Publications by authors named "Arunachalam Chinnathambi"

115 Publications

Leelamine Exerts Antineoplastic Effects in Association with Modulating Mitogen‑Activated Protein Kinase Signaling Cascade.

Nutr Cancer 2022 May 17:1-13. Epub 2022 May 17.

Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Mitogen‑activated protein kinase (MAPK) pathway is a prominent signaling cascade that modulates cell proliferation, apoptosis, stress response, drug resistance, immune response, and cell motility. Activation of MAPK by various small molecules/natural compounds has been demonstrated to induce apoptosis in cancer cells. Herein, the effect of leelamine (LEE, a triterpene derived from bark of pine trees) on the activation of MAPK in hepatocellular carcinoma (HCC) and breast cancer (BC) cells was investigated. LEE induced potent cytotoxicity of HCC (HepG2 and HCCLM3) and BC (MDA-MB-231 and MCF7) cells over normal counterparts (MCF10A). LEE significantly enhanced the phosphorylation of p38 and JNK MAPKs in a dose-dependent fashion and it did not affect the phosphorylation of ERK in HCC and BC cells. The apoptosis-driving effect of LEE was further demonstrated by cleavage of procaspase-3/Bid and suppression of prosurvival proteins (Bcl-xL and XIAP). Furthermore, LEE also reduced the SDF1-induced-migration and -invasion of HCC and BC cells. Taken together, the data demonstrated that LEE promotes apoptosis and induces an anti-motility effect by activating p38 and JNK MAPKs in HCC and BC cells.
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http://dx.doi.org/10.1080/01635581.2022.2059092DOI Listing
May 2022

Development of 1-(4-(Substituted)piperazin-1-yl)-2-((2-((4-methoxybenzyl)thio)pyrimidin-4-yl)oxy)ethanones That Target Poly (ADP-Ribose) Polymerase in Human Breast Cancer Cells.

Molecules 2022 Apr 29;27(9). Epub 2022 Apr 29.

Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Manasagangotri, Mysore 570006, India.

A number of uracil amides cleave poly (ADP-ribose) polymerase and therefore novel thiouracil amide compounds were synthesized and screened for the loss of cell viability in a human-estrogen-receptor-positive breast cancer cell line. The synthesized compounds exhibited moderate to significant efficacy against human breast cancer cells, where the compound IC value was found to be 18 μM. Thouracil amide compounds and inhibited the catalytical activity of PARP1, enhanced cleavage of PARP1, enhanced phosphorylation of H2AX, and increased CASPASE 3/7 activity. Finally, in silico analysis demonstrated that compound interacted with PARP1. Hence, specific thiouracil amides may serve as new drug-seeds for the development of PARP inhibitors for use in oncology.
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http://dx.doi.org/10.3390/molecules27092848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9100275PMC
April 2022

Oxytetracycline Degrading Potential of sp. Strain 3+I Isolated from Poultry Manure.

Evid Based Complement Alternat Med 2022 24;2022:2750009. Epub 2022 Mar 24.

Department of Environmental Sciences, Bharathiar University, Coimbatore, Tamil Nadu, India.

Oxytetracycline (OTC) which is a broad-spectrum veterinary tetracycline antibiotic is extensively used in poultry farms as a prophylactic, therapeutic, and growth stimulator. Upon administration, unmetabolized OTC is excreted from the animal body through droppings and accumulated in litter in the poultry industry. This study aimed at investigating the OTC degradation potential of an-OTC tolerant bacterial strain, isolated from poultry manure. The isolated strain's morphology, biochemical properties, and 16S ribosomal RNA (rRNA) gene sequence confirmed that it belonged to the genus. To measure the residual OTC concentration, a high-performance liquid chromatography method was used. OTC degradation rates were 2.579 mg Ld with strain 3+I and 1.149 mg Ld without strain 3+I. In the presence of strain 3+I, the half-life significantly reduced to 2.68 days, compared to 6.03 days without strain 3+I. The strain demonstrated 85% removal with the OTC concentration of 10 g/ml. The influence of pH, temperature, carbon sources, and nitrogen source, which influence degradation, were also investigated. The optimum condition favouring degradation was pH 6 at a temperature of 30°C. In addition, sp. strain 3+I's ability to degrade OTC in poultry litter offers a promising approach to treat poultry manure and effluent containing OTC, preventing its contamination in the environment.
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http://dx.doi.org/10.1155/2022/2750009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970894PMC
March 2022

Development of a Model System to Study Expression Profile of RAC2 Gene in Breast Cancer MDA-MB-231 Cell Line.

Evid Based Complement Alternat Med 2022 24;2022:2077850. Epub 2022 Mar 24.

Department of Botany and Microbiology, College of Science, King Saud University, PO Box-2455, Riyadh 11451, Saudi Arabia.

The RAC2 gene encoding GTPases involve cellular signaling of actin polymerization, cell migration, and formation of the phagocytic NADPH oxidase complex. Oncogenic mutations in the RAC2 gene have been identified in various cancers, and extensive research is in progress to delineate its signaling pathways and identify potential therapeutic targets in breast cancers. This paper explored developing a bioinformatics model system to understand the RAC2 gene expression pattern concerning estrogenic receptor status in breast cancers. We have used the MDA-MB-231 breast cancer cell line to identify RAC2 gene expression. To simplify the development of model system with one dataset, we retrieved the microarray dataset GSE27515 from the Gene Expression Omnibus (GEO) for the differential gene expression analysis. Then, network analysis, pathway enrichment analysis, volcano plot, ORA, and the up/downregulated genes were used to highlight genes involved in signaling network pathways. We observed that the RAC2 gene is upregulated in the GSM679722, GSM676923, and GSM679724 downregulated in the samples GSM676925, GSM676926, and GSM676927 from the GEO dataset. Our observation found that the RAC2 gene is upregulated in the estrogen receptor (ER) negative breast cancers and downregulated in ER-positive breast cancer, involving pathways such as focal adhesion, MAPK signaling, axon guidance, and VEGF signaling pathway.
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http://dx.doi.org/10.1155/2022/2077850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970810PMC
March 2022

Isolation, Identification, Characterization, and Plasmid Profile of Urinary Tract Infectious from Clinical Samples.

Evid Based Complement Alternat Med 2022 20;2022:7234586. Epub 2022 Mar 20.

Department of Plant Protection, Himalayan College of Agricultural Sciences and Technology, P.O. Box 44600, Kalanki, Kathmandu, Nepal.

Objective: In recent times, urinary tract infection (UTI) is one of the most widely recognized bacterial diseases all over the planet. UTI influences individuals of any age and gender. The target of this study is to concentrate on the recurrence of uropathogens, the antimicrobial susceptibility pattern of the isolates, and the plasmid profile of people from the government clinics of Karaikudi.

Methods: From July 2017 to December 2017, 100 urine tests were gathered and handled for the isolation of pathogenic microbes. In total, 89 isolates were found from the samples collected.

Results: was discovered as the most common bacterial isolate screened from the UTI-infected people, accounting for 28.09 percent of all isolates. was seen to be the highest prevalent bacterium for UTI in all age groups and demonstrated resistance to routinely used medications, especially cefpodoxime and novobiocin, which have been 100 percent resistant. The isolates screened were positive for beta-lactamase and film generation, and they have strong antimicrobial resistance. As a result, the strains with the highest prevalence of virulence determinants have become more resistant to many medications because they support the microorganism in overcoming the host's defense and colonizing or entering the urinary system. The amplified 16S rRNA product was analyzed, and phylogenetic relationships were determined. The presence of TEM (56 percent), CTX-M (64 percent), SHV (40 percent), and OXA (60 percent) was discovered. Among isolates, CTX-M was the most common extended spectrum-beta lactamase (ESBL). Multiplex PCR was also used to identify the existence of CTX-M subgroups in isolates.

Conclusion: Finally, we urge that antibiotic selection should be predicated on the awareness of the specific prevalence and that novel antimicrobial medicines for urinary infections be developed to combat the overuse of antibiotics.
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http://dx.doi.org/10.1155/2022/7234586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958076PMC
March 2022

Leelamine Modulates STAT5 Pathway Causing Both Autophagy and Apoptosis in Chronic Myelogenous Leukemia Cells.

Biology (Basel) 2022 Feb 25;11(3). Epub 2022 Feb 25.

Department of Science in Korean Medicine, Kyung Hee University, Seoul 02447, Korea.

Leelamine (LEE) has recently attracted significant attention for its growth inhibitory effects against melanoma, breast cancer, and prostate cancer cells; however, its impact on hematological malignancies remains unclear. Here, we first investigate the cytotoxic effects of LEE on several human chronic myeloid leukemia (CML) cells. We noted that LEE stimulated both apoptosis and autophagy in CML cells. In addition, the constitutive activation of signal transducer and activator of transcription 5 (STAT5) was suppressed substantially upon LEE treatment. Moreover, STAT5 knockdown with small interfering RNA (siRNA) increased LEE-induced apoptosis as well as autophagy and affected the levels of various oncogenic proteins. Thus, the targeted mitigation of STAT5 activation by LEE can contribute to its diverse anticancer effects by enhancing two distinct cell death pathways.
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http://dx.doi.org/10.3390/biology11030366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945775PMC
February 2022

STAT3/HIF1A and EMT specific transcription factors regulated genes: Novel predictors of breast cancer metastasis.

Gene 2022 Apr 22;818:146245. Epub 2022 Jan 22.

Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology-Guwahati, Guwahati 781 039, Assam, India; DBT-AIST International Center for Translational and Environmental Research, Indian Institute of Technology-Guwahati, Guwahati 781 039, Assam, India. Electronic address:

Metastasis, the fatal hallmark of breast cancer (BC), is a serious hurdle for therapy. Current prognostic approaches are not sufficient to predict the metastasis risk for BC patients. Therefore, in the present study, we analyzed gene expression data from GSE139038 and TCGA database to develop predictive markers for BC metastasis. Initially, the data from GSE139038 which contained 65 samples consisting of 41 breast tumor tissues, 18 paired morphologically normal tissues and 6 from non-malignant breast tissues were analyzed for differentially expressed genes (DEGs). DEGs were obtained from three different comparisons: paired morphologically normal (MN) versus tumor samples (C), apparently normal (AN) versus tumor samples (C), and paired morphologically normal (MN) versus apparently normal samples (AN). Multiple bioinformatic methods were employed to evaluate metastasis, EMT and triple negative breast cancer (TNBC) specific genes. Further, regulation of gene expression, clinicopathological factors and DNA methylation patterns of DEGs in BC were validated with TCGA datasets. Our bioinformatic analysis showed that 40 genes were upregulated and 294 were found to be downregulated between AN vs C; 124 were upregulated and 760 genes were downregulated between MN vs C; 4 were upregulated and 13 were downregulated between MN vs AN. Analysis using TCGA dataset revealed 18 genes were significantly altered in nodal positive BC patients compared to nodal negative BC patients. Our study showed novel candidate genes as predictive markers for BC metastasis which can also be used for therapeutic targets for BC treatment.
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http://dx.doi.org/10.1016/j.gene.2022.146245DOI Listing
April 2022

Green synthesis of Zirconium nanoparticles using Punica granatum (pomegranate) peel extract and their antimicrobial and antioxidant potency.

Environ Res 2022 06 19;209:112771. Epub 2022 Jan 19.

Research Center of Producing and Development of Products and Innovations for Animal Health and Production, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand; Department of Food Animal Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand. Electronic address:

The biosynthesis of metal oxide nanoparticles provides an excellent alternative to the chemical synthesis approach. The aim of the current study was a green and eco-friendly synthesis of zirconium nanoparticles (ZrNPs) from fruit peels of Punica granatum (Pomegranate). The synthesis of ZrNPs was confirmed using a UV-visible spectrophotometer. The functional groups present on surface of ZrNPs were analyzed using FTIR. The average size of obtained ZrNPs was analyzed using SEM and DLS and it was around 20-60 nm. The antimicrobial activity of obtained ZrNPs was tested against Gram-positive strains (Bacillus subtilis and Staphylococcus aureus), Gram-negative strains (Escherichia coli and Klebsiella pneumoniae) and Fungi (Aspergillus niger) by agar well diffusion method. ZrNPs showed maximum zone of inhibition against S. aureus (19 mm) and A. niger (18 mm) at the maximum concentration of 200 μg/mL. The antioxidant scavenging activity of obtained ZrNPs was analyzed using the following methods: DPPH radical scavenging activity, Hydroxyl radical scavenging activity, Ferric reducing antioxidant power and hydrogen peroxide radical scavenging activity. This the first and foremost study on ZrNPs synthesized using P. granatum fruit peel extract reporting their efficacy as antimicrobial agents against Bacteria and Fungi. Considering the tolerance of zirconium towards human body, it can also be used as antimicrobial coating material on human implants.
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http://dx.doi.org/10.1016/j.envres.2022.112771DOI Listing
June 2022

3-Formylchromone Counteracts STAT3 Signaling Pathway by Elevating SHP-2 Expression in Hepatocellular Carcinoma.

Biology (Basel) 2021 Dec 26;11(1). Epub 2021 Dec 26.

KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02447, Korea.

Hepatocellular carcinoma (HCC) is one of the leading cancers that contribute to a large number of deaths throughout the globe. The signal transducer and activator of transcription 3 (STAT3) is a tumorigenic protein that is overactivated in several human malignancies including HCC. In the present report, the effect of 3-formylchromone (3FC) on the STAT3 signaling pathway in the HCC model was investigated. 3FC downregulated the constitutive phosphorylation of STAT3 and non-receptor tyrosine kinases such as JAK1 and JAK2. It also suppressed the transportation of STAT3 to the nucleus and reduced its DNA-binding ability. Pervanadate treatment overrode the 3FC-triggered STAT3 inhibition, and the profiling of cellular phosphatase expression revealed an increase in SHP-2 levels upon 3FC treatment. The siRNA-driven deletion of SHP-2 led to reinstate STAT3 activation. 3FC downmodulated the levels of various oncogenic proteins and decreased CXCL12-driven cell migration and invasion. Interestingly, 3FC did not exhibit any substantial toxicity, whereas it significantly regressed tumor growth in an orthotopic HCC mouse model and abrogated lung metastasis. Overall, 3FC can function as a potent agent that can display antitumor activity by targeting STAT3 signaling in HCC models.
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http://dx.doi.org/10.3390/biology11010029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773260PMC
December 2021

Loss of TIPE3 reduced the proliferation, survival and migration of lung cancer cells through inactivation of Akt/mTOR, NF-κB, and STAT-3 signaling cascades.

Life Sci 2022 Mar 15;293:120332. Epub 2022 Jan 15.

Cancer Biology Laboratory and DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India. Electronic address:

Lung cancer is the foremost cause of cancer related mortality among men and one of the most fatal cancers among women. Notably, the 5-year survival rate of lung cancer is very low; 5% in developing countries. This low survival rate can be attributed to factors like late stage diagnosis, rapid postoperative recurrences in the patients undergoing treatment and development of chemoresistance against different agents used for treating lung cancer. Therefore, in this study we evaluated the potential of a recently identified protein namely TIPE3 which is known as a transfer protein of lipid second messengers as a lung cancer biomarker. TIPE3 was found to be significantly upregulated in lung cancer tissues indicating its role in the positive regulation of lung cancer. Supporting this finding, knockout of TIPE3 was also found to reduce the proliferation, survival and migration of lung cancer cells and arrested the G2 phase of cell cycle through inactivation of Akt/mTOR, NF-κB, STAT-3 signaling. It is well evinced that tobacco is the major risk factor of lung cancer which affects both males and females. Therefore, this study also evaluated the involvement of TIPE3 in tobacco mediated lung carcinogenesis. Notably, this study shows for the first time that TIPE3 positively regulates tobacco induced proliferation, survival and migration of lung cancer through modulation of Akt/mTOR signaling. Thus, TIPE3 plays critical role in the pathogenesis of lung cancer and hence it can be specifically targeted to develop novel therapeutic strategies.
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http://dx.doi.org/10.1016/j.lfs.2022.120332DOI Listing
March 2022

Fungi fabrication, characterization, and anticancer activity of silver nanoparticles using metals resistant Aspergillus niger.

Environ Res 2022 05 11;208:112721. Epub 2022 Jan 11.

School of Renewable Energy, Maejo University, Chiang Mai, 50290, Thailand; College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address:

The purpose of this study was to assess the bio-fabrication possibilities of pre-isolated (from bauxite mine tailings) metal-tolerant Aspergillus niger biomass filtrate and the anticancer potential of synthesized silver nanoparticles (AgNPs) tested with a Human Cervical cancer cell line (HeLa cells: Henrietta Lacks cells). The nitrate reduction test demonstrated that A. niger has the ability to reduce nitrate, and filtrate derived from A. niger biomass efficiently fabricated AgNPs from AgNO, as demonstrated by a visible color change from pale greenish to brownish. The UV-visible spectroscopy analysis revealed an absorbance peak at 435 nm, which corresponded to the AgNPs. These AgNPs have been capped and stabilized with several functional groups related to various bioactive molecules such as aldehyde, benzene rings, aldehydic, amines, alcohols, and carbonyl stretch protein molecules. Fourier-Transform Infrared Spectroscopy (FTIR) analysis confirmed the capping and stabilizing chemical bonding pattern. Scanning Electron Microscopy (SEM) revealed that the synthesized AgNPs were spherical, with an average size of 21.38 nm. This bio-fabricated AgNPs has in-vitro anticancer potential when tested against the HeLa cell line due to its potential size and shape. At 100 g mL concentrations of this bio-fabricated AgNPs, the anticancer activity percentage was found to be 70.2%, and the IC value was found to be 66.32 g m. These findings demonstrated that the metal-tolerant A. niger cell filtrate could produce AgNPs with anticancer potential.
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http://dx.doi.org/10.1016/j.envres.2022.112721DOI Listing
May 2022

Silver nanoparticles (AgNPs) fabricating potential of aqueous shoot extract of Aristolochia bracteolata and assessed their antioxidant efficiency.

Environ Res 2022 05 10;208:112683. Epub 2022 Jan 10.

Research Center of Producing and Development of Products and Innovations for Animal Health and Production, Chiang Mai University, Chiang Mai 50200, Thailand; Department of Food Animal Clinic, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai 50100, Thailand. Electronic address:

This research was performed to evaluate the silver nanoparticles (AgNPs) fabricating potential of aqueous shoot extract of Aristolochia bracteolata and also assess the free radicals scavenging potential of synthesized AgNPs. The results obtained from this study showed that the aqueous shoot extract of A. bracteolata has the potential to synthesize the AgNPs and it was initially confirmed by color change in the reaction blend as yellow to dark brownish. Subsequently, a clear absorbance peak was found at 425 nm in UV-visible spectrum analysis. The functional groups involved in the capping and stabilization of AgNPs were confirmed by Fourier Transform-Infrared spectroscopy (FTIR) analysis and recorded about 10 sharp peaks 3688, 3401, 2980, 2370, 1948, 1642, 1480, 1280, 782, and 628 cm. The Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) observations revealed that the predominant shape of the AgNPs was spherical and size ranged from 41.43 to 60.51 nm. Interestingly, the green fabricated AgNPs showed significant free radicals scavenging activity and were confirmed with ferric reducing assay, 1, 1-diphenyl-2-picryl-hydrazyl (DPPH), HO radicals, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals scavenging activity. Thus, after a few in-vivo antioxidant studies, Aristolochia bracteolata-mediated AgNPs can be considered as an antioxidant agent.
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http://dx.doi.org/10.1016/j.envres.2022.112683DOI Listing
May 2022

Fabrication, characterization, anti-inflammatory, and anti-diabetic activity of silver nanoparticles synthesized from Azadirachta indica kernel aqueous extract.

Environ Res 2022 05 5;208:112684. Epub 2022 Jan 5.

Research Center of Producing and Development of Products and Innovations for Animal Health and Production, Chiang Mai University, Chiang Mai 50200, Thailand. Electronic address:

The Azadirachta indica is an excellent and pharmaceutically valuable phytochemicals enriched traditional medicinal plant. The purpose of the research was to assess the ability of A. indica aqueous kernel extract to synthesize silver nanoparticles as well as their anti-inflammatory and anti-diabetic activity in vitro. The obtained results state that the aqueous kernel extract of A. indica can fabricate the silver nanoparticles and be confirmed by standard analytical techniques. Under UV-visible spectrophotometer analysis, the absorbance peak was found at 430 nm was related to the surface plasmon resonance of silver nanoparticles. The FTIR (Fourier-transform infrared spectroscopy) analysis revealed that numbers of functional groups belong to the pharmaceutically valuable phytochemicals, which act as reducing, capping, and stabilizing agent on silver nanoparticles synthesis. The size and shape of the silver nanoparticles were examined as 19.27-22.15 nm and spherical in shape. Interestingly, this kernel fabricated silver nanoparticles possess a reasonable anti-inflammatory (69.77%) and anti-diabetic (73.5%) activity at 100 μg mL and these were partially comparable with standards (anti-inflammatory: 81.15%; anti-diabetic: 87.9%). Thus, the aqueous kernel extract fabricated silver nanoparticles can be considered for further in-vivo study to assess the practical possibility to promote as a pharmaceutical agent.
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http://dx.doi.org/10.1016/j.envres.2022.112684DOI Listing
May 2022

Lung cancer induced by Benzo(A)Pyrene: ChemoProtective effect of sinapic acid in swiss albino mice.

Saudi J Biol Sci 2021 Dec 5;28(12):7125-7133. Epub 2021 Aug 5.

Department of Medical Laboratory Technology, Manipal College of Health Professions, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka 576104, India.

Cancer of lung is the utmost typical cause of death and the number of cases is increasing rapidly, which has emerged as a major leading health problem. A large amount of reports suggested that Benzo(a)pyrene [B(a)P] in cigarette smoke plays the major function in an initiation of cancer of lung. Cancer prevention or chemoprevention has become a compelling approach recently for treatment of lung cancer. So, discovering a fresh candidate with reduced toxicity for targeting lung cancer is vital and urgent. Sinapic acid which is a widely extracted in various vegetables and fruit exhibits rich anti-oxidant content, anti-inflammatory and anti-tumor activity. But, the chemopreventive action of sinapic acid against lung cancer initiated by B[a]P remain unclear. Following, an B[a]P-stimulated lung cancer in swiss albino mice and an human lung cancer cell (A549) model were established to examine the chemopreventive activities of sinapic acid. The levels of immunoglobulins (IgG and IgM), oxidative and inflammatory markers, and tumor markers level was studied using kits and standard methods. The results showed administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice by a decline in IgG and IgM level, leukocyte count, neutrophil function tests, soluble immune complex, lipid peroxidation, pro-inflammatory cytokines, tumor markers (AHH, LDH, GGT, 5'NT and CEA) and enhanced phagocytic index, activity index and antioxidant defense enzymes. In addition, studies showed potential cytotoxicity against human lung cancer and exhibited a potential cytotoxic (MTT assay) and apoptotic activity by elevation of ROS production and caspase activity (caspase-3 and caspase-9). Collectively, the results, clearly specifies sinapic acid can be utilized as an effective chemo preventative agent against lung carcinogenesis.
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http://dx.doi.org/10.1016/j.sjbs.2021.08.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626324PMC
December 2021

Tris(dibenzylideneacetone)dipalladium(0) (Tris DBA) Abrogates Tumor Progression in Hepatocellular Carcinoma and Multiple Myeloma Preclinical Models by Regulating the STAT3 Signaling Pathway.

Cancers (Basel) 2021 Oct 31;13(21). Epub 2021 Oct 31.

KHU-KIST Department of Converging Science and Technology and Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea.

STAT3 is an oncogenic transcription factor that controls the expression of genes associated with oncogenesis and malignant progression. Persistent activation of STAT3 is observed in human malignancies, including hepatocellular carcinoma (HCC) and multiple myeloma (MM). Here, we have investigated the action of Tris(dibenzylideneacetone) dipalladium 0 (Tris DBA) on STAT3 signaling in HCC and MM cells. Tris DBA decreased cell viability, increased apoptosis, and inhibited IL-6 induced/constitutive activation of STAT3, JAK1, JAK2, and Src in HCC and MM cells. Tris DBA downmodulated the nuclear translocation of STAT3 and reduced its DNA binding ability. It upregulated the expression of SHP2 (protein and mRNA) to induce STAT3 dephosphorylation, and the inhibition of SHP2 reversed this effect. Tris DBA downregulated the expression of STAT3-driven genes, suppressed cell migration/invasion. Tris DBA significantly inhibited tumor growth in xenograft MM and orthotopic HCC preclinical mice models with a reduction in the expression of various prosurvival biomarkers in MM tumor tissues without displaying significant toxicity. Overall, Tris DBA functions as a good inhibitor of STAT3 signaling in preclinical HCC and MM models.
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http://dx.doi.org/10.3390/cancers13215479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582575PMC
October 2021

Anticancer Effect of Troxerutin in Human Non-Small-Cell Lung Cancer Cell A549 and Inhibition of Tumor Formation in BALB/c Nude Mice.

J Environ Pathol Toxicol Oncol 2021 ;40(3):25-35

Department of Critical Care Medicine, Gaoling Hospital, Xi'an, Shaanxi, 710200, China.

This study is intended to explore the anticancer, antiproliferative, and chemopreventive action of troxerutin (TX) in human non-small-cell lung cancer cell (A549) using BALB/c nude mice. 2 × 106 A549 cells were subcutaneously injected into mice, along with 10 μM and 20 μM/kg body weight of TX orally for 19 days. On the last day, tumor weight and volume were assessed. Stress marker enzymes such as Aryl hydrocarbon hydroxylase (AHH), lactate dehydrogenase (LDH), 5'Nucleotidase (5'ND), and γ-glutamyltranspeptidase (γ-GT) were estimated in the lung tissues. Cytotoxicity of TX was assessed using MTT assay. Expression of carcinoembryonic antigen (CEA) and inflammatory cytokines were also analyzed. Histopathological examination of tissue sections and immunohistochemical examination of proliferating cell nuclear antigen (PCNA) were also performed. mRNA expression of p53, p21, cyclin D1, P13k, Akt, and mTOR were analyzed using RT-PCR. TX administered orally in a dose-dependent manner markedly reverted the level of stress marker enzymes to a significant extent. TX also exhibited significant protection against lung cancer cells, as evidenced by cytotoxicity assay and histopathological studies. It was also found to reduce the expression of PCNA, cyclin D1, P13k, Akt, and mTOR, but increase the expression of p53 and p21. TX has also been shown to reduce cancer cell inflammation, as was evidenced by reduced expression of inflammatory cytokines. Thus TX could be used as an effective chemopreventive and anticancer agent in treating cancer.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.2021037951DOI Listing
October 2021

Crocetin imparts antiproliferative activity via inhibiting STAT3 signaling in hepatocellular carcinoma.

IUBMB Life 2021 11 23;73(11):1348-1362. Epub 2021 Sep 23.

Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

STAT3 is a key oncogenic transcription factor, often overactivated in several human cancers including hepatocellular carcinoma (HCC). STAT3 modulates the expression of genes that are connected with cell proliferation, antiapoptosis, metastasis, angiogenesis, and immune evasion in tumor cells. In this study, we investigated the effect of crocetin on the growth of HCC cells and dissected its underlying molecular mechanism in imparting a cytotoxic effect. Crocetin suppressed proliferation, promoted apoptosis, and counteracted the invasive capacity of HCC cells. Besides, crocetin downregulated the constitutive/inducible STAT3 activation (STAT3 ), nuclear accumulation of STAT3 along with suppression of its DNA binding activity in HCC cells with no effect on STAT5 activation. Crocetin suppressed the activity of upstream kinases such as Src, JAK1, and JAK2. Sodium pervanadate treatment terminated the crocetin-propelled STAT3 inhibition suggesting the involvement of tyrosine phosphatases. Crocetin increased the expression of SHP-1 and siRNA-mediated SHP-1 silencing resulted in the negation of crocetin-driven STAT3 inhibition. Further investigation revealed that crocetin treatment inhibited the expression of STAT3 regulated genes (Bcl-2, Bcl-xL, cyclin D1, survivin, VEGF, COX-2, and MMP-9). Taken together, this report presents crocetin as a novel abrogator of the STAT3 pathway in HCC cell lines.
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http://dx.doi.org/10.1002/iub.2555DOI Listing
November 2021

Spectral and structure characterization of Ferula assafoetida fabricated silver nanoparticles and evaluation of its cytotoxic, and photocatalytic competence.

Environ Res 2022 03 30;204(Pt A):111987. Epub 2021 Aug 30.

Research Center in Bioresources for Agriculture, Industry and Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address:

This study aims to develop an eco-friendly method for rapidly synthesizing silver nanoparticles (AgNPs) using Asafoetida ethanol extracts and to validate AgNPs synthesis using UV-vis spectroscopy (absorption spectrum), FTIR (functional groups), XRD (crystallinity), FE-SEM (size of the particles) and SEM-EDAX (Purity). Furthermore, to evaluate the anti-proliferative effect of Ag NPs against grown cultured L6 cell lines, studies have shown that AgNPs biosynthesis inhibits cancer cell growth compared to control cell lines. UV-vis absorption verified the existence of Ag NPs, and the spectrum was observed at 480 nm. Functional groups are present in the synthesized Ag NPs were shifted on 528.48 cm confirmed using an FT-IR spectrum. Consequently, anti-cancer efficacy observed the IC value of As Ag NPs against L6 cells was 1.0 μg/mL for 48 h. Finally, using a halogen lamp, studies explored the photocatalytic degradation of AgNPs against the methylene blue radioactive dye and achieved a 96 percent degradation rate in 90 min. Asafoetida mediated silver nanoparticles show grater photodegradation for methylene blue dye, which is present in textile industries, when exposed to solar light, and it has a wide range of potential applications in wastewater treatment. As a whole, biosynthesized silver nanoparticles showed excellent cytotoxic, antioxidant, and photocatalytic dye degradation effects.
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http://dx.doi.org/10.1016/j.envres.2021.111987DOI Listing
March 2022

Optimization of extraction and quantification of Flavonoids from fruits using RP-HPLC and its correlation between total flavonoids content against antimicrobial activity.

Appl Nanosci 2021 Aug 17:1-8. Epub 2021 Aug 17.

PG Department of Environmental Science, Holy Cross College, Tiruchirappalli, Tamil Nadu India.

The present study was conducted to evaluate fruits flavonoids extraction and quantification analysis through RP-HPLC and its comparison study on total flavonoids concentration versus antimicrobial activity analysis based on minimum inhibitory concentrations. Optimization of extraction was carried out using three different methods; among all methods the ultrasonic conventional assistant extraction (UCAE) showed an excellent recovery of flavonoids with solid phase elution. UCAE was performed with ethanol using different solvents ratio, the total flavonoid content was quantified through spectrophotometrically (850 ± 25 mg/kg) and flavonoids (myricetin and luteolin) were quantified by RP-HPLC. Optimized yield of myricetin and luteolin were presented in fruits 336 ± 15 and 231 ± 18 mg/kg, respectively. Antimicrobial activity examined against and species using spectroscopically. The extracted sample with known quantity of total flavonoids content (10-200 µg/mL) used against and , MIC results shows 55.6 ± 6, 31 ± 3 and 28 ± 2 µg/mL respectively. Higher flavonoid content plays major role on antioxidant activities, which were evaluated and compared with commercial antioxidant butylated hydroxytoluene (BHT) employing superoxide anion scavenging activity and total reducing power IC value results shows 100 and 175 µg/mL, respectively. The maximum yield of flavonoid content results shows method suitability of flavonoids extraction and quantification.
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http://dx.doi.org/10.1007/s13204-021-02020-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369870PMC
August 2021

Pyrimidine-2,4-dione targets STAT3 signaling pathway to induce cytotoxicity in hepatocellular carcinoma cells.

Bioorg Med Chem Lett 2021 10 19;50:128332. Epub 2021 Aug 19.

Institution of Excellence, Vijnana Bhavan, University of Mysore, Manasagangotri, Mysore 570006, India. Electronic address:

Signal transducer and activator of transcription 3 (STAT3) is a tumorigenic transcription factor that is persistently activated in various human cancers including hepatocellular carcinoma (HCC). Therefore, STAT3 is considered as a prominent target to counteract the uncontrolled proliferation of cancer cells. In the present report, pyrimidine-2,4-diones (N-methyluracil derivatives) (MNK1-MNK14) were synthesized in an ionic liquid (BMIm PF) medium employing a ligand-free Suzuki-Miyaura cross-coupling process. Among the 14 derivatives, compound MNK8 showed good cytotoxicity towards both the tested cell lines and did not display a toxic effect against normal hepatocytes (LO2). MNK8 significantly increased the Sub-G1 cell count in both cell lines and the cytotoxic effect of MNK8 was found to be mediated through the suppression of constitutive phosphorylation of STAT3. It also decreased the DNA interaction ability of nuclear STAT3 in HCC cells. MNK8 downregulated the levels of apoptosis-related proteins (such as Bcl-2, cyclin D1, survivin) and increased cleaved caspase-3 inferring the apoptogenic effect of MNK8. It also reduced the CXCL12-triggered cell migration and invasion in in vitro assay systems. Overall, MNK8 has been demonstrated as a new inhibitor of STAT3 signaling cascade in HCC cells.
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http://dx.doi.org/10.1016/j.bmcl.2021.128332DOI Listing
October 2021

Arbutin exerts anticancer activity against rat C6 glioma cells by inducing apoptosis and inhibiting the inflammatory markers and P13/Akt/mTOR cascade.

J Biochem Mol Toxicol 2021 Sep 2;35(9):e22857. Epub 2021 Aug 2.

Scigen Research and Innovation Pvt. Ltd., Thanjavur, Tamil Nadu, India.

Gliomas are a type of brain cancer that occurs in the supporting glial cells of the brain. It is highly malignant and accounts for 80% of brain tumors with high mortality and morbidity. Phytomedicines are potent alternatives for allopathic drugs which cause side effects. They have been used from ancient times by traditional Chinese, Ayurveda, and Siddha medicine. Arubtin is a glycoside phytochemical extracted from plants and belongs to the family of Ericaceae. Arbutin possesses various pharmacological properties such as anti-inflammatory, antioxidant, antitumor, and so on. Hence in the present study, we analyzed the anticancer potency of arbutin against rat C6 glioma cells. Rat C6 glioma cells were procured from American Type Culture Collection and the cells were cultured in Roswell Park Memorial Institute-1640 medium. To assess the cytotoxicity effect of the arbutin against C6 glioma cells, an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test was performed with different doses from 10 to 60 µM. Arbutin effectively induced apoptosis in the cells and the IC dose was obtained at 30 µM. For further studies, we selected the 30 µM IC dose and a higher dose of 40 µM. Reactive oxygen species (ROS) generated were analyzed with DCFDA/H2DCFDA stain and the destruction of mitochondrial membrane permeability which is the initiator of apoptosis was analyzed with a cationic stain Rhodamine 123. Dual staining with acridine orange and ethidium bromide was performed to assess the viable and dead cells. Cell adhesion properties of glioma cells were analyzed with Matrigel assay. The apoptotic, inflammatory, and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling molecules were analyzed with quantitative polymerase chain reaction (qPCR) analysis to confirm the anticancer effect of arbutin. Arbutin generated excessive ROS and disrupted the mitochondrial membrane, which induced apoptosis in cells, it also inhibited the cell adhesion property of C6 glioma cells. qPCR analysis clearly indicates arbutin increases the apoptotic genes and decreased the inflammatory and PI3K/mTOR signaling molecules. Overall, our results authentically confirm that arbutin can be a potent alternative for treating glioma.
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http://dx.doi.org/10.1002/jbt.22857DOI Listing
September 2021

Biogenesis of copper nanoparticles (Cu-NPs) using leaf extract of , antioxidant and cytotoxicity.

Artif Cells Nanomed Biotechnol 2021 Dec;49(1):500-510

Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.

In this research, we formulated new chemotherapeutic copper nanoparticles (Cu NPs) containing Reut. ex Regel leaf for treating human endometrial cancer. For investigating the antioxidant activitiy, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was used. MTT test was used on normal (Human umbilical vein endothelial cells (HUVECs)) and human endometrial cancer (Ishikawa, HEC-1-A, HEC-1-B, and KLE) cell lines for comparing the anti-human endometrial cancer properties of Cu(NO), leaf aqueous extract, and copper nanoparticles. Copper nanoparticles had high cell death and anti-human endometrial cancer effects against Ishikawa, HEC-1-A, HEC-1-B, and KLE cell lines. The IC50 of leaf aqueous extract and copper nanoparticles against HEC-1-B cell line were 548 and 331 µg/mL, respectively; against HEC-1-A cell line were 583 and 356 µg/mL, respectively; against KLE cell line were 609 and 411 µg/mL, respectively; and against Ishikawa cell line were 560 and 357 µg/mL, respectively. Among the above cell lines, the best result of anti-human endometrial cancer properties of copper nanoparticles was gained in the cell line of HEC-1-B. This study indicated excellent anti-human endometrial cancer potentials of copper nanoparticles containing in the condition.
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http://dx.doi.org/10.1080/21691401.2021.1926275DOI Listing
December 2021

Diosgenin attenuates tumor growth and metastasis in transgenic prostate cancer mouse model by negatively regulating both NF-κB/STAT3 signaling cascades.

Eur J Pharmacol 2021 Sep 17;906:174274. Epub 2021 Jun 17.

KHU-KIST Department of Converging Science and Technology and Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea. Electronic address:

Prostate cancer (PCa) is a common disease among men especially in the old age. The deregulated activation of oncogenic and pro-survival transcription factors has been linked with tumor progression in PCa patients. The consequence of diosgenin treatment on NF-κB/STAT3 activation in PCa cells as well as transgenic mouse model was determined. We also validated the hypothesis of targeting these transcription factors using in silico proteomics simulation model. Diosgenin abrogated NF-κB/STAT3 activation and this action was caused as a result of suppression of protein kinases and reporter gene activity that led to a substantial reduction in the expression of various tumorigenic gene products. In vivo, diosgenin (2% w/w) when mixed in diet and fed to mice abrogated tumor progression in transgenic mice. Diosgenin was also detected in serum and was well absorbed orally. Overall, our data highlights the promising efficacy of diosgenin in PCa therapy.
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http://dx.doi.org/10.1016/j.ejphar.2021.174274DOI Listing
September 2021

Assessment of hexavalent chromium (VI) biosorption competence of indigenous Aspergillus tubingensis AF3 isolated from bauxite mine tailing.

Chemosphere 2021 Nov 1;282:131055. Epub 2021 Jun 1.

Faculty of Electrical and Electronics Engineering, Ton Duc Thang, University, Ho Chi Minh City, Viet Nam. Electronic address:

The intention of this research was to find the most eminent metal tolerant and absorbing autochthonous fungal species from the waste dump of a bauxite mine. Out of the 4 (BI-1, BI-II, BI-III, and BI-IV) predominant isolates, BI-II had an excellent metal tolerance potential against most of the metals in the subsequent order: Cr(VI) (1500), Cu(II) (600), Pb(II) (500), and Zn(II) (500-1500 μg mL). BI-II had shown tolerance to Cr(VI) up to 1500 mg L. The excellent metal tolerant isolate was characterized and identified as Aspergillus tubingensis AF3 through 18S rRNA sequencing method and submitted to GenBank and received an accession number (MN901243). A. tubingensis AF3 had the efficiency to absorb Cr(VI) and Cu(II) at <70 & 46.3% respectively under the standard growth conditions. Under the optimized conditions (25 °C, pH 7.0, 0.5% of dextrose, and 12 days of incubation), A. tubingensis AF3 absorbed 74.48% of Cr(VI) in 12 days (reduction occurred as 822.3, 719.13, 296.66, and 255.2 mg L of Cr(VI) on the 3, the 6, the 9 and the 12 day, respectively). The adsorbed metal was sequestered in the mycelia of the fungus in a precipitated form; it was confirmed by Scanning Electron Microscope (SEM) and Energy Dispersive X-ray analysis (EDX) analyses. The possible biosorption mechanisms were analyzed by Fourier-Transform Infrared Spectroscopy (FTIR) analysis, the results showed the presence of N-H primary amines (1649.98 cm) and Alkanes (914.30 cm) in the cell wall of the fungus, while being treated with Cr(VI) they supported and enhanced the Cr(VI) absorption. The entire results concluded that the biomass of A. tubingensis AF3 had the potential to absorb a high concentration of Cr(VI).
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http://dx.doi.org/10.1016/j.chemosphere.2021.131055DOI Listing
November 2021

Essential oils as an effective alternative for the treatment of COVID-19: Molecular interaction analysis of protease (M) with pharmacokinetics and toxicological properties.

J Infect Public Health 2021 May 10;14(5):601-610. Epub 2021 Feb 10.

Department of Clinical Pharmacology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea. Electronic address:

Background: The current health concern to the entire world is the chronic respiratory disease caused by coronavirus 2 (COVID-19). A specific treatment or proper therapy is still lacking, and the investigations from across the world for proper drug/vaccine development towards disease control are in progress. The Coronavirus replication takes place by the conversion of the polypeptide into functional protein and this occurs due to the key enzyme Main protease (M). Therefore, identification of natural and effective M inhibitors could be a safe and promising approach for COVID-19 control.

Methods: The present in silico study evaluates the effect of bioactive compounds found in Eucalyptus and Corymbia species essential oil on M by docking. Molecular docking of the major seven compounds of essential oil (citronellol, alpha-terpineol, eucalyptol, d-limonene, 3-carene, o-cymene, and alpha-pinene) with M was studied by AutoDock 4.2, and the properties were analysed by PreADMET and Biovia Discovery Studio visualizer.

Results: The calculated parameters such as binding energy, hydrophobic interactions, and hydrogen bond interactions of 6LU7 (M) with Eucalyptus and Corymbia volatile secondary metabolites represented its scope as an effective therapy option against covid-19. Among the docked compounds, eucalyptol shows the least binding energy without toxicity.

Conclusions: The outcome of this study reported that the essential oil of Eucalyptus and Corymbia species, mainly eucalyptol can be utilized as a potential inhibitor against COVID-19 and also it can be used in its treatment. Hence, further analysis was required to explore its potential application in medicine.
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http://dx.doi.org/10.1016/j.jiph.2020.12.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874929PMC
May 2021

Novel green synthesis and characterization of a chemotherapeutic supplement by silver nanoparticles containing Berberis thunbergii leaf for the treatment of human pancreatic cancer.

Biotechnol Appl Biochem 2021 Apr 3. Epub 2021 Apr 3.

Department of General Surgery, Qinghai Province People's Hospital, Xining, Qinghai, China.

In recent years, silver nanoparticles have been used as modern chemotherapeutic drugs to treat several cancers such as pancreatic, breast, prostate, and blood cancers. No previous reports demonstrated the in vitro anti-human pancreatic cancer effects of the novel chemotherapeutic drug formulated by silver nanoparticles containing Berberis thunbergii leaf (AgNPs). The synthesized AgNPs were characterized using different techniques including UV-vis. and FT-IR spectroscopy, X-ray diffraction, scanning electron microscopy (SEM), and TEM. All techniques approved the synthesized silver nanoparticles. The SEM and TEM exhibited a uniform spherical morphology and an average size of about 15 nm for the biosynthesized nanoparticles, respectively. The 4-(dimethylamino)benzaldehyde,2,2-diphenyl-1- pikrilhydrazil (DPPH) test revealed similar antioxidant potentials for B. thunbergii leaf aqueous extract, AgNPs, and butylated hydroxytoluene. AgNPs inhibited half of the DPPH molecules in the concentration of 108 μg/mL. To survey the anti-human pancreatic cancer activities of AgNO , B. thunbergii leaf aqueous extract, and AgNPs, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used on common human pancreatic cancer cell lines. AgNPs had very low cell viability and anti-human pancreatic cancer effects dose-dependently against PANC-1, AsPC-1, and MIA PaCa-2. The IC50 values of the AgNPs were 259, 268, and 141 μg/mL against PANC-1, AsPC-1, and MIA PaCa-2 cell lines, respectively. It is thought that the AgNPs obtained can be used as an anticancer drug for the diagnosis of pancreatic cancer in humans after acceptance of the above findings in clinical study trials.
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http://dx.doi.org/10.1002/bab.2160DOI Listing
April 2021

Phycoremediation potential of Chlorella sp. on the polluted Thirumanimutharu river water.

Chemosphere 2021 Aug 14;277:130246. Epub 2021 Mar 14.

School of Renewable Energy, Maejo University, Chiang Mai 50290, Thailand; College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address:

Rivers are the most significant natural resources that afford outstanding habitation and nourishment for numerous living organisms. Urbanization and industrialization pollute rivers rendering their water unhealthy for consumption. Hence, this work was designed to find a potential native pollutant removing algae from polluted water. The physicochemical properties of the tested river water such as Electric Conductivity (EC), turbidity, total hardness, Biochemical Oxygen Demand (BOD), Chemical Oxygen Demand (COD), Ca, SO-, and NH, NO, NO, PO, Mg, F and Cl contents were not within the permissible limits. Lab-scale and field-based phycoremediation treatments with the indigenous native microalgal species, Chlorella sp. from the Thirumanimutharu river water sample were set up for 15 days with three different (Group I, II, and III) biomass densities (4 × 10, 8 × 10, and 12 × 10 cells mL). Group III of both the lab-scale and field based treatments showed the maximum reduction in the physicochemical parameters compared to the other groups. Further, the group III of the field based study showed an extensive reduction in BOD (34.51%), COD (32.53%), NO, NO, free NH (100%) and increased dissolved oxygen (DO) (88.47%) compared to the lab scale study. In addition, the trace elements were also reduced significantly. The pollutant absorbing active functional moieties (O-H, CO, and CN) found on Chlorella sp. had been confirmed by Fourier-Transform Infrared Spectroscopy (FTIR) analysis. In the Scanning Electron Microscope (SEM) study, significant morphological changes on the surface of the treated Chlorella sp. were noticed compared with the untreated Chlorella sp. biomass, which also confirmed the absorption of the pollutants during treatment.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130246DOI Listing
August 2021

Phyllanthin inhibits MOLT-4 leukemic cancer cell growth and induces apoptosis through the inhibition of AKT and JNK signaling pathway.

J Biochem Mol Toxicol 2021 Jun 16;35(6):1-10. Epub 2021 Mar 16.

Scigen Research and Innovation Pvt. Ltd., Periyar Technology Business Incubator, Thanjavur, Tamil Nadu, India.

Among cancers, leukemia is a multistep progression that involves genetic modifications of normal hematopoietic progenitor cells to cancerous cells. In recent times, leukemia cases and their mortality rate have increased rapidly. Therefore, the immense need for a therapeutic approach is crucial that can control this type of cancer. Phyllanthin is a lignan compound constituent from the Phyllanthus species and has numerous beneficial effects as a dietary component. The present study aims to determine the impact of phyllanthin on the MOLT-4 cytotoxic effect. MOLT-4 cells and MS-5 cells were cultured at different concentrations of phyllanthin (5, 10, 25, 50, 75, and 100 μM/ml), and the viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. The level of reactive oxygen species, the membrane potential of mitochondria, apoptosis by 2',7'-dichlorofluorescin-diacetate (DCF-DA), rhodamine, acridine orange (AO)/ethidium bromide (EB), 4',6-diamidino-2-phenylindole (DAPI)/propidium iodide (PI) staining, gene expression of signaling molecules, and protein levels were assessed by reverse-transcription polymerase chain reaction and western blot analysis. Phyllanthin did not show toxicity toward MS-5 cells and significantly decreased the cell viability of MOLT-4 cells with an IC value of 25 µM/ml. Also, phyllanthin induced the production of reactive oxygen species and led to the loss of mitochondrial membrane potential. AO/EB and DAPI/PI staining fluorescent image confirmed the induction of apoptosis by phyllanthin treatment. The messenger RNA (mRNA) expression of cell cycle regulator cyclin D1, antiapoptotic gene Bcl-2, NF-κB, and TNF-α decreased, but the proapoptotic Bax mRNA expression was increased. The phosphorylated protein levels of p-PI3K1/2, p-ERK1/2, and p-AKT were decreased, whereas the levels of p-p38 and p-JNKT1/2 increased. Our results confirmed that phyllanthin inhibits the MOLT-4 cells, increases apoptosis, and inhibits MOLT-4 migration and cell invasion. Therefore, phyllanthin can be used as a potential target for leukemia treatment.
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http://dx.doi.org/10.1002/jbt.22758DOI Listing
June 2021

Tomentosin Reduces Behavior Deficits and Neuroinflammatory Response in MPTP-Induced Parkinson's Disease in Mice.

J Environ Pathol Toxicol Oncol 2021 ;40(1):75-84

Scigen Research and Innovation Pvt. Ltd., Periyar Technology Business Incubator, Thanjavur, Tamil Nadu, 613403, India.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Tomentosin is an active compound isolated from the I. viscosa plant that has extensive therapeutic value. In this exploration, the neuroprotective actions of tomentosin were investigated against MPTP-stimulated neuroinflammation in mice. PD was stimulated in C57/BL6 mice by injecting 20-mg/kg MPTP at 2-h intervals 4 times a day for 15 days simultaneously with tomentosin treatment. The rota-rod test, grasping test, and pole climbing test were executed to investigate the motor functioning of the test animals. Proinflammatory cytokines, reactive oxygen species, and myeloperoxidase were assayed using commercial ELISA kits. Superoxide dismutase enzyme levels were measured by the standard method. Expression of TLR-4/NF-κB was analyzed by Western blot. Brain tissues of investigational animals were analyzed microscopically. Tomentosin treatment of the MPTP-intoxicated PD mice promoted appreciable regains in body weight and noticeably prevented MPTP-stimulated impairments in motor function. In the PD mice, proinflammatory cytokine, ROS, and MPO levels were lowered by tomentosin, inhibited the TLR-4/NF-κB signaling pathway and prevented inflammation-mediated neuronal cell damage, and reduced glial cell damage and normalized ganglion layers. These findings confirmed the neuroprotective properties of tomentosin against MPTP-induced PD in mice.
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http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v40.i1.70DOI Listing
March 2021

Anti-inflammatory effects of rhaponticin on LPS-induced human endothelial cells through inhibition of MAPK/NF-κβ signaling pathways.

J Biochem Mol Toxicol 2021 May 18;35(5):e22733. Epub 2021 Feb 18.

SCIGEN Research and Innovation Pvt. Ltd., Thanjavur, Tamil Nadu, India.

The untreated systemic chronic inflammation leads to autoimmune diseases, hyperglycemia, cardiovascular diseases, type 2 diabetes, hypertension, osteoporosis, and so on. Phytochemicals effectively inhibit the inflammation, and numerous studies have proved that the phytocomponents possess anti-inflammatory property via inhibiting the cyclooxygenase and lipoxygenase signaling pathways. Rhaponticin is one such phytochemical obtained from the perennial plant Rheum rhaponticum L. belonging to Polygonaceae family. We assessed the anti-inflammatory potency of rhaponticin in endothelial cells induced with lipopolysaccharides (LPS). Four different endothelial cells induced with LPS were treated with rhaponticin and assessed for the nitric oxide generation. The cytotoxic potency of rhaponticin was evaluated in endothelial cells using the 3-(4,5-dimethylthizaol-2yl)-2,5-diphenyl tetrazolium bromide assay. The tumor necrosis factor-α (TNF-α) synthesis was quantified using the commercially available assay kit. The inflammatory signaling protein gene expression of TNF-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-1β (IL-1β) was analyzed with quantitative polymerase chain reaction (PCR) analysis. The gene expression of NADPH oxidase (NOX) cytoplasmic catalytic subunits gp91 , p47 , and p22 was assessed with real-time PCR analysis. Finally, to confirm the anti-inflammatory potency of rhaponticin, the nuclear factor kappa B (NFκB) and mitogen-activated protein kinase (MAPK) signaling protein expression was analyzed with immunoblotting analysis. Rhaponticin treatment significantly decreased the levels of nitric oxide and TNF-α synthesis in LPS-induced endothelial cells. It significantly decreased the gene expression of inflammatory proteins and NOX signaling protein. The protein expression of NFκB and MAPK signaling proteins was drastically decreased in rhaponticin-treated endothelial cells induced with LPS. Overall, our results confirm that rhaponticin effectively inhibited the inflammation triggered by LPS in endothelial cells via downregulating iNOS, COX2, and NFκB and MAPK signaling pathways.
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http://dx.doi.org/10.1002/jbt.22733DOI Listing
May 2021
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