In silico and in vitro studies for the identification of small molecular inhibitors from Euphorbia hirta Linn for rheumatoid arthritis: targeting TNF-α-mediated inflammation.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that is now potentially lethal and has a significant detrimental influence on people's daily lives by affecting bone joints. Inflammation plays a vital role in this type of autoimmune disorder. In rheumatoid arthritis, long-term production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) stimulates the immune system against cells in bone joints and helps to develop the pathogenesis of rheumatoid arthritis. So, while treating rheumatoid arthritis, we need to block these kinds of mechanisms. We employed soxhlet extraction, thin-layer chromatography (TLC), and gas chromatography-mass spectroscopy (GC-MS) to analyze the phytocompound information in E. hirta leaves. Furthermore, our research included in vitro investigations using Western blotting and mRNA expression analysis (TNF-α, IL-1ß, IL-6) to affirm the anti-inflammatory effectiveness of our extract. For identifying the lead-like molecules, virtual screening and molecular dynamics simulations were used. TLC results confirmed the presence of phytocompounds in E. hirta crude through spots. The structure elucidation of the phytocompounds was confirmed by the GC-MS chromatogram. The in vitro outcomes collectively underscore the inhibitory influence of E. hirta on cell proliferation and its capacity to attenuate the expression of TNF- α within THP-1 cells. The results of in silico methodologies confirmed six lead-like molecules. We could conclude that phytocompounds from ethanol leaf crude have effective lead-like molecules against the TNF-α.

Blueberry extract and its bioactive compounds mitigate oxidative stress and suppress human lung cancer cell (A549) growth by modulating the expression of p53/EGFR/STAT3/IL6-mediated signaling molecules.

Bioactive phytocompounds are crucial components in all plants. Since the time of traditional medicine, the utilization of plants has been grounded in the potential of these bioactive compounds to treat or manage specific illnesses. These natural bioactive compounds have sparked growing interest in employing medicinal plants for addressing various conditions, such as inflammatory diseases, diabetes, and cancer. This study focuses on assessing the qualitative phytochemical composition, antioxidant potential, and cytotoxic effects of blueberry (Vaccinium sect. Cyanococcus) extract using three different solvents, namely water, ethanol, and methanol. The extract exhibited notable antioxidant activities, as evidenced by DPPH and H2O2 free radical scavenging assays. The cell viability assay also demonstrated cell growth inhibition in A549 cells. Furthermore, nine specific phytocompounds sourced from existing literature were selected for molecular docking studies against CDK6 and, AMPK key protein kinases which enhance the cancer progression. The molecular docking results also revealed favorable binding scores, with a high score of -9.5 kcal/mol in CDK6 protein and a maximum score of AMPK with targets of -8.8 kcal/mol. The selected phytocompounds' pharmacodynamic properties such as ADMET also supported the study. Furthermore, rutin stated that pre-dominantly present in blueberry plants shows a potent cytotoxicity effect in A549 cells. Functional annotations by bioinformatic analysis for rutin also revealed the strong enrichment in the involvement of PI3K/AKT1/STAT, and p53 signaling pathways. Based on this analysis, the identified rutin and other compounds hold a promising anticancer activity. Overall, the comprehensive evaluation of both in vitro and in silico data suggests that the Vaccinium sect. Cyanococcus extract could serve as a valuable source of pharmaceutical agents and may prove effective in future therapeutic applications.

The role of MicroRNAs in the diagnosis and treatment of oral premalignant disorders.

Oral premalignant disorders (OPMDs) are a group of potentially malignant conditions that pose a significant health burden globally. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as crucial regulators of gene expression and have been implicated in various biological processes, including carcinogenesis. This review synthesizes existing knowledge to provide a comprehensive understanding of the molecular mechanisms underlying OPMDs and to highlight the potential of miRNAs as promising biomarkers and therapeutic targets. Additionally, this review seeks to explore the potential of miRNA-based diagnostic biomarkers for early detection of OPMDs in the current literature on miRNAs in OPMDs, examining their involvement in disease pathogenesis, diagnostic potential, and therapeutic implications. Dysregulated miRNAs can target genes involved in critical cellular processes, such as cell cycle regulation, apoptosis, and DNA repair, leading to disease progression. Notably, miR-21, miR-31, miR-135b, and miR-486-5p have shown promise as potential biomarkers for early detection of oral premalignant lesions. Furthermore, the paper discusses the therapeutic implications of miRNAs in OPMDs. Preclinical studies have demonstrated the efficacy of miRNA-targeted therapies, such as miRNA mimics and inhibitors, in suppressing the growth of oral premalignant lesions. Early-phase clinical trials have shown promising results, indicating the potential for personalized treatment approaches. The findings underscore the importance of understanding the molecular mechanisms underlying these disorders and provide insights for the development of improved diagnostic and therapeutic strategies. However, they pose certain limitations given their intrinsic variability in expression profiles, the need for optimized isolation and detection methods, and potential hurdles in transitioning from preclinical success to clinical applications. Thus, future clinical studies are warranted to fully exploit the potential of miRNAs in the management of OPMDs.

Carica Papaya Reduces High Fat Diet and Streptozotocin-Induced Development of Inflammation in Adipocyte via IL-1ß/IL-6/TNF-α Mediated Signaling Mechanisms in Type-2 Diabetic Rats.

The prevalence of obesity in contemporary society has brought attention to how serious it is all around the world. Obesity, a proinflammatory condition defined by hypertrophied adipocytes and immune cells that reside in adipose tissue, is characterized by elevated circulating levels of proinflammatory cytokines. The pro-inflammatory mediators trigger a number of inflammatory pathways and affect the phosphorylation of a number of insulin-signaling pathways in peripheral tissues. In this work, we pointed the outcome of the leaves of Carica papaya (C. papaya) on the inflammatory molecules by in vivo and in silico analysis in order to prove its mechanisms of action. Adipocytokines, antioxidant enzymes, gene and protein expression of pro-inflammatory signaling molecules (mTOR, TNF-α, IL-1ß, IL-6 and IKKß) by q-RT-PCR and immunohistochemistry, as well as histopathological analysis, in adipose tissues were carried out. C. papaya reinstated the levels of adipocytokines, antioxidant enzymes and mRNA levels of mTOR, TNF-α, IL-1ß, IL-6 and IKKß in the adipose tissues of type 2 diabetic rats. Molecular docking and dynamics simulation studies revealed that caffeic acid, transferulic acid and quercetin had the top hit rates against IKKß, TNF-α, IL-6, IL-1ß, and mTOR. This study concludes that C. papaya put back the altered effects in fatty tissue of type 2 diabetic rats by restoring the adipocytokines and the gene expression.

A Comprehensive Review on Bio-Based Materials for Chronic Diabetic Wounds.

Globally, millions of people suffer from poor wound healing, which is associated with higher mortality rates and higher healthcare costs. There are several factors that can complicate the healing process of wounds, including inadequate conditions for cell migration, proliferation, and angiogenesis, microbial infections, and prolonged inflammatory responses. Current therapeutic methods have not yet been able to resolve several primary problems; therefore, their effectiveness is limited. As a result of their remarkable properties, bio-based materials have been demonstrated to have a significant impact on wound healing in recent years. In the wound microenvironment, bio-based materials can stimulate numerous cellular and molecular processes that may enhance healing by inhibiting the growth of pathogens, preventing inflammation, and stimulating angiogenesis, potentially converting a non-healing environment to an appropriately healing one. The aim of this present review article is to provide an overview of the mechanisms underlying wound healing and its pathophysiology. The development of bio-based nanomaterials for chronic diabetic wounds as well as novel methodologies for stimulating wound healing mechanisms are also discussed.

Liquid biopsy: Exosomal microRNAs as novel diagnostic and prognostic biomarkers in cancer.

BACKGROUND: Detecting cancer at an early stage before clinical manifestation could be an effective strategy to decrease cancer mortality. Thus, identifying liquid biopsy biomarkers with high efficacy could be a promising approach for non-invasive diagnosis of cancer. MAIN TEXT: Liquid biopsies are increasingly used as a supplement to biopsy, as it enables disease progression to be detected months before clinical and radiographic confirmation. Many bodily fluids contain exosomal microRNAs (miRNAs) which could provide a new class of biomarkers for early and minimally invasive cancer diagnosis due to the stability of miRNAs in exosomes. In this review, we mainly focused on the exosomal miRNAs (liquid biopsy) as biomarkers in the diagnosis and prognosis of various cancers. CONCLUSION: Exosomal miRNAs can be used as diagnostic and prognosis biomarkers that provide unique insights and a more dynamic perspective of the progression and therapeutic responses in various malignancies. Therefore, the development of novel and more sensitive technologies that exploit exosomal miRNAs should be a priority for cancer management.

Thyroid-Stimulating Hormone Favors Runx2-Mediated Matrix Mineralization in HOS and SaOS2 Cells: An In Vitro and In Silico Approach.

Osteoporosis is a skeletal disease that is both systemic and silent characterized by an unbalanced activity of bone remodeling leading to bone loss. Rising evidences demonstrate that thyroid stimulating hormone (TSH) has an important role in the regulation on the metabolism of bone. However, TSH regulation on human osteoblast essential transcriptional factors has not been identified. Current study examined the role of TSH on human osteoblastic Runx2 expression and their functional genes by in vitro and in slico analysis. Human osteoblast like (HOS and SaoS-2) cells were cultured with DMEM and treated with hTSH at the concentration of 0.01 ng/mL and 10 ng/mL. After treatment, osteoblastic Runx2 and IGF-1R beta expression were studied using RT-PCR and western blot analysis. TSH treatment induced osteoblastic essential transcriptional factor, Runx2 in HOS and SaOS2 cells on 48 h duration and elevated the expression of IGF-IR ß gene and Protein in SaoS-2 cells. TSH also promotes Runx2 responsive genes such as ALP, Collagen and osteocalcin in SaOS2 cells on day 2 to day 14 of 10 ng/mL of treatment and favors' matrix mineralization matrix in these cells. In addition, TSH facilitated human osteoblastic cells to mineralize their matrix confirmed by day 21 of alizarin red calcium staining. In silico study was performed to check CREB and ELK1 interaction with Runx2. Results of in silico analysis showed that TSH mediated signalling molecules such as CREB and ELK1 showed interaction with Runx2 which involve in osteobalstic gene expression and differentiation. Present findings confirm that TSH promotes Runx2 expression, osteoblastic responsive genes and bone matrix formation.

A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach.

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body's healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.

Plant-Derived Antiviral Compounds as Potential Entry Inhibitors against Spike Protein of SARS-CoV-2 Wild-Type and Delta Variant: An Integrative in SilicoApproach.

The wild-type SARS-CoV-2 has continuously evolved into several variants with increased transmissibility and virulence. The Delta variant which was initially identified in India created a devastating impact throughout the country during the second wave. While the efficacy of the existing vaccines against the latest SARS-CoV-2 variants remains unclear, extensive research is being carried out to develop potential antiviral drugs through approaches like in silico screening and drug-repurposing. This study aimed to conduct the docking-based virtual screening of 50 potential phytochemical compounds against a Spike glycoprotein of the wild-type and the Delta SARS-CoV-2 variant. Subsequently, molecular docking was performed for the five best compounds, such as Lupeol, Betulin, Hypericin, Corilagin, and Geraniin, along with synthetic controls. From the results obtained, it was evident that Lupeol exhibited a remarkable binding affinity towards the wild-type Spike protein (-8.54 kcal/mol), while Betulin showed significant binding interactions with the mutated Spike protein (-8.83 kcal/mol), respectively. The binding energy values of the selected plant compounds were slightly higher than that of the controls. Key hydrogen bonding and hydrophobic interactions of the resulting complexes were visualized, which explained their greater binding affinity against the target proteins-the Delta S protein of SARS-CoV-2, in particular. The lower RMSD, the RMSF values of the complexes and the ligands, Rg, H-bonds, and the binding free energies of the complexes together revealed the stability of the complexes and significant binding affinities of the ligands towards the target proteins. Our study suggests that Lupeol and Betulin could be considered as potential ligands for SARS-CoV-2 spike antagonists. Further experimental validations might provide new insights for the possible antiviral therapeutic interventions of the identified lead compounds and their analogs against COVID-19 infection.

Berberine-A potent chemosensitizer and chemoprotector to conventional cancer therapies.

Chemotherapy and radiotherapy are mainstay treatments for cancer patients. However, their clinical outcomes are highly limited by the resistance of malignant tumors to these therapies and the incurrence of serious damages in vital organs. This in turn necessitates the development of adjunct drugs that overcomes chemo/radioresistance in refractory cancers and protects vital organs from the cytotoxic effects of cancer therapies. In recent years, Berberine (BBR), a natural isoquinoline alkaloid has garnered more attention due to its potent chemosensitizing and chemoprotective properties. BBR effectively sensitizes refractory cancers to chemotherapy and radiotherapy by ameliorating the diverse events underlying therapy resistance. Furthermore, it protects the heart, liver, lungs, and kidneys from severe damages caused by these therapies. In this review, we discuss the molecular mechanisms underlying the chemo/radiosensitizing and chemo/radioprotective potential of BBR during cancer treatment. Also, we highlight the limitations that hamper the clinical application of BBR as an adjunct drug and how novel innovations have been made in recent years to circumvent these challenges.

Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach.

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.

Deciphering the Role of MicroRNAs in Neuroblastoma.

Neuroblastoma (NB) is a type of peripheral sympathetic nervous system cancer that most commonly affects children. It is caused by the improper differentiation of primitive neural crest cells during embryonic development. Although NB occurs for 8% of paediatric cancers, it accounts for 15% of cancer-related deaths. Despite a considerable increase in cytotoxic chemo- and radiotherapy, patients in advanced stages remain virtually incurable. Therefore, there is a desperate necessity for new treatment strategies to be investigated. Accumulating evidence suggested that microRNAs (miRNAs) are a class of non-coding RNAs with 19-25 nucleotides lengths and play a central role in the development of NB carcinogenesis. Fascinatingly, miRNA inhibitors have an antisense property that can inhibit miRNA function and suppress the activity of mature miRNA. However, many studies have addressed miRNA inhibition in the treatment of NB, but their molecular mechanisms and signalling pathways are yet to be analysed. In this study, we impart the current state of knowledge about the role of miRNA inhibition in the aetiology of NB.

ß-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKß/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats.

ß-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator-activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKß) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKß/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.

Use of Toothbrush as a Cost-effective Noninvasive Source of DNA for Molecular Oral Oncology Investigations during COVID Pandemic.

Dear Editor, Oral cancer, specifically oral squamous cell carcinoma (OSCC) has shown to be a major contributor to morbidity and mortality among tobacco/alcohol users.1,2 A prominent area of research in oral oncology is in the development of economical noninvasive screening tools capable of stratifying high-risk individuals, especially among those with associated habits. Cancer cytopathology has developed into a major branch in onco-diagnostics. Its noninvasive nature has led to its acceptance as a screening tool, especially in larger populations. The major hindrance is that medical personnel is often required to collect the sample using cytological tools such as the cytobrush.3.

In Vitro Analysis of Camellia sinensis Leaf Extract Against Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus (DM) poses a significant global health challenge, with its prevalence steadily increasing. Natural compounds derived from plants have garnered attention for their potential therapeutic effects in managing this metabolic disorder. Camellia sinensis, commonly known as tea, is rich in bioactive compounds exhibiting various pharmacological properties. This study investigates the potential anti-diabetic activity of C. sinensis leaf extract through in vitro analysis. MATERIALS AND METHODS: Camella sinensis leaf extract was prepared by grinding the plant's leaf into a powder, mixing it with distilled water, and heating. The antidiabetic activity was assessed through α-Amylase and α-Glucosidase inhibitory assays, employing varying concentrations of the plant extract. Molecular docking analysis utilized Autodock 1.5.6 software (The Scripps Research Institute, California, US) to predict ligand-receptor interactions, guiding subsequent experimental validation. RESULT: Camella sinensis leaf extract exhibited high phenolic content, suggesting potential in managing hyperglycemia. Tannins may aid glucose absorption and inhibit adipogenesis, making them promising for non-insulin-dependent DM (NIDDM). Terpenoids, with antioxidant activity, inhibit advanced glycation. Saponins and steroids were absent. Molecular docking revealed residues like IR, IRS1, and AS160 with significant impact on α-Amylase and α-Glucosidase, comparable to metformin. CONCLUSION: The findings of this study highlight the promising potential of C. sinensis leaf extract in managing hyperglycemia associated with DM. The high phenolic content aids in glucose regulation. Specifically, the presence of tannins suggests a potential role in modulating glucose absorption and inhibiting adipogenesis, which could be particularly beneficial for individuals with NIDDM. These findings provide valuable insights into the molecular mechanisms underlying the potential therapeutic efficacy of C. sinensis leaf extract against DM, paving the way for further research and development of novel therapeutic interventions in diabetes management.

Antioxidant and Anti-Inflammatory Activity of the Ethanolic Extract of Euphorbia Hirta Leaf Extract: An In Vitro and In Silico Study.

Objectives: This study presents the antioxidant and anti-inflammatory activity of the ethanolic extract of Euphorbia hirta leaf extract. Materials and Methods: The antioxidant and anti-inflammatory activity of the extract was performed by in vitro assay. Our research employs a comprehensive approach combining experimental assays and computational simulations to assess the extract's potential bioactive components and their interactions with key biomolecules. Results: The study's results demonstrated a progressive rise in the percentage of inhibition, which was dependent on the dosage, in both antioxidant and anti-inflammatory activities. This trend was observed for both the extract and the standard, encompassing concentrations ranging from 100 to 500 µg/ml. Conclusion: The results showed that Euphorbia hirta's possesses antioxidant and anti-inflammatory activity, and this may contribute to a traditional medicinal. The discoveries of this study contribute to a deeper understanding of Euphorbia hirta's medicinal properties and its potential as a source of natural therapeutic agents.

Anticancer Effects of Rosmarinus officinalis Leaf Extract on KB Cell Lines.

Background The value and use of medicinal plants, including the widespread cultivation of Rosmarinus officinalis, have increased rapidly. R. officinalis, a medicinal plant native to the Mediterranean, has received attention for its potential therapeutic benefits. This study evaluates R. officinalis anticancer activity using human epithelial carcinoma (KB) cell lines derived from nasopharyngeal epidermoid carcinoma. The KB cell line is known for its increased sensitivity to specific chemotherapeutic agents (CA), making it a useful model in cancer research. The impact of R. officinalis is assessed using comprehensive analyses of cell viability and gene expression. Aim This study aims to evaluate the anti-cancer effects of R. officinalis on KB cell lines. Materials and methods The R. officinalis leaf extract was separated and used to treat KB cell lines. The cell viability of treated KB cells was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Real-time polymerase chain reaction (RT-PCR) was used to analyze the expressions of matrix metalloproteinase (MMP-9) and tumor-inducing metalloproteins (TIMP-1) messenger ribonucleic acid (mRNA) genes. The statistical analysis was performed. Results This study analyzes the anticancer properties of R. officinalis on KB cell lines. The results show that increasing the concentration of rosemary extract reduces cell viability in malignant cells. Furthermore, the R. officinalis effect on the apoptotic signaling system is demonstrated by a decrease in MMP-9 and TIMP-1 mRNA expressions, as observed by RT-PCR analysis. Conclusion Patients looking for natural anticancer treatments may benefit from biogenically prepared anticancer drugs. The current research focuses on R. officinalis as a potential alternative to chemically synthesized anticancer drugs.

Hesperidin Inhibits Oral Cancer Cell Growth via Apoptosis and Inflammatory Signaling-Mediated Mechanisms: Evidence From In Vitro and In Silico Analyses.

Background Oral carcinoma presents a significant health challenge, prompting the need for innovative therapeutic approaches. Elevation of inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), has promoted cellular proliferation, inhibited apoptosis, and fostered oral cancer progression through complex signaling pathways. Hesperidin, a flavanone glycoside found in citrus fruits, is of keen interest in this study as it has been proven to have multiple health benefits through in vivo and in vitro studies. However, the mechanism behind the anticancer activity of hesperidin in oral carcinoma remains obscure. Aim The study aimed to explore the anticancer potential of hesperidin on human oral cancer cells (KB cells) by modulating pro-inflammatory and apoptotic signaling mechanisms. Methods Cancer cell growth inhibitory activity was assessed using the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Gene expression analysis was performed using real-time RT-PCR analysis. In addition, in silico docking analysis was conducted to confirm the binding affinity of hesperidin with pro-inflammatory and apoptosis signaling molecules. The data were analyzed using one-way ANOVA and the "t" test. Results Utilizing the MTT assay, a dose-dependent cytotoxic effect of hesperidin was unveiled, with a remarkable IC50 value indicative of its potent inhibition of cell proliferation. Complementing these findings (p<0.05), qRT-PCR analysis demonstrated hesperidin's regulatory influence on key molecular targets within the KB cell line. Hesperidin treatment resulted in a noteworthy reduction in TNF-α, interleukin-1 beta (IL-1-ß), IL-6, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and B-cell lymphoma 2 (Bcl-2) mRNA expression levels (p<0.05), highlighting its inhibitory role in cell proliferation, migration, and inflammation processes. Simultaneously, hesperidin promoted the expression of BAX mRNA (p<0.05), indicating an enhancement in cell death. Molecular docking simulations further revealed robust binding affinities between hesperidin and target proteins, suggesting its potential to disrupt cellular functions and inflammatory signaling pathways in oral cancer cells. Conclusion The cytotoxic effects on the KB cell line and its anti-inflammatory properties position hesperidin as a compelling candidate for further exploration in the quest for effective oral carcinoma treatments. These findings shed light on the intricate molecular mechanisms underlying hesperidin's promise as a therapeutic agent against oral carcinoma.