ANTICANCER ACTIVITY OF GARCINIA MORELLA CHLOROFORM FRACTION AND ITS ACTIVE COMPOUND GARCINOL ON NEUROBLASTOMA

Objective: The aim of the present study is to evaluate the anticancer activity of G. morella fruit chloroform fraction and its isolated bioactive molecule garcinol on neuroblastoma cell line (SH-SY5Y). Method: Methanol extraction was performed for the G. morella fruits through cold maceration and further fractionated with chloroform. The presence of Garcinol was confirmed by measuring the melting point. Further, the bioactive chloroform fraction and pure Garcinol was tested for anticancer activity against SH-SY5Y cells through MTT assay. Result: The present study reveals the anticancer ability of bioactive chloroform fraction of G. morella fruit and its active molecule garcinol. Conclusion: G. morella fruit and its bioactive compound Garcinol have significant activity against neuroblastoma. This study opens an avenue to further elucidate the mechanism of action and development of alternative treatment of this dreaded disease.Â

A REVIEW ON ANTI-DIABETIC POTENTIAL OF GENUS SOLANUM (SOLANACEAE)

The Solanum genus (Solanaceae family) comprised of one thousand five hundred species and most of the members of the genus are widely used as food and traditional medicine. Diabetes mellitus is a common and serious metabolic disorder throughout the world. Traditionally used medicinal plants play an important role as alternative medicine due to less toxic effects and cost. The aim of this review is to report anti-diabetic potential of plants of Solanum genus on the basis of the secondary data published. This will help in identifying the state of anti-diabetic knowledge in regards to this genus and to propose future research priorities. The major scientific database including Science direct, SciFinder and Google scholar were searched for information on Solanum genus using various keyword combinations. A total of eight Solanum species were reported in literature to have anti-diabetic property. Some of the plant species reported to modify different complications of diabetes like hyperlipidemia, oxidative stress in diseased animals. On the basis of anti-diabetic and other related activities, plants of Solanumgenus are the most promising plant species to develop as efficacious and safer medicines for diabetes and its complications. Considering the present status of this disease and potential of Solanumgenus, there ismuch scope of studying this genus thoroughly, which may resultin development of affordable, efficacious and safer remedies against the silent killer disease. Key words: Solanum genus, anti-diabetic activity, hyperlipidemia, oxidative stress, methyl caffeate.Â

Targeted Oral Delivery of Paclitaxel Using Colostrum-Derived Exosomes

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small-cell lung cancer (NSCLC) is the most common type accounting for 84% of all lung cancers. Paclitaxel (PAC) is a widely used drug in the treatment of a broad spectrum of human cancers, including lung. While efficacious, PAC generally is not well tolerated and its limitations include low aqueous solubility, and significant toxicity. To overcome the dose-related toxicity of solvent-based PAC, we utilized bovine colostrum-derived exosomes as a delivery vehicle for PAC for the treatment of lung cancer. Colostrum provided higher yield of exosomes and could be loaded with higher amount of PAC compared to mature milk. Exosomal formulation of PAC (ExoPAC) showed higher antiproliferative activity and inhibition of colony formation against A549 cells compared with PAC alone, and also showed antiproliferative activity against a drug-resistant variant of A549. To further enhance its efficacy, exosomes were attached with a tumor-targeting ligand, folic acid (FA). FA-ExoPAC given orally showed significant inhibition (\u3e50%) of subcutaneous tumor xenograft while similar doses of PAC showed insignificant inhibition. In the orthotopic lung cancer model, oral dosing of FA-ExoPAC achieved greater efficacy (55% growth inhibition) than traditional i.v. PAC (24–32% growth inhibition) and similar efficacy as i.v. Abraxane (59% growth inhibition). The FA-ExoPAC given i.v. exceeded the therapeutic efficacy of Abraxane (76% growth inhibition). Finally, wild-type animals treated with p.o. ExoPAC did not show gross, systemic or immunotoxicity. Solvent-based PAC caused immunotoxicity which was either reduced or completely mitigated by its exosomal formulations. These studies show that a tumor-targeted oral formulation of PAC (FA-ExoPAC) significantly improved the overall efficacy and safety profile while providing a user-friendly, cost-effective alternative to bolus i.v. PAC and i.v. Abraxane

A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity

Artesunate (ART), a plant based semi-synthetic antimalarial drug, is emerging as a new class of effective cancer chemotherapeutics. However, the dosage of ART required to have an anti-cancer effect on cancer cells is greater than that needed to exterminate malarial parasites. The goal of this study was to develop an effective combination therapy to reduce the dose-dependent side effects of ART both in vitro and in vivo. In our study, 4-phenylbutyrate (4-PB), a histone deacetylase inhibitor (HDAC), exhibited significant synergistic induction of apoptosis in MCF-7 cells in combination with ART. The IC50 of ART decreased significantly from 55.56 ± 5.21 µM to 24.71 ± 3.44 µM in MCF-7 cells. ART treatment increased cellular oxidative stress, and the resulting generation of intracellular reactive oxygen species (ROS) caused extensive DNA damage in the cell. The extent of ROS production and cell cycle arrest were further enhanced by 4-PB treatment. In further investigation, we found that 4-PB attenuated mRNA expression of crucial DNA damage response (DDR) elements of the nonhomologous end-joining (NHEJ) pathway, consequently enhancing the DNA damaging effect of ART. Furthermore, the combination therapy resulted in improvement in the life expectancy of the treated mice and a prominent reduction in tumour volume without interfering with the normal biochemical, haematological and histological parameters of the mice. Overall, our study revealed a novel combination therapy in which 4-PB potentiated the cytotoxicity of ART synergistically and provided a promising combination drug for effective cancer therapy

A Histone Deacetylase Inhibitor Manifests Synergistic Interaction with Artesunate by Suppressing DNA Repair Activity

Artesunate (ART), a plant based semi-synthetic antimalarial drug, is emerging as a new class of effective cancer chemotherapeutics. However, the dosage of ART required to have an anti-cancer effect on cancer cells is greater than that needed to exterminate malarial parasites. The goal of this study was to develop an effective combination therapy to reduce the dose-dependent side effects of ART both in vitro and in vivo. In our study, 4-phenylbutyrate (4-PB), a histone deacetylase inhibitor (HDAC), exhibited significant synergistic induction of apoptosis in MCF-7 cells in combination with ART. The IC50 of ART decreased significantly from 55.56 ± 5.21 µM to 24.71 ± 3.44 µM in MCF-7 cells. ART treatment increased cellular oxidative stress, and the resulting generation of intracellular reactive oxygen species (ROS) caused extensive DNA damage in the cell. The extent of ROS production and cell cycle arrest were further enhanced by 4-PB treatment. In further investigation, we found that 4-PB attenuated mRNA expression of crucial DNA damage response (DDR) elements of the nonhomologous end-joining (NHEJ) pathway, consequently enhancing the DNA damaging effect of ART. Furthermore, the combination therapy resulted in improvement in the life expectancy of the treated mice and a prominent reduction in tumour volume without interfering with the normal biochemical, haematological and histological parameters of the mice. Overall, our study revealed a novel combination therapy in which 4-PB potentiated the cytotoxicity of ART synergistically and provided a promising combination drug for effective cancer therapy

Polyethylene Glycol-Encapsulated Histone Deacetylase Inhibitor Drug-Composite Nanoparticles for Combination Therapy with Artesunate

Combination drug therapy has become an effective clinical practice for cancer treatment because of low cytotoxicity by the synergistic effect of each medicine. Luminescent Au nanoclusters (Au NCs) were formulated into spherical polyethylene glycol (PEG)–Au NC-encapsulated drug–sodium butyrate (NaB) composite nanoparticles (PEG–Au NC–NaB-NPs) in the presence of PEG and NaB. Their effect on cancer cells was investigated using bio imaging, unravelling the mechanism of the endocytosis pathway and combination therapeutic interventions with a plant-based antimalarial drug artesunate (ART). PEG–Au NC–NaB-NPs showed bright red luminescence in the lysosomal compartment of the cells upon uptake predominantly through a caveolae-mediated pathway. Combination of PEG–Au NC–NaB-NPs with ART displayed enhanced therapeutic activity at a reduced dose compared to its individual doses and revealed heightened synergistic activity as identified from the combination index. The mechanism of synergism revealed elevated generation of reactive oxygen species with both NaB and ART, which disrupts mitochondrial membrane potential as evident from JC-1 staining. Remarkably, the histone deacetylase (HDAC) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay enlightened the role of NaB and ART in HDAC inhibition and DNA fragmentation, respectively. Thus, induction of apoptosis with the synergistic effect of both NaB and ART with its meticulous mechanism makes it a promising tool for combinational cancer therapy. In vivo activity of the NPs was evaluated on Daltons lymphoma ascites bearing mice, which exhibited significant reduction of tumor volume and viable tumor cells with a prolonged life span

Protective effect of bioactivity guided fractions of Ziziphus jujuba Mill. root bark against hepatic injury and chronic inflammation via inhibiting inflammatory markers and oxidative stress

The tribal communities of North Eastern India rely on herbal medicine to cure various disease conditions. Ziziphus jujuba Mill. (Rhamnaceae) is one of such medicinal plants used for curing liver ailments, insomnia, anemia, diarrhea, diabetic complications, cancer and loss of appetite. The present study was aimed to describe the protective ability of Z. jujuba root bark against hepatic injury and chronic inflammation. Bioactivity guided fractionation of Z. jujuba methanol extract (ZJME) was performed using different solvents of increasing polarity viz. hexane (ZJHF), chloroform (ZJCF), ethyl acetate (ZJEAF), water (ZJWF) and residue (ZJMR). In vitro antioxidant results revealed that both ZJME and ZJWF possess strong antioxidant activity among all the fractions and mother extract tested. Further, ZJME and ZJWF showed significant protection against CCl4 intoxicated HepG2 cell lines by means of increased cell viability and decreased LDH levels compared to control group. ZJME at 200, 400 mg/kg and ZJWF at 50, 100 mg/kg inhibited the lipid peroxidation and significantly restored the liver function markers (AST, ALT, ALP, LDH, SOD and CAT) and cytokine levels (TNF-α, Il-1β and Il-10) in CCl4 induced acute liver damage in rats. All the results were comparable with standard drug silymarin which was further confirmed by histopathology analysis of liver. Similarly, inflammation and increase inflammatory cytokines levels of carrageenan induced paw edema in rats have been refurbished to normal levels on par with the standard drug indomethacin. ZJWF demonstrated potent response than ZJME in all the biological tests conducted. The results of the study signify the ability of Z. jujuba root bark as good therapeutic agent for liver toxicity and chronic inflammation