The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment.
13 selected purslane accessions were subjected to five salinity levels 0, 8, 16, 24, and 32 dS m(-1). Salinity effect was evaluated on the basis of biomass yield reduction, physiological attributes, and stem-root anatomical changes. Aggravated salinity stress caused significant (P < 0.05) reduction in all measured parameters and the highest salinity showed more detrimental effect compared to control as well as lower salinity levels. The fresh and dry matter production was found to increase in Ac1, Ac9, and Ac13 from lower to higher salinity levels but others were badly affected. Considering salinity effect on purslane physiology, increase in chlorophyll content was seen in Ac2, Ac4, Ac6, and Ac8 at 16 dS m(-1) salinity, whereas Ac4, Ac9, and Ac12 showed increased photosynthesis at the same salinity levels compared to control. Anatomically, stem cortical tissues of Ac5, Ac9, and Ac12 were unaffected at control and 8 dS m(-1) salinity but root cortical tissues did not show any significant damage except a bit enlargement in Ac12 and Ac13. A dendrogram was constructed by UPGMA based on biomass yield and physiological traits where all 13 accessions were grouped into 5 clusters proving greater diversity among them. The 3-dimensional principal component analysis (PCA) has also confirmed the output of grouping from cluster analysis. Overall, salinity stressed among all 13 purslane accessions considering biomass production, physiological growth, and anatomical development Ac9 was the best salt-tolerant purslane accession and Ac13 was the most affected accession.
Obesity and obesity-related complications are on the increase both in the developed and developing world. Since existing pharmaceuticals fail to come up with long-term solutions to address this issue, there is an ever-pressing need to find and develop new drugs and alternatives. Natural products, particularly medicinal plants, are believed to harbor potential antiobesity agents that can act through various mechanisms either by preventing weight gain or promoting weight loss amongst others. The inhibition of key lipid and carbohydrate hydrolyzing and metabolizing enzymes, disruption of adipogenesis, and modulation of its factors or appetite suppression are some of the plethora of targeted approaches to probe the antiobesity potential of medicinal plants. A new technology such as metabolomics, which deals with the study of the whole metabolome, has been identified to be a promising technique to probe the progression of diseases, elucidate their pathologies, and assess the effects of natural health products on certain pathological conditions. This has been applied to drug research, bone health, and to a limited extent to obesity research. This paper thus endeavors to give an overview of those plants, which have been reported to have antiobesity effects and highlight the potential and relevance of metabolomics in obesity research.
Dehalogenase E (DehE) is a non-stereospecific enzyme produced by the soil bacterium, Rhizobium sp. RC1. Till now, the catalytic mechanism of DehE remains unclear although several literature concerning its structure and function are available. Since DehE is non-stereospecific, the enzyme was hypothesized to follow a 'direct attack mechanism' for the catalytic breakdown of a haloacid. For a molecular insight, the DehE modelled structure was docked in silico with the substrate 2-chloropropionic acid (2CP) in the active site. The ideal position of DehE residues that allowed a direct attack mechanism was then assessed via molecular dynamics (MD) simulation. It was revealed that the essential catalytic water was hydrogen bonded to the 'water-bearer', Asn114, at a relatively constant distance of ∼2.0 Å after 50 ns. The same water molecule was also closely sited to the catalytic Asp189 at an average distance of ∼2.0 Å, signifying the imperative role of the latter to initiate proton abstraction for water activation. This reaction was crucial to promote a direct attack on the α-carbon of 2CP to eject the halide ion. The water molecule was oriented favourably towards the α-carbon of 2CP at an angle of ∼75°, mirrored by the formation of stable enzyme-substrate orientations throughout the simulation. The data therefore substantiated that the degradation of a haloacid by DehE followed a 'direct attack mechanism'. Hence, this study offers valuable information into future advancements in the engineering of haloacid dehalogenases with improved activity and selectivity, as well as functionality in solvents other than water.
Efficacy of a β-1,4-glucosidase from Trichoderma harzianum T12 (ThBglT12) in disrupting the cell wall of the phytopathogenic fungus M. phaseolina (Macrophomina phaseolina) was studied, as the underlying molecular mechanisms of cell wall recognition remains elusive. In this study, the binding location identified by a consensus of residues predicted by COACH tool, blind docking, and multiple sequence alignment revealed that molecular recognition by ThBglT12 occurred through interactions between the α-1,3-glucan, β-1,3-glucan, β-1,3/1,4-glucan, and chitin components of M. phaseolina, with corresponding binding energies of -7.4, -7.6, -7.5 and -7.8 kcal/mol. The residue consensus verified the participation of Glu172, Tyr304, Trp345, Glu373, Glu430, and Trp431 in the active site pocket of ThBglT12 to bind the ligands, of which Trp345 was the common interacting residue. Root mean square deviation (RMSD), root mean square fluctuation (RMSF), total energy, and minimum distance calculation from molecular dynamics (MD) simulation further confirmed the stability and the closeness of the binding ligands into the ThBglT12 active site pocket. The h-bond occupancy by Glu373 and Trp431 instated the role of the nucleophile for substrate recognition and specificity, crucial for cleaving the β-1,4 linkage. Further investigation showed that the proximity of Glu373 to the anomeric carbon of β-1,3/1,4-glucan (3.5 Å) and chitin (5.5 Å) indicates the nucleophiles' readiness to form enzyme-substrate intermediates. Plus, the neighboring water molecule appeared to be correctly positioned and oriented towards the anomeric carbon to hydrolyze the β-1,3/1,4-glucan and chitin, in less than 4.0 Å. In a nutshell, the study verified that the ThBglT12 is a good alternative fungicide to inhibit the growth of M. phaseolina.Communicated by Ramaswamy H. Sarma.
Cisplatin is a potent platinum-based anticancer drug approved by the Food Drug Administration (FDA) in 1978. Despite its advantages against solid tumors, cisplatin confers toxicity to various tissues that limit its clinical uses. In cisplatin-induced hepatotoxicity, few mechanisms have been identified, which started as excess generation of reactive oxygen species that leads to oxidative stress, inflammation, DNA damage and apoptosis in the liver. Various natural products, plant extracts and oil rich in flavonoids, terpenoids, polyphenols, and phenolic acids were able to minimize oxidative stress by restoring the level of antioxidant enzymes and acting as an anti-inflammatory agent. Likewise, treatment with honey and royal jelly was demonstrated to decrease serum transaminases and scavenge free radicals in the liver after cisplatin administration. Medicinal properties of these natural products have a promising potential as a complementary therapy to counteract cisplatin-induced hepatotoxicity. This review concentrated on the protective role of several natural products, which has been proven in the laboratory findings to combat cisplatin-induced hepatotoxicity.
Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.
Alpha-lipoic acid, a potent antioxidant with multifarious pharmacological benefits has been reported to be neuroprotective in several neuronal models and used to treat neurological disorders such as Alzheimer's disease. Nonetheless, conclusive mechanisms of alpha-lipoic acid for its protective effects particularly in NG108-15 cells have never been investigated. In this study, the intricate neuroprotective molecular mechanisms by (R)-(+)-alpha-lipoic acid (R-LA) against H2O2-induced cell death in an in vitro model of neurodegeneration were elucidated. Pretreatment with R-LA (2 hours) significantly increased NG108-15 cell viability as compared to H2O2-treated cells and mitigated the induction of apoptosis as evidenced by Hoechst 33342/propidium iodide staining. R-LA (12.5-50 μM) aggrandized the reduced glutathione over glutathione disulfide ratio followed by a reduction in the intracellular reactive oxygen species level and an increase in mitochondrial membrane potential following H2O2 exposure. Moreover, pretreatment with R-LA stimulated the activation of PI3K-Akt through mTORC1 and mTORC2 components (mTOR, rictor and raptor) and production of antiinflammatory cytokine, IL-10 which led to the inactivation of glycogen synthase kinase-3β (GSK-3β) and reduction of both Bax/Bcl2 and Bax/Bcl-xL ratios, accompanied by inhibition of the cleaved caspase-3. Additionally, this observation was preceded by the suppression of NF-κβ p65 translocation and production of proinflammatory cytokines (IL-6 and TNF-α). The current findings accentuate new mechanistic insight of R-LA against apoptogenic and brain inflammatory factors in a neuronal model. These results further advocate the therapeutic potential of R-LA for the treatment of neurodegenerative diseases.
ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata known as "the cancer killer" has been widely used in the traditional medicine for the treatment of cancer and tumors. The purpose of this study is to investigate the anticancer properties of ethyl acetate extract of Annona muricata leaves (EEAM) on HT-29 and HCT-116 colon cancer cells and the underlying mechanisms.
MATERIALS AND METHODS: The effect of EEAM on the cell proliferation of HT-29 and HCT-116 cells was analyzed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. High content screening system (HCS) was applied to investigate the cell membrane permeability, mitochondrial membrane potential (MMP), nuclear condensation and cytochrome c translocation from mitochondria to cytosol. Reactive oxygen species (ROS) formation, lactate dehydrogenase (LDH) release and activation of caspase-3/7, -8 and -9 were measured while treatment. Flow cytometric analysis was used to determine the cell cycle distribution and phosphatidylserine externalization. The protein expression of Bax and Bcl-2 was determined using immunofluorescence analysis. In addition, the potential of EEAM to suppress the migration and invasion of colon cancer cells was also examined.
RESULTS: EEAM exerted significant cytotoxic effects on HCT-116 and HT-29 cells as determined by MTT and LDH assays. After 24 h treatment, EEAM exhibited the IC₅₀ value of 11.43 ± 1.87 µg/ml and 8.98 ± 1.24 µg/ml against HT-29 and HCT-116 cells, respectively. Flow cytometric analysis demonstrated the cell cycle arrest at G1 phase and phosphatidylserine externalization confirming the induction of apoptosis. EEAM treatment caused excessive accumulation of ROS followed by disruption of MMP, cytochrome c leakage and activation of the initiator and executioner caspases in both colon cancer cells. Immunofluorescence analysis depicted the up-regulation of Bax and down-regulation of Bcl-2 proteins while treated with EEAM. Furthermore, EEAM conspicuously blocked the migration and invasion of HT-29 and HCT-116 cells.
CONCLUSIONS: These findings provide a scientific basis for the use of A. muricata leaves in the treatment of cancer, although further in vivo studies are still required.
Swietenia macrophylla King is a traditional herb used to treat various diseases including hypertension, diabetes and cancer. Previous study demonstrated its anti-tumor effect but the potential mechanisms have not been clearly defined. The current study was to further investigate the underlying mechanism of ethyl acetate fraction of Swietenia macrophylla (SMEAF)-induced anti-proliferative effect and apoptosis in HCT116 colorectal carcinoma cell.
Annona muricata has been used in folk medicine for the treatment of cancer and tumors. This study evaluated the chemopreventive properties of an ethyl acetate extract of A. muricata leaves (EEAML) on azoxymethane-induced colonic aberrant crypt foci (ACF) in rats. Moreover, the cytotoxic compound of EEAML (Annomuricin E) was isolated, and its apoptosis-inducing effect was investigated against HT-29 colon cancer cell line using a bioassay-guided approach. This experiment was performed on five groups of rats: negative control, cancer control, EEAML (250 mg/kg), EEAML (500 mg/kg) and positive control (5-fluorouracil). Methylene blue staining of colorectal specimens showed that application of EEAML at both doses significantly reduced the colonic ACF formation compared with the cancer control group. Immunohistochemistry analysis showed the down-regulation of PCNA and Bcl-2 proteins and the up-regulation of Bax protein after administration of EEAML compared with the cancer control group. In addition, an increase in the levels of enzymatic antioxidants and a decrease in the malondialdehyde level of the colon tissue homogenates were observed, suggesting the suppression of lipid peroxidation. Annomuricin E inhibited the growth of HT-29 cells with an IC50 value of 1.62 ± 0.24 μg/ml after 48 h. The cytotoxic effect of annomuricin E was further substantiated by G1 cell cycle arrest and early apoptosis induction in HT-29 cells. Annomuricin E triggered mitochondria-initiated events, including the dissipation of the mitochondrial membrane potential and the leakage of cytochrome c from the mitochondria. Prior to these events, annomuricin E activated caspase 3/7 and caspase 9. Upstream, annomuricin E induced a time-dependent upregulation of Bax and downregulation of Bcl-2 at the mRNA and protein levels. In conclusion, these findings substantiate the usage of A. muricata leaves in ethnomedicine against cancer and highlight annomuricin E as one of the contributing compounds in the anticancer activity of A. muricata leaves.
Dioscorea bulbifera, also known as air potato, has been cultivated as food crop mainly in tropical countries in Asia and Australia. The tubers are edible and have often been used in Traditional Chinese Medicine (TCM) and Ayurvedic medicine to treat cancer, diabetes, thyroid disease, and inflammation. This study aimed to investigate the effects of D. bulbifera on HCT116 human colorectal carcinoma cells and to unravel the plausible mechanisms underlying its apoptotic effects. The ethanol crude and fractions (hexane, ethyl acetate and water) of D. bulbifera were subjected to cell viability MTT assay against various cancer cell lines. The lowest IC50 of the extract and fractions on selected cancer cells were selected for further apoptosis assay and western blot analysis. HCT116 cancer cells were treated with D. bulbifera and stained with Annexin/PI or Hoechst 33342/PI for preliminary confirmation of apoptosis. The dissipation of mitochondria membrane potential (MMP) was determined by flow cytometry. The protein expressions of apoptosis-related proteins such as Bcl-2 family, caspases, Fas, PARP, ERK1/2 and JNK were detected by western blot analysis. Moreover, the HCT116 cells were treated with UO126 and SP600125 inhibitors to verify the involvement of ERK1/2 and JNK protein expressions in inducing apoptotic cell death. Based on the result, D. bulbifera ethyl acetate fraction (DBEAF) exhibited the most compelling cytotoxicity on HCT116 cells with an IC50 of 37.91 ± 1.30 µg/mL. The induction of apoptosis was confirmed by phosphatidylserine externalization and chromatin condensation. Depolarization of MMP further conferred the induction of apoptosis was through the regulation of Bcl-2 family proteins. Activation of caspase cascades (caspase-3, -9, -8 and -10) was elicited followed by the observation of cleaved PARP accumulation in DBEAF-treated cells. Furthermore, death receptor, Fas was activated upon exposure to DBEAF. Collective apoptotic evidences suggested the involvement of intrinsic and extrinsic pathways by DBEAF in HCT116 cells. Interestingly, the attenuation of ERK1/2 phosphorylation accompanied by the activation of JNK was detected in DBEAF-treated cells. In conclusion, the findings revealed that DBEAF induced apoptosis through intrinsic and extrinsic pathways involving ERK1/2 and JNK.
Seaweed is one of the largest producers of biomass in marine environment and is a rich arsenal of active metabolites and functional ingredients with valuable beneficial health effects. Being a staple part of Asian cuisine, investigations on the crude extracts of Phaeophyceae or brown algae revealed marked antitumor activity, eliciting a variety of research to determine the active ingredients involved in this potential. The sulfated polysaccharide of fucoidan and carotenoid of fucoxanthin were found to be the most important active metabolites of brown algae as potential chemotherapeutic or chemopreventive agents. This review strives to provide detailed account of all current knowledge on the anticancer and antitumor activity of fucoidan and fucoxanthin as the two major metabolites isolated from brown algae.
Pistachio (Pistacia vera L.) hulls (PVLH) represents a significant by-product of industrial pistachio processing that contains high amounta of phenolic and flavonoid compounds known to act as antioxidants. The current study was designed to evaluate the anti-tumor and anti-angiogenic potentials of PVLH extracts. The cytotoxic effects of hexane, ethyl acetate, methanol, and water PVLH extracts toward human colon cancer (HT-29 and HCT-116), breast adenocarcinoma (MCF-7), lung adenocarcinoma (H23), liver hepatocellular carcinoma (HepG2), cervical cancer (Ca Ski), and normal fibroblast (BJ-5ta) cells were assessed using a MTT cell viability assay. Apoptosis induction was evaluated through the different nuclear staining assays and confirmed by flow cytometry analysis. Anti-angiogenic activities were also determined using chorioallantoic membrane (CAM) assay. PVLH ethyl acetate extracts (PVLH-EAE) demonstrated a suppressive effect with an IC50 value of 21.20 ± 1.35, 23.00 ± 1.2 and 25.15 ± 1.85 µg/mL against MCF-7, HT-29 and HCT-116, respectively, after 72 h of treatment. Morphological assessment and flow cytometry analysis showed the potential of PVLH-EAE to induce apoptosis. PVLH-EAE at the highest concentration demonstrated significant inhibition of angiogenesis as comparing with control group. Also the expression of Bax increased and the expression of Bcl-2 decreased in treated MCF-7 cells. Thus, the apoptosis induction and angiogenesis potential of PVLH-EAE make it to be the most suitable for further cancer research study to deal with selective antitumor active substances to human cancers especially breast cancer.
The effects of long-term administration of tocotrienol on hepatocarcinogenesis in rats induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) were investigated by determining the activities of gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), glutathione S-transferases (GSTs), and glutathione (GSH) levels in blood and liver. Twenty-eight male 7- to 8-wk-old Rattus norwegicus rats, weighing 120-160 g, were used in this study. The rats were divided into four treatment groups: a control group on a basal diet, a group fed a basal diet supplemented with tocotrienol (30 mg/kg food), a group treated with DEN/AAF, and a group treated with DEN/AAF and fed a diet supplemented with tocotrienol (30 mg/kg food). Blood was collected monthly, and GGT, ALP, and GSH levels were determined. The rats were killed after 9 mo, and the livers were examined morphologically. Grayish white nodules (2/liver) were found in all the DEN/AAF-treated rats (n = 10), but only one of the rats treated with DEN/AAF and supplemented with tocotrienol (n = 6) had liver nodules. A significant increase in the level of blood and liver GSH, ALP, and GGT activities was observed in the DEN/AAF-treated rats. Liver GSTs were similarly increased with DEN/AAF treatment. Tocotrienol supplementation attenuated the impact of the carcinogens in the rats.
The effect of tocotrienol on the activities of glutathione S-transferases (GSTs), glutathione reductase (GR) and glutathione peroxidase (GPx) in rats given 2-acetylaminofluorene (AAF) was investigated over a 20 week period. Liver and kidney GST and liver GR activities were significantly increased after AAF administration. Kidney GPx activities were significantly affected; activity assayed with cumene hydroperoxide (cu-OOH) was increased but activity assayed with H2O2 was reduced. Supplementation of the diet with tocotrienol in the AAF-treated rats reduced the increase in enzyme activities. Tocotrienol on its own had no effect on the enzyme activities.
The clinical value of tocotrienols is increasingly appreciated because of the unique therapeutic effects that are not shared by tocopherols. However, their effect on metabolic syndrome is not well-established. This study aimed to investigate the effects of a tocotrienol-rich fraction (TRF) from palm oil in high-fat-diet-treated rats. Male, post-weaning Sprague Dawley rats were provided high-fat (60% kcal) diet for eight weeks followed by a TRF (60 mg/kg) treatment for another four weeks. Physical, metabolic, and histological changes were compared to those on control and high-fat diets respectively. High-fat feeding for eight weeks induced all hallmarks of metabolic syndrome. The TRF reversed systolic and diastolic hypertension, hypercholesterolemia, hepatic steatosis, impaired antioxidant defense, and myeloperoxidase hyperactivity triggered by the high-fat diet. It also conferred an inhibitory effect on protein glycation to reduce glycated hemoglobin A1c and advanced glycation end products (AGE). This was accompanied by the suppression of the receptor for advanced glycation end product (RAGE) expression in the liver. The treatment effects on visceral adiposity, glycemic control, triglyceride level, as well as peroxisome proliferator-activated receptor α and γ expression were negligible. To conclude, treatment with a TRF exhibited protective effects on the cardiovascular and liver health in addition to the amelioration of plasma redox imbalance and AGE-RAGE activation. Further investigation as a therapy for metabolic syndrome is therefore worthwhile.
Matched MeSH terms: Advanced Glycosylation End Product-Specific Receptor/metabolism*; Glycosylation End Products, Advanced/metabolism*
11 beta-Hydroxysteroid dehydrogenase (11 beta-OHSD) is a microsomal enzyme that catalyzes the dehydrogenation of cortisol (F) to cortisone (E) in man and corticosterone (B) to 11-dehydrocorticosterone (A) in rats. 11 beta-OHSD has been identified in a wide variety of tissues. The differential distribution of 11 beta-OHSD suggests that this enzyme has locally defined functions that vary from region to region. The aim of this study was to investigate the effects of the glucocorticoids B and dexamethasone (DM), the mineralocorticoid deoxycorticosterone (DOC), and the inhibitors of 11 beta-OHSD glycyrrhizic acid (Gl) and glycyrrhetinic acid (GE) on 11 beta-OHSD bioactivity at the hypothalamus (HT) and anterior pituitary (AP). Male Wistar rats were treated with GI or were adrenalectomized (ADX) and treated with either B, DM, or DOC for 7 days. All treatments were in vivo except GE, which was used in vitro. At the end of treatment, homogenates of HT and AP were assayed for 11 beta-OHSD bioactivity, expressed as the percentage conversion of B to A in the presence of NADP, 11 beta-OHSD bioactivity is significantly higher (P < 0.0001) in the AP compared with the HT. Adrenalectomy significantly increased the enzyme activity in the AP (P < 0.05), an effect reversed by B or DM. ADX rats treated with DOC showed decreased enzyme activity in the AP (P < 0.001) but increased the activity in the HT (P < 0.0001). Gl increased activity in both HT and AP, whereas GE decreased activity significantly. We conclude that the modulation of 11 beta-OHSD is both steroid specific and tissue specific.
In this study the effects of vitamin E deficiency and supplementation on bone calcification were determined using 4-month-old female Sprague-Dawley rats. The rats weighed between 180 and 200 g. The study was divided in three parts. In experiment I the rats were given normal rat chow (RC, control group), a vitamin E deficient (VED) diet or a 50% vitamin E deficient (50%VED) diet. In experiment 2 the rats were given VED supplemented with 30 mg/kg palm vitamin E (PVE30), 60 mg/kg palm vitamin E (PVE60) or 30 mg/kg pure alpha-tocopherol (ATF). In experiment 3 the rats were fed RC and given the same supplements as in experiment 2. The treatment lasted 8 months. Vitamin E derived from palm oil contained a mixture of ATF and tocotrienols. Rats on the VED and 50%VED diets had lower bone calcium content in the left femur compared to the RC group (91.6 +/- 13.3 mg and 118.3 +/- 26.0 mg cf 165.7 +/- 15.2 mg; P < 0.05) and L5 vertebra (28.3 +/- 4.0 mg and 39.5 +/- 6.2 mg compared with 51.4 +/- 5.8 mg; P < 0.05). Supplementing the VED group with PVE60 improved bone calcification in the left femur (133.6 +/- 5.0 mg compared with 91.6 +/- 13.3 mg; P < 0.05) and L5 vertebra (41.3 +/- 3.3 mg compared with 28.3 +/- 4.0 mg; P < 0.05) while supplementation with PVE30 improved bone calcium content in the L5 vertebra (35.6 +/- 3.1 mg compared with 28.3 +/- 4.0 mg; P < 0.05). However, supplementation with ATF did not change the lumbar and femoral bone calcium content compared to the VED group. Supplementing the RC group with PVE30, PVE60 or ATF did not cause any significant changes in bone calcium content. In conclusion, vitamin E deficiency impaired bone calcification. Supplementation with the higher dose of palm vitamin E improved bone calcium content, but supplementation with pure ATF alone did not. This effect may be attributed to the tocotrienol content of palm vitamin E. Therefore, tocotrienols play an important role in bone calcification.
Matched MeSH terms: Antioxidants/metabolism*; Bone and Bones/metabolism; Tocotrienols/metabolism*
Skeletal muscle satellite cells are heavily involved in the regeneration of skeletal muscle in response to the aging-related deterioration of the skeletal muscle mass, strength, and regenerative capacity, termed as sarcopenia. This study focused on the effect of tocotrienol rich fraction (TRF) on regenerative capacity of myoblasts in stress-induced premature senescence (SIPS). The myoblasts was grouped as young control, SIPS-induced, TRF control, TRF pretreatment, and TRF posttreatment. Optimum dose of TRF, morphological observation, activity of senescence-associated β-galactosidase (SA-β-galactosidase), and cell proliferation were determined. 50 μg/mL TRF treatment exhibited the highest cell proliferation capacity. SIPS-induced myoblasts exhibit large flattened cells and prominent intermediate filaments (senescent-like morphology). The activity of SA-β-galactosidase was significantly increased, but the proliferation capacity was significantly reduced as compared to young control. The activity of SA-β-galactosidase was significantly reduced and cell proliferation was significantly increased in the posttreatment group whereas there was no significant difference in SA-β-galactosidase activity and proliferation capacity of pretreatment group as compared to SIPS-induced myoblasts. Based on the data, we hypothesized that TRF may reverse the myoblasts aging through replenishing the regenerative capacity of the cells. However, further investigation on the mechanism of TRF in reversing the myoblast aging is needed.