Young coconut juice, a potential therapeutic agent that could significantly reduce some pathologies associated with Alzheimer's disease: novel findings

Brains from ovariectomised (ovx) rats can display features similar to those observed in menopausal women with Alzheimer's disease (AD), and oestrogen seems to play a key role. Preliminary studies on young coconut juice (YCJ) have reported the presence of oestrogen-like components in it. The aim of the study was to investigate the effects of YCJ on the AD pathological changes in the brains of ovx rats. Rat groups included sham-operated, ovx, ovx+oestradiol benzoate (EB) and ovx+YCJ. Brain sections (4?μm) were taken and were immunostained with β-amyloid (Aβ) 1-42, glial fibrillary acidic protein (GFAP) (an intermediate neurofilament of astrocytes) and Tau-1 antibodies. Aβ 1-42, GFAP and Tau-1 are considered as reliable biomarkers of amyloidosis, astrogliosis and tauopathy (neurofibrillary tangles), respectively, which in turn are characteristic features associated with AD. The serum oestradiol (E2) level was measured using a chemiluminescent immunoassay technique. YCJ restored the serum E2 to levels significantly (P?相似文献   

Phytochemicals from Goniothalamus griffithii Induce Human Cancer Cell Apoptosis

Bioactive compounds extracted from leaves and twigs of Goniothalamus griffithii include pinocembrin (PCN) and goniothalamin (GTN). The objectives of this study were to investigate the cytotoxic activities of PCN and GTN and their influence on molecular signaling for cell death in several human cancer cell lines compared to normal murine fibroblast NIH3T3 cells. GTN exhibited the most potent cytotoxicity against MCF7 > HeLa > HepG2 > NIH3T3 cells with IC50 values of 7.33, 14.8, 37.1 and 65.4 M, respectively, whereas PCN was cytotoxic only to HepG2 cells with IC50 values of ~80 M. Apoptotic cell death was confirmed by staining the cells with annexin VFITC and propidium iodide (PI) employing flow cytometry. Apoptosis was shown by externalization of phosphatidylserine in goniothalamintreated MCF7 cells in a dose response manner. Positive PIstained cells with the typical morphology of apoptotic cells were increased dosedependently. Furthermore, reduction of mitochondrial transmembrane potential was found in goniothalamintreated MCF7, HepG2 and HeLa cells. GTN treatment in MCF7 increased caspase3, 8 and 9 activities while GTNinduced HeLa cells showed an increase of both caspase3 and 9 activities. But an increased caspase8 activity was demonstrated in GTN and PCNtreated MCF7 and HepG2 cells, respectively. Taken together, GTN and PCNinduced human cancer cell apoptosis was through different molecular mechanisms or signaling pathways, which might be due to different machineries in different types of cancer cells, as evidenced by the compoundmodulated caspase activities in both intrinsic and/or extrinsic pathways.     

Induction of G1 arrest and apoptosis in androgen-dependent human prostate cancer by Kuguacin J,a triterpenoid from Momordica charantia leaf

In this study, we focused on the effects of a bitter melon (Momordica charantia) leaf extract (BMLE) and a purified component, Kuguacin J (KuJ), on androgen-dependent LNCaP human prostate cancer cells. Both treatments exerted growth inhibition through G1 arrest and induction of apoptosis. In addition, KuJ markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (Cdk2 and Cdk4) and proliferating cell nuclear antigen, and caused an increase in p21 and p27 levels. Its induction of apoptosis was accompanied by an increase in cleavage of caspase-3 and poly (ADP-ribose) polymerase, attributable to augment of Bax/Bcl-2 and Bad/Bcl-xL and reduction of survivin levels. BMLE and KuJ also reduced the expression of androgen receptor (AR), prostate-specific antigen (PSA) while induced P53 protein level. Down-regulation of p53 by RNA interference indicated that BMLE and KuJ inhibited cell growth partly through p53-dependent cell cycle arrest and apoptotic pathways. Both BMLE and KuJ caused less toxicity in a normal prostate cell line, PNT1A. Our results suggest that BMLE and a purified component, KuJ, from its diethyl ether fraction could be promising candidate new antineoplastic and chemopreventive agents for androgen-dependent prostate cancer and carcinogenesis.     

Synthesis,cytotoxicity evaluation and molecular docking studies on 2′,4′-dihydroxy-6′-methoxy-3′,5′-dimethylchalcone derivatives

2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC, 1) was isolated from seeds of Syzygium nervosum A.Cunn. ex DC. exhibiting intriguing biological activities. Herein, thirty three DMC derivatives including 4′-O-monosubstituted-DMC (2), 7-O-acylated-4-hydroxycoumarin derivatives (3), stilbene–coumarin derivatives (4), 2′,4′-disubstituted-DMC (5), and flavanone derivatives (6), were synthesised through acylation, alkylations, and sulfonylation. These semi-synthetic DMC derivatives were evaluated for in vitro cytotoxicity against six carcinoma cell lines. It was found that most derivatives exhibited higher cytotoxicity than DMC. In particular, 4′-O-caproylated-DMC (2b) and 4′-O-methylated-DMC (2g) displayed the strongest cytotoxicity against SH-SY5Y with IC₅₀ values of 5.20 and 7.52 μM, respectively. Additionally, 4′-O-benzylated-DMC (2h) demonstrated the strongest cytotoxicity against A-549 and FaDu with IC₅₀ values of 9.99 and 13.98 μM, respectively. Our structure–activity relationship (SAR) highlights the importance of 2′-OH and the derivatisation pattern of 4′-OH. Furthermore, molecular docking simulation studies shed further light on how these bioactive compounds interact with cyclin-dependent kinase 2 (CDK2).

Semi-synthetic DMC derivatives were synthesised and displayed biological potency against various cancer cell lines.      

Effect of pinocembrin isolated from Boesenbergia pandurata on xenobiotic-metabolizing enzymes in rat liver

Pinocembrin, 5, 7-dihydroxyflavanone, is one of the flavanones found in the rhizomes of Boesenbergia pandurata. Previous study demonstrated that pinocembrin was neither toxic nor mutagenic to male rats. This study evaluated the effects of pinocembrin on phase I and II xenobiotic-metabolizing enzymes in rat liver. It was found that heme oxygenase activity significantly increased in 10 and 100 mg/kg bw of pinocembrin treated groups (p<0.05). However, pinocembrin did not affect the activities of NADPH: cytochrome P450 reductase, NADPH: quinone reductase, UDP-glucuronosyltransferase and glutathione-S-transferase. It also did not affect the expression of phase I metabolizing enzymes, including CYP1A1, CYP2B1, CYP2C11, CYP2E1, CYP3A2, and NADPH: cytochrome P450 reductase. In conclusion, short-term treatment of pinocembrin in Wistar rats increased the activity of heme oxygenase but did not affect on the activities of other phase II xenobiotic-metabolizing enzymes or the expression of cytochrome P450 enzymes.     

Effects of pinocembrin on the initiation and promotion stages of rat hepatocarcinogenesis

Pinocembrin (5, 7-dihydroxyflavanone) is a flavanone extracted from the rhizome of Boesenbergia pandurata. Our previous studies demonstrated that pinocembrin had no toxicity or mutagenicity in rats. We here evaluated its effects on the initiation and promotion stages in diethylnitrosamine-induced rat hepatocarcinogenesis, using short- and medium-term carcinogenicity tests. Micronucleated hepatocytes and liver glutathione-S-transferase placental form foci were used as end point markers. Pinocembrin was neither mutagenic nor carcinogenic in rat liver, and neither inhibited nor prevented micronucleus formation as well as GST-P positive foci formation induced by diethylnitrosamine. Interestingly, pinocembrin slightly increased the number of GST-P positive foci when given prior to diethylnitrosamine injection.     

Induction of G1 arrest and apoptosis in androgen-dependent human prostate cancer by Kuguacin J, a triterpenoid from Momordica charantia leaf

Glucocorticoid-induced tumor necrosis factor receptor and its ligand (GITRL) are critically involved in the regulation of immune response. In this study, we aimed to generate bone marrow-derived dendritic cells (BMDCs) transfected with recombinant adenovirus expressing GITRL (pAd-GITRL-BMDCs) and explore their therapeutic efficacy in murine Lewis lung carcinoma. In vitro, pAd-GITRL-BMDCs greatly enhanced effector T cells proliferation but markedly abrogate the suppression of Treg cells. Moreover, vaccination with pAd-GITRL-BMDCs significantly retarded tumor growth, which was accompanied with increased IFN-γ-producing CD8+ T cells and markedly decreased Treg cells in vivo. These findings suggest GITRL could enhance the immune stimulation of DC and might facilitate the potential development of DCs-based anti-tumor therapies.     

Kuguacin J,a triterpeniod from Momordica charantia leaf,modulates the progression of androgen-independent human prostate cancer cell line,PC3

In this study, we focused on the in vitro effects of Kuguacin J (KuJ), a purified component of bitter melon (Momordica charantia) leaf extract (BMLE), on the androgen-independent human prostate cancer cell line PC3 and the in vivo effect of dietary BMLE on prostate carcinogenesis using a PC3-xenograph model. KuJ exerted a strong growth-inhibitory effect on PC3 cells. Growth inhibition was mainly through G1-arrest: KuJ markedly decreased the levels of cyclins (D1 and E), cyclin-dependent kinases (Cdk2 and Cdk4) and proliferating cell nuclear antigen. Interestingly, KuJ also dramatically decreased the levels of survivin expressed by PC3 cells. In addition, KuJ exerted anti-invasive effects on PC3 cells, significantly inhibiting migration and invasion: KuJ inhibited secretion of the active forms of MMP-2, MMP-9 and uPA by PC3 cells. In addition, KuJ treatment significantly decreased the expression of membrane type 1-MMP (MT1-MMP) by PC3 cells. In vivo, 1% and 5% BMLE in the diet resulted in 63% and 57% inhibition of PC3 xenograft growth without adverse effect on host body weight. Our results suggest that KuJ is a promising new candidate chemopreventive and chemotherapeutic agent for prostate cancer.