIPs) in leaves of tomato (Solanum lycopersicum L. var. Huapiqiu) seedlings grown in 0 and 150 mM NaCl stress. NaCl stress severely inhibited plant growth, but P. occultum inoculation significantly improved plant growth. NaCl stress also suppressed the chlorophyll index, accompanied by an increase in the flavonoid index, whereas inoculation with AMF significantly promoted the chlorophyll index as well as reduced the flavonoid index under NaCl conditions, thus leading to an increase in the nitrogen balance index in inoculated plants. NaCl stress regulated the expression of SlPIP1 and SlPIP2 genes in leaves, and five SlPIPs genes were up-regulated after P. occultum colonization under NaCl stress, along with the down-regulation of only SlPIP1;2. Both NaCl stress and P. occultum inoculation induced diverse expression patterns in SlTIPs, coupled with a greater number of up-regulated TIPs in inoculated versus uninoculated plants under NaCl stress. NaCl stress up-regulated SlSOS2 expressions of mycorrhizal and non-mycorrhizal plants, while P. occultum significantly up-regulated SlSOS1 expressions by 1.13- and 0.45-fold under non-NaCl and NaCl conditions, respectively. It was concluded that P. occultum inoculation enhanced the salt tolerance of the tomato, associated with the nutrient status and stress-responsive gene (aquaporins and SOS1) expressions.

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.

Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite.

Assessing the Anti-inflammatory Effects of Bacopa-Derived Bioactive Compounds Using Network Pharmacology and In Vitro Studies.

Bacopa monnieri is reported as a potent Indian medicinal plant that possesses numerous pharmacological activities due to the presence of various bioactive compounds. These pharmacological activities were used in the ancient medicine system to cure inflammatory conditions. Bacopa has the ability to reduce acute pain and inflammation by inhibiting the enzyme cyclo-oxygenase-2 (COX-2) and reducing COX-2-arbitrated prostanoid mediators. Moreover, the anti-inflammatory property may also be associated with the neuroprotective activity of Bacopa. Considering this importance, the current pilot study focused on the anti-inflammatory potential of various phytocompounds of bacopa and their interaction with inflammation responsible genes such as COX2, iNOS, LOX, STAT3, CCR1, and MMP9 through pharmacology analysis of its systems. Docking results revealed that, quercetin (QR) showed significant binding energies with inflammatory genes. Hence, we selected QR as a potential phytocompound for further in vitro experiments. This existing study aimed to evaluate the efficacy of QR as a potent anti-inflammatory compound against lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. The in vitro analysis concludes that QR effectively reduces the production of nitric oxide (NO) in LPS-induced RAW264.7 cells and downregulates the expression of COX-2 and iNOS genes due to the inhibitory potential of QR on LPS-stimulated NO production.

Transcriptomics, Cheminformatics, and Systems Pharmacology Strategies Unveil the Potential Bioactives to Combat COVID-19.

Coronavirus disease (COVID-19) is a viral disease caused by the SARS-CoV-2 virus and is becoming a global threat again because of the higher transmission rate and lack of proper therapeutics as well as the rapid mutations in the genetic pattern of SARS-CoV-2. Despite vaccinations, the prevalence and recurrence of this infection are still on the rise, which urges the identification of potential global therapeutics for a complete cure. Plant-based alternative medicine is becoming popular worldwide because of its higher efficiency and minimal side effects. Yet, identifying the potential medicinal plants and formulating a plant-based medicine is still a bottleneck. Hence, in this study, the systems pharmacology, transcriptomics, and cheminformatics approaches were employed to uncover the multi-targeted mechanisms and to screen the potential phytocompounds from significant medicinal plants to treat COVID-19. These approaches have identified 30 unique COVID-19 human immune genes targeted by the 25 phytocompounds present in four selected ethnobotanical plants. Differential and co-expression profiling and pathway enrichment analyses delineate the molecular signaling and immune functional regulations of the COVID-19 unique genes. In addition, the credibility of these compounds was analyzed by the pharmacological features. The current holistic finding is the first to explore whether the identified potential bioactives could reform into a drug candidate to treat COVID-19. Furthermore, the molecular docking analysis was employed to identify the important bioactive compounds; thus, an ultimately significant medicinal plant was also determined. However, further laboratory evaluation and clinical validation are required to determine the efficiency of a therapeutic formulation against COVID-19.