In-vitro evaluation of Indigofera heterantha extracts for antibacterial, antifungal and anthelmintic activities.

BACKGROUND: Multidrug-resistant bacterial strains cause several serious infections that can be fatal, such as Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae (often referred to as ESKAPE pathogens). Since ancient times, several indigenous medical systems in India have utilized diverse medicinal plants (approximately 80,000 species) as conventional treatments for a variety of illnesses. A member of the Fabaceae family, also referred to as "Himalayan indigo," Indigofera heterantha Wall, is well known for its therapeutic properties. METHODS: The present study investigated the antibacterial, antifungal and antihelmintic properties of the roots, bark, leaves, and flowers of I. heterantha from the Kashmir Himalayas. The effectiveness of the extracts against bacteria, fungi, and earthworms. Three of the tested organisms for bacteria were ESKAPE pathogens, as they are responsible for creating fatal bacterial infections. The antifungal potency of I. heterantha aqueous and methanolic extracts was evaluated using the Agar Well Diffusion Assay. The antihelmintic activity was carried out on an adult Pheretima posthuma Indian earth worm, which shares physiological and anatomical similarities with human intestinal roundworm parasites. RESULTS: The methanolic extracts of root and bark have shown prominent activity against all bacterial strains, whereas aqueous extracts of flower, root, and leaves have shown promising activity against Staphylococcus aureus. The aqueous extract demonstrated good activity against S. cerevisiae at a concentration of 200 mg/ml with a zone of inhibition of 16 mm, while the methanolic extract displayed comparable activity against the fungal strains. The remaining two strains, P. crysogenum and A. fumigatus, were only moderately active in response to the extracts. All the extracts have shown anthelmintic activity except aqueous flower. CONCLUSION: These results will pave the way for the bioassay-guided isolation of bioactive constituents that may act as hits for further development as potential antibacterial agents against drug-resistant microbial and helminthic infections.

DMSO-KOH mediated stereoselective synthesis of Z-enamides: an expeditious route to Z-enamide bearing natural products.

An efficient strategy towards stereoselective amidation of alkynes is reported. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope and fast kinetics to furnish Z-enamides. Moreover, the method was successfully applied for the facile synthesis of the natural products lansiumamide A, lansiumamide B and Z-alatamide. Notably, DMSO plays two vital roles: hydrogen source and solvent.

Design, synthesis and neuroprotective evaluation of nitrogen heterocyclic and triazole derivatives of sarracinic acid.

Novel sarracinic acid derivatives bearing triazole or N-heterocyclic moiety were prepared via two separate reaction schemes. The triazoles and the N-heterocyclic derivatives were synthesised using standard click chemistry approach and amination of 2-bromoethyl ester of sarracinic acid respectively. All the synthesised derivatives were screened for in vitro neuroprotective activity against corticosterone induced impairment in neuroblastoma cell line SH-SY5Y. Two analogs SA-2 and SA-12 exhibited strong neuroprotective activity. The cell viability, after high dose corticosterone induced cell death, increased remarkably with the pre treatment of SA-2 and SA-12. The in vitro biological activity of SA-2 and SA-12 was verified through docking studies. The docking studies were in good agreement with the biological results. SA-2 and SA-12 showed strong binding affinities with the target protein having ΔGb = -8.88 and -7.52; inhibition constant (ki) = 3.08 nM and 30.9 nM respectively.

I2-DMSO Promoted Deaminative Coupling Reactions of Glycine Esters: Access to 5-(Methylthio)pyridazin-3(2H)-ones.

An unprecedented, one-step strategy for the synthesis of 5-(methylthio)pyridazin-3(2H)-one derivatives has been developed through iodine triggered deaminative coupling of glycine esters with methyl ketones and hydrazine hydrate in DMSO. These transformations in the absence of hydrazine helped to generate different 3-methylthio-4-oxo-enoates in good yields. Notably, DMSO played multiple roles such as oxidant, methylthiolating reagent, and solvent.

Iodine and ammonium persulfate mediated activation of DMSO: an approach to N-formylation of amides and synthesis of isatins.

An efficient strategy towards N-formylation of amides and oxidation of indolines to isatins is described. This method employs readily available (NH4)2S2O8, I2, and DMSO. The given method features operational simplicity, excellent functional group tolerance, broad substrate scope, and fast kinetics. Moreover, the method was applied to the synthesis of the natural product alatamide. Notably, DMSO plays three vital roles: a formyl group source, an oxidant, and a solvent.

Implication of ARID1A Undercurrents and PDL1, TP53 Overexpression in Advanced Gastric Cancer.

AT-rich interactive domain-containing protein 1A (ARID1A), TP53 and programmed cell death-ligand 1 (PDL1) are involved in several protein interactions that regulate the expression of various cancer-related genes involved in the progression of the cell cycle, cell proliferation, DNA repair, and apoptosis. In addition, gene expression analysis identified some common downstream targets of ARID1A and TP53. It has been established that tumors formed by ARID1A-deficient cancer cells exhibited elevated PDL1 expression. However, the aberrations in these molecules have not been studied in this population especially in Gastric Cancer (GC). In this backdrop we aimed to investigate the role of the ARID1A mutation and expression of ARID1A, TP53 and PDL1 genes in the etiopathogenesis of Gastric Cancer (GC) in the ethnic Kashmiri population (North India). The study included 103 histologically confirmed GC cases. The mutations, if any, in exon-9 of ARID1A gene was analysed by Polymerase Chain Reaction (PCR) followed by Sanger sequencing. The mRNA expression of the ARID1A, TP53 and PDL1 genes was analysed by Quantitative real time-PCR (qRT-PCR). We identified a nonsense mutation (c.3219; C > T) in exon-9 among two GC patients (∼2.0%), which introduces a premature stop codon at protein position 1073. The mRNA expression of the ARID1A, TP53 and PDL1 gene was significantly reduced in 25.3% and elevated in 47.6 and 39.8% of GC cases respectively with a mean fold change of 0.63, 2.93 and 2.43. The data revealed that reduced mRNA expression of ARID1A and elevated mRNA expression of TP53 and PDL1 was significantly associated with the high-grade and advanced stage of cancer. Our study proposes that ARAD1A under-expression and overexpression of TP53 and PDL1 might be crucial for tumor progression with TP53 and PDL1 acting synergistically.

Neuroprotective activity of natural products isolated from Senecio graciliflorus DC against corticosterone-induced impairment in SH-SY5Y cells.

Senecio graciliflorus DC root extract was studied for secondary metabolite composition following the bioactivity-guided isolation technique. The ethyl acetate extract of Senecio graciliflorus root yielded nine chemical constituents: 3,4-di-tert-butyl toluene, stigmasterol, ß-sitosterol, 2ß-(angeloyloxy)furanoeremophilane, gallic acid, 2ß-{[(Z)-2-hydroxymethylbut-2-enoyl]oxy}furanoeremophilane, 1-hydroxypentan-2-yl-4-methylbenzoate, sarcinic acid, and sitosterol 3-O-ß-D-glucopyranoside. The structures of the chemical constituents were elucidated on the basis of spectral data analysis in the light of literature. All the compounds are being reported for the first time from this plant. The isolated constituents were screened for neuroprotective effects against corticosterone-induced impairment in neuroblastoma cell lines (SH-SY5S cells). The viability of SH-SY5S cells was determined using MTT assay. Among various isolated compounds, three natural products (sarcinic acid, gallic acid, and ß-sitosterol) displayed robust neurotropic activity. The compounds increased neuronal cell survival in differentiated neuroblastoma cells (SH-SY5Y) from high-dose corticosterone (400 µM)-induced cell death. All the three constituents showed maximum AKT/ERK pathway activation at 20 µM concentration. The studies are aimed to explore small molecules for treating neurodegeneration underlying various neurological disorders to restore neuronal cell plasticity.

Scenario and future prospects of microRNAs in gastric cancer: A review.

Carcinoma of the stomach is one of the major prevalent and principal causes of cancer-related deaths worldwide. Current advancement in technology has improved the understanding of the pathogenesis and pathology of gastric cancers (GC). But, high mortality rates, unfavorable prognosis and lack of clinical predictive biomarkers provide an impetus to investigate novel early diagnostic/prognostic markers and therapeutic targets for GC, which are sufficiently sensitive to GC. Current biomedical investigations have explored several budding GC biomarker by utilizing serum proteins, natural oncogenic genes during improvement in molecular technologies as microarray, and RNA/DNA-Seq. Recently, small non-coding microRNAs (miRNAs) are becoming vital regulators in oncogenesis pathways and can act as handy clinical biomarkers. The newly introduced class of biomarkers is rising as new molecules for cancer diagnosis and prognosis. For better understanding of the gastric carcinogenesis, miRNAs may help to elucidate the mechanisms of tumor growth and can help to discover novel untimely potent markers for early detection of GC. Here in this review, we summarize the recent research studies supporting the utility of miRNAs as novel early diagnostic/prognostic tools and therapeutic targets. Thus, here we introduce potential future treatment strategies for gastrointestinal (GI) cancers, which indicate the practicality and clinical applications of miRNAs in GC.

Diagnostic utility of epigenetics in breast cancer - A review.

Epigenetic alterations are clearly involved in cancer initiation and progression as recent epigenetic studies of genomic DNA, histone modifications and micro-RNA alterations suggest that these are playing an important role in the incidence of breast cancer. Epigenetic information has recently gained the attention of researchers because epigenetic modification of the genome in breast cancer is still an evolving area for researchers. Several active compounds present in foods, poisons, drugs, and industrial chemicals may as a result of epigenetic mechanisms increase or decrease the risk of breast cancer. Epigenetic regulation is critical in normal growth and development and closely conditions the transcriptional potential of genes. Epigenetic mechanisms convey genomic adaption to an environment thereby ultimately contributing towards given phenotype. In addition to the use of epigenetic alterations as a means of screening, epigenetic alterations in a tumor or adjacent tissues or peripheral blood may also help clinicians in determining prognosis and treatment of breast cancer. As we understand specific epigenetic alterations contributing to breast tumorigenesis and prognosis, these discoveries will lead to significant advances for breast cancer treatment, like in therapeutics that target methylation and histone modifications in breast cancer and the newer versions of the drugs are likely to play an important role in future clinical treatment.

Zingerone (4-(4-hydroxy-3-methylphenyl)butan-2-one) ameliorates renal function via controlling oxidative burst and inflammation in experimental diabetic nephropathy.

Development of diabetic nephropathy (DN) is directly linked to oxidative stress and inflammation. In this context, inflammatory and oxidative markers have gained much attention as targets for therapeutic intervention. We studied the effect of zingerone in a streptozotocin/high fat diet (STZ/HFD)-induced type 2 diabetic Wistar rat model. Zingerone also known as vanillyl acetone is a pharmacologically active compound present usually in dry ginger. STZ/HFD caused excessive increase in ROS and inflammation in experimental animals. The treatment with zingerone markedly abrogated ROS levels, inhibited the NF-кB activation and considerably reduced level of other downstream inflammatory molecules (TNF-α, IL-6, IL-1ß), furthermore, zingerone treatment improved renal functioning by significantly decreasing the levels of kidney toxicity markers KIM-1, BUN, creatinine, and LDH and suppressed TGF-ß. Collectively, these findings indicate that zingerone treatment improved renal function by anti-hyperglycaemic, anti-oxidant, and anti-inflammatory effects, suggesting the efficacy of zingerone in the treatment of DN.

Diagnostic utility of glycosyltransferase mRNA expression in gastric cancer.

OBJECTIVE/BACKGROUND: Posttranslational modification of proteins, including glycosylation, is known to differ between normal and tumor cells. Altered glycosyltransferase levels have been observed in tumor tissues and their role in tumor metastasis and invasion has been implicated. In this study the role of altered glycosyltransferase messenger RNA (mRNA) levels in serum of gastric cancer patients as early markers of gastric cancer was evaluated. METHODS: In this case control study the expression profile of ppGalNAc-T6, GlcNAcT-V, ST3Gal I, ST3 Gal IV, and ST6GalNAc-I in normal healthy control and gastric cancer patients was compared. Serum was isolated from blood samples of gastric cancer patients (n = 200) and controls (n = 200). Following RNA extraction, reverse transcription was carried out and transcript levels of glycosyltransferases were determined using real-time quantitative polymerase chain reaction and normalized against glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression. The amount of target gene, normalized to an endogenous reference gene relative to calibrator was calculated by using ΔΔCT method. Transcript levels in the serum samples of gastric cancer patients were compared with those of controls; also the same was correlated within sex and different stages of disease. RESULTS: The mRNA expression of ppGalNAc-T6 and ST6GalNAc-I was significantly higher in serum samples of gastric cancer patients on comparison with controls (p = .008), however, there was no significant difference in mRNA expression of GlcNAcT-V, ST3Gal I, and ST3 Gal IV in serum samples of gastric cancer patients and controls (p = .097). In addition, no significant association of mRNA expression of these glycosyltransferases was found within sex and stages in this study. CONCLUSION: This study revealed the potential of ppGalNAc-T6 and ST6GalNAc-I mRNA transcript levels in serum as markers of gastric cancer. Further studies on the wider range of glycosyltransferases in various cancers are needed to establish signature mRNA batteries as minimally invasive markers of gastric cancer.

A Review on Pharmacological Properties of Zingerone (4-(4-Hydroxy-3-methoxyphenyl)-2-butanone).

Humans have been using natural products for medicinal use for ages. Natural products of therapeutic importance are compounds derived from plants, animals, or any microorganism. Ginger is also one of the most commonly used condiments and a natural drug in vogue. It is a traditional medicine, having some active ingredients used for the treatment of numerous diseases. During recent research on ginger, various ingredients like zingerone, shogaol, and paradol have been obtained from it. Zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone) is a nontoxic and inexpensive compound with varied pharmacological activities. It is the least pungent component of Zingiber officinale. Zingerone is absent in fresh ginger but cooking or heating transforms gingerol to zingerone. Zingerone closely related to vanillin from vanilla and eugenol from clove. Zingerone has potent anti-inflammatory, antidiabetic, antilipolytic, antidiarrhoeic, antispasmodic, and so forth properties. Besides, it displays the property of enhancing growth and immune stimulation. It behaves as appetite stimulant, anxiolytic, antithrombotic, radiation protective, and antimicrobial. Also, it inhibits the reactive nitrogen species which are important in causing Alzheimer's disease and many other disorders. This review is written to shed light on the various pharmacological properties of zingerone and its role in alleviating numerous human and animal diseases.