Therapeutic targeting of microtubule affinity-regulating kinase 4 in cancer and neurodegenerative diseases.

Microtubule affinity-regulating kinase 4 (MARK4) is a member of the Ser/Thr protein kinase family, phosphorylates the microtubule-connected proteins and plays a vital role in causing cancers and neurodegenerative diseases. This kinase modulates multiple signaling pathways, including mammalian target of rapamycin, nuclear factor-κB, and Hippo-signaling, presumably responsible for cancer and Alzheimer's. MARK4 acts as a negative controller of the Hippo-kinase cassette for promoting YAP/TAZ action, and the loss of MARK4 detains the tumorigenic properties of cancer cells. MARK4 is involved in tau hyperphosphorylation that consequently affects neurodegeneration. MARK4 is a promising drug target for cancer, diabetes, and Alzheimer's. Developing the potent and selective inhibitors of MAKR4 are promising in the therapeutic management of associated diseases. Despite its great significance, a few reviews are available to discuss its structure, function and clinical significance. In the current review, we aimed to provide detailed information on the structural features of MARK4 targeted in drug development and its role in various signaling pathways related to cancer and neurodegenerative diseases. We further described the therapeutic potential of MARK4 inhibitors in preventing numerous diseases. Finally, the updated information on MARK4 will be helpful in the further development of effective therapeutic molecules.

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.

Cellular signaling pathways involved in the maintenance of the equilibrium between cell proliferation and apoptosis have emerged as rational targets that can be exploited in the prevention and treatment of cancer. Epigallocatechin-3-gallate (EGCG) is the most abundant phenolic compound found in green tea. It has been shown to regulate multiple crucial cellular signaling pathways, including those mediated by EGFR, JAK-STAT, MAPKs, NF-κB, PI3K-AKT-mTOR, and others. Deregulation of the abovementioned pathways is involved in the pathophysiology of cancer. It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes. Furthermore, preclinical and clinical studies suggest that EGCG may be used in the treatment of numerous disorders, including cancer. This review aims to summarize the existing knowledge regarding the biological properties of EGCG, especially in the context of cancer treatment and prophylaxis.

Investigating binding mechanism of thymoquinone to human transferrin, targeting Alzheimer's disease therapy.

Iron deposition in the central nervous system (CNS) is one of the causes of neurodegenerative diseases. Human transferrin (hTf) acts as an iron carrier present in the blood plasma, preventing it from contributing to redox reactions. Plant compounds and their derivatives are frequently being used in preventing or delaying Alzheimer's disease (AD). Thymoquinone (TQ), a natural product has gained popularity because of its broad therapeutic applications. TQ is one of the significant phytoconstituent of Nigella sativa. The binding of TQ to hTf was determined by spectroscopic methods and isothermal titration calorimetry. We have observed that TQ strongly binds to hTf with a binding constant (K) of 0.22 × 106 M-1 and forming a stable complex. In addition, isothermal titration calorimetry revealed the spontaneous binding of TQ with hTf. Molecular docking analysis showed key residues of the hTf that were involved in the binding to TQ. We further performed a 250 ns molecular dynamics simulation which deciphered the dynamics and stability of the hTf-TQ complex. Structure analysis suggested that the binding of TQ doesn't cause any significant alterations in the hTf structure during the course of simulation and a stable complex is formed. Altogether, we have elucidated the mechanism of binding of TQ with hTf, which can be further implicated in the development of a novel strategy for AD therapy.

Enzymatic Activity and Horizontal Gene Transfer of Heavy Metals and Antibiotic Resistant Proteus vulgaris from Hospital Wastewater: An Insight.

Globally, the issue of microbial resistance to medicines and heavy metals is getting worse. There are few reports or data available for Proteus vulgaris (P. vulgaris), particularly in India. This investigation intends to reveal the bacteria's ability to transmit genes and their level of resistance as well. The wastewater samples were taken from several hospitals in Lucknow City, India, and examined for the presence of Gram-negative bacteria that were resistant to antibiotics and heavy metals. The microbial population count in different hospital wastewaters decreases with increasing concentrations of metal and antibiotics. Among all the examined metals, Ni and Zn had the highest viable counts, whereas Hg, Cd, and Co had the lowest viable counts. Penicillin, ampicillin, and amoxicillin, among the antibiotics, demonstrated higher viable counts, whereas tetracycline and erythromycin exhibited lower viable counts. The MIC values for the P. vulgaris isolates tested ranged from 50 to 16,00 µg/ml for each metal tested. The multiple metal resistance (MMR) index, which ranged from 0.04 to 0.50, showed diverse heavy metal resistance patterns in all P. vulgaris isolates (in the case of 2-7 metals in various combinations). All of the tested isolates had methicillin resistance, whereas the least number of isolates had ofloxacin, gentamycin, or neomycin resistance. The P. vulgaris isolates displayed multidrug resistance patterns (2-12 drugs) in various antibiotic combinations. The MAR indexes were shown to be between (0.02-0.7). From the total isolates, 98%, 84%, and 80% had urease, gelatinase, and amylase activity, whereas 68% and 56% displayed protease and beta-lactamase activity. Plasmids were present in all the selected resistant isolates and varied in size from 42.5 to 57.0 kb and molecular weight from 27.2 to 37.0 MD. The transmission of the antibiotic/metal resistance genes was evaluated between a total of 7 pairs of isolates. A higher transfer frequency (4.4 × 10-1) was observed among antibiotics, although a lower transfer frequency (1.0 × 10-2) was observed against metals in both the media from the entire site tested. According to exponential decay, the population of hospital wastewater declined in the following order across all sites: Site II > Site IV > Site III > Site I for antibiotics and site IV > site II > site I >site III for metal. Different metal and antibiotic concentrations have varying effects on the population. The metal-tolerant P. vulgaris from hospital wastewater was studied in the current study had multiple distinct patterns of antibiotic resistance. It could provide cutting-edge methods for treating infectious diseases, which are essential for managing and assessing the risks associated with hospital wastewater, especially in the case of P. vulgaris.

B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy.

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.

Therapeutic Potential of Ursolic Acid in Cancer and Diabetic Neuropathy Diseases.

Ursolic acid (UA) is a pentacyclic triterpenoid frequently found in medicinal herbs and plants, having numerous pharmacological effects. UA and its analogs treat multiple diseases, including cancer, diabetic neuropathy, and inflammatory diseases. UA inhibits cancer proliferation, metastasis, angiogenesis, and induced cell death, scavenging free radicals and triggering numerous anti- and pro-apoptotic proteins. The biochemistry of UA has been examined broadly based on the literature, with alterations frequently having been prepared on positions C-3 (hydroxyl), C12-C13 (double bonds), and C-28 (carboxylic acid), leading to several UA derivatives with increased potency, bioavailability and water solubility. UA could be used as a protective agent to counter neural dysfunction via anti-oxidant and anti-inflammatory effects. It is a potential therapeutic drug implicated in the treatment of cancer and diabetic complications diseases provide novel machinery to the anti-inflammatory properties of UA. The pharmacological efficiency of UA is exhibited by the therapeutic theory of one-drug → several targets → one/multiple diseases. Hence, UA shows promising therapeutic potential for cancer and diabetic neuropathy diseases. This review aims to discuss mechanistic insights into promising beneficial effects of UA. We further explained the pharmacological aspects, clinical trials, and potential limitations of UA for the management of cancer and diabetic neuropathy diseases.

The elevated activation of NFκB and AP-1 is correlated with differential regulation of Bcl-2 and associated with oral squamous cell carcinoma progression and resistance.

OBJECTIVES: Oral cancer is the sixth most common cancer in the world. Failure of chemoradiation therapy is a major concern for treating oral cancer patients. The objective of this study is to determine the B cell lymphoma-2 (bcl-2) expression and its regulation by nuclear factor κB (NFκB) and activator protein 1 (AP-1) in oral cancer progression and chemoradiation resistance. MATERIALS AND METHODS: In the present study, a total of 123 (n = 123) human samples were included. Briefly, 64 fresh samples were from adjacent normal (AN), primary oral tumors without treatment (PT), and tumors with resistance to chemoradiation therapy with local recurrence (RCRT). Fifty-nine samples were human tongue cancers and normal samples (TMA). Messenger RNA (mRNA) expression levels of bcl-2 and protein levels of bcl-2, NFκB, AP-1, and inactive GSK3α/ß were measured by semiquantitative RT-PCR, immunohistochemistry, Western blot, and ChIP analysis. RESULTS: Increased bcl-2 expression was observed in PT compared to AN. The RCRT tumors showed maximum expression of bcl-2 mRNA and protein over the PT and AN groups. Bcl-2 protein and mRNA expression were positively correlated with NFκB and AP-1 expression. AP-1 expression was strongly correlated with bcl-2 in the RCRT group of tumors. Further, inactive GSK3α/ß showed a positive trend with bcl-2 expression in oral tongue cancer specimens. CONCLUSION: Collectively, our results demonstrated cumulative effect of AP-1 and NFĸB for bcl-2 gene regulation in overall PT progression and chemoradiation resistance. The study provides evidence of increased bcl-2 mRNA/protein fueled by NFĸB in PT and AP-1 in RCRT. These regulations of bcl-2 by NFκB and AP-1 are important in OSCC progression and chemoradiation resistance.

Reversion-inducing cysteine-rich protein with Kazal motifs and its regulation by glycogen synthase kinase 3 signaling in oral cancer.

The reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and glycogen synthase kinase (GSK3) are novel tumor suppressors, and emerging evidence has suggested their active role in oral cancer pathogenesis. In the present study, 112 human samples, including 55 fresh samples of 14 adjacent normal tissues, 25 noninvasive oral tumors, and 18 invasive tumors, were included. The messenger RNA (mRNA) expression, protein expression, and promoter methylation of the RECK gene, as well as the expression of GSK3ß, phospho/total ß-catenin, and c-myc, were measured by RT-PCR, bisulphate modification-PCR, immunohistochemistry, and Western blot analysis. Additionally, ectopic expression of in/active GSK3ß was performed in cell culture experiments. This study provided information on the progressive silencing of RECK gene expression at the protein and mRNA levels paralleled with promoter hypermethylation at various stages of oral tumor invasion. RECK expression and the hypermethylation of the RECK gene promoter were negatively and positively correlated with pS9GSK3ß/c-myc expression, respectively. Further, a negative trend of RECK protein expression with nuclear ß-catenin expression was observed. Induced expression of active GSK3ß reversed the RECK silencing in SCC9 cells. Collectively, our results demonstrated that the silencing of the RECK gene, possibly regulated by the GSK3ß pathway, is an important event in oral cancer invasion and this pathway could be exploited for therapeutic interventions.

Sophorin mitigates flutamide-induced hepatotoxicity in wistar rats.

Flutamide is frequently used in the management of prostate cancer, hirsutism, and acne. It is a non-steroidal anti-androgenic drug and causes hepatotoxicity. The current study's objective is to evaluate sophorin's hepatoprotective effectiveness against flutamide-induced hepatotoxicity in Wistar rats. Sophorin is a citrus flavonoid glycoside, also known as rutin, which is a low molecular weight polyphenolic compound with natural antioxidant properties and reported to have promising hepatoprotective efficacy. In this study, sophorin was used at a dose of 100 mg/kg body weight in purified water via oral route for 4 week daily whereas, flutamide was used at a dose of 100 mg kg/b.wt for 4 weeks daily in 0.5% carboxy methyl cellulose (CMC) through the oral route for the induction of hepatotoxicity. Flutamide administration leads to enhanced reactive oxygen species (ROS) generation, an imbalance in redox homeostasis and peroxidation of lipid resulted in reduced natural antioxidant level in liver tissue. Our result demonstrated that sophorin significantly abrogate flutamide induced lipid peroxidation, protein carbonyl (PC), and also significantly increasesed in enzymatic activity/level of tissue natural antioxidant such as reduced glutathione(GSH), glutathione reductase(GR), catalase, and superoxide dismutase(SOD). Additionally, sophorin reduced the activity of cytochrome P450 3A1 in liver tissue which was elevated due to flutamide treatment. Furthermore, sophorin treatment significantly decreased the pro-inflammatory cytokines (TNF-α and IL-6) level. Immunohistochemical analysis for the expression of inflammatory proteins (iNOS and COX-2) in hepatic tissue was decreased after sophorin treatment against flutamide-induced hepatotoxicity. Moreover, sophorin suppressed the infiltration of mast cells in liver tissue which further showed anti-inflammatory potential of sophorin. Our histological investigation further demonstrated sophorin's hepatoprotective function by restoring the typical histology of the liver. Based on the aforementioned information, we are able to come to the conclusion that sophorin supplementation might benefit wistar rats with flutamide-induced hepatic damage by reducing oxidative stress and hepatocellular inflammation.

Structure-Based Identification of Natural Compounds as Potential RET-Kinase Inhibitors for Therapeutic Targeting of Neurodegenerative Diseases.

BACKGROUND: Tyrosine-protein kinase receptor Ret (RET), a proto-oncogene, is considered as an attractive drug target for cancer and neurodegenerative diseases, including Alzheimer's disease (AD). OBJECTIVE: We aimed to identify potential inhibitors of RET kinase among natural compounds present in the ZINC database. METHODS: A multistep structure-based virtual screening approach was used to identify potential RET kinase inhibitors based on their binding affinities, docking scores, and interactions with the biologically important residues of RET kinase. To further validate the potential of these compounds as therapeutic leads, molecular dynamics (MD) simulations for 100 ns were carried out and subsequently evaluated the stability, conformational changes, and interaction mechanism of RET in-complex with the elucidated compounds. RESULTS: Two natural compounds, ZINC02092851 and ZINC02726682, demonstrated high affinity, specificity for the ATP-binding pocket of RET and drug-likeness properties. The MD simulation outputs indicated that the binding of both compounds stabilizes the RET structure and leads to fewer conformational changes. CONCLUSIONS: The findings suggest that ZINC02092851 and ZINC02726682 may be potential inhibitors for RET, offering valuable leads for drug development against RET-associated diseases. Our study provides a promising avenue for developing new therapeutic strategies against complex diseases, including AD. Identifying natural compounds with high affinity and specificity for RET provides a valuable starting point for developing novel drugs that could help combat these debilitating diseases.

Therapeutic Targeting of Regulated Signaling Pathways of Non-Small Cell Lung Carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common cancer globally. Phytochemicals and small molecule inhibitors significantly prevent varying types of cancers, including NSCLC. These therapeutic molecules serve as important sources for new drugs that interfere with cellular proliferation, apoptosis, metastasis, and angiogenesis by regulating signaling pathways. These molecules affect several cellular signaling cascades, including p53, NF-κB, STAT3, RAS, MAPK/ERK, Wnt, and AKT/PI3K, and are thus implicated in the therapeutic management of cancers. This review aims to describe the bioactive compounds and small-molecule inhibitors, their anticancer action, and targeting cellular signaling cascades in NSCLC. We highlighted the therapeutic potential of Epigallocatechin gallate (EGCG), Perifosine, ABT-737, Thymoquinine, Quercetin, Venetoclax, Gefitinib, and Genistein. These compounds are implicated in the therapeutic management of NSCLC. This review further offers deeper mechanistic insights into different signaling pathways that could be targeted for NSCLC therapy by phytochemicals and small-molecule inhibitors.

Integrated virtual screening and MD simulation study to discover potential inhibitors of Lyn-kinase: targeting cancer therapy.

Tyrosine-protein kinase Lyn (LynK) has emerged as one of the most attractive therapeutic targets for cancer and diabetes. In this study, we used a multistep virtual screening process of natural compounds to discover potential inhibitors of LynK from the IMPPAT database. The primary filters were based on Lipinski rules, ADMET properties, and PAINS patterns. Then, binding affinities and interaction analyses were carried out for the high-affinity selectivity of the compounds towards LynK. Eventually, two natural compounds, Glabrene and Lactupicrin, were identified with high affinity and specificity for the LynK-binding pocket. Both compounds exhibited drug-like properties, as predicted by ADMET analysis and physicochemical parameters. The molecular dynamics (MD) simulation study revealed that these compounds bind to the ATP-binding pocket of LynK and interact with functionally significant residues with stability without inducing any significant structural changes to the protein. Ultimately, the identified compounds may be regarded as promising LynK inhibitors and can be used as lead molecules in the drug development against LynK-related diseases.Communicated by Ramaswamy H. Sarma.

Investigating regulated signaling pathways in therapeutic targeting of non-small cell lung carcinoma.

Non-small cell lung carcinoma (NSCLC) is the most common malignancy worldwide. The signaling cascades are stimulated via genetic modifications in upstream signaling molecules, which affect apoptotic, proliferative, and differentiation pathways. Dysregulation of these signaling cascades causes cancer-initiating cell proliferation, cancer development, and drug resistance. Numerous efforts in the treatment of NSCLC have been undertaken in the past few decades, enhancing our understanding of the mechanisms of cancer development and moving forward to develop effective therapeutic approaches. Modifications of transcription factors and connected pathways are utilized to develop new treatment options for NSCLC. Developing designed inhibitors targeting specific cellular signaling pathways in tumor progression has been recommended for the therapeutic management of NSCLC. This comprehensive review provided deeper mechanistic insights into the molecular mechanism of action of various signaling molecules and their targeting in the clinical management of NSCLC.

Crosstalk between PD-L1 and Jak2-Stat3/ MAPK-AP1 signaling promotes oral cancer progression, invasion and therapy resistance.

BACKGROUND: Programmed cell death ligand-1 (PD-L1)is an antitumor immunity molecule and a great target to cure oral cancer; nonetheless, the limited success can be attributed to many complex pathways and tumor-related interferences. METHODS: In the present study, 150 human oral squamous cell carcinoma (OSCC) tissue samples, including 17 adjacent normals, 56 primary tumors, 47 invasive tumors, and 30 therapy-resistant (RT) samples, were included. The parental/cisplatin-resistant (CisR-SCC4/9) cells were utilized for overexpression (Jak1-3 wild type and catalytically inactive), knockdown (PD-L1 siRNA), targeting MAPK/PI3K/Jak-Stat pathways (SMIs) and checking microsomes. The expression of PD-L1, transcription factors (TFs), signaling pathways, survival/apoptosis, therapy resistance, and invasiveness-related molecules/their activity were determined by RT-PCR, Immunohistochemistry, Western blot, Gelatin Zymography, and MTT assay. RESULTS: Advanced OSCC tumors (invasive and drug-resistance), CisR-SCC4/9 cells, and secretory exosomes (CisR-SCC4/9) were found with increased PD-L1 expression. PD-L1 mRNA/protein showed a positive correlation with different TFs (AP1 > Stat3 > c-myc > NFκB) in tumor samples. The PD-L1 expression was more influenced by Jak-Stat/ MAPK-AP1 pathways over PI3K. The ectopic expression of Jak1-3 suggests Jak2 inducted PD-L1 level over Jak1/Jak3. Finally, PD-L1 directly supports survival (Bcl-xL, Bax, cleaved caspase-3), invasion (MMP2/9), and drug-resistance (ALDH-1A1/-3A1) program in OSCC through its link with several molecules. CONCLUSIONS: PD-L1 was regulated mainly by the Jak2-Stat3/ MAPK-AP1 pathway, and besides the routine immunological functions, it supports OSCC survival, invasion, and therapy resistance. PD-L1 can be used as an indicator of severity and can be targeted along with Jak2-Stat3/ MAPK-AP1 for a better outcome OSCC.

Biochemical features and therapeutic potential of α-Mangostin: Mechanism of action, medicinal values, and health benefits.

α-Mangostin (α-MG) is a natural xanthone obtained from the pericarps of mangosteen. It exhibits excellent potential, including anti-cancer, neuroprotective, antimicrobial, antioxidant, and anti-inflammatory properties, and induces apoptosis. α-MG controls cell proliferation by modulating signaling molecules, thus implicated in cancer therapy. It possesses incredible pharmacological features and modulates crucial cellular and molecular factors. Due to its lesser water solubility and pitiable target selectivity, α-MG has limited clinical application. As a known antioxidant, α-MG has gained significant attention from the scientific community, increasing interest in extensive technical and biomedical applications. Nanoparticle-based drug delivery systems were designed to improve the pharmacological features and efficiency of α-MG. This review is focused on recent developments on the therapeutic potential of α-MG in managing cancer and neurological diseases, with a special focus on its mechanism of action. In addition, we highlighted biochemical and pharmacological features, metabolism, functions, anti-inflammatory, antioxidant effects and pre-clinical applications of α-MG.

Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective.

The multidrug resistance developed in many organisms due to the prolonged use of antibiotics has been an increasing global health crisis. Klebsiella pneumoniae is a causal organism for various infections, including respiratory, urinary tract and biliary diseases. Initially, immunocompromised individuals are primarily affected by K. pneumoniae. Due to the emergence of hypervirulent strains recently, both healthy and immunocompetent individuals are equally susceptible to K. pneumoniae infections. The infections caused by multidrug-resistant and hypervirulent K. pneumoniae strains are complicated to treat, illustrating an urgent need to develop novel and more practical approaches to combat the pathogen. We focused on the previously performed high-throughput analyses by other groups to discover several novel enzymes that may be considered attractive drug targets of K. pneumoniae. These targets qualify most of the selection criteria for drug targeting, including an absence of its homolog's gene in the host. The capsule, lipopolysaccharide, fimbriae, siderophores and essential virulence factors facilitate the pathogen entry, infection and survival inside the host. This review discusses K. pneumoniae pathophysiology, including its virulence determinants and further the potential drug targets that might facilitate the discovery of novel drugs and effective treatment regimens shortly.

Epigallocatechin 3-gallate: From green tea to cancer therapeutics.

Epigallocatechin 3-gallate (EGCG) possesses various biological functions, including anti-cancer and anti-inflammatory properties. EGCG is an abundant polyphenolic component originating from green tea extract that has exhibited versatile bioactivities in combating several cancers. This review highlights the pharmacological features of EGCG and its therapeutic implications in cancer and other metabolic diseases. It modulates numerous signaling pathways, regulating cells' undesired survival and proliferation, thus imparting strong tumor chemopreventive and therapeutic effects. EGCG initiates cell death through the intrinsic pathway and causes inhibition of EGFR, STAT3, and ERK pathways in several cancers. EGCG alters and inhibits ERK1/2, NF-κB, and Akt-mediated signaling, altering the Bcl-2 family proteins ratio and activating caspases in tumor cells. This review focuses on anti-cancer, anti-oxidant, anti-inflammatory, anti-angiogenesis, and apoptotic effects of EGCG. We further highlighted the potential of EGCG in different types of cancer, emphasizing clinical trials formulations that further improve our understanding of the therapeutic management of cancer and inflammatory diseases.

Therapeutic implications and clinical manifestations of thymoquinone.

Thymoquinone (TQ), a natural phytochemical predominantly found in Nigella sativa, has been investigated for its numerous health benefits. TQ showed anti-cancer, anti-oxidant, and anti-inflammatory properties, validated in various disease models. The anti-cancer potential of TQ is goverened by anti-proliferation, cell cycle arrest, apoptosis induction, ROS production, anti-metastasis and anti-angiogenesis, inhibition of cell migration and invasion action. Additionally, TQ exhibited antitumor activity via the modulation of multiple pathways and molecular targets, including Akt, ERK1/2, STAT3, and NF-κB. The present review highlighted the anticancer potential of TQ . We summarize the anti-cancer, anti-oxidant, and anti-inflammatory properties of TQ, focusing on its molecular targets and its promising action in cancer therapy. We further described the molecular mechanisms by which TQ prevents signaling pathways that mediate cancer progression, invasion, and metastasis.

Synergistic Role of Plant Extracts and Essential Oils against Multidrug Resistance and Gram-Negative Bacterial Strains Producing Extended-Spectrum ß-Lactamases.

Plants, being the significant and natural source of medication for humankind against several ailments with characteristic substances hidden on them, have been recognized for many centuries. Accessibility of various methodologies for the revelation of therapeutically characteristic items has opened new avenues to redefine plants as the best reservoirs of new structural types. The role of plant metabolites to hinder the development and movement of pathogenic microbes is cherished. Production of extended-spectrum ß-lactamases is an amazing tolerance mechanism that hinders the antibacterial treatment of infections caused by Gram-negative bacteria and is a serious problem for the current antimicrobial compounds. The exploration of the invention from sources of plant metabolites gives sustenance against the concern of the development of resistant pathogens. Essential oils are volatile, natural, complex compounds described by a solid odor and are framed by aromatic plants as secondary metabolites. The bioactive properties of essential oils are commonly controlled by the characteristic compounds present in them. They have been commonly utilized for bactericidal, virucidal, fungicidal, antiparasitic, insecticidal, medicinal, and antioxidant applications. Alkaloids are plant secondary metabolites that have appeared to have strong pharmacological properties. The impact of alkaloids from Callistemon citrinus and Vernonia adoensis leaves on bacterial development and efflux pump activity was assessed on Pseudomonas aeruginosa. Plant-derived chemicals may have direct antibacterial activity and/or indirect antibacterial activity as antibiotic resistance modifying agents, increasing the efficiency of antibiotics when used in combination. The thorough screening of plant-derived bioactive chemicals as resistance-modifying agents, including those that can act synergistically with antibiotics, is a viable method to overcome bacterial resistance. The synergistic assessment studies with the plant extract/essential oil and the antibiotic compounds is essential with a target for achieving a redesigned model with sustainable effects which are appreciably noticeable in specific sites of the plants compared to the entirety of their individual parts.

Natural products can be used in therapeutic management of COVID-19: Probable mechanistic insights.

The unexpected emergence of the new Coronavirus disease (COVID-19) has affected more than three hundred million individuals and resulted in more than five million deaths worldwide. The ongoing pandemic has underscored the urgent need for effective preventive and therapeutic measures to develop anti-viral therapy. The natural compounds possess various pharmaceutical properties and are reported as effective anti-virals. The interest to develop an anti-viral drug against the novel severe acute respiratory syndrome Coronavirus (SARS-CoV-2) from natural compounds has increased globally. Here, we investigated the anti-viral potential of selected promising natural products. Sources of data for this paper are current literature published in the context of therapeutic uses of phytoconstituents and their mechanism of action published in various reputed peer-reviewed journals. An extensive literature survey was done and data were critically analyzed to get deeper insights into the mechanism of action of a few important phytoconstituents. The consumption of natural products such as thymoquinone, quercetin, caffeic acid, ursolic acid, ellagic acid, vanillin, thymol, and rosmarinic acid could improve our immune response and thus possesses excellent therapeutic potential. This review focuses on the anti-viral functions of various phytoconstituent and alkaloids and their potential therapeutic implications against SARS-CoV-2. Our comprehensive analysis provides mechanistic insights into phytoconstituents to restrain viral infection and provide a better solution through natural, therapeutically active agents.