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.

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.

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.

Multi-Omics and Integrative Approach towards Understanding Salinity Tolerance in Rice: A Review.

Rice (Oryza sativa L.) plants are simultaneously encountered by environmental stressors, most importantly salinity stress. Salinity is the major hurdle that can negatively impact growth and crop yield. Understanding the salt stress and its associated complex trait mechanisms for enhancing salt tolerance in rice plants would ensure future food security. The main aim of this review is to provide insights and impacts of molecular-physiological responses, biochemical alterations, and plant hormonal signal transduction pathways in rice under saline stress. Furthermore, the review highlights the emerging breakthrough in multi-omics and computational biology in identifying the saline stress-responsive candidate genes and transcription factors (TFs). In addition, the review also summarizes the biotechnological tools, genetic engineering, breeding, and agricultural practicing factors that can be implemented to realize the bottlenecks and opportunities to enhance salt tolerance and develop salinity tolerant rice varieties. Future studies pinpointed the augmentation of powerful tools to dissect the salinity stress-related novel players, reveal in-depth mechanisms and ways to incorporate the available literature, and recent advancements to throw more light on salinity responsive transduction pathways in plants. Particularly, this review unravels the whole picture of salinity stress tolerance in rice by expanding knowledge that focuses on molecular aspects.

Global Integrated Genomic and Transcriptomic Analyses of MYB Transcription Factor Superfamily in C3 Model Plant Oryza sativa (L.) Unravel Potential Candidates Involved in Abiotic Stress Signaling.

Plant transcription factors (TFs) are significant players in transcriptional regulations, signal transduction, and constitute an integral part of signaling networks. MYB TFs are major TF superfamilies that play pivotal roles in regulation of transcriptional reprogramming, physiological processes, and abiotic stress (AbS) responses. To explore the understanding of MYB TFs, genome and transcriptome-wide identification was performed in the C3 model plant, Oryza sativa (OsMYB). This study retrieved 114 OsMYB TFs that were computationally analyzed for their expression profiling, gene organization, cis-acting elements, and physicochemical properties. Based on the microarray datasets, six OsMYB genes which were sorted out and identified by a differential expression pattern were noted in various tissues. Systematic expression profiling of OsMYB TFs showed their meta-differential expression of different AbS treatments, spatio-temporal gene expression of various tissues and their growth in the field, and gene expression profiling in responses to phytohormones. In addition, the circular ideogram of OsMYB genes in related C4 grass plants conferred the gene synteny. Protein-protein interactions of these genes revealed the molecular crosstalk of OsMYB TFs. Transcriptional analysis (qPCR) of six OsMYB players in response to drought and salinity stress suggested the involvement in individual and combined AbS responses. To decipher how these OsMYB play functional roles in AbS dynamics, further research is a prerequisite.

Molecular Insights into Freezing Stress in Peach Based on Multi-Omics and Biotechnology: An Overview.

In nature or field conditions, plants are frequently exposed to diverse environmental stressors. Among abiotic stresses, the low temperature of freezing conditions is a critical factor that influences plants, including horticultural crops, decreasing their growth, development, and eventually quality and productivity. Fortunately, plants have developed a mechanism to improve the tolerance to freezing during exposure to a range of low temperatures. In this present review, current findings on freezing stress physiology and genetics in peach (Prunus persica) were refined with an emphasis on adaptive mechanisms for cold acclimation, deacclimation, and reacclimation. In addition, advancements using multi-omics and genetic engineering approaches unravel the molecular physiological mechanisms, including hormonal regulations and their general perceptions of freezing tolerance in peach were comprehensively described. This review might pave the way for future research to the horticulturalists and research scientists to overcome the challenges of freezing temperature and improvement of crop management in these conditions.

Vitex negundo L. derived specialized molecules unveil the multi-targeted therapeutic avenues against COPD: a systems pharmacology approach.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is an inflammatory disease caused by increasing breathing passage obstruction which completely disrupts human homeostasis. Some patients require lung transplantation or long-term oxygen therapy. COPD is one of the noxious diseases and its fourth leading cause of death around the globe. There is an immediate need for potential drug development to tackle this serious disease. Folk medicines are used to combat complex diseases that have shown effectiveness in the treatment of breathing diseases. Vitex negundo L. is an ethnobotanically important medicinal plant used for various ailments and modulates human cellular events. This shrub has diverse specialized metabolites and is being used as complementary medicine in various countries. Though systems-level understanding is there on the mode of action, the multi-target treatment strategy for COPD is still a bottleneck. METHODS: In this investigation, systems pharmacology, cheminformatics, and molecular docking analyses were performed to unravel the multi-targeted mechanisms of V. negundo L. potential bioactives to combat COPD. RESULTS: Cheminformatics analysis combined with the target mining process identified 86 specialized metabolites and their corresponding 1300 direct human receptors, which were further imputed and validated systematically. Furthermore, molecular docking approaches were employed to evaluate the potential activity of identified potential compounds. In addition, pharmacological features of these bioactives were compared with available COPD drugs to recognize potential compounds that were found to be more efficacious with higher bioactive scores. CONCLUSIONS: The present study unravels the druggable targets and identifies the bioactive compounds present in V. negundo L., that may be utilized for potential treatment against COPD. However, further in vivo analyses and clinical trials of these molecules are essential to deciphering their efficacy.

An Overview of Abiotic Stress in Cereal Crops: Negative Impacts, Regulation, Biotechnology and Integrated Omics.

Abiotic stresses (AbS), such as drought, salinity, and thermal stresses, could highly affect the growth and development of plants. For decades, researchers have attempted to unravel the mechanisms of AbS for enhancing the corresponding tolerance of plants, especially for crop production in agriculture. In the present communication, we summarized the significant factors (atmosphere, soil and water) of AbS, their regulations, and integrated omics in the most important cereal crops in the world, especially rice, wheat, sorghum, and maize. It has been suggested that using systems biology and advanced sequencing approaches in genomics could help solve the AbS response in cereals. An emphasis was given to holistic approaches such as, bioinformatics and functional omics, gene mining and agronomic traits, genome-wide association studies (GWAS), and transcription factors (TFs) family with respect to AbS. In addition, the development of omics studies has improved to address the identification of AbS responsive genes and it enables the interaction between signaling pathways, molecular insights, novel traits and their significance in cereal crops. This review compares AbS mechanisms to omics and bioinformatics resources to provide a comprehensive view of the mechanisms. Moreover, further studies are needed to obtain the information from the integrated omics databases to understand the AbS mechanisms for the development of large spectrum AbS-tolerant crop production.

Global transcriptome analysis of novel stress associated protein (SAP) genes expression dynamism of combined abiotic stresses in Oryza sativa (L.).

Genes encoding proteins with A20/AN1 zinc-finger domains, belonging to the stress associated protein (SAP) gene family, are present in all eukaryotes and play a decisive role in plant response to diverse physiological and molecular activities particularly on biotic and abiotic stresses (AbS). In this first and foremost study, global transcriptome analysis of members of the SAP gene family was carried out in C3 model-Oryza sativa (OsSAP) aiming at the identification of OsSAP genes activated in response to unique or Combined AbS (CAbS). Based on the available spatio-temporal and phytohormonal RNA-Seq expression profile datasets, nine OsSAP genes were filtered out and identified by a differential expression signature noted in various tissues as well as plant hormones. Comparative genome ideogram of OsSAP genes confirmed the orthologous collinearity with C4 panicoid genomes. Interactome of these genes, revealed the molecular cross-talks of OsSAP. Thus, the computational expression signature of OsSAP genes led to a better understanding of gene dynamism in diverse developmental tissues/organs. Transcriptional regulation analysis of key OsSAP genes in response to stress (drought and salinity) suggested the novel role of OsSAP1, OsSAP2, OsSAP5, OsSAP7, OsSAP8 and OsSAP11 in AbS. Altogether, the study provides deeper insights on molecular characteristics of OsSAP genes, which could be deployed further to decipher their precise functional roles in AbS responses.Communicated by Ramaswamy H. Sarma.

Global multi-omics and systems pharmacological strategy unravel the multi-targeted therapeutic potential of natural bioactive molecules against COVID-19: An in silico approach.

Understanding the immunological behavior of COVID-19 cases at molecular level is essential for therapeutic development. In this study, multi-omics and systems pharmacology analyses were performed to unravel the multi-targeted mechanisms of novel bioactives to combat COVID-19. Immuno-transcriptomic dataset of healthy controls and COVID-19 cases was retrieved from ArrayExpress. Phytocompounds from ethnobotanical plants were collected from PubChem. Differentially expressed 98 immune genes associated with COVID-19 were derived through NetworkAnalyst 3.0. Among 259 plant derived compounds, 154 compounds were targeting 13 COVID-19 immune genes involved in diverse signaling pathways. In addition, pharmacological properties of these phytocompounds were compared with COVID-19 drugs prescribed by WHO, and 25 novel phytocompounds were found to be more efficient with higher bioactive scores. The current study unravels the virogenomic signatures which can serve as therapeutic targets and identified phytocompounds with anti-COVID-19 efficacy. However, further experimental validation is essential to bring out these molecules as commercial drug candidates.

Integrated transcriptomic and metabolomic analyses of glutamine metabolism genes unveil key players in Oryza sativa (L.) to ameliorate the unique and combined abiotic stress tolerance.

Plants can be considered to biosynthesize the specialized metabolites to adapt to various environmental stressors mainly on abiotic stresses (AbS). Among specialized metabolites, glutamine (Gln) is an essential plant metabolite to achieve sustainable plant growth, yield and food security. In this pilot study, swe employed computational metabolomics genome wide association survey (cmGWAS) of Gln metabolite profiling in Oryza sativa, targeting at the identification of abiotic stress responsible (AbSR) - Gln metabolite producing genes (GlnMPG). Identified 5 AbSR-GlnMPG alter the metabolite levels and play a predominant role in delineating the physiological significance of rice. These genes were systematically analysed for their biological features via OryzaCyc. Spatio-temporal and plant hormonal expression pattern of AbSR-GlnMPG was analysed and their differential expression profiling were noted in 48 different tissues and hormones, respectively. Furthermore, comparative ideogram of these genes revealed the chromosomal synteny with C4 grass genomes. Molecular crosstalks of these proteins, unravelled the various metabolic interaction. The systems expression profiling of AbSR-GlnMPG will lead to unravel the metabolite signaling and putative responses in multiple AbS. On the whole, this holistic study provides deeper insights on biomolecular features of AbSR-GlnMPG, which could be analysed further to decipher their functional metabolisms in AbS dynamism.

In Vitro Propagation, Phytochemical and Neuropharmacological Profiles of Bacopa monnieri (L.) Wettst.: A Review.

Bacopa monnieri has been used as a reputed drug in the Indian traditional ayurvedic system for centuries. This medicinal herb with important phytopharmaceuticals has been popularly known as "Brahmi". In recent years, B. monnieri has been extensively studied for its bioactive constituents, constituents responsible for memory enhancing effect, and also its diverse other useful effects. It possesses many pharmacological activities such as antioxidant, gastrointestinal, endocrine, antimicrobial, anti-inflammatory etc. The plant has been also used for the treatment of neurological and neuropsychiatric diseases. Due to its multipurpose therapeutic potential, micropropagation using axillary meristems and de novo organogenesis has been extensively studied in the species and is being reviewed. High frequency direct shoot organogenesis can be induced in excised leaf and internode explants in the absence of exogenous phytohormones and the rate of induction is enhanced in the presence of exogenous cytokinins, supplements, growth regulators, etc. Using explants from tissue culture raised plants, direct shoot regeneration leading to production of more than 100 rooted plants/explant within 8-12 weeks period with 85%-100% survival in the field after acclimatization can be expected following optimized protocols. Bioreactor based micropropagation was found to increase the multiplication rate of shoot cultures for the commercial propagation of B. monnieri plants. The maximum content of bacosides has been recorded in shoot biomass using an airlift bioreactor system. Further studies for the biosynthesis of bacosides and other secondary metabolites need to be conducted in the species utilizing untransformed shoot cultures in bioreactors.

Bacopa monnieri and Their Bioactive Compounds Inferred Multi-Target Treatment Strategy for Neurological Diseases: A Cheminformatics and System Pharmacology Approach.

Neurological diseases (NDs), especially Alzheimer's and Spinocerebellar ataxia (SCA), can severely cause biochemical abnormalities in the brain, spinal cord and other nerves of human beings. Their ever-increasing prevalence has led to a demand for new drug development. Indian traditional and Ayurvedic medicine used to combat the complex diseases from a holistic and integrative point of view has shown efficiency and effectiveness in the treatment of NDs. Bacopa monnieri is a potent Indian medicinal herb used for multiple ailments, but is significantly known as a nootropic or brain tonic and memory enhancer. This annual herb has various active compounds and acts as an alternative and complementary medicine in various countries. However, system-level insights of the molecular mechanism of a multiscale treatment strategy for NDs is still a bottleneck. Considering its prominence, we used cheminformatics and system pharmacological approaches, with the aim to unravel the various molecular mechanisms represented by Bacopa-derived compounds in identifying the active human targets when treating NDs. First, using cheminformatics analysis combined with the drug target mining process, 52 active compounds and their corresponding 780 direct receptors were retrieved and computationally validated. Based on the molecular properties, bioactive scores and comparative analysis with commercially available drugs, novel and active compounds such as asiatic acid (ASTA) and loliolide (LLD) to treat the Alzheimer's and SCA were identified. According to the interactions among the active compounds, the targets and diseases were further analyzed to decipher the deeper pharmacological actions of the drug. NDs consist of complex regulatory modules that are integrated to dissect the therapeutic effects of compounds derived from Bacopa in various pathological features and their encoding biological processes. All these revealed that Bacopa compounds have several curative activities in regulating the various biological processes of NDs and also pave the way for the treatment of various diseases in modern medicine.

Global integrated omics expression analyses of abiotic stress signaling HSF transcription factor genes in Oryza sativa L.: An in silico approach.

Among the significant transcription factors (TFs), HSF proteins play pivotal roles in the regulation of hormonal signal transduction and different abiotic stress (AbS) responses. Hence considering its importance, global omics expression analysis of HSF candidates was performed in rice (OsHSF). The current study identified 25 HSF family members and physically plotted them against the rice genome. These proteins were systematically analyzed for their physicochemical features, organization and expression signatures. Further, heatmap of both spatio-temporal and global plant hormones revealed the developmental tissues and hormone specific expression profiling of these genes respectively. Comparative genome mapping between OsHSF players in interrelated C4 grass species revealed the chromosome level synteny. Signalome analysis revealed the protein - protein interactions of OsHSF. Expression profiling of key players in response to stresses exhibited the new involvement in combined AbS (CAbS) responses. Our results are significantly valuable to decipher their functional analysis of CAbS tolerant in rice.