Preethi Vetrivel | Avinashilingam University For Women (original) (raw)

Papers by Preethi Vetrivel

Molecular & Cellular Toxicology

Purpose of review Every year, the cancer patient registry increases, and the leading cause of dea... more Purpose of review Every year, the cancer patient registry increases, and the leading cause of death in a global context. Plant-based molecules are gaining attention in cancer research due to the side effects of chemotherapy. A glycosidic derivative of flavonoid (GDF) plays a significant role in cancer proliferation mechanisms. GDF inhibits cell proliferation by elevating the expression of apoptotic proteins, altering the expression of nuclear factor-kappa B (NF- κB), and decreasing mitochondrial membrane potential (Δψm) in cancer cells. Recent findings Reported studies on the flavonoids orientin, vitexin, prunetionoside, chrysin, and scutellarein increased attention and are being widely investigated for their potential role in different parts of cancer research. Prunetionoside is a flavonoid with high cytotoxic potential and capable of inducing necroptosis in AGS gastric cancer cells. Similarly, scutellarein is a flavonol, induces an extrinsic apoptotic pathway and downregulates the...

International Journal of Molecular Sciences, 2021

Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against se... more Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 μM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) μM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In a...

Pyometra, a common disorder in intact bitches, can lead to canine sepsis. Identification of bioma... more Pyometra, a common disorder in intact bitches, can lead to canine sepsis. Identification of biomarkers for sources of infection in the uterus using two-dimensional electrophoresis (2-DE)-mass spectrometry (MS) analysis may enable the discovery of novel diagnostic markers of sepsis. Toward this end, surgically resected uterus samples from four bitches (three pyometra and one healthy) were randomly selected for 2-DE-MS, which identified 32 differentially expressed proteins, including seven inflammatory proteins, five non-inflammatory proteins, and 20 functionally unknown proteins. Despite the limited information on canine uterus proteomics, we suggest the potential use of differentially expressed uterus proteins as candidate biomarkers to discover targets to attenuate inflammation in pyometra. Further identification of the functionally unknown proteins is warranted.

Oncology Letters, 2021

Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of... more Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of liver cancer globally, making the identification of biomarkers critically important. The aim of the present study was to identify the genes involved in the anticancer effects of flavonoid compounds so that they may be used as targets for cancer treatment. Sinensetin (SIN), an isolated polymethoxyflavone monomer compound, possesses broad antitumor activities in vitro. Therefore, the identification of a transcriptome profile on the condition of cells treated with SIN may aid to better understand the genes involved and its mechanism of action. Genomic profiling studies of cancer are increasing rapidly in order to provide gene expression data that can reveal prognostic biomarkers to combat liver cancer. In the present study, high-throughput RNA sequencing (RNA-seq) was performed to reveal differential gene expression patterns between SIN-treated and SIN-untreated human liver cancer HepG2 ce...

International Journal of Molecular Sciences, 2021

The antioxidant and anti-inflammatory potentials of polyphenols contained in Gynura procumbens (G... more The antioxidant and anti-inflammatory potentials of polyphenols contained in Gynura procumbens (GP) extract were systematically analyzed. Polyphenols in GP were analyzed for nine peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS), and quantitatively determined through each standard. A total of nine polyphenolic compounds were identified in the samples and their MS data were tabulated. To determine the potential of bioactive ingredients targeting DPPH and COX-2, we analyzed them by ultrafiltration combined with LC. The results identified the major compounds exhibiting binding affinity for DPPH and COX-2. Caffeic acid, kynurenic acid, and chlorogenic acid showed excellent binding affinity to DPPH and COX-2, suggesting that they can be considered as major active compounds. Additionally, the anti-inflammatory effect of GP was confirmed in vitro. This study will not only be used to provide basic data for the application of GP to the food and ph...

Journal of Biomedical Research, 2019

Cell death in the living system plays a vital role in maintaining the homeostasis and balancing t... more Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body. Programmed cell death (PCD) is a crucial component of several development and defense mechanisms. PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division. Depending on the execution of cell death and its role in destruction, PCD is categorized into several subtypes. The major different forms of PCD in animals are apoptosis, autophagy and necrosis, which can be distinct in morphological terms. More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer. Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms. The significant potential of natural flavonoids in the induction of distinct signaling casc...

Simple Summary Identification of pharmacological targets in cancer provides a major walkthrough t... more Simple Summary Identification of pharmacological targets in cancer provides a major walkthrough toward treatment strategies. The present research adopted a network pharmacology approach utilizing a flavonoid glucoside prunetin-5-O-glucoside (PG) compound against gastric cancer. The correlative targets were analyzed using Swiss target prediction and DiGeNET databases. Functional enrichment and significant pathways enriched were predicted for the targets to associate its biological mechanisms with cancer. Protein interaction network and cluster analysis was performed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Our analysis revealed three core targets among the clustered modules that plays a crucial role in relation with cancer. With this information, the core targets were examined for the binding affinity with PG using molecular docking analysis and validations on the protein targets was performed using western blot analysis and Human Protein Atlas. Our...

Plants

Citrus unshiu is a popular medicinal herb in several Asian countries, in particular South Korea. ... more Citrus unshiu is a popular medicinal herb in several Asian countries, in particular South Korea. C. unshiu peel (CUP) has several biologically active compounds, including flavonoids. Hence, this research aimed to label the flavonoids from CUP by HPLC-MS/MS analysis and examine their anti-inflammatory and antioxidant potential on LPS-stimulated RAW 264.7 macrophages. A total of four flavonoids (Rutin, naringin, hesperidin, and poncirin) were characterized, and their contents were quantified from CUP. It showed that the naringin is rich in CUP. Further, treatment with the flavonoids at concentrations of 2.5 and 5 μg/mL had no effect on the cell viability of RAW 264.7 macrophages. On the other hand, it decreased the production and expression of inflammatory mediators and pro-inflammatory cytokines such as NO, PGE2, TNF-α, IL-1β, iNOS, and COX2 in the LPS-stimulated RAW 264.7 macrophages. In addition, flavonoids treatment inhibited the NF-κB activation by downregulating the p-p65 and p-...

Biologics

Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities... more Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be nec...

Translational Cancer Research

Cancer is a major health concern as the incidence is growing worldwide and still lacks successful... more Cancer is a major health concern as the incidence is growing worldwide and still lacks successful therapies. Plant-derived functional foods are getting considerable attention, primarily due to their safety and therapeutic potential. Polyphenols are a group of mostly natural, water-soluble organic compounds. Here, we review the functions of selected polyphenols and their anticancer properties on numerous cancer cell lines and their mechanisms. The literature search was performed using the electronic database PubMed, Google scholar up to June 2020, with the following keywords-polyphenol, polyphenol anticancer, quercetin anticancer, resveratrol anticancer, curcumin anticancer, and kaempferol anticancer. Chemical structures of the selected polyphenols were obtained using the ChemDraw program. The initial search identified 40,554 polyphenols papers and among that, 2,559 were limited to polyphenol and cancer, 987 quercetin and cancer, 2,174 curcumin and cancer, 1,079 resveratrol and cancer, and 226 were limited to kaempferol and cancer. A total of 84 papers are included in this review paper. Most studies report the multiple anticarcinogenic properties of plant-derived polyphenols, including its inhibitory effects on the proliferation of cancer cells, tumor expansion, angiogenesis, inflammation, and metastasis. Besides, some studies shows potential synergistic effects when polyphenol treatment combined with chemotherapeutic agents. Anticancer effects of polyphenolic compounds like quercetin, curcumin, resveratrol, and kaempferol are investigated on numerous cancer cell lines and have shown prominent results. The present review provides a direction to determine the anticarcinogenic ability of the selected polyphenols in vitro and in vivo. Consequently, the use of polyphenols in cancer treatment should be investigated in-depth in the future.

ACS Omega

Aging is associated with loss of muscle mass and strength that leads to a condition termed sarcop... more Aging is associated with loss of muscle mass and strength that leads to a condition termed sarcopenia. Impaired conditions, morbidity, and malnutrition are the factors of devaluation of muscle fibers in aged animals. Satellite cells play an important role in maintaining muscle homeostasis during tissue regeneration and repair. Proteomic profiling on the skeletal muscle tissues of different age group rats helps to determine the differentially expressed (DE) proteins, which may eventually lead to the development of biomarkers in treating the conditions of sarcopenia. In this study, nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis was implemented in the calf tissues of young and old groups of rats. The mass spectrometry (MS) analysis revealed the presence of 335 differentially expressed proteins between the two different age conditions, among which those based on log-fold change 25 proteins were upregulated and 77 were downregulated. The protein−protein interaction network analysis revealed 18 upregulated proteins with three distinct interconnected networks and 57 downregulated proteins with two networks. Further, gene ontology (GO) enrichment analysis showed the biological process, cellular component, and molecular function of the differential proteins. Pathway enrichment analysis of the DE proteins identified nine significantly enriched pathways with a list of eight significant genes (Cryab, Hspb2, Acat1, Ak1, Adssl1, Anxa5, Gys1, Ogdh, Gc, and Adssl1). Quantification of significant genes by quantitative realtime polymerase chain reaction (qRT-PCR) confirmed the downregulation at the mRNA level. Western blot analysis of their protein expression showed concordant results on two candidate proteins (Ogdh and annexin 5) confirming their differential regulation between the two age groups of rats. Thus, these proteomic approaches on young and aged rats provide insights into the development of protein targets in the treatment of sarcopenia (muscle loss).

Molecules

Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of ... more Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of biological activities like antioxidant, antitumor, and antiproliferative effects. In the present study, we have investigated the antitumor potential of iridin in AGS gastric cancer cells. Iridin treatment decreases AGS cell growth and promotes G2/M phase cell cycle arrest by attenuating the expression of Cdc25C, CDK1, and Cyclin B1 proteins. Iridin-treatment also triggered apoptotic cell death in AGS cells, which was verified by cleaved Caspase-3 (Cl- Caspase-3) and poly ADP-ribose polymerase (PARP) protein expression. Further apoptotic cell death was confirmed by increased apoptotic cell death fraction shown in allophycocyanin (APC)/Annexin V and propidium iodide staining. Iridin also increased the expression of extrinsic apoptotic pathway proteins like Fas, FasL, and cleaved Caspase-8 in AGS cells. On the contrary, iridin-treated AGS cells did not show variations in proteins related to...

Oncology Reports

Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scut... more Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scutellaria baicalensis a flowering plant in the family Lamiaceae, has been reported to exhibit anticancer effects in several cancer cell lines including gastric cancer (GC). Although our previous study documented the mechanisms of Scutellarein-induced cytotoxic effects, the literature shows that the proteomic changes that are associated with the cellular response to SCU have been poorly understood. To avoid adverse side-effects and significant toxicity of chemotherapy in patients who react poorly, biomarkers anticipating therapeutic responses are imperative. In the present study, we utilized a comparative proteomic analysis to identify proteins associated with Scutellarein (SCU)-induced cell death in GC cells (AGS and SNU484), by integrating two-dimensional gel electrophoresis (2-DE), mass spectrometry (MS), and bioinformatics to analyze the proteins. Proteomic analysis between SCU-treated and DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484) proteins by MALDI-TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and SNU484 cells treated with SCU revealed a total of 7 protein identities commonly expressed and western blot analysis validated a subset of identified critical proteins, which were consistent with those of the 2-DE outcome. Molecular docking studies also confirmed the binding affinity of SCU towards these critical proteins. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit β isoform (PIK3CB) protein expression was accompanied by a distinct group of cellular functions, including cell growth, and proliferation. Cancerous inhibitor of protein phosphatase 2A (CIP2A), is one of the oncogenic molecules that have been shown to promote tumor growth and resistance to apoptosis and senescence-inducing therapies. In the present study, both PIK3CB and CIP2A proteins were downregulated in SCU-treated cells, which boosts our previous results of SCU to induce apoptosis and inhibits GC cell growth by regulating these critical proteins. The comparative proteomic analysis has yielded candidate biomarkers of response to SCU treatment in GC cell models and further validation of these biomarkers will help the future clinical development of SCU as a novel therapeutic drug.

Biomolecules

Gastric cancer is the common type of malignancy positioned at second in mortality rate causing bu... more Gastric cancer is the common type of malignancy positioned at second in mortality rate causing burden worldwide with increasing treatment options. Prunetin (PRU) is an O-methylated flavonoid that belongs to the group of isoflavone executing beneficial activities. In the present study, we investigated the anti-proliferative and cell death effect of the compound PRU in AGS gastric cancer cell line. The in vitro cytotoxic potential of PRU was evaluated and significant proliferation was observed. We identified that the mechanism of cell death was due to necroptosis through double staining and was confirmed by co-treatment with inhibitor necrostatin (Nec-1). We further elucidated the mechanism of action of necroptosis via receptor interacting protein kinase 3 (RIPK3) protein expression and it has been attributed by ROS generation through JNK activation. Furthermore, through computational analysis by molecular docking and dynamics simulation, the efficiency of compound prunetin against RI...

Nutrients

Inflammation of the skin is the most common dermatological problem in human. The anti-inflammator... more Inflammation of the skin is the most common dermatological problem in human. The anti-inflammatory mediated responses of the skin cells provide a mechanism for combating these conditions. Annexin A1 (AnxA1) is one of the proteins that has been shown to have a potent anti-inflammatory effect. However, the effects and mechanisms of AnxA1 in skin keratinocyte and fibroblast have not been reported yet. In the current study, we hypothesized that Ac2-26, AnxA1 mimetic peptide, ameliorates inflammation and wrinkle formation in human skin cells. Therefore, we aimed to identify whether Ac2-26 has anti-inflammatory and anti-wrinkle effects in human keratinocyte (HaCaT) and fibroblast (Detroit 551) cells, respectively. Human HaCaT cells were stimulated by TNF-α/IFN-γ with or without Ac2-26, to identify the anti-inflammatory effect. Human Detroit 551 cells were treated with Ac2-26 to verify the anti-wrinkle effect. Initially, cell cytotoxicity was carried out in each cell line treated using Ac2...

Nutrients

Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However... more Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effect...

Journal of Biomedical Translational Research

The development of drugs from natural plant sources is at growing interest due to the limitations... more The development of drugs from natural plant sources is at growing interest due to the limitations of chemical drugs in terms of side effects and cost-effective factors of natural medicines. Among the various components contained in natural plant materials, flavonoids are of increasing interest because of their extended biological benefits. Flavonoids are classified into various types according to their structure and possess different activities depending on the structure. In this study, the flavonoids contained in Artemisia, native to Korea were examined and reviewed. HPLC chromatograms of three Artemisia species (Artemisia annua L., Artemisia iwayomogi and Artemisia argyi H.) were examined from published sources and their component analysis by MS data were summarized. The various flavonoids of Artemisia were classified into 12 types according to the main structure, and 10 flavonoids based on various activities were examined. The 10 flavonoids were identified as quercetin, kaempferol, rhamnetin, diosmetin, luteolin, methoxyflavone, catechin, apigenin, malvidin and genkwanin with extensive reported studies till date. The ten flavonoids examined have been reported to be effective in preventing and treating various diseases and exhibit activities such as anti-cancer, anti-inflammatory, antioxidant, antiviral, anti-obesity, anti-diabetic and anti-Alzheimer. The collective results from the reported studies suggest that the three types of Korean native Artemisia, contains various flavonoids with beneficial activities and may have therapeutic effects against diseases.

Journal of Biomedical Translational Research

Cancer is the second leading cause of death worldwide and currently there are many approaches dev... more Cancer is the second leading cause of death worldwide and currently there are many approaches developing towards cancer treatment. Cancer treatments like chemotherapy and radiation therapy are often painful and have adverse effects. The mechanism of apoptosis is a complex process and it involves different pathways in its mechanism of action. Apoptosis can be caused by signals within the cell such as stress, or by extrinsic signals such as ligands binding to cell surface death receptors. The programmed cell death plays a important role in the several physiological and pathological processes. It plays important role in homeostasis. Flavonoids have gained importance as anticancer agents promoting cytotoxicity and apoptosis in cancer cells. Flavonoids are present in many medicinal plants which are a kind of ubiquitous natural products and essential active ingredients. They have strong biological activities with high efficiency and low toxicity, possessing good preventive and cure effects on different tumor forms. Flavonoids such as Scutellarein, Pectolinarigenin and Naringin have reported to possess significant anti-cancer effects on different cancer cell lines till date. In this review, we provide a summary about the anti-cancer effect of the three flavonoids and its mechanisms of action that can be used in future for understanding their potent anti-tumor properties.

The Journal of Nutritional Biochemistry

Apigetrin is a flavonoid glycoside phytonutrient derived from fruits and vegetables that is well ... more Apigetrin is a flavonoid glycoside phytonutrient derived from fruits and vegetables that is well known for a variety of biological activities such as antioxidant and anti-inflammatory activities. In the current study, we determined the effect of apigetrin on AGS gastric cancer cell. Apigetrin reduced cancer cell proliferation and induced G2/M phase cell cycle arrest by regulating cyclin B1, cdc25c and cdk1 protein expression in AGS cell. Apigetrin treatment caused apoptotic cell death in AGS cells, characterized by the accumulation of apoptosis portion, cleavage of caspase-3 and poly ADP-ribose polymerase (PARP). Apigetrin-treated cells increased the expression of extrinsic apoptosis pathway proteins and mRNA. However, intrinsic apoptosis pathway related proteins were not altered. In addition, AGS cells treated with apigetrin increased autophagic cell death, featured by the formation of autophagic vacuole and acidic vesicular organelles. Autophagy marker proteins, such as LC3B-II and beclin-1, were increased, and p62, an autophagy flux marker protein, was also increased by endoplasmic reticulum stress. Also, the phosphorylation of PI3K/AKT/mTOR pathway proteins and its downstream targets in apigetrin-treated AGS cells was identified to be decreased. Taken together, these data suggest that apigetrin-treated AGS cells induced G2/M phase cell cycle arrest, extrinsic apoptosis and autophagic cell death through PI3K/AKT/mTOR pathway, which can lead to the inhibition of gastric cancer development. Thus, our findings strongly indicate that apigetrin is a basic natural derived compound that could be used as a nutrient source with potential anticancer activities against gastric cancer.

Experimental and Therapeutic Medicine

Inflammatory diseases are an important health concern and have a growing incidence worldwide. Thu... more Inflammatory diseases are an important health concern and have a growing incidence worldwide. Thus, developing novel and safe drugs to treat these disorders remains an important pursuit. Artemisia iwayomogi, locally known as Dowijigi (DJ), is a perennial herb found primarily in Korea and is used to treat various diseases such as hepatitis, inflammation and immune disorders. In the present study, the anti-inflammatory effects of a polyphenolic extract from the DJ flower (PDJ) in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells were investigated. Cell cytotoxicity was assessed using the MTT assay. The production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) was measured by Griess and ELISA analysis, respectively. The expression levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) were examined by western blot analysis. Reverse transcription-quantitative PCR was performed to detect the mRNA expression levels of pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β, as well as COX2 and iNOS. The production of NO and PGE 2 was significantly decreased following treatment with PDJ. The mRNA expression levels of TNFα, IL-6, IL-1β, COX2 and iNOS were significantly decreased in LPS-induced PDJ co-treated cells compared with the group treated with LPS alone. Western blot analysis indicated that PDJ downregulated the LPS-induced expression of iNOS and COX2, as well as the expression of NF-κB proteins. In conclusion, the present study demonstrated that PDJ exerted anti-inflammatory effects in LPS-induced macrophage cells by suppressing the NF-κB signaling pathway. Therefore, PDJ may be used as a potential therapeutic agent in inflammation.

Molecular & Cellular Toxicology

Purpose of review Every year, the cancer patient registry increases, and the leading cause of dea... more Purpose of review Every year, the cancer patient registry increases, and the leading cause of death in a global context. Plant-based molecules are gaining attention in cancer research due to the side effects of chemotherapy. A glycosidic derivative of flavonoid (GDF) plays a significant role in cancer proliferation mechanisms. GDF inhibits cell proliferation by elevating the expression of apoptotic proteins, altering the expression of nuclear factor-kappa B (NF- κB), and decreasing mitochondrial membrane potential (Δψm) in cancer cells. Recent findings Reported studies on the flavonoids orientin, vitexin, prunetionoside, chrysin, and scutellarein increased attention and are being widely investigated for their potential role in different parts of cancer research. Prunetionoside is a flavonoid with high cytotoxic potential and capable of inducing necroptosis in AGS gastric cancer cells. Similarly, scutellarein is a flavonol, induces an extrinsic apoptotic pathway and downregulates the...

International Journal of Molecular Sciences, 2021

Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against se... more Scutellarein (SCU) is a well-known flavone with a broad range of biological activities against several cancers. Human hepatocellular carcinoma (HCC) is major cancer type due to its poor prognosis even after treatment with chemotherapeutic drugs, which causes a variety of side effects in patients. Therefore, efforts have been made to develop effective biomarkers in the treatment of HCC in order to improve therapeutic outcomes using natural based agents. The current study used SCU as a treatment approach against HCC using the HepG2 cell line. Based on the cell viability assessment up to a 200 μM concentration of SCU, three low-toxic concentrations of (25, 50, and 100) μM were adopted for further investigation. SCU induced cell cycle arrest at the G2/M phase and inhibited cell migration and proliferation in HepG2 cells in a dose-dependent manner. Furthermore, increased PTEN expression by SCU led to the subsequent downregulation of PI3K/Akt/NF-κB signaling pathway related proteins. In a...

Pyometra, a common disorder in intact bitches, can lead to canine sepsis. Identification of bioma... more Pyometra, a common disorder in intact bitches, can lead to canine sepsis. Identification of biomarkers for sources of infection in the uterus using two-dimensional electrophoresis (2-DE)-mass spectrometry (MS) analysis may enable the discovery of novel diagnostic markers of sepsis. Toward this end, surgically resected uterus samples from four bitches (three pyometra and one healthy) were randomly selected for 2-DE-MS, which identified 32 differentially expressed proteins, including seven inflammatory proteins, five non-inflammatory proteins, and 20 functionally unknown proteins. Despite the limited information on canine uterus proteomics, we suggest the potential use of differentially expressed uterus proteins as candidate biomarkers to discover targets to attenuate inflammation in pyometra. Further identification of the functionally unknown proteins is warranted.

Oncology Letters, 2021

Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of... more Hepatocellular carcinoma is recognized as one of the most frequently occurring malignant types of liver cancer globally, making the identification of biomarkers critically important. The aim of the present study was to identify the genes involved in the anticancer effects of flavonoid compounds so that they may be used as targets for cancer treatment. Sinensetin (SIN), an isolated polymethoxyflavone monomer compound, possesses broad antitumor activities in vitro. Therefore, the identification of a transcriptome profile on the condition of cells treated with SIN may aid to better understand the genes involved and its mechanism of action. Genomic profiling studies of cancer are increasing rapidly in order to provide gene expression data that can reveal prognostic biomarkers to combat liver cancer. In the present study, high-throughput RNA sequencing (RNA-seq) was performed to reveal differential gene expression patterns between SIN-treated and SIN-untreated human liver cancer HepG2 ce...

International Journal of Molecular Sciences, 2021

The antioxidant and anti-inflammatory potentials of polyphenols contained in Gynura procumbens (G... more The antioxidant and anti-inflammatory potentials of polyphenols contained in Gynura procumbens (GP) extract were systematically analyzed. Polyphenols in GP were analyzed for nine peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS), and quantitatively determined through each standard. A total of nine polyphenolic compounds were identified in the samples and their MS data were tabulated. To determine the potential of bioactive ingredients targeting DPPH and COX-2, we analyzed them by ultrafiltration combined with LC. The results identified the major compounds exhibiting binding affinity for DPPH and COX-2. Caffeic acid, kynurenic acid, and chlorogenic acid showed excellent binding affinity to DPPH and COX-2, suggesting that they can be considered as major active compounds. Additionally, the anti-inflammatory effect of GP was confirmed in vitro. This study will not only be used to provide basic data for the application of GP to the food and ph...

Journal of Biomedical Research, 2019

Cell death in the living system plays a vital role in maintaining the homeostasis and balancing t... more Cell death in the living system plays a vital role in maintaining the homeostasis and balancing the cell count in the body. Programmed cell death (PCD) is a crucial component of several development and defense mechanisms. PCD is also important in terms of aging which avoids the accumulation of cellular damage by maintaining cell division. Depending on the execution of cell death and its role in destruction, PCD is categorized into several subtypes. The major different forms of PCD in animals are apoptosis, autophagy and necrosis, which can be distinct in morphological terms. More intense investigations of cell death have given close insight showing other important types of cellular destruction and their pivotal roles in treating disease conditions like cancer. Flavonoids have been acquired a great interest for disease therapies and chemoprevention through activation of several PCD mechanisms. The significant potential of natural flavonoids in the induction of distinct signaling casc...

Simple Summary Identification of pharmacological targets in cancer provides a major walkthrough t... more Simple Summary Identification of pharmacological targets in cancer provides a major walkthrough toward treatment strategies. The present research adopted a network pharmacology approach utilizing a flavonoid glucoside prunetin-5-O-glucoside (PG) compound against gastric cancer. The correlative targets were analyzed using Swiss target prediction and DiGeNET databases. Functional enrichment and significant pathways enriched were predicted for the targets to associate its biological mechanisms with cancer. Protein interaction network and cluster analysis was performed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING). Our analysis revealed three core targets among the clustered modules that plays a crucial role in relation with cancer. With this information, the core targets were examined for the binding affinity with PG using molecular docking analysis and validations on the protein targets was performed using western blot analysis and Human Protein Atlas. Our...

Plants

Citrus unshiu is a popular medicinal herb in several Asian countries, in particular South Korea. ... more Citrus unshiu is a popular medicinal herb in several Asian countries, in particular South Korea. C. unshiu peel (CUP) has several biologically active compounds, including flavonoids. Hence, this research aimed to label the flavonoids from CUP by HPLC-MS/MS analysis and examine their anti-inflammatory and antioxidant potential on LPS-stimulated RAW 264.7 macrophages. A total of four flavonoids (Rutin, naringin, hesperidin, and poncirin) were characterized, and their contents were quantified from CUP. It showed that the naringin is rich in CUP. Further, treatment with the flavonoids at concentrations of 2.5 and 5 μg/mL had no effect on the cell viability of RAW 264.7 macrophages. On the other hand, it decreased the production and expression of inflammatory mediators and pro-inflammatory cytokines such as NO, PGE2, TNF-α, IL-1β, iNOS, and COX2 in the LPS-stimulated RAW 264.7 macrophages. In addition, flavonoids treatment inhibited the NF-κB activation by downregulating the p-p65 and p-...

Biologics

Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities... more Microbes are hardly seen as planktonic species and are most commonly found as biofilm communities in cases of chronic infections. Biofilms are regarded as a biological condition, where a large group of microorganisms gets adhered to a biotic or abiotic surface. In this context, Pseudomonas aeruginosa, a Gram-negative nosocomial pathogen is the main causative organism responsible for life-threatening and persistent infections in individuals affected with cystic fibrosis and other lung ailments. The bacteria can form a strong biofilm structure when it adheres to a surface suitable for the development of a biofilm matrix. These bacterial biofilms pose higher natural resistance to conventional antibiotic therapy due to their multiple tolerance mechanisms. This prevailing condition has led to an increasing rate of treatment failures associated with P. aeruginosa biofilm infections. A better understanding of the effect of a diverse group of antibiotics on established biofilms would be nec...

Translational Cancer Research

Cancer is a major health concern as the incidence is growing worldwide and still lacks successful... more Cancer is a major health concern as the incidence is growing worldwide and still lacks successful therapies. Plant-derived functional foods are getting considerable attention, primarily due to their safety and therapeutic potential. Polyphenols are a group of mostly natural, water-soluble organic compounds. Here, we review the functions of selected polyphenols and their anticancer properties on numerous cancer cell lines and their mechanisms. The literature search was performed using the electronic database PubMed, Google scholar up to June 2020, with the following keywords-polyphenol, polyphenol anticancer, quercetin anticancer, resveratrol anticancer, curcumin anticancer, and kaempferol anticancer. Chemical structures of the selected polyphenols were obtained using the ChemDraw program. The initial search identified 40,554 polyphenols papers and among that, 2,559 were limited to polyphenol and cancer, 987 quercetin and cancer, 2,174 curcumin and cancer, 1,079 resveratrol and cancer, and 226 were limited to kaempferol and cancer. A total of 84 papers are included in this review paper. Most studies report the multiple anticarcinogenic properties of plant-derived polyphenols, including its inhibitory effects on the proliferation of cancer cells, tumor expansion, angiogenesis, inflammation, and metastasis. Besides, some studies shows potential synergistic effects when polyphenol treatment combined with chemotherapeutic agents. Anticancer effects of polyphenolic compounds like quercetin, curcumin, resveratrol, and kaempferol are investigated on numerous cancer cell lines and have shown prominent results. The present review provides a direction to determine the anticarcinogenic ability of the selected polyphenols in vitro and in vivo. Consequently, the use of polyphenols in cancer treatment should be investigated in-depth in the future.

ACS Omega

Aging is associated with loss of muscle mass and strength that leads to a condition termed sarcop... more Aging is associated with loss of muscle mass and strength that leads to a condition termed sarcopenia. Impaired conditions, morbidity, and malnutrition are the factors of devaluation of muscle fibers in aged animals. Satellite cells play an important role in maintaining muscle homeostasis during tissue regeneration and repair. Proteomic profiling on the skeletal muscle tissues of different age group rats helps to determine the differentially expressed (DE) proteins, which may eventually lead to the development of biomarkers in treating the conditions of sarcopenia. In this study, nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS) analysis was implemented in the calf tissues of young and old groups of rats. The mass spectrometry (MS) analysis revealed the presence of 335 differentially expressed proteins between the two different age conditions, among which those based on log-fold change 25 proteins were upregulated and 77 were downregulated. The protein−protein interaction network analysis revealed 18 upregulated proteins with three distinct interconnected networks and 57 downregulated proteins with two networks. Further, gene ontology (GO) enrichment analysis showed the biological process, cellular component, and molecular function of the differential proteins. Pathway enrichment analysis of the DE proteins identified nine significantly enriched pathways with a list of eight significant genes (Cryab, Hspb2, Acat1, Ak1, Adssl1, Anxa5, Gys1, Ogdh, Gc, and Adssl1). Quantification of significant genes by quantitative realtime polymerase chain reaction (qRT-PCR) confirmed the downregulation at the mRNA level. Western blot analysis of their protein expression showed concordant results on two candidate proteins (Ogdh and annexin 5) confirming their differential regulation between the two age groups of rats. Thus, these proteomic approaches on young and aged rats provide insights into the development of protein targets in the treatment of sarcopenia (muscle loss).

Molecules

Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of ... more Iridin is a natural flavonoid found in Belamcanda chinensis documented for its broad spectrum of biological activities like antioxidant, antitumor, and antiproliferative effects. In the present study, we have investigated the antitumor potential of iridin in AGS gastric cancer cells. Iridin treatment decreases AGS cell growth and promotes G2/M phase cell cycle arrest by attenuating the expression of Cdc25C, CDK1, and Cyclin B1 proteins. Iridin-treatment also triggered apoptotic cell death in AGS cells, which was verified by cleaved Caspase-3 (Cl- Caspase-3) and poly ADP-ribose polymerase (PARP) protein expression. Further apoptotic cell death was confirmed by increased apoptotic cell death fraction shown in allophycocyanin (APC)/Annexin V and propidium iodide staining. Iridin also increased the expression of extrinsic apoptotic pathway proteins like Fas, FasL, and cleaved Caspase-8 in AGS cells. On the contrary, iridin-treated AGS cells did not show variations in proteins related to...

Oncology Reports

Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scut... more Scutellarein (SCU), a flavone that belongs to the flavonoid family and abundantly present in Scutellaria baicalensis a flowering plant in the family Lamiaceae, has been reported to exhibit anticancer effects in several cancer cell lines including gastric cancer (GC). Although our previous study documented the mechanisms of Scutellarein-induced cytotoxic effects, the literature shows that the proteomic changes that are associated with the cellular response to SCU have been poorly understood. To avoid adverse side-effects and significant toxicity of chemotherapy in patients who react poorly, biomarkers anticipating therapeutic responses are imperative. In the present study, we utilized a comparative proteomic analysis to identify proteins associated with Scutellarein (SCU)-induced cell death in GC cells (AGS and SNU484), by integrating two-dimensional gel electrophoresis (2-DE), mass spectrometry (MS), and bioinformatics to analyze the proteins. Proteomic analysis between SCU-treated and DMSO (control) samples successfully identified 41 (AGS) and 31 (SNU484) proteins by MALDI-TOF/MS analysis and protein database search. Comparative proteomics analysis between AGS and SNU484 cells treated with SCU revealed a total of 7 protein identities commonly expressed and western blot analysis validated a subset of identified critical proteins, which were consistent with those of the 2-DE outcome. Molecular docking studies also confirmed the binding affinity of SCU towards these critical proteins. Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit β isoform (PIK3CB) protein expression was accompanied by a distinct group of cellular functions, including cell growth, and proliferation. Cancerous inhibitor of protein phosphatase 2A (CIP2A), is one of the oncogenic molecules that have been shown to promote tumor growth and resistance to apoptosis and senescence-inducing therapies. In the present study, both PIK3CB and CIP2A proteins were downregulated in SCU-treated cells, which boosts our previous results of SCU to induce apoptosis and inhibits GC cell growth by regulating these critical proteins. The comparative proteomic analysis has yielded candidate biomarkers of response to SCU treatment in GC cell models and further validation of these biomarkers will help the future clinical development of SCU as a novel therapeutic drug.

Biomolecules

Gastric cancer is the common type of malignancy positioned at second in mortality rate causing bu... more Gastric cancer is the common type of malignancy positioned at second in mortality rate causing burden worldwide with increasing treatment options. Prunetin (PRU) is an O-methylated flavonoid that belongs to the group of isoflavone executing beneficial activities. In the present study, we investigated the anti-proliferative and cell death effect of the compound PRU in AGS gastric cancer cell line. The in vitro cytotoxic potential of PRU was evaluated and significant proliferation was observed. We identified that the mechanism of cell death was due to necroptosis through double staining and was confirmed by co-treatment with inhibitor necrostatin (Nec-1). We further elucidated the mechanism of action of necroptosis via receptor interacting protein kinase 3 (RIPK3) protein expression and it has been attributed by ROS generation through JNK activation. Furthermore, through computational analysis by molecular docking and dynamics simulation, the efficiency of compound prunetin against RI...

Nutrients

Inflammation of the skin is the most common dermatological problem in human. The anti-inflammator... more Inflammation of the skin is the most common dermatological problem in human. The anti-inflammatory mediated responses of the skin cells provide a mechanism for combating these conditions. Annexin A1 (AnxA1) is one of the proteins that has been shown to have a potent anti-inflammatory effect. However, the effects and mechanisms of AnxA1 in skin keratinocyte and fibroblast have not been reported yet. In the current study, we hypothesized that Ac2-26, AnxA1 mimetic peptide, ameliorates inflammation and wrinkle formation in human skin cells. Therefore, we aimed to identify whether Ac2-26 has anti-inflammatory and anti-wrinkle effects in human keratinocyte (HaCaT) and fibroblast (Detroit 551) cells, respectively. Human HaCaT cells were stimulated by TNF-α/IFN-γ with or without Ac2-26, to identify the anti-inflammatory effect. Human Detroit 551 cells were treated with Ac2-26 to verify the anti-wrinkle effect. Initially, cell cytotoxicity was carried out in each cell line treated using Ac2...

Nutrients

Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However... more Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effect...

Journal of Biomedical Translational Research

The development of drugs from natural plant sources is at growing interest due to the limitations... more The development of drugs from natural plant sources is at growing interest due to the limitations of chemical drugs in terms of side effects and cost-effective factors of natural medicines. Among the various components contained in natural plant materials, flavonoids are of increasing interest because of their extended biological benefits. Flavonoids are classified into various types according to their structure and possess different activities depending on the structure. In this study, the flavonoids contained in Artemisia, native to Korea were examined and reviewed. HPLC chromatograms of three Artemisia species (Artemisia annua L., Artemisia iwayomogi and Artemisia argyi H.) were examined from published sources and their component analysis by MS data were summarized. The various flavonoids of Artemisia were classified into 12 types according to the main structure, and 10 flavonoids based on various activities were examined. The 10 flavonoids were identified as quercetin, kaempferol, rhamnetin, diosmetin, luteolin, methoxyflavone, catechin, apigenin, malvidin and genkwanin with extensive reported studies till date. The ten flavonoids examined have been reported to be effective in preventing and treating various diseases and exhibit activities such as anti-cancer, anti-inflammatory, antioxidant, antiviral, anti-obesity, anti-diabetic and anti-Alzheimer. The collective results from the reported studies suggest that the three types of Korean native Artemisia, contains various flavonoids with beneficial activities and may have therapeutic effects against diseases.

Journal of Biomedical Translational Research

Cancer is the second leading cause of death worldwide and currently there are many approaches dev... more Cancer is the second leading cause of death worldwide and currently there are many approaches developing towards cancer treatment. Cancer treatments like chemotherapy and radiation therapy are often painful and have adverse effects. The mechanism of apoptosis is a complex process and it involves different pathways in its mechanism of action. Apoptosis can be caused by signals within the cell such as stress, or by extrinsic signals such as ligands binding to cell surface death receptors. The programmed cell death plays a important role in the several physiological and pathological processes. It plays important role in homeostasis. Flavonoids have gained importance as anticancer agents promoting cytotoxicity and apoptosis in cancer cells. Flavonoids are present in many medicinal plants which are a kind of ubiquitous natural products and essential active ingredients. They have strong biological activities with high efficiency and low toxicity, possessing good preventive and cure effects on different tumor forms. Flavonoids such as Scutellarein, Pectolinarigenin and Naringin have reported to possess significant anti-cancer effects on different cancer cell lines till date. In this review, we provide a summary about the anti-cancer effect of the three flavonoids and its mechanisms of action that can be used in future for understanding their potent anti-tumor properties.

The Journal of Nutritional Biochemistry

Apigetrin is a flavonoid glycoside phytonutrient derived from fruits and vegetables that is well ... more Apigetrin is a flavonoid glycoside phytonutrient derived from fruits and vegetables that is well known for a variety of biological activities such as antioxidant and anti-inflammatory activities. In the current study, we determined the effect of apigetrin on AGS gastric cancer cell. Apigetrin reduced cancer cell proliferation and induced G2/M phase cell cycle arrest by regulating cyclin B1, cdc25c and cdk1 protein expression in AGS cell. Apigetrin treatment caused apoptotic cell death in AGS cells, characterized by the accumulation of apoptosis portion, cleavage of caspase-3 and poly ADP-ribose polymerase (PARP). Apigetrin-treated cells increased the expression of extrinsic apoptosis pathway proteins and mRNA. However, intrinsic apoptosis pathway related proteins were not altered. In addition, AGS cells treated with apigetrin increased autophagic cell death, featured by the formation of autophagic vacuole and acidic vesicular organelles. Autophagy marker proteins, such as LC3B-II and beclin-1, were increased, and p62, an autophagy flux marker protein, was also increased by endoplasmic reticulum stress. Also, the phosphorylation of PI3K/AKT/mTOR pathway proteins and its downstream targets in apigetrin-treated AGS cells was identified to be decreased. Taken together, these data suggest that apigetrin-treated AGS cells induced G2/M phase cell cycle arrest, extrinsic apoptosis and autophagic cell death through PI3K/AKT/mTOR pathway, which can lead to the inhibition of gastric cancer development. Thus, our findings strongly indicate that apigetrin is a basic natural derived compound that could be used as a nutrient source with potential anticancer activities against gastric cancer.

Experimental and Therapeutic Medicine

Inflammatory diseases are an important health concern and have a growing incidence worldwide. Thu... more Inflammatory diseases are an important health concern and have a growing incidence worldwide. Thus, developing novel and safe drugs to treat these disorders remains an important pursuit. Artemisia iwayomogi, locally known as Dowijigi (DJ), is a perennial herb found primarily in Korea and is used to treat various diseases such as hepatitis, inflammation and immune disorders. In the present study, the anti-inflammatory effects of a polyphenolic extract from the DJ flower (PDJ) in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells were investigated. Cell cytotoxicity was assessed using the MTT assay. The production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) was measured by Griess and ELISA analysis, respectively. The expression levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) were examined by western blot analysis. Reverse transcription-quantitative PCR was performed to detect the mRNA expression levels of pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β, as well as COX2 and iNOS. The production of NO and PGE 2 was significantly decreased following treatment with PDJ. The mRNA expression levels of TNFα, IL-6, IL-1β, COX2 and iNOS were significantly decreased in LPS-induced PDJ co-treated cells compared with the group treated with LPS alone. Western blot analysis indicated that PDJ downregulated the LPS-induced expression of iNOS and COX2, as well as the expression of NF-κB proteins. In conclusion, the present study demonstrated that PDJ exerted anti-inflammatory effects in LPS-induced macrophage cells by suppressing the NF-κB signaling pathway. Therefore, PDJ may be used as a potential therapeutic agent in inflammation.