Hericium erinaceus (Bull.: Fr.) Pers. is an edible and medicinal mushroom used traditionally to improve memory. In this study, we investigated the neuritogenic effects of hericenones isolated from H. erinaceus and the mechanisms of action involved. H. erinaceus was cultivated and the secondary metabolites were elucidated by high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR). The secondary metabolites were tested for neurite outgrowth activity (if any). Rat pheochromocytoma (PC12) cells were employed and the nerve growth factor (NGF) level was also determined. The signaling pathways involved in the mushroom-induced neuritogenesis were investigated using several pharmacological inhibitors. Hericenones B-E (1-4), erinacerin A (5) and isohericerin (6) were isolated from the basidiocarps of H. erinaceus. The hericenones did not promote neurite outgrowth but when induced with a low concentration of NGF (5 ng mL(-1)), the neuritogenic activity was comparable to that of the positive control (50 ng mL(-1) of NGF). Hericenone E was able to stimulate NGF secretion which was two-fold higher than that of the positive control. The neuritogenesis process was partially blocked by the tyrosine kinase receptor (Trk) inhibitor, K252a, suggesting that the neuritogenic effect was not solely due to NGF. Hericenone E also increased the phosphorylation of extracellular-signal regulated kinases (ERKs) and protein kinase B (Akt). Taken together, this study suggests that hericenone E potentiated NGF-induced neuritogenesis in PC12 cells via the MEK/ERK and PI3K/Akt pathways.
Hypertension is one of the major causes of cardiovascular-related diseases, which is highly associated with angiotensin-I-converting enzyme (ACE) activity and oxidative stress. In this study, winged bean seed (WBS), a potential source of protein, was utilised for the production of bifunctional proteolysate and biopeptides with ACE inhibitory and antioxidative properties. An enzymatic approach was applied, coupled with pretreatment of shaking and centrifuging techniques to remove endogenous ACE inhibitors prior to proteolysis. ACE inhibition reached its highest activity, 78.5%, after 12 h proteolysis while antioxidative activities, determined using assays involving DPPH˙ radical scavenging activity and metal ion-chelating activity, reached peaks of 65.0% and 65.7% at 8 h and 14 h, respectively. The said bioactivities were proposed to share some common structural requirements among peptides. A two-dimensional approach was employed for characterisation of effective peptides based on hydrophobicity, using RP-HPLC, and isoelectric property, using isoelectric focusing technique. Results revealed that acidic and basic peptides with partially higher hydrophobicity provided higher ACE inhibition activity than did neutral peptides. Finally, by using Q-TOF mass spectrometry, two peptide sequences (YPNQKV and FDIRA) with ACE inhibitory and antioxidative activities were successfully matched with a database. This study indicates that the WBS proteolysate can be a potential bifunctional food ingredient as the identified biopeptides demonstrated both ACE inhibitory and antioxidative activities in vitro.
The decreased cancer risk associated with consumption of olive oil may be due to the presence of phenolics which can modulate pathways including apoptosis and invasion that are relevant to carcinogenesis. We have previously shown that a virgin olive oil phenolics extract (OVP) inhibited invasion of HT115 colon cancer cells in vitro. In the current study we assessed the in vitro effects of OVP (25 μg mL(-1)) on HT115 cell migration, spreading and integrin expression. Furthermore, the anti-metastatic activity of OVP - at a dose equivalent to 25 mg per kg per day for 2, 8 or 10 weeks - was assessed in a Severe Combined ImmunoDeficiency (SCID) Balb-c mouse model. After 24 h OVP did not inhibit cell migration but significantly reduced cell spreading on fibronectin (65% of control; p < 0.05) and expression of a range of α and β integrins was modulated. In vivo, OVP by gavage significantly (p < 0.05) decreased not only tumour volume but also the number of metastases in SCID Balb-c mice. Collectively, the data suggest that - possibly through modulation of integrin expression - OVP decreases invasion in vitro and also inhibits metastasis in vivo.
Solubility and matrix play an important role in the gut lumen in delivering bioactive compounds to the absorptive surface of enterocytes. The purpose of this study was to determine the effect of certain commonly consumed lipids, soybean, olive and corn oil, on the transport and conjugation of flavonols (myricetin, quercetin, kaempferol and galangin) using the conjugation-competent co-cultured Caco-2/HT29-MTX intestinal cell monolayer model. To enable identification and quantification of conjugates, each flavonol was enzymatically glucuronidated or sulphated, then analysed by HPLC with triple quadrupole mass spectrometric detection. Quantification showed large differences in mass spectrometric peak area response factors between the aglycones and many of the conjugates, with galangin-sulphate for example ionising ∼15-fold better than galangin. Flavonol aglycones and conjugates were transported to the basolateral side of Caco-2/HT29-MTX co-cultures. The total amount of methyl, sulphate and glucuronide conjugates was in the order: galangin > quercetin > kaempferol > myricetin. All oils inhibited the transport and conjugation of galangin, the most hydrophobic flavonol, whereas they increased the sulphation, and to some extent glucuronidation, of quercetin and kaempferol. The results show that the lipid matrix has the potential to modify both transport and conjugation of dietary flavonols, but that the effect depends upon the structure and hydrophobicity.
Structured lipid medium- and long-chain triacylglycerols (MLCT) are claimed to be able to manage obesity. The present study investigated the body fat influence of enzymatically interesterifed palm-based medium- and long-chain triacylglycerols (P-MLCT) on diet-induced obesity (DIO) C57BL/6J mice compared with commercial MLCT oil (C-MLCT) and a control, which was the non enzymatically modified palm kernel and palm oil blend (PKO-PO blend). It also investigated the low fat and high fat effects of P-MLCT. DIO C57BL/6J mice were fed ad libitum with low fat (7%) and high fat (30%) experimental diets for 8 weeks before being sacrificed to obtain blood serum for analysis. From the results, there is a trend that P-MLCT fed mice were found to have the lowest body weight, body weight gain, total fat pad accumulation (perirenal, retroperitoneal, epididymal and mesenteric), total triglyceride levels and efficiency in controlling blood glucose level, compared with C-MLCT and the PKO-PO blend in both low fat and high fat diets. Nevertheless, the PKO-PO blend and P-MLCT caused significantly (P < 0.05) higher total cholesterol levels compared to C-MLCT. P-MLCT present in low fat and high fat dosage were shown to be able to suppress body fat accumulation. This effect is more prominent with the low fat dosage.
The fresh leaves of Murraya koenigii are often added to various dishes in Asian countries due to the delicious taste and flavour that they impart. In the present study, the effect of the total alkaloidal extract from Murraya koenigii leaves (MKA) with respect to anti-inflammatory, analgesic and anti-ulcerogenic effects were evaluated using different experimental animal models. Oral supplementation of MKA at 10, 20 and 40 mg kg(-1) body weight successfully and dose-dependently reduced the formation of oedema induced by carrageenan, histamine and serotonin as well as formaldehyde-induced arthritis. In addition, the extract (10, 20 and 40 mg kg(-1), p.o.) attenuated the writhing responses induced by an intraperitoneal injection of acetic acid and late phase of pain response induced by a subplantar injection of formalin in mice. MKA at higher doses (20 and 40 mg kg(-1), p.o) reduced the early phase response induced by formalin as well as reaction time on hot plate models. Interestingly, there was no ulcer score with the ulcerogenic effect of MKA. Moreover, all the doses of MKA (10, 20 and 40 mg kg(-1), p.o) showed promising anti-ulcerogenic activity with protection against acute gastric ulcers induced by ethanol plus hydrochloric acid and aspirin models in a dose dependent manner.
Lung cancer causes 1.4 million deaths annually. In the search for functional foods as complementary therapies against lung cancer, the immuno-stimulatory properties of the vegetable Morinda citrifolia leaves were investigated and compared with the anti-cancer drug erlotinib. Lung tumour-induced BALB/c mice were fed with 150 mg kg(-1) or 300 mg kg(-1) body weight of the leaf extract, or erlotinib (50 mg kg(-1) body-weight) for 21 days. The 300 mg kg(-1) body weight extract significantly (and dose-dependently) suppressed lung tumour growth; the extract worked more effectively than the 50 mg kg(-1) body weight erlotinib treatment. The extract significantly increased blood lymphocyte counts, and spleen tissue B cells, T cells and natural killer cells, and reduced the epidermal growth factor receptor (EGFR) which is a lung adenocarcinoma biomarker. The extract also suppressed the cyclooxygenase 2 (COX2) inflammatory markers, and enhanced the tumour suppressor gene (phosphatase and tensin homolog, PTEN). It inhibited tumour growth cellular gene (transformed mouse 3T3 cell double minute 2 (MDM2), V-raf-leukemia viral oncogene 1 (RAF1), and mechanistic target of rapamycin (MTOR)) mRNA expression in the tumours. The extract is rich in scopoletin and epicatechin, which are the main phenolic compounds. The 300 mg kg(-1)Morinda citrifolia leaf 50% ethanolic extract showed promising potential as a complementary therapeutic dietary supplement which was more effective than the 50 mg kg(-1) erlotinib in suppressing lung adenocarcinoma. Part of the mechanisms involved enhancing immune responses, suppressing proliferation and interfering with various tumour growth signalling pathways.
Standardized extract of Tinospora crispa has been shown to exhibit immunostimulatory effects on innate immune responses in Wistar-Kyoto rats by enhancing neutrophil and T cell-mediated immunity. In this study the immunostimulatory effects of T. crispa were further investigated on the cellular immune response by determining its effect on nitric oxide (NO) production ability, peritoneal macrophage phagocytosis and delayed type hypersensitivity (DTH), whereas the humoral immune response was evaluated through the measurement of serum immunoglobulins (IgG and IgM) and serum lysozyme levels. Male Balb/c mice were immunized with 200 μL of 5 × 10(9) sheep red blood cells (sRBCs) per mL on day 0 and orally administered with 50, 100 and 200 mg per kg of ethanol extract of T. crispa for 14 days. Syringin and magnoflorine were qualitatively and quantitatively analyzed in the extract as chemical markers by using a validated reversed-phase high performance liquid chromatography method. T. crispa extract (TCE) considerably improved the peritoneal macrophages' ability to engulf FITC-labeled E. coli in a dose-dependent manner. TCE also dose-dependently promoted NO production in peritoneal macrophages activated by a lipopolysaccharide (LPS) and markedly potentiated the sRBS-induced swelling rate of the mice paw in DTH. The extract significantly enhanced the level of serum immunoglobulins, showing maximum activity at 100 mg kg(-1). Compared to the control groups, the serum lysozyme level and myeloperoxidase (MPO) activity were significantly higher in extract-treated groups. These findings suggest that T. crispa possesses strong immunostimulatory activities and might act as a natural immunomodulator as well as a potential nutraceutical for the modulation of the immune response.
Curcumenol, a sesquiterpene isolated from Curcuma zedoaria is known to possess a variety of health and medicinal values which includes neuroprotection, anti-inflammatory, anti-tumor and hepatoprotective activities. The current study aim is to investigate the modulatory effects of curcumenol towards the lipopolysaccharides (LPS)-induced inflammation in BV-2 microglia. Curcumenol markedly decreased LPS-induced production of nitric oxide (NO), pro-inflammatory cytokines [(IL-6) and (TNF-α)] and pro-inflammatory proteins expression, iNOS and COX-2. Moreover, curcumenol inhibited NF-κB activation by suppressing the nuclear translocation of the NF-κB p65 subunit and blocking IκBα phosphorylation and degradation. Furthermore, an NF-κB inhibitor, ethyl 3,4-dihydroxycinnamate also known as caffeic acid ethyl ester (CAEE), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a regulator in the expression of iNOS and COX-2 proteins. Further mechanistic study with an Akt inhibitor, triciribine hydrate (API-2), revealed that curcumenol acted through Akt-dependent NF-κB activation. Moreover, curcumenol inhibition on LPS-induced phosphorylation of p38 MAPK is confirmed by its inhibitor (SB 202190). These results indicate that curcumenol diminishes the proinflammatory mediators and the expression of the regulatory genes in LPS-stimulated BV-2 by inhibiting Akt-dependent NF-κB activation and downregulation of Akt and p38 MAPKs signaling.
The aim of this research is to investigate whether edible bird's nest (EBN) attenuates cortical and hippocampal neurodegeneration in ovariectomized rats. Ovariectomized rats were randomly divided into seven experimental groups (n = 6): the ovariectomy (OVX) group had their ovaries surgically removed; the sham group underwent surgical procedure similar to OVX group, but ovaries were left intact; estrogen group had OVX and received estrogen therapy (0.2 mg kg(-1) per day); EBN treatment groups received 6%, 3%, and 1.5% EBN, respectively. Control group was not ovariectomized. After 12 weeks of intervention, biochemical assays were performed for markers of neurodegeneration, and messenger ribonucleic acid (mRNA) levels of oxidative stress-related genes in the hippocampus and frontal cortex of the brain were analysed. Caspase 3 (cysteine-aspartic proteases 3) protein levels in the hippocampus and frontal cortex were also determined using western blotting. The results show that EBNs significantly decreased estrogen deficiency-associated serum elevation of advanced glycation end-products (AGEs), and they changed redox status as evidenced by oxidative damage (malondialdehyde content) and enzymatic antioxidant defense (superoxide dismutase and catalase) markers. Furthermore, genes associated with neurodegeneration and apoptosis were downregulated in the hippocampus and frontal cortex by EBN supplementation. Taken together, the results suggest that EBN has potential for neuroprotection against estrogen deficiency-associated senescence, at least in part via modification of the redox system and attenuation of AGEs.
In this study, we prepared a series of lutein nanodispersions via the solvent displacement method, by using surfactants with different stabilizing mechanisms. The surfactants used include Tween 80 (steric stabilization), sodium dodecyl sulfate (SDS; electrostatic stabilization), sodium caseinate (electrosteric stabilization) and SDS-Tween 80 (electrostatic-steric stabilization). We then characterized the resulting lutein nanodispersions in terms of their particle size, particle size distribution, zeta potential, lutein content, flow behavior, apparent viscosity, transmittance, color, morphological properties and their effects on cell viability and cellular uptake. The type of surfactant used significantly (p < 0.05) affected the physical properties of the nanodispersions, but the chemical properties (lutein content) remained unaffected. Transmission electron microscopy (TEM) images obtained from this study demonstrated that the solvent displacement method was capable of producing lutein nanodispersions containing spherical particles with sizes ranging from 66.20-125.25 nm, depending on the type of surfactant used. SDS and SDS-Tween 80 surfactants negatively affected the viability of the HT-29 cells used in this study. Thus, for the cellular uptake determination, only Tween 80 and sodium caseinate surfactants were used. The cellular uptake of the lutein nanodispersion stabilized by sodium caseinate was higher than that which was stabilized by Tween 80. All things considered, the type of surfactant with different stabilizing mechanisms did produce lutein nanodispersions with different characteristics. These findings would aid in future selection of surfactants in order to produce nanodispersions with desirable properties.
Winged bean seed (WBS) is an underutilized tropical crop. The current study evaluates its potential to reduce blood pressure (BP) in spontaneously hypertensive rats and finds that it reduces BP significantly, in a dose-dependent manner. Five peptides with the sequences, RGVFPCLK, TQLDLPTQ, EPALVP, MRSVVT and DMKP, have been characterized in terms of their stability against ACE via in vitro and in silico modelling. All peptides exhibited IC50 values between 0.019 and 6.885 mM and various inhibitory modes, including substrate, prodrug and true inhibitor modes. The toxicity status of non-Current Good Manufacturing Practice (non-CGMP) peptides is evaluated and the results show that such peptides are toxic, and thus are not suitable to be tested in animals, particularly in repeated-dose studies. In short, WBS hydrolysate demonstrated in vitro ACE inhibitory properties and in vivo blood pressure lowering efficacy in rat models, fostering its potential as a functional food ingredient. Non-CGMP grade peptides are toxic and unfit for testing in animal models.
In this study, the effect of lecithin (LEC) on the crystallization and gelation of fruit wax (FW) with sunflower oil was researched. A synergistic effect on the gel strength was observed at FW : LEC ratios of 75 : 25 and 50 : 50, compared to the corresponding single component formulations (100 : 0 and 0 : 100). Even below the critical gelling concentration (Cg) of FW, the addition of lecithin enabled gel formation. Lecithin affected the thermal behavior of the structure by delaying both crystallization and gel formation. The phospholipid acted as a crystal habit modifier changing the microstructure of the oleogel, as was observed by polarized light microscopy. Cryo-scanning electron microscopy revealed a similar platelet-like arrangement for both FW as a single oleogelator and FW in combination with LEC. However, a denser structure could be observed in the FW : LEC oleogelator mixture. Both the oil-binding capacity and the thixotropic recovery were enhanced upon lecithin addition. These improvements were attributed to the hydrogen bonding between FW and LEC, as suggested by Raman spectroscopy. We hypothesized that lecithin alters the molecular assembly properties of the FW due to the interactions between the polar moieties of the oleogelators, which consequently impacts the hydrophobic tail (re)arrangement in gelator-gelator and solvent-gelator interactions. The lipid crystal engineering approach followed here offered prospects of obtaining harder self-standing structures at a lower oleogelator concentration. These synergistic interactions provide an opportunity to reduce the wax concentration and, as such, the waxy mouthfeel without compromising the oleogel properties.
Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model. Hypercholesterolemia was induced in Sprague-Dawley rats via atherogenic diet feeding and dietary interventions were conducted by incorporating DKSM (15% and 30%) and equivalent levels of PSRE (2.3% and 4.6%, respectively, equivalent to the total content of phenolics and saponins in DKSM groups) into the atherogenic diets. After 10 weeks of DKSM and PSRE supplementation, the hepatosomatic index, hepatosteatosis, serum lipid profile, Castelli risk indexes as well as hepatic and renal functions of hypercholesterolemic rats were significantly improved (p < 0.05). Besides, the levels of hepatic Hmgcr and serum Pcsk9 were lowered, along with transcriptional upregulations of hepatic Cyp7a1, Abca1, Lcat, ApoA2 and ApoE (p < 0.05). The gene expression of hepatic Ldlr was marginally enhanced by DKSM supplementation (p > 0.05), but superiorly upregulated by PSRE (p < 0.05). The combined results showed that hypercholesterolemia and the atherogenic risk in rats were effectively attenuated by DKSM and PSRE supplementation, possibly via modulations of multiple vital processes in hepatic cholesterol metabolism. Furthermore, phenolics and saponins may be the bioactives conferring DKSM and PSRE with their anti-hypercholesterolemic properties. In conclusion, DKSM and PSRE are prospective cardioprotective functional food ingredients for hypercholesterolemic individuals.
Vanilloid (4-hydroxy-3-methoxyphenyl benzenoid) containing foods are reported to possess many biological activities including anti-inflammatory properties. Homodimerisation of the Toll-like receptor-4 (TLR-4)/Myeloid differentiation factor 2 (MD-2) complex results in life-threatening complications in inflammatory disorders. In this study, we report activity of vanilloids in inhibition of TLR-4/MD-2 homodimersization and their molecular interactions with the receptor. The inhibitory activities of vanilloids were assessed in vitro by determining their antagonistic actions of lipopolysaccharide from Escherichia coli (LPSEc) in activation of TLR-4/MD-2 homodimerisation in TLR-4/MD-2/CD-14 transfected HEK-293 cells. The in vitro anti-inflammatory activity of vanilloids was also determined using RAW 264.7 cells. All the vanilloids were found to be active in the inhibition of TLR-4/MD-2 homodimersiation and nitric oxide production in RAW 264.7 cells. Rigid and flexible molecular docking studies were performed to gain insight into interactions between vanilloids and the binding site of the TLR-4/MD-2 complex.
This study assessed the cholesterol lowering effect of Pediococcus acidilactici LAB4 and Lactobacillus plantarum LAB12 using adult zebrafish. Animals were fed with a high cholesterol diet (HCD) with/without LAB for seven weeks. Serum and liver cholesterol was quantified using colorimetric and dye staining methods. Expressions of npc1l1 and abca1 in the liver and intestine and appa in the brain were quantified using RT-PCR. Serum and liver cholesterol was significantly lowered in LAB4- and LAB12-fed zebrafish (≤64% and ≤71%, respectively), with reduced liver cholesterol deposition. The cholesterol lowering effect was accompanied by down-regulation of npc1l1 in intestines (≤28.7%), up-regulation of abca1 in the liver (≥30.5%) and down-regulation of appa in the brain (≤24.5%). A moderately strong positive Pearson correlation (r = 0.617, p < 0.01) was found between appa and serum cholesterol. LAB-fed zebrafish exhibited improved spatial learning and memory. LAB4 and LAB12 can be potentially used in preventing hypercholesterolaemia and Alzheimer's diseases.
Plant-derived immunomodulators and anti-cancer agents have attracted a lot of interest from natural product scientists for their efficacy and safety and their significant contribution towards understanding targeted drug action and drug delivery mechanisms. Zerumbone, the main constituent of Zingiber zerumbet rhizomes, has been investigated for its wide-spectrum role in treating multitargeted diseases. The rhizomes have been used as food flavoring agents in various cuisines and in herbal medicine. Many in vivo and in vitro studies have provided evidence of zerumbone as a potent immunomodulator as well as a potential anti-cancer agent. This review is an interesting compilation of all those significant outcomes from investigations carried out to date to explore the immunomodulatory and anticancer properties of zerumbone. The ultimate objective of this comprehensive review is to provide updated information and a critical assessment on zerumbone including its chemistry and immunomodulating and anticancer properties, which may be of paramount importance to provide a new path for ensuing research to discover new agents to treat cancers and immune-related diseases. In addition, updated information on the toxicology of zerumbone has also been summarized to provide its safety profile.
Varying the β-carotene (0.1-0.3 g kg(-1)) and whey protein isolate (WPI) (2-20 g kg(-1)) concentrations in an oil-in-water (O/W) emulsion influenced the partitioning and stability of β-carotene upon 30 d storage at 25 and 40 °C. The total β-carotene in the emulsion was extracted with a solvent and quantified using UV/visible spectroscopy. The β-carotene in oil phase was obtained using in situ Raman micro-spectroscopy. The β-carotene in the aqueous phase was obtained by difference. Increasing β-carotene concentration resulted in increased partitioning of β-carotene into the aqueous phase whereas increasing WPI concentration had the opposite effect. With all freshly made emulsions, there was a higher proportion of β-carotene found in the oil phase. At the end of the storage period, the higher proportion and concentration of β-carotene was in the aqueous phase. This suggested that oxidation of β-carotene occurred faster in the oil phase and that WPI in the aqueous phase protected β-carotene against oxidation. This work informs the formulation of protein-based emulsions for the delivery of β-carotene.
Edible bird's nest (EBN) is widely consumed as a delicacy and traditional medicine amongst the Chinese. In the present study, for the first time, the antioxidant properties of an EBN pepsin-trypsin hydrolysate of the swiftlet species Aerodramus fuciphagus and its ultrafiltration fractions were investigated. Thirteen peptides with molecular weights between 514.29 and 954.52 Da were identified in the EBN fraction with the use of mass spectrometry. Two novel pentapeptides Pro-Phe-His-Pro-Tyr and Leu-Leu-Gly-Asp-Pro, corresponding to f134-138 and f164-168 of cytochrome b of A. fuciphagus, indicated the highest ORAC values of 14.95 and 14.32 μM of TE μM(-1) peptide, respectively. Both purified peptides showed resistance against simulated gastrointestinal proteases. In addition, both peptides had no in vitro cytotoxicity on human lung MRC-5 cells and prevented human liver carcinoma HepG2 cellular damage caused by hydroxyl radicals. Therefore, it is suggested that EBN protein hydrolysates are a good source of natural antioxidants and could be applied as nutraceutical compounds.
Ellagitannins, found abundantly in berries, pomegranates, walnuts and almonds, have been increasingly investigated for their health benefits. Geraniin (GE), an ellagitannin, found predominantly in herbal plants, as well has been shown to exhibit a number of biological activities. Like many hydrolysable tannins, geraniin is water-soluble and readily undergoes hydrolysis in the presence of hot water, weak acids and weak bases to yield several metabolites including corilagin (CO), ellagic acid (EA) and gallic acid (GA). There are numerous studies on the pharmacological effectiveness of GE, CO and GA. However, the intestinal permeability of GE and CO has never been investigated before. Caco-2 cell transport assay was utilized to evaluate the in vitro permeability of GE and its metabolites. GE, CO and EA were found to have no apparent permeability (Papp) while GA displayed a Papp value of 31.3 ± 1.1 × 10-6 cm s-1. Mass balance studies showed a loss of geraniin and its metabolites during transport. Chemical stability studies in the transport buffers revealed that GE and CO were hydrolyzed in the HBSS buffers. Experiments using lysed cells revealed that GE and its metabolites were metabolized during transport. Absorption and desorption studies confirmed the accumulation of EA inside the cells. The above results indicate that the compounds have poor oral absorption. To consider these compounds or their natural extracts as oral nutraceutical candidates, formulation strategies are mandatory.