Cardioprotective potential of the antioxidant-rich bioactive fraction of Garcinia pedunculata Roxb. ex Buch.-Ham. against isoproterenol-induced myocardial infarction in Wistar rats.

This Study aimed to characterise the phenolic compounds in Garcinia pedunculata extract and assess their potential antioxidant activity as well as its cardioprotective potential in isoproterenol-induced cardiac hypertrophy in an experimental animal model. In vitro antioxidant properties were determined using DPPH, ABTS, FRAP, PMD assays. In vitro lipid peroxidation experiment was also performed with heart tissues. Cardioprotective and cardiotoxicity effects were determined using the cell line studies. The cardioprotective effect of GP was assessed in a rat model of isoproterenol-(ISO-) induced cardiac hypertrophy by subcutaneous administration. Heart weight/tail length ratio and cardiac hypertrophy indicators were reduced after oral administration of GP. Additionally, GP reduced oxidative stress and heart inflammation brought on by ISO. In H9c2 cells, the antihypertrophic and anti-inflammatory effects of the extract of GP were seen in the presence of ISO, which were further supported by the in vivo observations. This study makes a compelling case for the possibility that supplementing with dried GP fruit can prevent heart hypertrophy by reducing oxidative stress and inflammation.

Musa balbisiana Fruit Rich in Polyphenols Attenuates Isoproterenol-Induced Cardiac Hypertrophy in Rats via Inhibition of Inflammation and Oxidative Stress.

Musa balbisiana Colla (Family: Musaceae), commonly known as banana and native to India and other parts of Asia, is very rich in nutritional value and has strong antioxidant potential. In the present study, we have developed Musa balbisiana (MB) fruit pulp powder and evaluated its cardioprotective effect in cardiac hypertrophy, which is often associated with inflammation and oxidative stress. An ultra-high-pressure liquid chromatography-mass spectrometer (UPLC-MS/MS) has been used for the detection and systematic characterization of the phenolic compounds present in Musa balbisiana fruit pulp. The cardioprotective effect of MB was evaluated in a rat model of isoproterenol- (ISO-) induced cardiac hypertrophy by subcutaneous administration of isoproterenol (5 mg/kg-1/day-1), delivered through an alzet minipump for 14 days. Oral administration of MB fruit pulp powder (200 mg/kg/day) significantly (p < 0.001) decreased heart weight/tail length ratio and cardiac hypertrophy markers like ANP, BNP, ß-MHC, and collagen-1 gene expression. MB also attenuated ISO-induced cardiac inflammation and oxidative stress. The in vivo data were further confirmed in vitro in H9c2 cells where the antihypertrophic and anti-inflammatory effect of the aqueous extract of MB was observed in the presence of ISO and lipopolysaccharide (LPS), respectively. This study strongly suggests that supplementation of dried Musa balbisiana fruit powder can be useful for the prevention of cardiac hypertrophy via the inhibition of inflammation and oxidative stress.

Crystal structure, DFT and Hirshfeld surface analysis of (E)-N'-[(1-chloro-3,4-di-hydro-naph-thal-en-2-yl)methyl-idene]benzohydrazide monohydrate.

In the title compound, C18H15ClN2O·H2O, a benzohydrazide derivative, the dihedral angle between the mean plane of the di-hydro-naphthalene ring system and the phenyl ring is 17.1 (2)°. In the crystal, O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds link the benzohydrazide and water mol-ecules, forming a layer parallel to the bc plane. Hirshfeld surface analysis and two-dimensional fingerprint plots indicate that the most important contributions to the crystal packing are from H⋯H (45.7%) and H⋯C/C⋯H (20.2%) contacts.

Design, synthesis and biological evaluation of 2-(phenoxymethyl)-5-phenyl-1,3,4-oxadiazole derivatives as anti-breast cancer agents.

Structural based molecular docking approach revealed the findings of 2-(phenoxymethyl) -5-phenyl-1,3,4-oxadiazole derivatives. The compounds (7a-o) were synthesized and characterized well by using conventional methods. The compounds, 7b and 7m were reconfirmed through single crystal XRD analysis. The synthesized compounds (7a-o) were evaluated their antiproliferative activities against MCF-7 and MDA-MB-453. Furthermore, Lipinski's rule of five and pharmacokinetic properties were predicted for the test compounds. These results demonstrate that the compounds 7b and 7d exhibit more potent cytotoxicity and 7d exhibits dose-dependent activity and reduced cell viability. Further, the mechanism of action for the induced apoptosis was observed through morphological changes and western blotting analysis. These findings may furnish the lead for further development.

In silico Molecular Modelling of Selected Natural Ligands and their Binding Features with Estrogen Receptor Alpha.

BACKGROUND: Breast cancer is one of the most common cancers diagnosed among women. It is now recognized that two receptors mediate estrogen action and the presence of estrogen receptor alpha (ERα) correlates with better prognosis and the likelihood of response to hormonal therapy. ERα is an attractive target for the treatment of breast cancer. Most of the drugs currently used for the breast cancer treatment have numerous side effects and they are often unsuccessful in removing the tumour completely. Hence, we focused on natural compounds like flavonoids, polyphenols, etc. which do not exhibit any high toxic effects against normal cells. OBJECTIVES: To identify the potential natural inhibitors for BCa through an optimised in silico approach. METHODS: Structural modification and molecular docking-based screening approaches were imposed to identify the novel natural compounds by using Schrödinger (Maestro 9.5). The Qikprop v3.5 was used for the evaluation of important ADME parameters and its permissible ranges. Cytotoxicity of the compounds was evaluated by MTT assay against MCF-7 Cell lines. RESULTS: From the docking studies, we found that the compounds, Myricetin, Quercetin, Apigenin, Luteolin and Baicalein showed the highest Glide Scores -10.78, -9.48, -8.92, -8.87 and -8.82 kcal mol-1 respectively. Of these, Luteolin and Baicalein showed the significant IC50 values (25 ± 4.0 and 58.3 ± 4.4 µM, respectively) against MCF-7 cell line. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. CONCLUSION: We mainly focused on in silico study to dock the compounds into the human estrogen receptor ligand binding domain (hERLBD) and compare their predicted binding affinity with known antiestrogens. Myricetin, Quercetin, Apigenin, Luteolin and Baicalein were identified as the most promising among all. Of these, Luteolin and Baicalein showed significant anticancer activities against MCF-7 cell line. These findings may provide basic information for the development of anti-breast cancer agents.

Phytochemical screening, antioxidant, antityrosinase, and antigenotoxic potential of Amaranthus viridis extract.

OBJECTIVE: Amaranthus viridis (Amaranthaceae) widely distributed all over the world, growing under a wide range of climatic conditions and has been utilized as a medicinal herb in traditional Ayurvedic medicine as antipyretic agents, also for the treatment of inflammation, ulcer, diabetic, asthma and hyperlipidemia. The aim of the study was designed to evaluate the chemical composition and antioxidant and biological properties of different fractions obtained from A. viridis. MATERIALS AND METHODS: Four different extracts of A. viridis were prepared using aqueous, methanol, chloroform, and hexane and investigated their antioxidant potential using free radical scavenging activities such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and nitric oxide (NO) radical scavenging activity, as well as metal chelating activity. In addition, antityrosinase and antigenotoxicity properties were also evaluated by the standard in vitro methods. Finally, the active methanolic extract (ME) was investigated for identifying the phenolic compounds using UPLC-MS/MS. RESULTS: In the present study, chlorogenic acid, gulonic acid, and kaempferol were found to be the major components responsible for the antioxidant activity of A. viridis extract as evidenced from UPLC-MS/MS. Furthermore, the ME of A. viridis revealed excellent antioxidant activities such as DPPH radical scavenging activity (IC50= 47.23 ± 0.66 µg/mL), NO radical scavenging activity (IC50= 64.33 ± 2.01 µg/mL), hydrogen peroxide (H2O2) radical scavenging activity (IC50= 33.21 ± 3.3 µg/mL), ABTS radical scavenging activity (IC50= 47.61 ± 1.31 µg/mL), metal chelating activity (IC50= 32.1 ± 1.11 µg/mL), as well as lipid peroxidation inhibiting activity (IC50= 112 ± 1.21 µg/mL). Furthermore, ME revealed that the protective effects of extract were observed on H2O2-induced DNA damages with alkaline comet assay. CONCLUSIONS: Taken together, the study concluded that the promising antioxidant capacities of A. viridis extract can further be utilized in various agricultural, pharmaceutical, and food applications.

Garcinia morella fruit, a promising source of antioxidant and anti-inflammatory agents induces breast cancer cell death via triggering apoptotic pathway.

A rapid rise in cancer cases worldwide, especially breast cancer in females, instigates the need for more effective and less side effect causing drugs from natural origin. Thereby, in the present study, Garcinia morella fruit was investigated for antioxidant, anti-inflammatory and anti-breast cancer activity. Preliminary antioxidant and anticancer evaluation of different fractions and crude methanol extract of G. morella fruit suggested chloroform fraction as the bioactive fraction. Time course analysis (by 24 h, 48 h and 72 h) of the bioactive fraction (1.56-25) µg/ml treatment on breast cancer cell lines (MCF7, MDAMB231 and SKBR3) showed dose and time dependent antiproliferative responses. Further, mechanistic studies involving morphological observation and western blotting analysis, revealed its apoptosis inducing effect on breast cancer. P53 dependent up-regulation of Bax and down-regulation of Bcl XL is suggested as the possible pathway of apoptosis followed by MCF7 cells on exposure to the bioactive fraction. The anti-inflammatory assays revealed that it significantly lowered the release of nitrite and TNF-α level of LPS induced RAW 264.7 cells (p < 0.05). Moreover, pre treatment of Carrageenan induced paw edema animals with 20 mg/kg of the bioactive fraction significantly (p < 0.05) inhibited paw inflammation and controlled the cytokine and nitrite levels of the edema induced rat. Its main bioactive component was identified to be Garcinol by UHPLC and ESI-MS/MS. Thereby, this study clearly reflects that G. morella fruit is a valuable antioxidant and anti-inflammatory gift of nature with the potential to be used against breast cancer. This is also the first report of isolation of bioactive compound Garcinol from G. morella fruit.

Iminoenamine based novel androgen receptor antagonist exhibited anti-prostate cancer activity in androgen independent prostate cancer cells through inhibition of AKT pathway.

Treatment by androgen receptor (AR) antagonists is one of the regimens for prostate cancer. The prolonged treatment with AR antagonist leads to the expression of point mutation in the ligand binding domain of the AR. This point mutation causes resistance to AR antagonist by converting them into an agonist. The T887A mutated AR was frequently expressed in androgen independent prostate cancer (AIPC) patients. Through literature survey and molecular modelling, we have identified a novel AR antagonist having a bulky ß-iminoenamine BF2 complex scaffold. The tested and standard ligands were screened in AR positive (LNCaP, MCF-7 and MDA-MB-453), AR negative (PC3), and non-cancerous (3T3) cell lines through anti-proliferation assay. The ligand, ARA3 was the most potent molecule among all the tested ligands and was 7.6 folds selective for AR positive cell lines. The mechanism of anti-prostate cancer activity of ARA3 was confirmed by western blot, qPCR, and apoptotic assays in LNCaP (T887A positive AR) cells. Structural activity relationship was derived by correlating the in-vitro and in-silico data. Consequently, we have identified the essential functional groups that could prevent the resistance concerning mutant AR. The ARA3 induces the apoptosis in AIPC cells by preventing the AR mediated activation of AKT pathway. The bicalutamide did not induce the apoptosis because it failed to prevent the AR mediated activation of AKT.

Design, synthesis and biological evaluation of 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives as anti-prostate cancer agents.

The structural modification and molecular docking-based screening approaches on thiazole-based isoindolinediones were imposed to find the novel 2-(4-phenylthiazol-2-yl) isoindoline-1,3-dione derivatives. The best fit compounds (6a-n) were synthesized and evaluated their antiproliferative activities on the prostate cancer cell lines (PC-3 & LNCaP). Among them, the compound, 6m exhibited good activity, particularly on LNCaP (IC50=5.96±1.6µM), moderately active against PC-3 cell lines as compared to bicalutamide. The compound, 6m decreased the androgen-mediated transcription of ARE-mRNA in PSA, TMPRSS2, c-myc and cyclin D1 than R-bicalutamide. The compounds, 6e and 6f were reconfirmed through single crystal XRD analysis. The ADME profiling of the test compounds was evaluated to find the drug-likeness and pharmacokinetic parameters. These findings may provide vital information for the development of anti-prostate cancer agents.

Recent development of targeted approaches for the treatment of breast cancer.

Breast cancer is the most prominent cause of cancer death in women worldwide. The highlights of this review are to provide an overview of the targeted therapeutic agents, challenges with metastatic breast cancer (MBCa), mechanisms of action through Hedgehog/Gli 1 signaling pathway and future prospective. Over a decade of success, several drugs have been approved and are in the advanced stages of clinical trials that target the receptors such as estrogen receptor, growth factor receptor, receptor activator of nuclear factor kappa-B, etc. Currently, several monoclonal antibodies are also used for the treatment of breast cancer. Advances in understanding tumor biology, particularly signaling pathways such as Notch signaling pathway, Hedgehog/Gli 1 signaling pathway, and inhibitors are considered to be important for bone metastasis. These studies may provide vital information for the design and development of new strategies with respect to efficacy, reduction of the side effects, and treatment strategies.

In vitro and In vivo Antioxidant, Anti-hyperlipidemic Properties and Chemical Characterization of Centella asiatica (L.) Extract.

The study aimed to identify the phenolic compounds present in Centella asiatica (L.) (C. asiatica) extract and evaluate the respective antioxidant potential as well as its cholesterol-lowering effects in the experimental animal model. Herein, the antioxidant potential of extracts was assessed by its free radical scavenging activity such as 2, 2-diphenyl -1- picrylhydrazyl as well as reducing capability. The anti-hyperlipidemic effects of C. asiatica extract (CAE) were evaluated in high cholesterol-fed (HCF) rats for 4 weeks, where different concentrations of extracts (0.25, 0.5, and 1 g/kg/day) were orally administrated daily. Lipid and antioxidant profiles, including total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and superoxide dismutase (SOD), together with the indices of hepatic functions were also examined. C. asiatica revealed excellent free radical scavenging activity as revealed by 2-2- diphenyl-1-picryl-hydrazyl (DPPH) assay, with the IC50 values (9.62 ± 0.88 µg/mL). Furthermore, C. asiatica extracts and fenofibrate remarkably lowered the level of TC, TG, LDL-C, and showed elevated levels of HDL-C, SOD. The histopathological observations further demonstrated clear differentiation and structural changes in liver of HCF and CAE treated group. Furthermore, gulonic acid, ferulic acid, kaempferol, chlorogenic acid, and asiatic acid were identified to be the major components which might be responsible for the antioxidant activity of the C. asiatica extract as evidenced from an ultra-high performance liquid chromatography-mass spectrometer. Taken together, these results signifies the excellent antioxidant and anti-hyperlipidemic properties of C. asiatica leaf extracts, which might be useful for the treatment of oxidative-stress related diseases such as hyperlipidemia.

Rapid screening and identification of phenolic antioxidants in Hydrocotyle sibthorpioides Lam. by UPLC-ESI-MS/MS.

The aim of the study was to identify the phenolic compounds present in Hydrocotyle sibthorpioides (HS), Centella asiatica (CA) and Amaranthus viridis (AV) extracts and investigate their respective antioxidant activities. Herein, an ultra-high pressure liquid chromatography-mass spectrometer (UPLC-MS/MS) analytical method has been developed for the separation, and systematic characterization of the phenolic compounds in HS, CA and AV extracts and was compared along with ten standard phenolic compounds. Additionally, in vitro antioxidant activity of the phenolic compounds was also determined. The HS extract revealed excellent antioxidant activity such as 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (IC50=19.7 ± 1.2 µg/mL), total reduction capability (0.169 ± 0.003 at 100 µg/mL), nitric oxide radical scavenging activity (IC50=39.33 ± 3.2 µg/mL), metal chelating activity (IC50=56.51 ± 3.6 µg/mL) and inhibition of lipid peroxidation (IC50=12.34 ± 2.3 µg/mL) as compared to CA and AV extracts. Furthermore, catechin, epicatechin, quercetin and chlorogenic acid were found to be the major components responsible for the antioxidant activity of the HS extract as evidenced from UPLC-MS/MS. Taken together, this study demonstrates the promising antioxidant properties of the HS extract, which can further be utilized in various pharmaceutical, food, and agricultural applications.