The Prebiotic Potential of Geraniin and Geraniin-Enriched Extract against High-Fat-Diet-Induced Metabolic Syndrome in Sprague Dawley Rats.

Geraniin, an ellagitannin, has ameliorative properties against high-fat diet (HFD)-induced metabolic syndrome. Since geraniin has poor bioavailability, we hypothesised the interaction of this compound with gut microbiota as the main mechanism for improving metabolic aberrations. Male Sprague Dawley rats were divided into normal diet (ND)- and HFD-fed animals and treated with geraniin and an enriched extract of geraniin (GEE). We observed that 5 mg geraniin and 115 mg GEE supplementation significantly attenuated glucose intolerance, lipopolysaccharide-binding protein, total cholesterol, triacylglyceride, and low-density lipoprotein; improved insulin sensitivity; and significantly increased adiponectin and hepatic PPARα expression. Although geraniin and GEE did not significantly alter the gut microbial composition, we found an increment in the relative abundance of a few butyrate producers such as Alloprevotella, Blautia, Lachnospiraceae NK4A136 group, and Clostridium sensu stricto 1. Geraniin and its enriched extract's ability to ameliorate metabolic syndrome parameters while positively affecting the growth of butyrate-producing bacteria suggests its potential prebiotic role.

Assessment of community pharmacists' communication and comfort levels when interacting with Deaf and hard of hearing patients.

BACKGROUND: Deaf and hard of hearing patients who use sign language face considerable communication barriers while accessing pharmacy services. Low comfort-levels between community pharmacists and Deaf and hard of hearing patients result in poor interactions and increase patient safety risks. OBJECTIVE: 1) To examine the way community pharmacists interact with Deaf and hard of hearing patients in Malaysia, and their level of comfort in such interactions. 2) To examine how comfort-levels vary by the preferred communication methods, resources and employer support. METHODS: This cross-sectional study was conducted among registered community pharmacists practicing in Malaysia. Questionnaire items included comfort-levels of community pharmacists when interacting with Deaf and hard of hearing patients, used and preferred communication methods, necessary resources, and perceived employer's level of support. Based on the list of registered pharmacies, the questionnaire with a pre-paid return envelope was mailed out while pharmacies close to the university were approached in person. This questionnaire was distributed online using Google Form. Comparisons between comfort-levels and study parameters were analyzed using independent t-tests and ANOVA. RESULTS: A total of 297 community pharmacists responded (response rate 29.2%). Higher comfort-levels were reported in those who had received between 1 to 5 prescriptions as compared to those who did not receive prescriptions from Deaf and hard of hearing patients (MD= -0.257, SD=0.104, p=0.042). More than 80% used written information and only 3.4% had used the services of a qualified sign language interpreter throughout their community pharmacist career. Significantly lower comfort-levels (p=0.0004) were reported in community pharmacists who perceived training in sign language as a necessity to interact with Deaf and hard of hearing patients (M=3.6, SD=0.9) versus those who were not interested in sign language training (M=3.8, SD=0.6). CONCLUSIONS: The results suggest that community pharmacists were neither extremely comfortable nor averse when interacting with Deaf and hard of hearing patients. The lack of significant findings in terms of comfort-levels may indicate other potential drivers for their choice of communication method when interacting with Deaf and hard of hearing patients.

Assessment of community pharmacists’ communication and comfort levels when interacting with Deaf and hard of hearing patients

Background: Deaf and hard of hearing patients who use sign language face considerable communication barriers while accessing pharmacy services. Low comfort-levels between community pharmacists and Deaf and hard of hearing patients result in poor interactions and increase patient safety risks. Objective: 1) To examine the way community pharmacists interact with Deaf and hard of hearing patients in Malaysia, and their level of comfort in such interactions. 2) To examine how comfort-levels vary by the preferred communication methods, resources and employer support. Methods: This cross-sectional study was conducted among registered community pharmacists practicing in Malaysia. Questionnaire items included comfort-levels of community pharmacists when interacting with Deaf and hard of hearing patients, used and preferred communication methods, necessary resources, and perceived employer’s level of support. Based on the list of registered pharmacies, the questionnaire with a pre-paid return envelope was mailed out while pharmacies close to the university were approached in person. This questionnaire was distributed online using Google Form. Comparisons between comfort-levels and study parameters were analyzed using independent t-tests and ANOVA. Results: A total of 297 community pharmacists responded (response rate 29.2%). Higher comfort-levels were reported in those who had received between 1 to 5 prescriptions as compared to those who did not receive prescriptions from Deaf and hard of hearing patients (MD= -0.257, SD=0.104, p=0.042). More than 80% used written information and only 3.4% had used the services of a qualified sign language interpreter throughout their community pharmacist career. Significantly lower comfort-levels (p=0.0004) were reported in community pharmacists who perceived training in sign language as a necessity to interact with (AU)

Polyphenols as Prebiotics in the Management of High-Fat Diet-Induced Obesity: A Systematic Review of Animal Studies.

Obesity is a disease growing at an alarming rate and numerous preclinical studies have proven the role of polyphenols in managing this disease. This systematic review explores the prebiotic effect of polyphenols in the management of obesity among animals fed on a high-fat diet. A literature search was carried out in PubMed, Scopus, CINAHL, Web of Science, and Embase databases following the PRISMA guidelines. Forty-four studies reported a significant reduction in obesity-related parameters. Most notably, 83% of the studies showed a decrease in either body weight/visceral adiposity/plasma triacylglyceride. Furthermore, 42 studies reported a significant improvement in gut microbiota (GM), significantly affecting the genera Akkermansia, Bacteroides, Blautia, Roseburia, Bifidobacteria, Lactobacillus, Alistipes, and Desulfovibrio. Polyphenols' anti-obesity, anti-hyperglycaemic, and anti-inflammatory properties were associated with their ability to modulate GM. This review supports the notion of polyphenols as effective prebiotics in ameliorating HFD-induced metabolic derangements in animal models.

Metabolites of the ellagitannin, geraniin inhibit human ACE; in vitro and in silico evidence.

Hypertension is defined as the persistence of elevated blood pressure in the circulation system. The renin-angiotensin-aldosterone system is a major modulator of blood pressure. Among the risk factors of cardiovascular disease, hypertension is the most preventable and treatable, with drugs such as ACE inhibitors. Many ACE inhibitors are known to have undesirable side effects and hence, natural alternatives are being sought. Dietary polyphenols, particularly ellagitannins, are derived from plant products and are known to exhibit a variety of bioactivities. Geraniin, an ellagitannin has been shown to have antihypertensive activity in animal experiments. It is speculated that the metabolites of geraniin are responsible for its ACE inhibitory activity. We have performed in vitro ACE inhibition and in silico studies with geraniin and its metabolites (ellagic acid, urolithins). Our studies confirm that ellagic acid exhibited similar inhibitory potential to ACE as the positive control captopril.

Ratite oils for local transdermal therapy of 4-OH tamoxifen: development, characterization, and ex vivo evaluation.

The anti-inflammatory property of ratite oils as well as its ability to act as a penetration enhancer makes it an ideal agent to be used in transdermal formulations. The present study aims to develop an effective transfersomal delivery of 4-hydroxytamoxifen (4-OHT), an anti-cancer drug, using ratite oil as a carrier agent for the treatment of breast cancer (BC). The 4-OHT transfersomes were prepared with and without ratite oils using soy phosphatidylcholine and three different edge activators (EAs) in five different molar ratios using the rotary evaporation-ultrasonication method. Optimal transfersome formulations were selected using physical-chemical characterization and ex vivo studies. Results from physical-chemical characterization of the developed formulations found sodium taurocholate to be the most suitable EA, which recorded highest entrapment efficiency of 95.1 ± 2.70% with 85:15, (w/w) and lowest vesicle size of 82.3 ± 0.02 nm with 75:25, (w/w) molar ratios. TEM and DSC studies showed that the vesicles were readily identified and present in a nearly perfect spherical shape. In addition, formulations with emu oil had better stability than formulations with ostrich oil. Physical stability studies at 4 °C showed that ratite oil transfersomes were stable up to 4 weeks, while transfersomes without ratite oils were stable for 8 weeks. Ex vivo permeability studies using porcine skin concluded that 4-OHT transfersomal formulations with (85:15, w/w) without emu oil have the potential to be used in transdermal delivery approach to enhance permeation of 4-OHT, which may be beneficial in the treatment of BC.

Efficacy of Emu Oil Transfersomes for Local Transdermal Delivery of 4-OH Tamoxifen in the Treatment of Breast Cancer.

Oral tamoxifen used in the prevention and treatment of ductal carcinoma in situ (DCIS) (estrogen-positive) patients has limited acceptance, due to its adverse side effects. The efficacy of tamoxifen is related to its major metabolite, 4-hydroxytamoxifen. Local transdermal therapy of 4-hydroxytamoxifen to the breast might avert the toxicity of oral tamoxifen, while maintaining efficacy. We aim to study the skin irritancy, as well as to evaluate the efficacy of the developed transfersome formulations, with/without emu oil, using a syngeneic mouse model of breast cancer. We also quantified tamoxifen/4-hydroxytamoxifen concentrations in blood plasma and performed histopathology. The skin irritancy test showed that the pure emu oil and transfersome formulations with or without the emu oil did not cause skin irritancy in the animals studied. A sensitive and specific LC-MS/MS method for the quantification of tamoxifen and 4-hydroxytamoxifen was developed and validated. Studies on tumor volume and necrosis (histopathology) using the breast cancer mouse model showed that the 4-OHT transfersomal formulations, with and without emu oil, showed comparable efficacy with that of orally administered tamoxifen. However, the transfersomal formulations, with and without emu oil, resulted in significantly lower (10.24 ± 0.07 and 32.45 ± 0.48 ng/mL, respectively) plasma concentrations of 4-hydroxytamoxifen, compared to the oral tamoxifen (TAMX) group (634.42 ± 7.54 ng/mL). This study demonstrated the potential use of emu oil in a local transdermal formulation for the treatment of breast cancer and its reduced adverse effects.

Acute oral toxicity of the ellagitannin geraniin and a geraniin-enriched extract from Nephelium lappaceum L rind in Sprague Dawley rats.

Despite the lack of its toxicity evaluation, traditional herbal products are being widely used for various health indications. Geraniin, an ellagitannin, is a bioactive compound found in many traditional herbal medicines. In spite its numerous health benefits ranging from anti-inflammatory, anti-hyperglycaemic, hepatoprotective, anti-cancer and anti-microbial, no toxicity data on geraniin is available. The objective of this study is to evaluate the acute oral toxicity of geraniin and an enriched geraniin-extract of Nephelium lappaceum L rind. This study followed the guidelines of the OECD 423 acute oral toxicity test. Subsequent to a single oral administration of the test compounds, the rats were observed for 14 days for signs of toxicity and mortality. Following euthanasia, full blood count, biochemistry of blood and histopathology assessment of organs were carried out. All parameters analysed indicated insignificant difference compared to control. The LD50 cut-off values for both geraniin and geraniin-enriched extract was established to be 2000 mg/kg b. w., following a single oral dose. It was however observed that the hepatocytes of three geraniin-administered rats exhibited a 'foamy appearance'. As such, the no-observed-adverse-effect level of geraniin is below 2000 mg/kg, while that of geraniin-enriched extract is up to 2000 mg/kg. Further detailed toxicity studies are required to establish geraniin or its enriched extract from Nephelium lappaceum L rind safe for human consumption.

Review: Patient-controlled transdermal 4-hydroxytamoxifen (4-OHT) vs. oral tamoxifen: A systematic review and meta analysis.

There has been a number of studies looking into an alternative mode of therapy for the treament of breast cancer via 4-hydroxytamoxifen (4-OHT) transdermal administration.This systematic review aims to compare the safety and efficacy of a transdermal 4-OHT local therapy and oral tamoxifen (oral-T) on the treatment of ductal carcinoma in situ breast cancer. Through a systematic search of health science databases, eligible trials were located and the end points assessed were Ki-67 labeling index, concentration of 4-OHT in breast adipose tissue (ng/g) and plasma (ng/ml). Revman 5.3 version was used to perfom the meta-analysis. Three trials were identified (n=103), while only two were included for meta analysis. The mean difference between the two studies included were 0.40 and -10.58. Overall the I2 value was 89.0%, (Tau2 =53.86) and the differences between the two trials were statistically significant p=0.002. The meta analysis of the randomized controlled trials showed that the use of local transdermal therapy of 4-OHT gel is more safer than oral-T. However, due to the limited number of studies, the potential use of 4-OHT topical transdermal therapy for the treatment of breast cancer could not be concluded for healthcare professionals.

Efficacy of geraniin on dengue virus type-2 infected BALB/c mice.

BACKGROUND: Dengue continues to be a major international public health concern. Despite that, there is no clinically approved antiviral for treatment of dengue virus (DENV) infections. In this study, geraniin extracted from the rind of Nephelium lappaceum was shown to inhibit the replication of DENV-2 in both in vitro and in vivo experiments. METHODS: The effect of geraniin on DENV-2 RNA synthesis in infected Vero cells was tested using quantitative RT-PCR. The in vivo efficacy of geraniin in inhibiting DENV-2 infection was then tested using BALB/c mice with geraniin administered at three different times. The differences in spleen to body weight ratio, DENV-2 RNA load and liver damage between the three treatment groups as compared to DENV-2 infected mice without geraniin administration were determined on day eight post-infection. RESULTS: Quantitative RT-PCR confirmed the decrease in viral RNA synthesis of infected Vero cells when treated with geraniin. Geraniin seemed to provide a protective effect on infected BALB/c mice liver when given at 24 h pre- and 24 h post-infection as liver damage was observed to be very mild even though a significant reduction of DENV-2 RNA load in serum was not observed in these two treatment groups. However, when administered at 72 h post-infection, severe liver damage in the form of necrosis and haemorrhage had prevailed despite a substantial reduction of DENV-2 RNA load in serum. CONCLUSIONS: Geraniin was found to be effective in reducing DENV-2 RNA load when administered at 72 h post-infection while earlier administration could prevent severe liver damage caused by DENV-2 infection. These results provide evidence that geraniin is a potential candidate for the development of anti-dengue drug.

Permeability of the ellagitannin geraniin and its metabolites in a human colon adenocarcinoma Caco-2 cell culture model.

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.

Geraniin Protects High-Fat Diet-Induced Oxidative Stress in Sprague Dawley Rats.

Geraniin, a hydrolysable polyphenol derived from Nephelium lappaceum L. fruit rind, has been shown to possess significant antioxidant activity in vitro and recently been recognized for its therapeutic potential in metabolic syndrome. This study investigated its antioxidative strength and protective effects on organs in high-fat diet (HFD)-induced rodents. Rats were fed HFD for 6 weeks to induce obesity, followed by 10 and 50 mg/kg of geraniin supplementation for 4 weeks to assess its protective potential. The control groups were maintained on standard rat chows and HFD for the same period. At the 10th week, oxidative status was assessed and the pancreas, liver, heart and aorta, kidney, and brain of the Sprague Dawley rats were harvested and subjected to pathological studies. HFD rats demonstrated changes in redox balance; increased protein carbonyl content, decreased levels of superoxide dismutase, glutathione peroxidase, and glutathione reductase with a reduction in the non-enzymatic antioxidant mechanisms and total antioxidant capacity, indicating a higher oxidative stress (OS) index. In addition, HFD rats demonstrated significant diet-induced changes particularly in the pancreas. Four-week oral geraniin supplementation, restored the OS observed in the HFD rats. It was able to restore OS biomarkers, serum antioxidants, and the glutathione redox balance (reduced glutathione/oxidized glutathione ratio) to levels comparable with that of the control group, particularly at dosage of 50 mg geraniin. Geraniin was not toxic to the HFD rats but exhibited protection against glucotoxicity and lipotoxicity particularly in the pancreas of the obese rodents. It is suggested that geraniin has the pharmaceutical potential to be developed as a supplement to primary drugs in the treatment of obesity and its pathophysiological sequels.

Geraniin extracted from the rind of Nephelium lappaceum binds to dengue virus type-2 envelope protein and inhibits early stage of virus replication.

BACKGROUND: The rapid rise and spread in dengue cases, together with the unavailability of safe vaccines and effective antiviral drugs, warrant the need to discover and develop novel anti-dengue treatments. In this study the antiviral activity of geraniin, extracted from the rind of Nephelium lappaceum, against dengue virus type-2 (DENV-2) was investigated. METHODS: Geraniin was prepared from Nephelium lappaceum rind by reverse phase C-18 column chromatography. Cytotoxicity of geraniin towards Vero cells was evaluated using MTT assay while IC50 value was determined by plaque reduction assay. The mode-of-action of geraniin was characterized using the virucidal, attachment, penetration and the time-of-addition assays'. Docking experiments with geraniin molecule and the DENV envelope (E) protein was also performed. Finally, recombinant E Domain III (rE-DIII) protein was produced to physiologically test the binding of geraniin to DENV-2 E-DIII protein, through ELISA competitive binding assay. RESULTS: Cytotoxicity assay confirmed that geraniin was not toxic to Vero cells, even at the highest concentration tested. The compound exhibited DENV-2 plaque formation inhibition, with an IC50 of 1.75 µM. We further revealed that geraniin reduced viral infectivity and inhibited DENV-2 from attaching to the cells but had little effect on its penetration. Geraniin was observed to be most effective when added at the early stage of DENV-2 infection. Docking experiments showed that geraniin binds to DENV E protein, specifically at the DIII region, while the ELISA competitive binding assay confirmed geraniin's interaction with rE-DIII with high affinity. CONCLUSIONS: Geraniin from the rind of Nephelium lappaceum has antiviral activity against DENV-2. It is postulated that the compound inhibits viral attachment by binding to the E-DIII protein and interferes with the initial cell-virus interaction. Our results demonstrate that geraniin has the potential to be developed into an effective antiviral treatment, particularly for early phase dengue viral infection.

Valorization of Dacryodes rostrata fruit through the characterization of its oil.

Dacryodes rostrata (kembayau) is an important food and oil resource for local communities in Borneo, but it is not commonly known to wider community. The objective of this work is to valorize kembayau fruit by evaluating the characteristics of the oil from the fruit. In this study, the physicochemical characteristics and the lipophilic essential nutrient; the fatty acid composition, vitamin E and beta-carotene content of oils obtained from the peel, pulp and seeds of kembayau fruits were studied. The pulp of the kembayau fruit contained highest proportion of oil, followed by peel and seed. Kembayau fruit contained vitamin E and had trace amount of beta-carotene. Besides, kembayau fruit oils were not toxic to BRL3A cells, provided hepatoprotection and reversed lipid peroxidation in paracetamol-induced toxicity. Our results suggest that kembayau can be a potential source for cooking oil as the physicochemical characteristics are comparable with commercial source such as oil palm.

Streptomyces antioxidans sp. nov., a Novel Mangrove Soil Actinobacterium with Antioxidative and Neuroprotective Potentials.

A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL-diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 ± 0.3% to 53.1 ± 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities.

Role of Fenugreek in the prevention of type 2 diabetes mellitus in prediabetes.

BACKGROUND: It is hypothesized that dietary supplementation with Fenugreek modulates glucose homeostasis and potentially prevents diabetes mellitus in people with prediabetes. The objective of present study is to determine whether Fenugreek can prevent the outcome of T2DM in non diabetic people with prediabetes. METHODS: A 3-year randomized, controlled, parallel study for efficacy of Fenugreek (n = 66) and matched controls (n = 74) was conducted in men and women aged 30-70 years with criteria of prediabetes. Fenugreek powder, 5 g twice a day before meals, was given to study subjects and progression of type 2 diabetes mellitus (T2DM) was monitored at baseline and every 3 months for the 3-year study. RESULTS: By the end of intervention period, cumulative incidence rate of diabetes reduced significantly in Fenugreek group when compared to controls. The Fenugreek group also saw a significant reduction in fasting plasma glucose (FPG), postprandial plasma glucose (PPPG) and low density lipoprotein cholesterol (LDLc) whereas serum insulin increased significantly. It was observed that controls had 4.2 times higher chance of developing diabetes compared to subjects in the Fenugreek group. The outcome of diabetes in Fenugreek group was positively associated with serum insulin and negatively associated with insulin resistance (HOMA IR). CONCLUSIONS: Dietary supplementation of 10 g Fenugreek/day in prediabetes subjects was associated with lower conversion to diabetes with no adverse effects and beneficial possibly due to its decreased insulin resistance.

Presence of antioxidative agent, Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro- in newly isolated Streptomyces mangrovisoli sp. nov.

A novel Streptomyces, strain MUSC 149(T) was isolated from mangrove soil. A polyphasic approach was used to study the taxonomy of MUSC 149(T), which shows a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The diamino acid of the cell wall peptidoglycan was LL-diaminopimelic acid. The predominant menaquinones were identified as MK9(H8) and MK9(H6). Phylogenetic analysis indicated that closely related strains include Streptomyces rhizophilus NBRC 108885(T) (99.2% sequence similarity), S. gramineus NBRC 107863(T) (98.7%) and S. graminisoli NBRC 108883(T) (98.5%). The DNA-DNA relatedness values between MUSC 149(T) and closely related type strains ranged from 12.4 ± 3.3% to 27.3 ± 1.9%. The DNA G + C content was determined to be 72.7 mol%. The extract of MUSC 149(T) exhibited strong antioxidant activity and chemical analysis reported identification of an antioxidant agent, Pyrrolo[1,2-a]pyrazine-1,4-dione, hexahydro-. These data showed that metabolites of MUSC 149(T) shall be useful as preventive agent against free-radical associated diseases. Based on the polyphasic study of MUSC 149(T), the strain merits assignment to a novel species, for which the name S. mangrovisoli sp. nov. is proposed. The type strain is MUSC 149(T) (=MCCC 1K00699(T)=DSM 100438(T)).

The physicochemical properties of geraniin, a potential antihyperglycemic agent.

CONTEXT: Natural products play a vital role in the discovery of leads for novel pharmacologically active drugs. Geraniin (GE) was identified as the major compound in the rind of Nephelium lappaceum L. (Sapindaceae), while ellagic and gallic acids have been shown to be its main metabolites. GE and its metabolites possess a range of bioactive properties including being an anti-infective, anticarcinogenic, antihyperglycemic, and antihypertensive. OBJECTIVE: GE and its metabolites were investigated to establish its gastrointestinal absorption and physicochemical properties. MATERIALS AND METHODS: GE was purified from N. lappaceum rind extract using reverse-phase C18 column chromatography. Lipophilicity (log P) was determined using the 1-octanol/water shake-flask method. Equilibrium solubility of GE and its metabolites (20 mg) was determined in water and four biorelevant media: simulated gastric, simulated intestinal, fasted state-simulated intestinal, and fed state-simulated intestinal after 72 h. RESULTS AND DISCUSSION: The purification yield was 10.8%; where a 97-99% pure GE was obtained. Log P values for GE, ellagic, and gallic acids were established as -0.73 ± 0.17, 0.11 ± 0.06, and 0.71 ± 0.21, respectively, establishing them as polar compounds. All three compounds were found to exhibit poor solubility in gastric (0.61-8.10 mg/mL) but good solubility in intestinal fluids (3.59-14.32 mg/mL). CONCLUSION: The above results indicate that the compounds have limited gastrointestinal absorption due to its polarities. To consider these compounds as oral drug candidates, formulation strategies are being developed.

Syzygium aqueum leaf extract and its bioactive compounds enhances pre-adipocyte differentiation and 2-NBDG uptake in 3T3-L1 cells.

The insulin-like and/or insulin-sensitising effects of Syzygium aqueum leaf extract and its six bioactive compounds; 4-hydroxybenzaldehyde, myricetin-3-O-rhamnoside, europetin-3-O-rhamnoside, phloretin, myrigalone-G and myrigalone-B were investigated in 3T3-L1 adipocytes. We observed that, S. aqueum leaf extract (0.04-5 µg/ml) and its six bioactive compounds (0.08-10 µM) at non-cytotoxic concentrations were effectively enhance adipogenesis, stimulate glucose uptake and increase adiponectin secretion in 3T3-L1 adipocytes. Clearly, the compounds myricetin-3-O-rhamnoside and europetin-3-O-rhamnoside showed insulin-like and insulin-sensitising effects on adipocytes from a concentration of 0.08 µM. These compounds were far better than rosiglitazone and the other isolated compounds in enhancing adipogenesis, stimulating 2-NBDG uptake and increasing adiponectin secretion at all the concentrations tested. These suggest the antidiabetic potential of S. aqueum leaf extract and its six bioactive compounds. However, further molecular interaction studies to explain the mechanisms of action are highly warranted.