Obesity may cause behavioral alterations, while maternal obesity can contribute to metabolic disorders in subsequent generations. The effect of β-glucan-rich Pleurotus pulmonarius (βgPp) was investigated on mouse neurobehavior and hippocampus and its offspring's hippocampus development. Female ICR mice were fed with normal diet (ND), ND with βgPp, high-fat diet (HFD), or HFD with βgPp for 3 months followed by behavioral test and mating. Immunohistochemistry for the expression of neuronal nuclear protein (NeuN) and ionized calcium binding adaptor molecule-1 (Iba-1) in the hippocampus was carried out. βgPp significantly enhanced short-term object recognition memory in HFD-fed mice. βgPp also ameliorated the histological alterations and neuronal loss and increased Iba-1-positive microglia in the hippocampus regions of HFD-fed mice and their male offspring. These findings demonstrated that βgPp supplementation attenuated the effects of HFD on object recognition memory and the alterations on the hippocampal regions of maternal mice and their male offspring.
Vietnamese coriander (Polygonum odoratum Lour.) is a plant native to northern Thailand. The biological activities of P. odoratum Lour. extract (POE) include antibacterial, antiviral, and expectorant. However, the effect of POE on intestinal smooth muscle motility is unclear. The aim of this study was to evaluate the relaxant effects of POE on isolated rat ileum. Propranolol (1 μM), calcium chloride (1-20 mM), and Nω-nitro-l-arginine methylester (l-NAME, 100 μM) were used to investigate the mechanisms of action. The results showed that POE (0.01-5 mg/mL) reduced KCl-induced contraction. In addition, POE (1 mg/mL) reduced the contraction by propranolol and l-NAME and attenuated CaCl2-induced contractions. Our results indicate that the relaxation effect of POE on ileum contractions seems to involve nitric oxide and β-adrenergic pathways, and blockade of calcium influx. These findings provide a pharmacological basis for the traditional use of POE to treat gastrointestinal disorders such as irritable bowel syndrome or diarrhea.
Changes in weather often trigger a myriad of negative impacts on the environment, which eventually affect human health. During the early months of 2016, Malaysia experienced El Niño, with an extremely dry season of almost zero rainfall. At the same time, an increase of more than twofold in fecal secretary immunoglobulin-A (SIgA) levels of healthy preschool children aged 2-6 years was observed, accompanied by an increase in phylum Bacteroidetes, predominantly attributed to genus Bacteroides and Odoribacter, which also positively correlated with fecal SIgA levels. Here, we present evidence to illustrate the detrimental effects of weather change on a microscopic "environment," the human gut ecosystem. We also discuss the protective effects of probiotic against dysbiosis as induced by weather change. The increase in Bacteroidetes was at an expense of decreased genus Faecalibacterium and Veillonella (phylum Firmicutes), whereas children consuming probiotic had a decrease in genus Collinsella, Atopobium, and Eggerthella (phylum Actinobacteria) instead.
Aging is an inevitable and ubiquitous progress that affects all living organisms. A total of 18 strains of lactic acid bacteria (LAB) were evaluated on the activation of adenosine monophosphate-activated protein kinase (AMPK), an intracellular energy sensor mediating lifespan extension. The cell-free supernatant (CFS) of Lactobacillus fermentum DR9 (LF-DR9), Lactobacillus paracasei OFS 0291 (LP-0291), and Lactobacillus helveticus OFS 1515 (LH-1515) showed the highest activation of AMPK and was further evaluated. The phosphorylation of AMPK by these three LAB strains was more evident in U2OS and C2C12 cells, compared to the other cell lines and control (P
The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3',5'-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension.
Hypertension, one of the famous "silent killers" that can attack people at any age, is a current hot topic among scientists due to multiple syndromic behavior and concomitant diseases. The new scientific-based Traditional Chinese Medicine (TCM) formulation approach was used in a previous study by combining five TCM herbs, including Gastrodia elata Bl., Uncaria rhynchophylla (Miq.) Miq. ex Havil., Pueraria thomsonii Benth., Panax notoginseng (Burk.) F.H. Chen, and Alisma orientalis (Sam.) Juzep in optimized ratio (named BPAid). The objective of the present study was to evaluate the mechanism pathways employed by BPAid for vasodilatory effect with the use of an in vitro isolated aortic rings assay. Interestingly, all the mechanisms investigated were involved in the BPAid's vasodilation activity in which the majority contributed through the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) pathways, followed by prostacyclin (PGI2), β2-adrenergic, and M3-receptors pathways. Furthermore, the BPAid appeared to manage vascular tone by regulating action potential through potassium and both voltage-operated calcium channel and inositol triphosphate receptor (IP3R) pathways. The results obtained has confirmed the expected outcome that the benefits of TCM herbs in BPAid can meet the criteria of counteracting multiple signaling mechanism pathways involved in the etiology of hypertension. In addition to this study, the fingerprints and chemical properties of BPAid was identified by using tri-step Fourier transform infrared spectroscopy and compared with its derivatives. The results obtained suggested that the majority of the vasodilatory effects exerted by BPAid were attributed to the presence of saponins and aromatic ring-containing vasoactive compounds.
Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel.
Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L25 (5(5)) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed.
Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.
There is an exponential increase in dementia in old age at a global level because of increasing life expectancy. The prevalence of neurodegenerative diseases such as dementia and Alzheimer's disease (AD) will continue to rise steadily, and is expected to reach 42 million cases worldwide in 2020. Despite the advancement of medication, the management of these diseases remains largely ineffective. Therefore, it is vital to explore novel nature-based nutraceuticals to mitigate AD and other age-related neurodegenerative disorders. Mushrooms and their extracts appear to hold many health benefits, including immune-modulating effects. A number of edible mushrooms have been shown to contain rare and exotic compounds that exhibit positive effects on brain cells both in vitro and in vivo. In this review, we summarize the scientific information on edible and culinary mushrooms with regard to their antidementia/AD active compounds and/or pharmacological test results. The bioactive components in these mushrooms and the underlying mechanism of their activities are discussed. In short, these mushrooms may be regarded as functional foods for the mitigation of neurodegenerative diseases.
Quercetin could have profound effects on uterine morphology and proliferation, which are known to be influenced by estrogen. This study investigated the effect of quercetin on these uterine parameters in the presence and in the absence of estrogen. Ovariectomized adult female rats received peanut oil, quercetin (10, 50, and 100 mg/kg/day), estrogen, or estrogen+quercetin (10, 50, or 100 mg/kg/day) treatment for 7 consecutive days. At the end of the treatment, uteri were harvested for histological and molecular biological analyses. Distribution of proliferative cell nuclear antigen (PCNA) protein in the uterus was observed by immunohistochemistry. Levels of expression of PCNA protein and mRNA in uterine tissue homogenates were determined by Western blotting and real-time polymerase chain reaction, respectively. Our findings indicated that administration of 10 mg/kg/day of quercetin either alone or with estrogen resulted in decreased uterine expression of PCNA protein and mRNA with the percentage of PCNA-positive cells in uterine luminal and glandular epithelia markedly reduced compared with estrogen-only treatment. Changes in uterine morphology were the opposite of changes observed following estrogen treatment. Treatment with 100 mg/kg/day of quercetin either alone or with estrogen resulted in elevated PCNA protein and mRNA expression. In addition, the percentages of PCNA-positive cells in the epithelia, which line the lumen and glands, were increased with morphological features mimicking changes that occur following estrogen treatment. Following 50 mg/kg/day quercetin treatment, the changes observed were in between those changes that occur following 10 and 100 mg/kg/day quercetin treatment. In conclusion, changes in uterine morphology and proliferation following 10 mg/kg/day quercetin treatment could be attributed to quercetin's antiestrogenic properties, while changes that occur following 100 mg/kg/day quercetin treatment could be attributed to quercetin's estrogenic properties.
Synsepalum dulcificum or the "miracle fruit" is well known for its taste-modifying ability. The aim of this review was to assess the published medically beneficial as well as potential characteristics of this fruit. A search in three databases, including PubMed, ScienceDirect, and Google Scholar, was made with appropriate keywords. The resulting articles were screened in different stages based on the title, abstract, and content. A total of nine articles were included in this review. This review summarized the findings of previously published studies on the effects of miracle fruit. The main studied characteristic of the fruit was its effect on the taste receptors, resulting in the sweet sensation when substances with acidic content were ingested. This effect was shown to be related to a glycoprotein called "miraculin." Other beneficial characteristics of this fruit were its antioxidant and anticancer abilities that are due to the various amides existing in the miracle fruit. Apart from the above, the other observed effect of this fruit was its antidiabetic effect that was tested in rats. Further studies should be conducted to establish the findings. The miracle fruit can be a healthy additive due to its unique characteristics, including sour taste sensation modification as well as its antioxidant and antidiabetic effects.
This study evaluated the effectiveness and safety of Labisia pumila var alata (L. pumila) water extract for improving quality of life, cardiovascular and hormonal balance. A randomized, double-blind, placebo-controlled, parallel group, 16-week study in healthy pre- and postmenopausal women aged 40-60 years was conducted in Kelantan, Malaysia. The subjects were randomized to 400 mg propriety extract of L. pumila or placebo. A Women's Health Questionnaire was used to assess quality of life. Repeated-measures analysis of variance was used to evaluate the data. A total of 197 subjects (L. pumila: n=102 and placebo: n=95) were analyzed. Subjects in the herbal group showed improved memory/concentration, vasomotor symptoms, menstrual symptoms, and sleep problems by 8.3%, 15.9%, 11.8%, and 31.0%, respectively. The greatest improvement was observed for the question: "I get frightened or panic feelings for apparently no reason at all" with a 53% decrease as compared with placebo. Improvements were also seen in the cardiovascular parameters, and the safety profiles were normal. Postmenopausal women supplemented with L. pumila showed no changes in gynecological relevant hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), and 17β-Estradiol. Water extract of L. pumila was shown to be safe and effective for improving several parameters of quality of life and cardiovascular risks factors (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C]).
Nigella sativa, commonly referred as black cumin, is a popular spice that has been used since the ancient Egyptians. It has traditionally been used for treatment of various human ailments ranging from fever to intestinal disturbances to cancer. This study investigated the apoptotic, antimetastatic, and anticancer activities of supercritical carbon dioxide (SC-CO2) extracts of the seeds of N. sativa Linn. against estrogen-dependent human breast cancer cells (MCF-7). Twelve extracts were prepared from N. sativa seeds using the SC-CO2 extraction method by varying pressure and temperature. Extracts were analyzed using FTIR and UV-Vis spectrometry. Cytotoxicity of the extracts was evaluated on various human cancer and normal cell lines. Of the 12 extracts, 1 extract (A3) that was prepared at 60°C and 2500 psi (~17.24 MPa) showed selective antiproliferative activity against MCF-7 cells with an IC50 of 53.34±2.15 μg/mL. Induction of apoptosis was confirmed by evaluating caspases activities and observing the cells under a scanning electron microscope. In vitro antimetastatic properties of A3 were investigated by colony formation, cell migration, and cell invasion assays. The elevated levels of caspases in A3 treated MCF-7 cells suggest that A3 is proapoptotic. Further nuclear condensation and fragmentation studies confirmed that A3 induces cytotoxicity through the apoptosis pathway. A3 also demonstrated remarkable inhibition in migration and invasion assays of MCF-7 cells at subcytotoxic concentrations. Thus, this study highlights the therapeutic potentials of SC-CO2 extract of N. sativa in targeting breast cancer.
Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.
Orthosiphon stamineus Benth. (Lambiaceae) is an important plant in traditional folk medicine. This review is a comprehensive summary of the currently available chemical, pharmacological, and toxicological investigations as well as the traditional and therapeutic uses of this plant. Different in vitro and in vivo models have been addressed along with a survey of all phytochemicals identified in this plant, including flavonoids, terpenoids, and essential oils. Previous studies revealed that O. stamineus possesses several pharmacological activities, which are attributed to its phytochemical content. It was found that O. stamineus exhibits diuretic, hypouricemic, renal protective, antioxidant, anti-inflammatory, hepatoprotective, gastroprotective, antihypertensive, antidiabetic, antihyperlipidemic, antimicrobial, and anorexic activities. In conclusion, O. stamineus has wide traditional and pharmacological uses in various pathophysiological conditions. Therefore, it is an attractive subject for further experimental and clinical investigations.
Oil palm (Elaeis guineensis) leaf extract (OPLE) possesses good ex vivo vasodilation and antioxidant properties. This study evaluated the catechin-rich OPLE antioxidant, antihypertensive, and cardiovascular effects in normal and nitric oxide (NO)-deficient hypertensive rats. OPLE was administered orally (500 mg/kg of body weight/day) to normotensive Wistar rats and N(ω)-nitro-L-arginine methyl ester (L-NAME)-induced NO-deficient hypertensive rats. OPLE significantly (P
This study was designed to investigate the comparative in vivo cardiovascular protective effects of red, green, and brown tropical seaweeds, namely, Kappaphycus alvarezii (or Eucheuma cottonii), Caulerpa lentillifera, and Sargassum polycystum, in rats fed on high-cholesterol/high-fat (HCF) diets. Male Sprague-Dawley rats (weighing 260-300 g) on the HCF diet had significantly increased body weight, plasma total cholesterol (TC), plasma low-density lipoprotein cholesterol (LDL-C), plasma triglycerides (TG), lipid peroxidation, and erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase levels after 16 weeks. Supplementing 5% seaweeds to HCF diet significantly reduced plasma TC (-11.4% to -18.5%), LDL-C (-22% to -49.3%), and TG (-33.7% to -36.1%) levels and significantly increased HDL-C levels (16.3-55%). Among the seaweeds, S. polycystum showed the best anti-obesity and blood GSH-Px properties, K. alvarezii showed the best antihyperlipemic and in vivo antioxidation effects, and C. lentillifera was most effective at reducing plasma TC. All seaweeds significantly reduced body weight gain, erythrocyte GSH-Px, and plasma lipid peroxidation of HCF diet rats towards the values of normal rats.
Orthosiphon stamineus Benth., which is used as a gastroprotective herbal remedy in Malaysia, was assessed for its anti-ulcerogenic activity against ethanol-induced ulcers in rats. Fifty percent methanol was used to extract the oven-dried O. stamineus leaves. The extract was then lyophilized with a rotary evaporator and freeze-dried. Oral administration of O. stamineus methanolic extract (OSME) (125, 250, 500, and 1,000 mg/kg) was found to significantly decrease the ulcer index (P < .01, P < .001, P < .001, and P < .001, respectively). Histological study of a section of the rat stomach also showed a marked improvement in the gastric mucosal damage in groups receiving OSME. In order to further investigate the gastroprotective mechanism of OSME, mucus secretion and lipid peroxidation level were estimated in vitro and ex vivo. OSME exhibited dose-dependent stimulation of mucus secretion (r = 0.718, P < .001) and inhibition of lipid peroxidation in rat gastric mucosal homogenates (both in vitro [r = 0.819, P < .05] and ex vivo [r = 0.981, P < .05]). It was concluded that the gastroprotective mechanism of OSME was partly due to its ability to inhibit lipid peroxidation and stimulate gastric mucus secretion.
Auricularia auricula-judae is currently grown in Malaysia. In the present study, the methanolic extracts from fruit bodies (fresh, oven-dried, and freeze-dried) and mycelium of A. auricula-judae were evaluated for their antioxidant capacities based on 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and ferric reducing antioxidant power (FRAP) assay. The total phenolic content in the extracts were also measured. The extract of freeze-dried fruit bodies of A. auricula-judae had potent DPPH free radical scavenging activity with a 50% effective concentration of 2.87 mg/mL, whereas the FRAP value of A. auricula-judae mycelium was 5.22 micromol of FeSO(4).7H(2)O equivalents/g of mycelium sample. Further, a positive correlation (R(2) = 0.7668) between FRAP level of A. auricula-judae extracts and the total phenolic contents was observed. Thus the method of processing of fresh fruit bodies had an effect on the antioxidant potential of A. auricula-judae.