A new flavonoid, dihydroglychalcone-A, was isolated from the leaves extract of Glycosmis chlorosperma in addition to two known sulphur-containing amides, dambullin and gerambullin. The structure of the new compound was assigned as 2'-hydroxy-4,6'-dimethoxy-3',4'-(2",2"-dimethylpyrano)dihydrochalcone. The extract of the leaves was also found to exhibit antimicrobial and cytotoxic activities.
Azadirachta indica has long been used in traditional medicine. This study focused on isolation and characterisation of active ingredients in the extract, its fractions (NF-EA, NF-AQ, NF-G) and its effect on the cholesterol absorption activity. The NF-EA fraction was identified by marker compounds by LC-ESI-QTOF/MS. Cholesterol absorption activity was performed by measuring the solubility and size of cholesterol micelles. The intestinal motility was also examined by isolated rat's ileum to test the contraction. The extract and its fractions consist of flavonoids and phenolic compounds, like quercetin, kaempferol and myricetin. We found that A. indica extract and NF-EA increase cholesterol micelles size, while the extract, NF-AQ, myricetin and quercetin, reduced the solubility of cholesterol in micelles. The extract and quercetin inhibited the contraction induced by KCl up to 29 and 18%, respectively, and also decreased CaCl2-induced contraction. This finding is in support to traditional uses of A. indica as cholesterol-lowering agents and regulator of gastrointestinal motility.
Chalcones are a group of compounds widely distributed in plant kingdom. The aim of this study was to assess the neurite outgrowth stimulatory activity of selected chalcones, namely helichrysetin, xanthohumol and flavokawin-C. Using adherent rat pheochromocytoma (PC12 Adh) cells, the chalcones were subjected to neurite outgrowth assay and the extracellular nerve growth factor (NGF) levels were determined. Xanthohumol (10 μg/mL) displayed the highest (p
The aim of the study was to isolate digestive enzymes inhibitors from Mimosa pudica through a bioassay-guided fractionation approach. Repeated silica gel and sephadex LH 20 column chromatographies of bioactive fractions afforded stigmasterol, quercetin and avicularin as digestive enzymes inhibitors whose IC50 values as compared to acarbose (351.02 ± 1.46 μg mL-1) were found to be as 91.08 ± 1.54, 75.16 ± 0.92 and 481.7 ± 0.703 μg mL-1, respectively. In conclusion, M. pudica could be a good and safe source of digestive enzymes inhibitors for the management of diabetes in future.
In this study the antioxidant and cytotoxicity activity of the Adonidia merrillii fruits were investigated using different solvent polarities (methanol, ethyl acetate and water). The results showed that the total phenolic and flavonoid contents of the methanolic extract was higher compare with other extract with respective values of 17.80 ± 0.45 mg gallic acid equivalents/g dry weight (DW) and 5.43 ± 0.33 mg rutin equivalents/g DW. Beside that The RP-HPLC analyses indicated the presence of gallic acid, pyrogallol, caffeic acid, vanillic acid, syringic acid, naringin and rutin. In the DPPH, NO2 and ABTS scavenging assays, the methanolic extract exhibited higher antioxidant activity as compared to the ethyl acetate and water extracts. The extracts exhibited moderate to weak cytotoxic activity in the assays using human hepatocytes (Chang liver cells) and NIH/3T3 (fibroblasts cell) cell lines. The findings showed the Adonidia merrillii fruit extracts to possess considerable antioxidant and cytotoxicity properties. The fruit, therefore, is a potential candidate for further work to discover antioxidant and cytotoxic drugs from natural sources.
The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components.
A new pyranoflavone, methoxycyclocommunol (1) together with four known flavonoids, artonin F (2), heteroflavanone A (3), cudraflavone C (4) and cyclocommunol (5) were isolated from the bark of Artocarpus integer var. silvestris Corner. Their structures were elucidated through extensive spectroscopic- techniques (UV, IR, MS, 1D-NMR and 2D-NMR) and by comparison with literature data. All the pure compounds were tested for their anti-inflammatory activities by using screening kit and radioimmunoassay methods. In a 15-lipoxygenase (15-LOX) inhibitory assay, compounds 1, 2, 4 and 5 gave weak percentages of inhibition, 16.5, 18.3, 17.6, 10.2%, respectively at the concentration of 100 μM. Compounds 1, 3 and 4, however, showed strong dose- dependent inhibition towards prostaglandin E₂ (PGE₂) production in lipopolysaccharide-induced human whole blood using a radioimmunoassay method with IC₅₀ values of 4.3, 0.8, and 0.07 μM, respectively suggesting that they strongly exhibited cyclooxygenase-2 (COX-2) activity.
Flavonoids represent a major group of polyphenolic compounds. Their capacity to inhibit tumor proliferation, cell cycle, angiogenesis, migration and invasion is substantially responsible for their chemotherapeutic activity against lung cancer. However, their clinical application is limited due to poor aqueous solubility, low permeability and quick blood clearance, which leads to their low bioavailability. Nanoengineered systems such as liposomes, nanoparticles, micelles, dendrimers and nanotubes can considerably enhance the targeted action of the flavonoids with improved efficacy and pharmacokinetic properties, and flavonoids can be successfully translated from bench to bedside through various nanoengineering approaches. This review addresses the therapeutic potential of various flavonoids and highlights the cutting-edge progress in the nanoengineered systems that incorporate flavonoids for treating lung cancer.
The effects of different drying methods (freeze drying, vacuum oven drying, and shade drying) on the phytochemical constituents associated with the antioxidant activities of Z. officinale var. rubrum Theilade were evaluated to determine the optimal drying process for these rhizomes. Total flavonoid content (TFC), total phenolic content (TPC), and polyphenol oxidase (PPO) activity were measured using the spectrophotometric method. Individual phenolic acids and flavonoids, 6- and 8-gingerol and shogaol were identified by ultra-high performance liquid chromatography method. Ferric reducing antioxidant potential (FRAP) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays were used for the evaluation of antioxidant activities. The highest reduction in moisture content was observed after freeze drying (82.97%), followed by vacuum oven drying (80.43%) and shade drying (72.65%). The highest TPC, TFC, and 6- and 8-shogaol contents were observed in samples dried by the vacuum oven drying method compared to other drying methods. The highest content of 6- and 8-gingerol was observed after freeze drying, followed by vacuum oven drying and shade drying methods. Fresh samples had the highest PPO activity and lowest content of flavonoid and phenolic acid compounds compared to dried samples. Rhizomes dried by the vacuum oven drying method represent the highest DPPH (52.9%) and FRAP activities (566.5 μM of Fe (II)/g DM), followed by freeze drying (48.3% and 527.1 μM of Fe (II)/g DM, respectively) and shade drying methods (37.64% and 471.8 μM of Fe (II)/g DM, respectively) with IC50 values of 27.2, 29.1, and 34.8 μg/mL, respectively. Negative and significant correlations were observed between PPO and antioxidant activity of rhizomes. Vacuum oven dried rhizomes can be utilized as an ingredient for the development of value-added food products as they contain high contents of phytochemicals with valuable antioxidant potential.
In the current study, changes in secondary metabolite synthesis and the pharmaceutical quality of sabah snake grass leaves and buds were considered in relation to plant age (1 month, 6 months, and 1 year old). The activity of the enzyme chalcone synthase (CHS, EC 2.3.1.74) was measured, as it is a key enzyme for flavonoid production. Significant differences in total flavonoid (TF) production were observed between the three plant growth periods and the different plant parts. The highest contents of TF (6.32 mg/g dry weight [DW]) and total phenolic (TP) (18.21 mg/g DW) were recorded in 6-month-old buds. Among the flavonoids isolated in this study the most important ones based on concentration were from high to low as follows: catechin > quercetin > kaempferol > luteolin. Production of phenolic acids increased from 1 to 6 months, but after 6 months up to 1 year of age, they decreased significantly. The highest contents of caffeic acid (0.307 mg/g DW) and gallic acid (5.96 mg/g DW) were recorded in 1-year and 6-month-old buds, respectively. The lowest and highest activity of CHS was recorded in 1-month and 6-month-old buds with values of 3.6 and 9.5 nkat/mg protein, respectively. These results indicate that the increment in flavonoids and phenolic acids in 6-month-old buds can be attributed to an increase in CHS activity. The highest 1,1-diphenyl-2-picrylhydrazyl (DPPH) activity was observed in the extract of 1-year-old buds followed by 6-month-old buds, with 50% of free radical scavenging (IC50) values of 64.6 and 73.5 µg/mL, respectively. Interestingly, a ferric reducing antioxidant power (FRAP) assay showed a higher activity in 6-month-old buds (488 μM of Fe(II)/g) than in 1-year-old buds (453 μM of Fe(II)/g), in contrast to the DPPH result. Significant correlations (p < 0.05) were observed between CHS enzyme activity and FRAP activity, TF, catechin, and kaempferol content. Extracts of 6-month-old bud exhibited a significant in vitro anticancer activity against HeLa cancer cells with IC50 value of 56.8 µg/mL. These results indicate that early harvesting of snake grass (6-month-old) may yield increased concentrations of secondary metabolites, which are potent antioxidant compounds.
Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using ³H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE(2) production (IC₅₀ value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB₂ production with IC₅₀ values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC₅₀ values of 24.3 and 24.5 µM, respectively.
Corn silk (Stigma maydis) is an important herb used traditionally by the Chinese, and Native Americans to treat many diseases. It is also used as traditional medicine in many parts of the world such as Turkey, United States and France. Its potential antioxidant and healthcare applications as diuretic agent, in hyperglycemia reduction, as anti-depressant and anti-fatigue use have been claimed in several reports. Other uses of corn silk include teas and supplements to treat urinary related problems. The potential use is very much related to its properties and mechanism of action of its plant's bioactive constituents such as flavonoids and terpenoids. As such, this review will cover the research findings on the potential applications of corn silk in healthcare which include its phytochemical and pharmacological activities. In addition, the botanical description and its toxicological studies are also included.
Cocoa and cocoa products have received much attention due to their significant polyphenol contents. Cocoa and cocoa products, namely cocoa liquor, cocoa powder and chocolates (milk and dark chocolates) may present varied polyphenol contents and possess different levels of antioxidant potentials. For the past ten years, at least 28 human studies have been conducted utilizing one of these cocoa products. However, questions arise on which of these products would deliver the best polyphenol contents and antioxidant effects. Moreover, the presence of methylxanthines, peptides, and minerals could synergistically enhance or reduce antioxidant properties of cocoa and cocoa products. To a greater extent, cocoa beans from different countries of origins and the methods of preparation (primary and secondary) could also partially influence the antioxidant polyphenols of cocoa products. Hence, comprehensive studies on the aforementioned factors could provide the understanding of health-promoting activities of cocoa or cocoa products components.
Continuing our interest in the Uncaria genus, the phytochemistry and the in-vitro α-glucosidase inhibitory activities of Malaysian Uncaria cordata var. ferruginea were investigated. The phytochemical study of this plant, which employed various chromatographic techniques including recycling preparative HPLC, led to the isolation of ten compounds with diverse structures comprising three phenolic acids, two coumarins, three flavonoids, a terpene and an iridoid glycoside. These constituents were identified as 2-hydroxybenzoic acid or salicylic acid (1), 2,4-dihydroxybenzoic acid (2), 3,4-dihydroxybenzoic acid (3), scopoletin or 7-hydroxy-6-methoxy-coumarin (4), 3,4-dihydroxy-7-methoxycoumarin (5), quercetin (6), kaempferol (7), taxifolin (8), loganin (9) and β-sitosterol (10). Structure elucidation of the compounds was accomplished with the aid of 1D and 2D Nuclear Magnetic Resonance (NMR) spectral data and Ultraviolet-Visible (UV-Vis), Fourier Transform Infrared (FTIR) spectroscopy and mass spectrometry (MS). In the α-glucosidase inhibitory assay, the crude methanolic extract of the stems of the plant and its acetone fraction exhibited strong α-glucosidase inhibition activity of 87.7% and 89.2%, respectively, while its DCM fraction exhibited only moderate inhibition (75.3%) at a concentration of 1 mg/mL. The IC50 values of both fractions were found to be significantly lower than the standard acarbose suggesting the presence of potential α-glucosidase inhibitors. Selected compounds isolated from the active fractions were then subjected to α-glucosidase assay in which 2,4-dihydroxybenzoic acid and quercetin showed strong inhibitory effects against the enzyme with IC50 values of 549 and 556 μg/mL compared to acarbose (IC50 580 μg/mL) while loganin and scopoletin only showed weak α-glucosidase inhibition of 44.9% and 34.5%, respectively. This is the first report of the isolation of 2-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid and loganin from the genus and the first report of the α-glucosidase inhibitory potential of 2,4-dihydroxybenzoic acid.
Breast cancer is the most common and the second leading cause of cancer-related deaths in women. It has two distinctive hallmarks: rapid abnormal growth and the ability to invade and metastasize. During metastasis, cancer cells are thought to form actin-rich protrusions, called invadopodia, which degrade the extracellular matrix. Current breast cancer treatments, particularly chemotherapy, comes with adverse effects like immunosuppression, resistance development and secondary tumour formation. Hence, naturally-occurring molecules claimed to be less toxic are being studied as new drug candidates. Ampelopsin E, a natural oligostilbene extracted from Dryobalanops species, has exhibited various pharmacological properties, including anticancer and anti-inflammatory activities. However, there is yet no scientific evidence of the effects of ampelopsin E towards metastasis. Scratch assay, transwell migration and invasion assays, invadopodia and gelatin degradation assays, and ELISA were used to determine the effects of ampelopsin E towards the invasiveness of MDA-MB-231 cells. Strikingly in this study, ampelopsin E was able to halt migration, transmigration and invasion in MDA-MB-231 cells by reducing formation of invadopodia and its degradation capability through significant reduction (p < 0.05) in expression levels of PDGF, MMP2, MMP9 and MMP14. In conclusion, ampelopsin E reduced the invasiveness of MDA-MB-231 cells and was proven to be a potential alternative in treating TNBC.
Colon cancer is the third most common type of cancer in the world. Diosmetin (Dis), a natural O-methylated flavone, has been reported to have anti-cancer effects against different types of cancer. Although the mechanisms of action of Dis against several cancer cell lines are well reported, in vivo anti-tumorigenesis properties of this compound are still obscure. Therefore, this study aimed to investigate the anti-tumorigenesis properties of Dis against HCT-116 colon cancer xenografts in nude mice. HCT-116 colon cancer cells were injected in NCr nu/nu nude mice and treatment with Dis was initiated after the tumor volumes reached 100 mm3 and continued for four weeks. On the sacrificing date nude mice treated with 100 mg/kg of Dis showed significant lower tumor volume (264 ± 238.3 mm3) as compared to the untreated group (1428.8 ± 459.6 mm3). Anti-apoptotic Bcl-2 protein was significantly downregulated, while apoptotic protein (Bax) was significantly overexpressed in nude mice treated with 100 mg/kg Dis as compared to untreated mice. In conclusion, our in vivo results indicate that Dis significantly reduces tumor growth rate of HCT-116 colon cancer cells in nude mice at a dose of 100 mg/kg, and has no toxic effects in ICR mice up to 2000 mg/kg.
Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in α-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.
Clinically, gliomas are classified into four grades, with grade IV glioblastoma multiforme being the most malignant and deadly, which accounts for 50% of all gliomas. Characteristically, glioblastoma involves the aggressive proliferation of cells and invasion of normal brain tissue, outcomes as poor patient prognosis. With the current standard therapy of glioblastoma; surgical resection and radiotherapy followed by adjuvant chemotherapy with temozolomide, it remains fatal, because of the development of drug resistance, tumor recurrence, and metastasis. Therefore, the need for the effective therapeutic option for glioblastoma remains elusive. Previous studies have demonstrated the chemopreventive role of naturally occurring pharmacological agents through preventing or reversing the initiation phase of carcinogenesis or arresting the cancer progression phase. In this review, we discuss the role of natural phytochemicals in the amelioration of glioblastoma, with the aim to improve therapeutic outcomes, and minimize the adverse side effects to improve patient's prognosis and enhancing their quality of life.
In this study, the combination of parameters required for optimal extraction of anti-oxidative components from the Chinese lotus (CLR) and Malaysian lotus (MLR) roots were carefully investigated. Box-Behnken design was employed to optimize the pH (X1: 2-3), extraction time (X2: 0.5-1.5 h) and solvent-to-sample ratio (X3: 20-40 mL/g) to obtain a high flavonoid yield with high % DPPHsc free radical scavenging and Ferric-reducing power assay (FRAP). The analysis of variance clearly showed the significant contribution of quadratic model for all responses. The optimal conditions for both Chinese lotus (CLR) and Malaysian lotus (MLR) roots were obtained as: CLR: X1 = 2.5; X2 = 0.5 h; X3 = 40 mL/g; MLR: X1 = 2.4; X2 = 0.5 h; X3 = 40 mL/g. These optimum conditions gave (a) Total flavonoid content (TFC) of 0.599 mg PCE/g sample and 0.549 mg PCE/g sample, respectively; (b) % DPPHsc of 48.36% and 29.11%, respectively; (c) FRAP value of 2.07 mM FeSO4 and 1.89 mM FeSO4, respectively. A close agreement between predicted and experimental values was found. The result obtained succinctly revealed that the Chinese lotus exhibited higher antioxidant and total flavonoid content when compared with the Malaysia lotus root at optimum extraction condition.