Phytochemical and pharmacological overview on Liriopes radix

Liriopogons (Liriope and Opiopogon) species are used as the main medicinal ingredient in traditional medicine in several Asian countries. The roots or tubers of Liriope plants (Liriopes radix; LR) have traditionally been used for hundreds of years to treat cough, insomnia, constipation, asthma, and inflammation. The present review discusses extensively the available knowledge on its phytochemical and pharmacological activities in vitro and in vivo. The review does not include other parts of these plants. Literature evidence has been analyzed to identify responsible phytochemicals and their wide range of pharmacological activities. Further studies are needed for the isolation of purified compounds in order to understand their mechanisms of action and for clinical application.Keywords: Diabetes, Liriope platyphylla, Neuroprotective, Phytochemistry, Steroidal glycoside

GAS CHROMATOGRAPHY-MASS SPECTROMETRY ANALYSIS, IN VITRO CYTOTOXIC AND ANTIOXIDANT EFFICACY STUDIES ON CLEOME GYNANDRA L. (LEAVES): A TRADITIONAL DRUG SOURCE

  Objective: This study was aimed to assess the phytoconstituents, cytotoxic, and antioxidant efficacy of ethyl extract of Cleome gynandra leaves.Methods: Qualitative phytochemical analysis with different solvent extracts was performed. Quantitative and gas chromatography-mass spectrometry (GC-MS) analysis of the extract was performed with ethyl acetate extract. The cytotoxic effect of the ethyl acetate extract was determined by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide (MTT) assay on Michigan Cancer Foundation-7 (MCF-7) cells using taxol as standard and free radical scavenging ability using 1,1-diphenyl-2-picrylhydrazyl (DPPH).Results: Leaves extracts with different solvents revealed the presence of alkaloids, cardiac glycosides, flavonoids, phenols, and tannins. GC-MS analysis of ethyl acetate of the plant leaves showed the presence of n-hexadecanoic acid. The IC50 value of the ethyl acetate extract was found to be 90.2 μg/ml on MCF-7 cell line, and the extract was found to possess significant DPPH free radical scavenging activity.Conclusion: From the results, we conclude that the C. gynandra extract possesses antioxidant and antiproliferating activity against MCF-7 cells

IN VITRO CYTOTOXIC AND GAS CHROMATOGRAPHY-MASS SPECTROMETRY STUDIES ON ORTHOSIPHON STAMINEUS BENTH. (LEAF) AGAINST MCF–7 CELL LINES

ABSTRACTObjective: The objective of the study was to determine the anticancer efficacy of Orthosiphon stamineus extract against Michigan Cancer Foundation-7(MCF-7) and its phytochemical analysis through gas chromatography-mass spectrometry (GC-MS).Methods: Different solvents were used for leaf extraction and used for qualitative assay of phytochemicals using standard protocols. Differentconcentration (12.5, 25, 50, 100, and 200 μg/ml) of methanol extract and ethyl acetate extract of O. stamineus leaves were used to assess the in vitrocytotoxic effect using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Further, the ethyl acetate extract was subjected toGC-MS analysis, and the identification of components was based on the National Institute of Standards and Technology library database.Result: Of the hexane, methanol and ethyl acetate extracts, methanol extract found to contain more of phytochemicals followed by ethyl acetate. Theinhibitory concentration 50 for methanol extract and ethyl acetate extract was found be 93.42 μg/ml and 215.3 μg/ml, respectively.GC-MS mass spectrum of ethyl acetate extract revealed the presence of squalene and phytol and antioxidants such as flavones. Sterols compoundssuch as vitamin E, ergosterol, cholesterol, and 3,7,11,15-tetramethyl-2-hexadecen-1-ol and terpenoids were also identified.Conclusion: The data obtained in this work could be useful as a chemical standard in checking the genuineness of this plant source. Data of the resultsfurther depicted that the selected traditional anti-cancer plants could be used not only as an anti-cancer but also as a good antioxidant.Keywords: Anti-cancer, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Orthosiphon stamineus, Michigan cancer fsoundation-7cells

Study of prosthetic heart valve thrombosis and outcomes after thrombolysis

Background: The study aimed to evaluate the clinical presentation, diagnostic features, treatment strategies, and complications of prosthetic heart valve thrombosis (PHVT) and to determine efficacy, outcomes and complications of thrombolytic therapy during hospital stay.Methods: This was a prospective, observational, single-centre study carried out between March, 2016 and December, 2017 at a tertiary care centre in India. Total 110 patients with history of prosthetic heart valve replacement and symptoms related to PHVT were included in the study. Patients underwent thrombolysis, surgery or conservative management for treatment of PHVT, as per their individual clinical presentation. Clinical profile and treatment outcomes were assessed using a pre-tested, semi-structured questionnaire and clinical assessment.Results: Mean age of the patients was 39.4±12.5 years. Most of the patients presented with NYHA class II and III (85.4%) symptoms. Total 20.9% of patients were poorly compliant with anticoagulants. Thrombolysis was initial treatment in 105 (95.5%) patients. Five (4.6%) patients were treated with heparin. Two patients underwent surgery after failed thrombolysis. Mortality in the thrombolysis group was 6.6%. Embolism occurred in 8.6% of the group and major bleeding in 1.9%. One patient who underwent surgery died.Conclusions: In light of these results, it can be concluded that most cases of PHVT are due to inadequate anticoagulation and poor monitoring mainly in patients belonging to the lower socioeconomic group. Thrombolysis can be considered as first line therapy where the immediate surgical options are remote

Phytochemical and Pharmacological Role of Liquiritigenin and Isoliquiritigenin From Radix Glycyrrhizae in Human Health and Disease Models

The increasing lifespan in developed countries results in age-associated chronic diseases. Biological aging is a complex process associated with accumulated cellular damage by environmental or genetic factors with increasing age. Aging results in marked changes in brain structure and function. Age-related neurodegenerative diseases and disorders (NDDs) represent an ever-growing socioeconomic challenge and lead to an overall reduction in quality of life around the world. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are most common degenerative neurological disorders of the central nervous system (CNS) in aging process. The low levels of acetylcholine and dopamine are major neuropathological feature of NDDs in addition to oxidative stress, intracellular calcium ion imbalance, mitochondrial dysfunction, ubiquitin-proteasome system impairment and endoplasmic reticulum stress. Current treatments minimally influence these diseases and are ineffective in curing the multifunctional pathological mechanisms. Synthetic neuroprotective agents sometimes have negative reactions as an adverse effect in humans. Recently, numerous ethnobotanical studies have reported that herbal medicines for the treatment or prevention of NDDs are significantly better than synthetic drug treatment. Medicinal herbs have traditionally been used around the world for centuries. Radix Glycyrrhizae (RG) is the dried roots and rhizomes of Glycyrrhiza uralensis or G. glabra or G. inflata from the Leguminosae/Fabaceae family. It has been used for centuries in traditional medicine as a life enhancer, for the treatment of coughs and influenza, and for detoxification. Diverse chemical constituents from RG have reported including flavanones, chalcones, triterpenoid saponins, coumarines, and other glycosides. Among them, flavanone liquiritigenin (LG) and its precursor and isomer chalcone isoliquiritigenin (ILG) are the main bioactive constituents of RG. In the present review, we summarize evidence in the literature on the structure and phytochemical properties and pharmacological applications of LG and ILG in age-related diseases to establish new therapeutics to improve human health and lifespan

Meridianin C inhibits the growth of YD-10B human tongue cancer cells through macropinocytosis and the down-regulation of Dickkopf-related protein-3

Meridianin C is a marine natural product known for its anti‐cancer activity. At present, the anti‐tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, YD‐8, YD‐10B, YD‐38 and HSC‐3. Among the cells tested, meridianin C most strongly reduced the growth of YD‐10B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the YD‐10B cells; confirmed by the microscopic and TEM analysis as well as the entry of FITC‐dextran, which was sensitive to the macropinocytosis inhibitor amiloride. SEM data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of YD‐10B cells treated with meridianin C, pointing out that meridianin C‐induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf‐related protein‐3 (DKK‐3), a known negative regulator of macropinocytosis. A role for DKK‐3 in regulating macropinocytosis in the YD‐10B cells was confirmed by siRNA knockdown of endogenous DKK‐3, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous DKK‐3 overexpression, which resulted in a considerable inhibition of the meridianin C‐induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti‐proliferative effects via macropinocytosis in the highly tumorigenic YD‐10B cell line and the effects are mediated in part through down‐regulation of DKK‐3

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Supramolecular assistance of [2+2] photocycloaddition for cross-photodimerization

271-280[2+2]&nbsp;Photocycloaddition (PCA) of alkenes is an important reaction as it is used in several areas of fundamental and applied research. Due to its significance, there are numerous articles and reviews in chemical literature that document various aspect of this reaction &ndash; such as application in synthesis, photopolymerization, materials research, etc. Despite its importance, the vast majority of the reports are focused on the reaction between identical alkenes (homo-dimerization), while PCA between non-identical alkenes (cross-dimerization) has been grossly under-explored. In this review we have complied the reports on cross-dimerization reactions affected through supramolecular methods, which can be broadly classified based on two broad approaches: (a) crystal-engineering or (b) templation in solution or slurry. Both methods are based on the utilization of favorable intermolecular interaction between non-identical alkenes, and the use of a templating agent that promotes hetero-alkene arrangement in the ground state, which, upon photoexcitation yield the cross-dimer selectively

Therapeutic Effects of Conditioned Medium of Neural Differentiated Human Bone Marrow-Derived Stem Cells on Rotenone-Induced Alpha-Synuclein Aggregation and Apoptosis

Mesenchymal stem cells (MSCs) have been used against several diseases. Their potential mainly appears from its secreted biomolecules. Human bone marrow-derived stem cells (hBMSC) displayed neuronal functional characteristics after differentiation by basic fibroblast growth factor (bFGF) and forskolin. PD is a chronic age-related neurodegenerative disease (NDD) characterized by loss of dopaminergic neurons in the substantia nigra (SN) and abnormal accumulation of α-synuclein (α-syn) aggregations. In this present study, we evaluated the therapeutic effects of neural differentiated hBMSC (NI-hBMSC) conditioned medium (NI-hBMSC-CM) to a rotenone- (ROT-) induced Parkinson’s disease (PD) model in SH-SY5Y cells. NI-hBMSC-CM treatment (50% diluted) in the last 24 h of 48 h ROT (0.5 μM) toxicity showed a significant increase in cell survival. The decreased tyrosine hydroxylase (TH) expression as a hallmark of PD was increased by NI-hBMSC-CM. The Triton X-100-soluble and Triton X-100-insoluble cell lysate fractions were used in Western blotting. The oligomeric, dimeric, and monomeric phosphorylated serine129 (p-S129) α-syn and total monomeric α-syn were decreased during ROT toxicity in the Triton X-100-soluble fraction. The Triton X-100-insoluble fraction revealed that ROT toxicity significantly increased the oligomeric but decreased the dimeric and monomeric p-S129 α-syn expressions while all forms of total α-syn were increased in SH-SY5Y cells. NI-hBMSC-CM stabilized the physiological α-syn monomers and reduced aggregated insoluble p-S129 α-syn against ROT. The cytoskeletal proteins, neurofilament-H (NF-H), β3-tubulin (Tuj1), neuronal nuclei (NeuN), and synaptophysin (SYP) were significantly decreased during ROT toxicity. In addition, proapoptotic Bax was increased by ROT with decreased antiapoptotic Bcl-2 and Mcl-1 as well as proforms of caspase-9, caspase-3, caspase-7, and PARP-1. NI-hBMSC-CM ameliorated the neurotrophic protein expressions, controlled the Bax/Bcl-2 ratio, upregulated procaspases, and inactivated PARP-1. From our results, we conclude that NI-hBMSC-CM containing released biomolecules during neural differentiation employs regenerative effects on the ROT model of PD in SH-SY5Y cells