Anti-Cancer Studies Of Garcinia Mangostana L. And Syzygium Campanulatum Korth Towards Colorectal Carcinoma

This study aims to investigate the anti-angiogenic and anti-colon cancer activity of the extracts and isolates of Syzygium campanulatum and Garcinia mangostana. And to prepare G. mangostana toluene extract in nanoparticles and α-mangostin in solid dispersions in order to improve their aqueous solubility. Phytochemical analysis of S. campanulatum extracts reveals relatively high concentration of betulinic acid (BA) and polyphenols. BA fraction from S. campanulatum showed potent cytotoxicity on colon cancer cells by inducting the mitochondrial pathway of apoptosis. Extracts also showed potent inhibition of angiogenesis in several in vitro and in vivo models, by inhibiting the expression of vascular endothelial growth factor and inhibiting migration of human endothelial cells. The methanolic extract also inhibits tumor growth in xenograft tumor model with inhibition of intratumor blood vessels

Analysis of L-citrulline and L-arginine in Ficus deltoidea leaf extracts by reverse phase high performance liquid chromatography

Ficus deltoidea (FD) is one of the native plants widely distributed in several countries in Southeast Asia. Previous studies have shown that FD leaf possess antinociceptive, wound healing and antioxidant properties. These beneficial effects have been attributed to the presence of primary and secondary metabolites such as polyphenols, amino acids and flavonoids. Objective: The aim was to develop a reverse phase high-performance liquid chromatography method with ultraviolet detection that involves precolumn derivatisation with O-phthaladehyde for simultaneous analysis of two amino acids L-citrulline and L-arginine in FD leaf extracts. Materials and Methods: An isocratic elution program consisting of methanol: acetonitrile: Water at 45:45:10 v/v (solvent A) and 0.1 M phosphate buffer pH 7.5 (solvent B) at A: B v/v ratio of 80:20 on Zorbax Eclipse C18 SB-Aq column (250 × 4.6 mm, 5 μm) were used. The flow rate was set at 1 ml/min and detection was carried out at 338 nm with 30 min separation time. Results: Good linearity for L-citrulline and L-arginine was obtained in the range 0.1-1000 μg/ml at R2 ≥ 0.998. The limit of detection and limit of quantification values for both L-citrulline and L-arginine were 1 and 5 μg/ml, respectively. The average of recoveries was in the range 94.94-101.95%, with relative standard deviation (%RSD) less than 3%. Intra- and inter-day precision was in the range 96.36-102.43% with RSD less than 2%. Conclusion: All validation parameters of the developed method indicate the method is reliable and efficient for simultaneous determination of L-citrulline and L-arginine for routine analysis of FD

PHARMACOKINETICS AND BIOAVAILABILITY OF ORTHOSIPHON STAMINEUS ETHANOLIC EXTRACT AND ITS-NANO LIPOSOMES IN SPRAGUE-DAWLEY RATS

Objective: This study aimed to perform pharmacokinetic profile of rosmarinic acid (RA), sinensitin (SIN), eupatorin (EUP) and 3΄-hydroxy-5,6,7,4΄-tetramethoxyflavone (TMF) in Orthosiphon stamineus ethanolic extract (OS-E) and its nanoliposomes (OS-EL) after oral and intravenous administration in Sprague-Dawley rat's plasma by developing and validating a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection.Methods: An isocratic elution program consisting of methanol: tetrahydrofuran: water (0.1% H3PO4) mixture in the volume ratio 55: 5: 40 on Nucleosil C18 column (250 × 4.6 mm internal diameter × 5 µm particles size) was applied. The current study followed a two-ways crossover study design. OS-E and OS-EL were administered orally at 1000 and 500 mg/kg, respectively. They were also administered intravenously at 250 mg/kg via the tail vein.Results: The HPLC-UV method was successfully developed and validated for simultaneous determination of major chemical constituent from OS-E and OS-EL in rat's plasma. The method recorded the mean recoveries from extraction were between 91.39 and 100.32%. With regards to the intravenous administration of OS-EL, all four marker compounds appeared to be poorly distributed and cleared slowly from the body compared to OS-E. Whilst in oral administration of OS-EL, the bioavailability of all marker compounds were higher than OS-E due to higher solubility of encapsulation in phospholipids.Conclusion: The higher solubility and bioavailability of OS-EL may contribute to encapsulation in phospholipids

Development of Polymeric Nanoparticles of Garcinia mangostana Xanthones in Eudragit RL100/RS100 for Anti-Colon Cancer Drug Delivery

Xanthones are a group of oxygenated heterocyclic compounds with anticancer properties, but poor aqueous solubility and low oral bioavailability hinder their therapeutic application. This study sought to prepare a xanthones extract (81

Flavonoids-Rich Orthosiphon stamineus Extract as New Candidate for Angiotensin I-Converting Enzyme Inhibition: A Molecular Docking Study

This study aims to evaluate the in vitro angiotensin-converting enzyme (ACE) inhibition activity of different extracts of Orthosiphon stamineus (OS) leaves and their main flavonoids, namely rosmarinic acid (RA), sinensetin (SIN), eupatorin (EUP) and 30-hydroxy-5,6,7,40-tetramethoxyflavone (TMF). Furthermore, to identify possible mechanisms of action based on structure–activity relationships and molecular docking. The in vitro ACE inhibition activity relied on determining hippuric acid (HA) formation from ACE-specific substrate (hippuryl-histidyl-leucine (HHL)) by the action of ACE enzyme. A High Performance Liquid Chromatography method combined with UV detection was developed and validated for measurement the concentration of produced HA. The chelation ability of OS extract and its reference compounds was evaluated by tetramethylmurexide reagent. Furthermore, molecular docking study was performed by LeadIT-FlexX: BioSolveIT’s LeadIT program. OS ethanolic extract (OS-E) exhibited highest inhibition and lowest IC50 value (45.77 � 1.17 �g/mL) against ACE compared to the other extracts. Among the tested reference compounds, EUP with IC50 15.35 � 4.49 �g/mL had highest inhibition against ACE and binding ability with Zn (II) (56.03% � 1.26%) compared to RA, TMF and SIN. Molecular docking studies also confirmed that flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. In this study, we have demonstrated that changes in flavonoids active core affect their capacity to inhibit ACE. Moreover, we showed that ACE inhibition activity of flavonoids compounds is directly related to their ability to bind with zinc ion in the active site of ACE enzyme. It was also revealed that OS extract contained high amount of flavonoids other than RA, TMF, SIN and EUP. As such, application of OS extract is useful as inhibitors of ACE

Isolation, Characterization, Crystal Structure Elucidation, and Anticancer Study of Dimethyl Cardamonin, Isolated from Syzygium campanulatum

Syzygium campanulatum Korth is an equatorial, evergreen, aboriginal shrub of Malaysia. Conventionally it has been used as a stomachic. However, in the currently conducted study dimethyl cardamonin or 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC) was isolated from S. campanulatum Korth, leaf extract. The structural characterization of DMC was carried out by making use of various techniques including UV, IR, NMR spectral followed by LC-MS, and X-ray crystallographic techniques. For determining the purity of compound, highly effective techniques including TLC, HPLC, and melting point were used. The cytotoxicity of DMC and three different extracts of S. campanulatum was evaluated against human colon cancer cell line (HT-29) by three different assays. DMC and ethanolic extract revealed potent and dose-dependent cytotoxic activity on the cancer cell line with IC50 12.6 and 90.1 µg/mL, respectively. Quite astonishingly to our knowledge, this is the very first report on S. campanulatum as being a rich source (3.5%) of DMC, X-ray crystallography, and anticancer activity on human colon cancer cells

α-Mangostin Enhances Betulinic Acid Cytotoxicity and Inhibits Cisplatin Cytotoxicity on HCT 116 Colorectal Carcinoma Cells

Despite the progress in colon cancer treatment, relapse is still a major obstacle. Hence, new drugs or drug combinations are required in the battle against colon cancer. α-Mangostin and betulinic acid (BA) are cytotoxic compounds that work by inducing the mitochondrial apoptosis pathway, and cisplatin is one of the most potent broad spectrum anti-tumor agents. This study aims to investigate the enhancement of BA cytotoxicity by α-mangostin, and the cytoprotection effect of α-mangostin and BA on cisplatin-induced cytotoxicity on HCT 116 human colorectal carcinoma cells. Cytotoxicity was investigated by the XTT cell proliferation test, and the apoptotic effects were investigated on early and late markers including caspases-3/7, mitochondrial membrane potential, cytoplasmic shrinkage, and chromatin condensation. The effect of α-mangostin on four signalling pathways was also investigated by the luciferase assay. α-Mangostin and BA were more cytotoxic to the colon cancer cells than to the normal colonic cells, and both compounds showed a cytoprotective effect against cisplatin-induced cytotoxicity. On the other hand, α-mangostin enhanced the cytotoxic and apoptotic effects of BA. Combination therapy hits multiple targets, which may improve the overall response to the treatment, and may reduce the likelihood of developing drug resistance by the tumor cells. Therefore, α-mangostin and BA may provide a novel combination for the treatment of colorectal carcinoma. The cytoprotective effect of the compounds against cisplatin-induced cytotoxicity may find applications as chemopreventive agents against carcinogens, irradiation and oxidative stress, or to neutralize cisplatin side effects

Solid dispersions of a-mangostin improve its aqueous solubility through self-assembly of nanomicelles

α-Mangostin is an oxygenated heterocyclic xanthone with remarkable pharmacological properties, but poor aqueous solubility and low oral bioavailability hinder its therapeutic application. This study sought to improve the compound's solubility and study the mechanism underlying solubility enhancement. Solid dispersions of α-mangostin were prepared in polyvinylpyrrolidone (PVP) by solvent evaporation method and showed substantial enhancement of α-mangostin's solubility from 0.2 ± 0.2 μg/mL to 2743 ± 11 μg/mL. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated interaction between α-mangostin and PVP. Transmission electron microscopy and dynamic light scattering showed self-assembly of round anionic nanomicelles with particle size in the range 99–127 nm. Powder X-ray diffraction indicated conversion of α-mangostin from crystalline into amorphous state, and scanning electron microscopy showed the presence of highly porous powder. Studies using the fluorescent probe pyrene showed that the critical micellar concentration is about 77.4 ± 4 μg/mL. Cellular uptake of nanomicelles was found to be mediated via endocytosis and indicated intracellular delivery of α-mangostin associated with potent cytotoxicity (median inhibitory concentration of 8.9 ± 0.2 μg/mL). Improved solubility, self-assembly of nanomicelles, and intracellular delivery through endocytosis may enhance the pharmacological properties of α-mangostin, particularly antitumor efficacy

Retraction Note: In vitro and in vivo anti-colon cancer effects of Garcinia mangostana xanthones extract

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/1472-6882-12-104