AIM OF THE STUDY: This review is an attempt to assess the anti-inflammatory activity of Polyalthia species by giving critical appraisal and establishing evidences of their traditional uses. Moreover this review will highlight the lead compounds for future drug development that can serve as a potential anti-inflammatory drug with comparative efficacy and minimum side effects.
MATERIALS AND METHODS: An extensive literature review, focusing the anti-inflammatory potential of Polyalthia species was conducted using the following databases: PubMed, ScienceDirect, SpringerLink, Ovid, Scopus and ProQuest, as well as the locally available books, journals and relevant documents. The reference lists of retrieved papers were also searched for additional studies.
RESULTS: The Polyalthia species have shown significant anti-inflammatory activity through various mechanism of action. The most significant anti-inflammatory mechanism includes the inhibition of nuclear factor kappa B (NF-κB), prostaglandins (PGs), pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS). The data suggests that hydroxycleroda-3,13-dien-15,16-olide and 16-oxocleroda-3,13-dien-15-oic acid, quercetin, rutin, spinasterol, α-spinasterol, goniothalamin and (-)-5-hydroxygoniothalamin are the most potent anti-inflammatory compounds from Polyalthia species with comparable IC50 with positive controls.
CONCLUSIONS: Numerous pharmacological studies have supported the use of Polyalthia species against pain, rheumatic fever, haemorrhages and inflammation in traditional medicine. Flavonoids, diterpenoids, sterols and styrylpyrones from genus Polyalthia are the most significant class of compounds with potent anti-inflammatory activity. Secondary metabolites from these classes should be brought into further research to fill the gaps of knowledge in pharmacokinetics, pharmacodynamics, bioavailability, and toxicity in order to convert the pre-clinical results into clinical data for further investigation.
METHODS: E. elatior flowers grown in three different locations of Malaysia (Kelantan, Pahang and Johor), were investigated for differences in their content of secondary metabolites (total phenolics [TPC], total flavonoids [TFC], and total tannin content [TTC]) as well as for their antioxidant, anticancer, and antibacterial properties. Phenolic acids and flavonoids were isolated and identified using ultra-high performance liquid chromatography (UHPLC). Ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used to evaluate the antioxidant activities. The anticancer activity of extracts was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.
RESULTS: When extracted with various solvents (aqueous and ethanolic), samples from the different locations yielded significantly different results for TPC, TFC, and TTC as well as antioxidant activity. Aqueous extracts of E. elatior flowers collected from Kelantan exhibited the highest values: TPC (618.9 mg/100 g DM), TFC (354.2 mg/100 g DM), TTC (129.5 mg/100 g DM), DPPH (76.4 %), and FRAP (6.88 mM of Fe (II)/g) activity with a half-maximal inhibitory concentration (IC50) of 34.5 μg/mL compared with extracts of flowers collected from the other two locations. The most important phenolic compounds isolated in this study, based on concentration, were: gallic acid > caffeic acid > tannic acid > chlorogenic acid; and the most important flavonoids were: quercetin > apigenin > kaempferol > luteolin > myricetin. Extracts of flowers from Kelantan exhibited potent anticancer activity with a IC50of 173.1 and 196.2 μg/mL against the tumor cell lines MCF-7 and MDA-MB-231 respectively, compared with extracts from Pahang (IC50 = 204.5 and 246.2 μg/mL) and Johor samples (IC50 = 277.1 and 296.7 μg/mL). Extracts of E. elatior flowers also showed antibacterial activities against Staphylococcus aureus, Bacillus subtilis, Listeria monocytogenes, Escherichia coli, Salmonella typhimurium, and Pseudomonas aeruginosa with minimal inhibitory concentrations (MIC) ranging from 30 to >100 μg/mL.
CONCLUSIONS: In general, therefore, based on the potent antioxidant and anticancer activity of flower extracts, it appears that E. elatior grown in the North-east of Malaysia (Kelantan) is a potential source of therapeutic compounds with anti-cancer activity.
OBJECTIVE: Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to overcome these biopharmaceutical drawbacks.
METHODS: Curcumin liposomes with/without quercetin were prepared by lipid hydration technique. The liposomes were characterized for their particle size, zeta potential, surface morphology, drug loading and release characteristics. The toxicity of the liposomes were evaluated in-vitro and their invivo efficacy were tested against Dalton's ascites lymphoma in mice.
RESULTS: Liposomes designed showed particle size of 261.8 ± 2.1 nm with a negative zeta potential of -22.6±1.6 mV. Quercetin decorated liposomes were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to those without quercetin. Similarly, the presence of quercetin also contributed to enhanced cytotoxicity of the liposomal formulation towards HT-29 cells and HCT-15 cells.
CONCLUSION: Newer liposomal design exhibited promising potential to emerge as alternative anticancer therapeutics.
METHODS: Female rats were treated with quercetin (10, 25 and 50mg/kg/day) subcutaneously beginning from day-1 pregnancy. Uterus was harvested at day-4 (following three days quercetin treatment) for morphological, ultra-structural, protein and mRNA expressional changes and plasma sex-steroid levels analyses. In another cohort of rats, implantation rate was determined at day-6 (following five days quercetin treatment).
RESULTS: Administration of 50mg/kg/day quercetin causes increased in uterine fluid volume and CFTR expression but decreased in γ-ENaC, AQP-5, AQP-9 claudin-4, occludin, E-cadherin, integrin αnβЗ, FGF, Ihh and Msx-1expression in the uterus. Pinopodes were poorly develop, tight junctions appear less complex and implantation rate decreased. Serum estradiol levels increased but serum progesterone levels decreased.
CONCLUSIONS: Interference in the fluid volume and receptivity development of the uterus during peri-implantation period by quercetin could adversely affect embryo implantation.