Targeting the key players of phenotypic plasticity in cancer cells by phytochemicals.

Plasticity of phenotypic traits refers to an organism's ability to change in response to environmental stimuli. As a result, the response may alter an organism's physiological state, morphology, behavior, and phenotype. Phenotypic plasticity in cancer cells describes the considerable ability of cancer cells to transform phenotypes through non-genetic molecular signaling activities that promote therapy evasion and tumor metastasis via amplifying cancer heterogeneity. As a result of metastable phenotypic state transitions, cancer cells can tolerate chemotherapy or develop transient adaptive resistance. Therefore, new findings have paved the road in identifying factors and agents that inhibit or suppress phenotypic plasticity. It has also investigated novel multitargeted agents that may promise new effective strategies in cancer treatment. Despite the efficiency of conventional chemotherapeutic agents, drug toxicity, development of resistance, and high-cost limit their use in cancer therapy. Recent research has shown that small molecules derived from natural sources are capable of suppressing cancer by focusing on the plasticity of phenotypic responses. This systematic, comprehensive, and critical review analyzes the current state of knowledge regarding the ability of phytocompounds to target phenotypic plasticity at both preclinical and clinical levels. Current challenges/pitfalls, limitations, and future perspectives are also discussed.

Wnt/ß-catenin-driven EMT regulation in human cancers.

Metastasis accounts for 90% of cancer-related deaths among the patients. The transformation of epithelial cells into mesenchymal cells with molecular alterations can occur during epithelial-mesenchymal transition (EMT). The EMT mechanism accelerates the cancer metastasis and drug resistance ability in human cancers. Among the different regulators of EMT, Wnt/ß-catenin axis has been emerged as a versatile modulator. Wnt is in active form in physiological condition due to the function of GSK-3ß that destructs ß-catenin, while ligand-receptor interaction impairs GSK-3ß function to increase ß-catenin stability and promote its nuclear transfer. Regarding the oncogenic function of Wnt/ß-catenin, its upregulation occurs in human cancers and it can accelerate EMT-mediated metastasis and drug resistance. The stimulation of Wnt by binding Wnt ligands into Frizzled receptors can enhance ß-catenin accumulation in cytoplasm that stimulates EMT and related genes upon nuclear translocation. Wnt/ß-catenin/EMT axis has been implicated in augmenting metastasis of both solid and hematological tumors. The Wnt/EMT-mediated cancer metastasis promotes the malignant behavior of tumor cells, causing therapy resistance. The Wnt/ß-catenin/EMT axis can be modulated by upstream mediators in which non-coding RNAs are main regulators. Moreover, pharmacological intervention, mainly using phytochemicals, suppresses Wnt/EMT axis in metastasis suppression.

Additive genetic effects in interacting species jointly determine the outcome of caterpillar herbivory.

Plant-insect interactions are common and important in basic and applied biology. Trait and genetic variation can affect the outcome and evolution of these interactions, but the relative contributions of plant and insect genetic variation and how these interact remain unclear and are rarely subject to assessment in the same experimental context. Here, we address this knowledge gap using a recent host-range expansion onto alfalfa by the Melissa blue butterfly. Common garden rearing experiments and genomic data show that caterpillar performance depends on plant and insect genetic variation, with insect genetics contributing to performance earlier in development and plant genetics later. Our models of performance based on caterpillar genetics retained predictive power when applied to a second common garden. Much of the plant genetic effect could be explained by heritable variation in plant phytochemicals, especially saponins, peptides, and phosphatidyl cholines, providing a possible mechanistic understanding of variation in the species interaction. We find evidence of polygenic, mostly additive effects within and between species, with consistent effects of plant genotype on growth and development across multiple butterfly species. Our results inform theories of plant-insect coevolution and the evolution of diet breadth in herbivorous insects and other host-specific parasites.

Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone.

Cancer, a major challenge to global health and healthcare systems, requires the study of alternative and supportive treatments due to the limitations of conventional therapies. This review examines the chemopreventive potential of three natural compounds: rosmarinic acid, apigenin, and thymoquinone. Derived from various plants, these compounds have demonstrated promising chemopreventive properties in in vitro, in vivo, and in silico studies. Specifically, they have been shown to inhibit cancer cell growth, induce apoptosis, and modulate key signaling pathways involved in cancer progression. The aim of this review is to provide a comprehensive overview of the current research on these phytochemicals, elucidating their mechanisms of action, therapeutic efficacy, and potential as adjuncts to traditional cancer therapies. This information serves as a valuable resource for researchers and healthcare providers interested in expanding their knowledge within the field of alternative cancer therapies.

Using Multiscale Molecular Modeling to Analyze Possible NS2b-NS3 Protease Inhibitors from Philippine Medicinal Plants.

Within the field of Philippine folkloric medicine, the utilization of indigenous plants like Euphorbia hirta (tawa-tawa), Carica papaya (papaya), and Psidium guajava (guava) as potential dengue remedies has gained attention. Yet, limited research exists on their comprehensive effects, particularly their anti-dengue activity. This study screened 2944 phytochemicals from various Philippine plants for anti-dengue activity. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling provided 1265 compounds demonstrating pharmacokinetic profiles suitable for human use. Molecular docking targeting the dengue virus NS2b-NS3 protease's catalytic triad (Asp 75, Ser 135, and His 51) identified ten ligands with higher docking scores than reference compounds idelalisib and nintedanib. Molecular dynamics simulations confirmed the stability of eight of these ligand-protease complexes. Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis highlighted six ligands, including veramiline (-80.682 kJ/mol), cyclobranol (-70.943 kJ/mol), chlorogenin (-63.279 kJ/mol), 25beta-Hydroxyverazine (-61.951 kJ/mol), etiolin (-59.923 kJ/mol), and ecliptalbine (-56.932 kJ/mol) with favorable binding energies, high oral bioavailability, and drug-like properties. This integration of traditional medical knowledge with advanced computational drug discovery methods paves new pathways for the development of treatments for dengue.

Green iron oxide nanoparticles and magnetic nanobiochar: enhancing tomato performance, phytochemicals, and root-knot nematode resistance.

BACKGROUND: Green nanoparticles are considered to be an effective strategy for improving phytochemicals and raising productivity in soil infected by root-knot nematodes. This work aims to understand the characteristics of certain nanomaterials, including non-iron (nFe), green non-iron (GnFe), and green magnetic nanobiochar (GMnB), and the effect of adding them at 3 and 6 mg kg- 1 on phytochemicals and tomato (Solanum lycopersicum) plant growth in soils infected by root-knot nematodes. RESULTS: Spectroscopic characterization of nanomaterials showed that nFe, GnFe, and GMnB contained functional groups (e.g., Fe-O, S-H, C-H, OH, and C = C) and possessed a large surface area. Application of GMB at 6 mg kg- 1 was the most efficient treatment for increasing the phytochemicals of the tomato plant, with a rise of 123.2% in total phenolic, 194.7% in total flavonoids, 89.7% in total carbohydrate, 185.2% in total free amino acids, and 165.1% in total tannin compared to the untreated soil. Tomato plant growth and attributes increased with increasing levels of soil nano-amendment in this investigation. The addition of GnFe3 and GnFe6 increased the reduction of root galls of root-knot nematodes by 22.44% and 17.76% compared with nFe3 and nFe6, respectively. The inclusion of the examined soil nano-amendments increased phytochemicals and reduced the total number of root-knot nematodes on tomato plants at varying rates, which played a significant role in enhancing tomato growth. CONCLUSIONS: In conclusion, treating tomato plants with GnFe or GMnB can be used as a promising green nanomaterial to eliminate root-knot nematodes and increase tomato yield in sandy clay loam soil.

Analysing potent biomarkers along phytochemicals for breast cancer therapy: an in silico approach.

PURPOSE: This research focused on the identification of herbal compounds as potential anti-cancer drugs, especially for breast cancer, that involved the recognition of Notch downstream targets NOTCH proteins (1-4) specifically expressed in breast tumours as biomarkers for prognosis, along with P53 tumour antigens, that were used as comparisons to check the sensitivity of the herbal bio-compounds. METHODS: After investigating phytochemical candidates, we employed an approach for computer-aided drug design and analysis to find strong breast cancer inhibitors. The present study utilized in silico analyses and protein docking techniques to characterize and rank selected bio-compounds for their efficiency in oncogenic inhibition for use in precise carcinomic cell growth control. RESULTS: Several of the identified phytocompounds found in herbs followed Lipinski's Rule of Five and could be further investigated as potential medicinal molecules. Based on the Vina score obtained after the docking process, the active compound Epigallocatechin gallate in green tea with NOTCH (1-4) and P53 proteins showed promising results for future drug repurposing. The stiffness and binding stability of green tea pharmacological complexes were further elucidated by the molecular dynamic simulations carried out for the highest scoring phytochemical ligand complex. CONCLUSION: The target-ligand complex of green tea active compound Epigallocatechin gallate with NOTCH (1-4) had the potential to become potent anti-breast cancer therapeutic candidates following further research involving wet-lab experiments.

Novel two-tiered screening approach identifies synergistic combinations of natural compounds for prostate cancer prevention and treatment.

Prostate cancer (PCa) is the second most common cancer type among American men and it is estimated that in 2023, 34,700 men will die from PCa. Since it can take a considerable amount of time for the disease to progress to clinically evident cancer, there is ample opportunity for effective chemopreventive strategies to be applied for the successful management of PCa progression. In the current study, we have developed a two-tiered metabolomics-based screen to identify synergistic combinations of phytochemicals for PCa chemoprevention. This involves an initial screen for ATP depletion in PCa cells followed by a targeted screen for blocking glutamine uptake in the same cells. One of the phytochemical combinations (enoxolone [ENO] + silibinin [SIL]), identified via this screen, was examined for effects on PCa cell survival, oncogenic signaling and tumor growth in vivo. This combination was found to synergistically reduce cell survival, colony formation and cell cycle progression of PCa cell lines to a greater extent than either agent alone. The combination of ENO and SIL also synergistically reduced tumor growth when administered ad libitum through the diet in a HMVP2 allograft PCa tumor model. Treatment with the combination also significantly reduced STAT3 and mTORC1 signaling pathways in mouse and human PCa cells while significantly reducing levels of critical cell cycle regulatory proteins, contributing to the synergistic inhibition of tumor growth observed. Collectively, the current results demonstrate a novel approach to identifying synergistic combinations of phytochemicals for chemoprevention of PCa and possibly other cancers.

Fitness trade-offs of multidrug efflux pumps in Escherichia coli K-12 in acid or base, and with aromatic phytochemicals.

Multidrug efflux pumps are the frontline defense mechanisms of Gram-negative bacteria, yet little is known of their relative fitness trade-offs under gut conditions such as low pH and the presence of antimicrobial food molecules. Low pH contributes to the proton-motive force (PMF) that drives most efflux pumps. We show how the PMF-dependent pumps AcrAB-TolC, MdtEF-TolC, and EmrAB-TolC undergo selection at low pH and in the presence of membrane-permeant phytochemicals. Competition assays were performed by flow cytometry of co-cultured Escherichia coli K-12 strains possessing or lacking a given pump complex. All three pumps showed negative selection under conditions that deplete PMF (pH 5.5 with carbonyl cyanide 3-chlorophenylhydrazone or at pH 8.0). At pH 5.5, selection against AcrAB-TolC was increased by aromatic acids, alcohols, and related phytochemicals such as methyl salicylate. The degree of fitness cost for AcrA was correlated with the phytochemical's lipophilicity (logP). Methyl salicylate and salicylamide selected strongly against AcrA, without genetic induction of drug resistance regulons. MdtEF-TolC and EmrAB-TolC each had a fitness cost at pH 5.5, but salicylate or benzoate made the fitness contribution positive. Pump fitness effects were not explained by gene expression (measured by digital PCR). Between pH 5.5 and 8.0, acrA and emrA were upregulated in the log phase, whereas mdtE expression was upregulated in the transition-to-stationary phase and at pH 5.5 in the log phase. Methyl salicylate did not affect pump gene expression. Our results suggest that lipophilic non-acidic molecules select against a major efflux pump without inducing antibiotic resistance regulons.IMPORTANCEFor drugs that are administered orally, we need to understand how ingested phytochemicals modulate drug resistance in our gut microbiome. Bacteria maintain low-level resistance by proton-motive force (PMF)-driven pumps that efflux many different antibiotics and cell waste products. These pumps play a key role in bacterial defense by conferring resistance to antimicrobial agents at first exposure while providing time for a pathogen to evolve resistance to higher levels of the antibiotic exposed. Nevertheless, efflux pumps confer energetic costs due to gene expression and pump energy expense. The bacterial PMF includes the transmembrane pH difference (ΔpH), which may be depleted by permeant acids and membrane disruptors. Understanding the fitness costs of efflux pumps may enable us to develop resistance breakers, that is, molecules that work together with antibiotics to potentiate their effect. Non-acidic aromatic molecules have the advantage that they avoid the Mar-dependent induction of regulons conferring other forms of drug resistance. We show that different pumps have distinct selection criteria, and we identified non-acidic aromatic molecules as promising candidates for drug resistance breakers.

Characterization of effective phytochemicals in traditional Chinese medicine by mass spectrometry.

Traditional Chinese medicines (TCMs) have been widely used in clinical and healthcare applications around the world. The characterization of the phytochemical components in TCMs is very important for studying the therapeutic mechanism of TCMs. In the analysis process, sample preparation and instrument analysis are key steps to improve analysis performance and accuracy. In recent years, chromatography combined with mass spectrometry (MS) has been widely used for the separation and detection of trace components in complex TCM samples. This article reviews various sample preparation techniques and chromatography-MS techniques, including the application of gas chromatography-MS and liquid chromatography-MS and other MS techniques in the characterization of phytochemicals in TCM materials and Chinese medicine products. This article also describes a new ambient ionization MS method for rapid and high-throughput analysis of TCM components.

Botanicals as promising antimicrobial agents for enhancing oral health: a comprehensive review.

The mouth houses the second largest diversity of microorganisms in the body, harboring more than 700 bacterial species colonizing the soft mucosa and hard tooth surfaces. Microbes are the cause of several health-related problems, such as dental carries, gingivitis, periodontitis, etc., in the mouth across different age groups and socioeconomic/demographic groups. Oral infections are major health problems that affect the standard of living. Compromised oral health is related to chronic conditions and systemic disorders. Microbes responsible for dental caries are acid-producing and aciduric Gram-positive bacteria (Streptococci, Lactobacilli). Gram-negative bacteria (Porphyromonas, Prevotella, Actinobacillus, and Fusobacterium) capable of growing in anaerobic environments are responsible for periodontal diseases. Due to the high prevalence of oral diseases, negative effects associated with the use of antimicrobial agents and increased antibiotic resistance in oral pathogens, suitable alternative methods (effective, economical and safe) to suppress microbes disturbing oral health need to be adopted. Side effects associated with the chemical antimicrobial agents are vomiting, diarrhea and tooth staining. Several researchers have studied the antimicrobial properties of plant extracts and phytochemicals and have used them as indigenous practices to control several infections. Therefore, phytochemicals extracted from plants can be suitable alternatives. This review focuses on the various phytochemical/plant extracts suppressing the growth of oral pathogens either by preventing their attachment to the surfaces or by preventing biofilm formation or other mechanisms.

Sustainable management of tea wastes: resource recovery and conversion techniques.

As the demand for tea (Camellia sinensis) has grown across the world, the amount of biomass waste that has been produced during the harvesting process has also increased. Tea consumption was estimated at about 6.3 million tonnes in 2020 and is anticipated to reach 7.4 million tonnes by 2025. The generation of tea waste (TW) after use has also increased concurrently with rising tea consumption. TW includes clipped stems, wasted tea leaves, and buds. Many TW-derived products have proven benefits in various applications, including energy generation, energy storage, wastewater treatment, and pharmaceuticals. TW is widely used in environmental and energy-related applications. Energy recovery from low- and medium-calorific value fuels may be accomplished in a highly efficient manner using pyrolysis, anaerobic digestion, and gasification. TW-made biochar and activated carbon are also promising adsorbents for use in environmental applications. Another area where TW shows promise is in the synthesis of phytochemicals. This review offers an overview of the conversion procedures for TW into value-added products. Further, the improvements in their applications for energy generation, energy storage, removal of different contaminants, and extraction of phytochemicals have been reviewed. A comprehensive assessment of the sustainable use of TWs as environmentally acceptable renewable resources is compiled in this review.

Assessment of the antidiabetic potential of extract and novel phytoniosomes formulation of Tradescantia pallida leaves in the alloxan-induced diabetic mouse model.

Diabetes inflicts health and economic burdens on communities and the present antidiabetic therapies have several drawbacks. Tradescantia pallida leaves have been used as a food colorant and food preservative; however, to our knowledge antidiabetic potential of the leaves of T. pallida has not been explored yet. The current study aimed to investigate the antidiabetic potential of T. pallida leaves extract and its comparison with the novel nisosome formulation of the extract. The leaves extract and phytoniosomes of T. pallida in doses of 15, 25 and 50 mg/kg were used to assess the oral glucose loaded, and alloxan-induced diabetic mice models. The biological parameters evaluated were; change in body weight, blood biochemistry, relative organ to body weight ratio and histopathology of the liver, pancreas and kidney. Results revealed that the extract 50 mg/kg and phytoniosomes 25 and 50 mg/kg remarkably reduced the blood glucose level in all hyperglycemic mice by possibly inhibiting α-amylase and α-glucosidase production. Body weight and blood biochemical parameters were considerably improved in phytoniosomes 50 mg/kg treated group. The relative body weight was similar to those of healthy mice in extract 50 mg/kg, phytoniosomes 25 mg/kg, and phytoniosomes 50 mg/kg treated groups. Histopathology showed the regeneration of cells in the CHN50 treated group. Hyphenated chromatographic analysis revealed potent metabolites, which confirmed the antidiabetic potential of the extract by inhibiting α-amylase and α-glucosidase using in silico analysis. The present data suggested that phytoniosomes have shown better antidiabetic potential than crude extract of these leaves.

A comprehensive review on antibacterial analysis of natural extract-based metal and metal oxide nanoparticles.

Pharmaceutical, food packing, cosmetics, agriculture, energy storage devices widely utilize metal and metal oxide nanoparticles prepared via different physical and chemical methods. It resulted in the release of several dangerous compounds and solvents as the nanoparticles were being formed. Currently, Researchers interested in preparing nanoparticles (NPs) via biological approach due to their unique physiochemical properties which took part in reducing the environmental risks. However, a number of microbial species are causing dangerous illnesses and are a threat to the entire planet. The metal and metal oxide nanoparticles played a significant role in the identification and elimination of microbes when prepared using natural extract. Its biological performance is thus also becoming exponentially more apparent than it was using in conventional techniques. Despite the fact that they hurt germs, their small size and well-defined shape encourage surface contact with them. The generation of Reactive Oxygen Species (ROS), weakens the bacterial cell membrane by allowing internal cellular components to seep out. The bacterium dies as a result of this. Numerous studies on different nanoparticles and their antibacterial efficacy against various diseases are still accessible. The main objective of the biogenic research on the synthesis of key metals and metal oxides (such as gold, silver, titanium dioxide, nickel oxide, and zinc oxide) using various plant extracts is reviewed in this study along with the process of nanoparticle formation and the importance of phytochemicals found in the plant extract.

Gut microbiota: a superior operator for dietary phytochemicals to improve atherosclerosis.

Mounting evidence implicates the gut microbiota as a possible key susceptibility factor for atherosclerosis (AS). The employment of dietary phytochemicals that strive to target the gut microbiota has gained scientific support for treating AS. This study conducted a general overview of the links between the gut microbiota and AS, and summarized available evidence that dietary phytochemicals improve AS via manipulating gut microbiota. Then, the microbial metabolism of several dietary phytochemicals was summarized, along with a discussion on the metabolites formed and the biotransformation pathways involving key gut bacteria and enzymes. This study additionally focused on the anti-atherosclerotic potential of representative metabolites from dietary phytochemicals, and investigated their underlying molecular mechanisms. In summary, microbiota-dependent dietary phytochemical therapy is a promising strategy for AS management, and knowledge of "phytochemical-microbiota-biotransformation" may be a breakthrough in the search for novel anti-atherogenic agents.

Exploring faba beans (Vicia faba L.): bioactive compounds, cardiovascular health, and processing insights.

Faba beans (Vicia faba L.), integral to the legume family, are a significant component of the global pulse market because of their nutritional richness and positive health implications. While existing reviews have extensively covered the nutritional composition and anti-nutritional factors of faba beans, and their utilization in food product development, the insights into the optimization of processing methods and upcycling the wastewater during faba bean processing remain insufficient. Therefore, this review focuses on consolidating information about their bioactive compounds, elucidating associated health benefits and unveiling the possible application of processing water derived from faba beans. Key issues discussed include the impact of bioactive compounds in faba beans on cardiovascular health and carcinogenic condition, the challenges in processing that affect bioactive content, and the potential nutritional and functional applications of processing water in food production.

Inhibitory effect of food-functioned phytochemicals on dysregulated inflammatory pathways triggered by SARS-CoV-2: a mechanistic review.

Inflammatory cascades of the dysregulated inflammatory pathways in COVID-19 can cause excessive production of pro-inflammatory cytokines and chemokines leading to cytokine storm syndrome (CSS). The molecular cascades involved in the pathways may be targeted for discovery of new anti-inflammatory agents. Many plant extracts have been used clinically in the management of COVID-19, however, their immunosuppressive activities were mainly investigated based on in silico activity. Dietary flavonoids of the extracts such as quercetin, luteolin, kaempferol, naringenin, isorhamnetin, baicalein, wogonin, and rutin were commonly identified as responsible for their inhibitory effects. The present review critically analyzes the anti-inflammatory effects and mechanisms of phytochemicals, including dietary compounds against cytokine storm (CS) and hyperinflammation via inhibition of the altered inflammatory pathways triggered by SARS-CoV-2, published since the emergence of COVID-19 in December 2019. Only a few phytochemicals, mainly dietary compounds such as nanocurcumin, melatonin, quercetin, 6-shagoal, kaempferol, resveratrol, andrographolide, and colchicine have been investigated either in in silico or preliminary clinical studies to evaluate their anti-inflammatory effects against COVID-19. Sufficient pre-clinical studies on safety and efficacy of anti-inflammatory effects of the phytochemicals must be performed prior to proper clinical studies to develop them into therapeutic adjuvants in the prevention and treatmemt of COVID-19 symptoms.

Groundnut and tree nuts: a comprehensive review on their lipid components, phytochemicals, and nutraceutical properties.

The health benefits of nut consumption have been extensively demonstrated in observational studies and intervention trials. Besides the high nutritional value, countless evidences show that incorporating nuts into the diet may contribute to health promotion and prevention of certain diseases. Such benefits have been mostly and certainly attributed not only to their richness in healthy lipids (plentiful in unsaturated fatty acids), but also to the presence of a vast array of phytochemicals, such as polar lipids, squalene, phytosterols, tocochromanols, and polyphenolic compounds. Thus, many nut chemical compounds apply well to the designation "nutraceuticals," a broad umbrella term used to describe any food component that, in addition to the basic nutritional value, can contribute extra health benefits. This contribution analyses the general chemical profile of groundnut and common tree nuts (almond, walnut, cashew, hazelnut, pistachio, macadamia, pecan), focusing on lipid components and phytochemicals, with a view on their bioactive properties. Relevant scientific literature linking consumption of nuts, and/or some of their components, with ameliorative and/or preventive effects on selected diseases - such as cancer, cardiovascular, metabolic, and neurodegenerative pathologies - was also reviewed. In addition, the bioactive properties were analyzed in the light of known mechanistic frameworks.

Pharmacological and immunomodulatory modes of action of medically important phytochemicals against arthritis: A molecular insight.

Arthritis is a common illness that affects joints and it may result in inflammation and pain. Even though arthritis usually affects older people, it can also affect children, adults, and both genders. Numerous arthritic mouse models have been developed but the CIA model of rheumatoid arthritis (RA) has received the most attention. With the use of steroids, DMARDs, and NSAIDs, therapy objectives such as reduced disease incidence and better pain management are achieved. Long-term usage of these therapeutic approaches may have negative side effects. Herbal medications are the source of several medicinal substances. Studies have explored the potential benefits of medicinal plants in treating RA. These benefits include up-regulating antioxidant potential, inhibiting cartilage degradation, down-regulating inflammatory cytokines such as NF-kB, IL-6, and TNF-α, and suppressing oxidative stress. In this review, we systematically discuss the role of traditional medicinal plants in rheumatoid arthritis (RA) disease treatment. The role of different medicinal plants such as Curcuma longa, Syzygium aromaticum, Zingiber officinale and Withania somnifera, against arthritis is discussed in this review.

Identification of Phytochemicals with Inhibitory Potential Against Beta-lactamase Enzymes via Computer-aided Approach.

INTRODUCTION: Antibacterial drugs have been widely used for the past century to treat diseases, but their efficacy has been limited by multi-resistant pathogens, particularly those that utilize beta-lactamase enzymes. The inhibition of beta-lactamase enzymes holds great promise for reducing the influence of such pathogens. OBJECTIVE: This study aims to evaluate the mechanism of inhibition of phytochemicals with antibacterial activity against two classes of beta-lactamases using computational methods. METHODS: To achieve this objective, a total of thirty phytochemicals were docked against SHV-1 beta-lactamase and AmpC beta-lactamase after procurement from Protein Data Bank. The pharmacokinetics (ADMET) and density functional theory (DFT) analysis study were also conducted to unravel the nature of the top six most promising compounds on each protein. RESULTS: The results showed that a significant percentage of the compounds had binding affinities greater than that of avibactam, the positive control. Quercetin-3-O-rutinoside showed the most promising results against SHV-1 beta-lactamase with an affinity of -9.4 kcal/mol, while luteolin was found to be the most promising candidate against AmpC beta-lactamase with an affinity of -8.5 kcal/mol. DFT analysis demonstrated the reactivity of these compounds, and the ADMET study indicated that they were relatively safe. CONCLUSION: In conclusion, the study's findings suggest that the selected compounds have significant potential to inhibit beta-lactamase and may be used in combination with antibiotics against organisms that produce beta-lactamase. This study provides a basis for further research in a wet-lab setting to validate the results.