Exploring TLR signaling pathways as promising targets in cervical cancer: The road less traveled.

Cervical cancer is the leading cause of cancer-related deaths for women globally. Despite notable advancements in prevention and treatment, the identification of novel therapeutic targets remains crucial for cervical cancer. Toll-like receptors (TLRs) play an essential role in innate immunity as pattern-recognition receptors. There are several types of pathogen-associated molecular patterns (PAMPs), including those present in cervical cancer cells, which have the ability to activate toll-like receptors (TLRs). Recent studies have revealed dysregulated toll-like receptor (TLR) signaling pathways in cervical cancer, leading to the production of inflammatory cytokines and chemokines that can facilitate tumor growth and metastasis. Consequently, TLRs hold significant promise as potential targets for innovative therapeutic agents against cervical cancer. This book chapter explores the role of TLR signaling pathways in cervical cancer, highlighting their potential for targeted therapy while addressing challenges such as tumor heterogeneity and off-target effects. Despite these obstacles, targeting TLR signaling pathways presents a promising approach for the development of novel and effective treatments for cervical cancer.

Nano-gel formulation of polyphenolic fraction of tobacco stem for wound healing and its inhibitory efficacies against the receptors of chronic wound development.

Current investigation deals with the gel formulation of purified polyphenol loaded nanoparticles for enhanced wound healing. Polyphenols purified using column chromatography an were characterized using HPLC in fractions. Silver nanoparticles were characterization using SEM, AFM, TEM, DLS. Cytotoxic effect was checked on L929 (Mouse fibroblast cells). Bioactive loaded nanoparticles were formulated in gel and subjected for physical characterization. Excision wound wistar rat models were established to measure the wound contraction measurement, histopathological studies, and biochemical assays. Docking and Simulation studies were performed to check the binding and stability with receptors progressing the chronic wound. From the column chromatography, B fraction has shown the presence of maximum polyphenolic content and as well as the polyphenol compounds such as quercetin, rutin and tannic acid as confirmed by the HPLC. Synthesize B fraction-AgNP were found to be below 100 nm in size and spherical in shape as per the characterization. No cytotoxic effect was observed on L929 cells treated with B fraction and its nanoparticles. Formulated B fraction-AgNP gel has revealed the better stability and earlier wound contraction, i.e. before the completion of 14 days of topical treatment. Histopathology studies and collagen content has confirmed the re-epithelization in skin wounds. MD simulation revealed the stability with PI3K and AKT. This can be concluded that tobacco stem polyphenol loaded nanoparticles has potent wound healing activity that can be utilized as nano-drug delivery system for suppression of chronic wound development.Communicated by Ramaswamy H. Sarma.

Effective seed cake extract of O. sanctum inducing the p53 dependent apoptotic pathway in oral cancer cells.

OBJECTIVE: Present study was to observe the therapeutic aspects of seed cake extracts of Ocimum sanctum against the oral cancer cell line with the activation of p53 apoptotic pathway. METHOD: Seed cake extracts were characterized using GC-MS analysis. Cytotoxic activity was observed on KB cells and L929 cell through MTT assay and scratch assay. Antioxidant activity on KB cells were determined using enzymatic and non enzyme content in the treated cells. Chick chorioallantoic membrane (CAM) was established to check the presence of blood vessel formation and neuvasculature pattern in the treated fertilized eggs. DNA fragmentation and gene expression studies were also determined in the treated cells to check the upregulation of apoptotic pathways. RESULTS: GC-MS analysis confirmed alkaloids, phenols, and many. The cytotoxic activity showed maximum antiproliferative potential with aqueous extract, whereas no cytotoxic effect was observed on L929 cells. The ethanolic and aqueous extract has shown a greater SI value. Scratch assay has signified that aqueous extract has a lower migration rate of KB cells. Aqueous extract showed maximum enzymatic activity and lower malondialdehyde content in cells treated with ethanolic extract. CAM model confirmed that eggs treated with aqueous extract has shown inhibition of vasculature pattern and dissolutions of blood vessels. DNA Fragmentation and Gene expression studies confirmed maximum fold in the KB cell treated with an aqueous extract of seed cake leading to activation of p53 dependent apoptotic pathway. CONCLUSION: The potent therapeutic properties of seed cake extracts have been proven, and they can be used as herbal treatments to prevent oral cancer.

Novel biogenic silver nanoconjugates of Abrus precatorius seed extracts and their antiproliferative and antiangiogenic efficacies.

Biogenic silver nanoconjugates (AgNCs), derived from medicinal plants, have been widely explored in the field of biomedicines. AgNCs for the first-time were synthesized using ethyl acetate seed extracts of Abrus precatorius and their antiproliferative and antiangiogenic efficacies were evaluated against cervical and oral carcinoma. Ultraviolet-Visible spectrophotometry, dynamic light Scattering (DLS), and scanning electron microscopy (SEM) were used for characterization of AgNCs. Antiproliferative activity was investigated using MTT, DNA fragmentation and in-vitro antioxidant enzyme activity assays. In-vivo chick chorioallantoic membrane (CAM) model was used to evaluate antiangiogenic activity. A total of 11 compounds were identified in both the extracts in GCMS analysis. The synthesized AgNCs were spherical shaped with an average size of 97.4 nm for AgAPE (Sox) and 64.3 nm for AgAPE (Mac). AgNCs possessed effective inhibition against Hep2C and KB cells. In Hep2C cells, AgAPE (Mac) revealed the highest SOD, catalase, GST activity and lower MDA content, whereas AgAPE (Sox) showed the highest GSH content. On the other hand, in KB cells, AgAPE (Sox) exhibited the higher SOD, GST activity, GSH content, and least MDA content, while AgAPE (Mac) displayed the highest levels of catalase activity. Docking analysis revealed maximum binding affinity of safrole and linoleic acid with selected targets. AgAPE (Sox), AgAPE (Mac) treatment profoundly reduced the thickness, branching, and sprouting of blood vessels in the chick embryos. This study indicates that A. precatorius-derived AgNCs have enhanced efficacies against cervical and oral carcinoma as well as against angiogenesis, potentially limiting tumour growth.

Assessing the potential of rosary pea (Abrus precatorius L.) derived aqueous seed extracts as anticancer agents and their phytoconstituents as COX-2 inhibitor: an in-vitro and in-silico approach.

Abrus precatorius L. is a traditional remedy with a long history of use in medicine around the globe due to its diverse phytochemical composition and bioactivities which are of utmost significance to the scientific community. With the aim to provide new insights into the antioxidant, antiproliferative and antiangiogenic properties of A. precatorius aqueous seed extracts, different extraction methods were employed. Aqueous extract prepared by Soxhlet method APW (Sox) had higher total phenolics, flavonoids and tannin content. In DPPH assay, APW (Sox) had the maximum free radical scavenging activity. The maximum FRAP value was displayed by APW (Mac). The maximum inhibition was shown by APW (Sox) against HPV18 (Hep2C) cells and APW (Mac) against HPV18 (KB) cells. In cervical cancer (Hep2C) cells, catalase (CAT), glutathione-s-transferase (GST) activity, and glutathione (GSH) content were all highest in APW (Sox) extract, whereas APW (Mac) extract demonstrated the highest superoxide dismutase (SOD) activity and the lowest malondialdehyde (MDA) content. Similarly, in oral cancer (KB) cells, APW (Mac) extract showed the highest SOD, CAT, GST activity and GSH content whereas APW (Sox) extract showed the least MDA content. Docking studies showed that tannic acid and rutin had the highest binding affinity, while MD simulations showed that they were stable in complex with COX-2 for at least 90 ns. Promising antiangiogenic activities were observed in both APW (Sox) and APW (Mac) in a dose dependent manner. Therefore, aqueous seed extracts of A. precatorius could be considered promising candidates for anticancer and antiangiogenic drugs.Communicated by Ramaswamy H. Sarma.

Antiproliferative efficacy of the antioxidant bioactive compounds of defatted seeds of Azadirachta indica and Momordica charantia against the regulatory function of tumor suppressor gene inducing oral carcinoma.

The present study focuses on the antiproliferative activity of polyphenolic flavonoids found in defatted seeds of Azadirachta indica and Momordica charantia with the regulatory function of tumor suppressor genes inducing Oral Squamous Cell Carcinoma. Polyphenolic flavonoid in extracts was characterized using chromatographic analysis and has confirmed the presence of quercetin, rutin and tannic acid in the extracts of A. indica and M. charantia. According to DPPH assay and reducing power assays, free radical scavenging was found to be high in ethanolic extract of defatted seeds. Antiproliferative efficacies of defatted seed extracts against KB cell line (mouth) were studied by MTT assay and revealed that aqueous extract of defatted seeds of M. charantia has exhibited maximum antiproliferative activity against KB cells. Antioxidant activity of defatted seed extracts were observed on treated KB cells by determining enzymatic activity (SOD, Cat, and GST) and nonenzyme content (GSH and MDA Content). Using the AutoDock tool, quercetin, rutin and tannin acid revealed that mutant p53, TWIST related protein, TGF-ß and Snail I have the best binging energy results. MD simulation was observed on best docking results between the molecule and identified flavonoid by Desmond V 5.9 package . This leads to the conclusion that bioactive extracts with antiproliferative activity, antioxidant capacity and polyphenols with binding efficacy against tumor suppressor gene regulatory function could be used as a herbal remedy.Communicated by Ramaswamy H. Sarma.

In-vitro antiproliferative efficacy of Abrus precatorius seed extracts on cervical carcinoma.

Abrus precatorius is a tropical medicinal plant with multiple medicinal benefits whose seeds have not yet been studied against cervical cancer. Herein, we have assessed the antioxidant and antiproliferative properties of seed extracts (ethyl acetate and 70% ethanol) prepared from Soxhlet and Maceration extraction methods against Hep2C and HeLa Cells. We observed that the APE (Sox) extract had a significantly higher total flavonoid content, APA (Mac) extract had a high total phenolic content, and APA (Sox) extract had a high total tannin content. Further, HPLC analysis of extracts revealed the presence of tannic acid and rutin. Moreover, APA (Sox) exhibited the highest free radical scavenging activity. APE (Mac) had the best antiproliferative activity against Hep2C cells, while APA (Sox) had the best antiproliferative activity against HeLa cells. In Hep2C cells, APE (Mac) extract revealed the highest SOD, catalase activity, GSH content, and the lowest MDA content, whereas APA (Mac) extract demonstrated the highest GST activity. In HeLa cells, APA (Sox) extract showed the highest SOD, GST activity, GSH content, and the least MDA content, whereas APA (Mac) extract showed the highest catalase activity. Lastly, docking results suggested maximum binding affinity of tannic acid with HER2 and GCR receptors. This study provides evidence that A. precatorius seed extracts possess promising bioactive compounds with probable anticancer and antioxidant properties against cervical cancer for restricting tumor growth.

Preclinical assessment of stem of Nicotiana tabacum on excision wound model.

Agro-waste material derived from N. tabacum has shown enormous potential antioxidant and antimicrobial activity. Hence in the present study, we investigated the wound healing efficacy of ethanolic extract of stem of Nicotiana tabacum on wistar rat model. Ethanolic extract prepared from defatted stem was to check various phytochemicals using spectrophotometric and chromatographic technique. The antioxidant potential was determined by FRAP and Reducing Power assay in extract. Cytotoxicity of extracts was determined using mouse fibroblast L929 cell lines by MTT assay. In vivo angiogenic activity was observed on chick chorioallantoic membrane (CAM) model by observing blood vessels formation and its branching. In vivo wound healing activity was observed on excision wounds in rat model by quantifying percentage of wound contraction, antioxidant activity and histopathology studies. From the present study, polyphenols, tannins and alkaloids were found to be determined in the ethanolic extract by means of spectrophotometric and chromatographic analysis against standards. Antioxidant assay revealed maximum antioxidant potential in ethanolic extract. Cytotoxic effect of extract has not been shown on L929 cell line. From CAM model, extract has shown growth of blood vessels formation at concentration of 480 µg/ml. Topical application of extracts on excision wounds, revealed wound healing activity i.e. 98.7% ± 0.002 on 14th day as well as enzymatic activity (SOD, CAT, GST) and non enzyme content (GSH and Lipid peroxidation) has been found to be high in granulated tissue. Hisopathological studies confirmed the re-epithelization in skin wounds. It can be concluded that stem of N. tabacum can be used as herbal remedy in wound healing process as a topical application.

Role of Toll like receptor in progression and suppression of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) is one of the most common type of head and neck squamous cell carcinoma and one of the multifactorial process that consists of most contributing factors such as tobacco smoking, chewing and alcohol consumption that altered the intracellular environment. Recent studies have shown relevance of Toll like receptor (TLR) associated with carcinogenesis. This review aim's to explore that how TLR associates with progression and suppression of OSCC. This review is a classical review that has confined to articles published in the past 19 years (i.e. 2000-2019) and has summarized the perspective of the authors. 62 articles were reviewed and it was found that progression and suppression of OSCC is associated with different TLRs promoting tumor development and also inhibiting the progression of oral neoplasm. It was found that TLR2, TLR3, TLR4, TLR5, TLR7 and TLR9 are associated with tumor development i.e. in progression of OSCC, where as suppression of OSCC through TLR3 and TLR7. We authors would like to conclude that literature survey has indicated effective TLR's against OSCC development and can be explored to investigate other TLRs that can be used for therapeutic purposes in near future.

Neuroprotective ability of TMV coat protein on rat PC-12 cells and it's in silico study with LRRK2 receptor.

OBJECTIVE: Present study was to observe the neuroprotective ability of TMV coat protein by observing both in vitro studies on Rat PC-12 cells and in silico studies with LRRK2 receptor by molecular docking. METHODS: TMV coat protein was extracted out from the stem of Nicotiana tabacum and was purified and identified by MALDI-TOF/MS/MS analysis. We confer antioxidant activity of TMV coat protein by enzyme activity like superoxide dismutase (SOD), catalase (CAT) and glutathione-s-transferase (GST) and nonenzyme content by glutathione (GSH) and malondialdehyde (MDA) content. Neuroprotective ability of TMV coat protein was observed by determining the enzyme activity and nonenzyme content in treated cells that were exposed to neurotoxic shock. In silico studies were done in order to observe the molecular docking studies against LRRK2 receptor. RESULTS: Antioxidant content was found to be high in TMV coat protein and in treated Rat PC-12 cells as well. Enzyme activity and nonenzyme content were determined and their levels were found to be in increasing level with respect to the volume of 0.2 mg/ml of TMV coat protein. In silico studies revealed the binding efficacy of TMV coat protein with LRRK2 receptor by observing the molecular docking using automated servers. CONCLUSION: From the present study, it was found that TMV coat protein can be utilized as neuroprotective agent and inhibitor of LRRK2 receptor.