scholarly journals Combined Effects of Oligopeptides Isolated from Panax ginseng C.A. Meyer and Ostrea gigas Thunberg on Sexual Function in Male Mice

Author(s):  
Di Li ◽  
Jinwei Ren ◽  
Lixia He ◽  
Jingqin Sun ◽  
Peng Liu ◽  
...  

Male sexual debility affects patients’ confidence and damages the relationship between the couples and thus affects the stability of the family. This study aimed to investigate the effects of oligopeptides isolated from ginseng and oyster (GOPs and OOPs), separately and in combination, on sexual function in male mice. In the first experiment, male mice were randomly divided into five groups: vehicle control group; whey protein (125.0 mg kg−1) group; and GOPs 62.5, 125.0, and 250.0 mg kg−1 groups. In the second experiment, male mice were randomly divided into five groups: vehicle control group, whey protein (160.0 mg kg−1) group, and OOPs 80.0, 160.0, and 320.0 mg kg−1 groups. In the third experiment, male mice were randomly divided into six groups: vehicle control group, whey protein (222.5 mg kg−1) group, and GOPs + OOPs 62.5 + 160.0, 62.5 + 320.0, and 125.0 + 160.0, 125.0 + 320.0 mg kg−1 groups. Test substances were given by gavage once a day for 30 days. The sexual behavior parameters, serum nitric oxide (NO), testosterone, cyclic guanosine monophosphate (cGMP), and phosphodiesterase-5 (PDE5) concentrations were detected. We found that GOPs at 250.0 mg kg−1 improved male sexual behavior, NO, and testosterone content, whereas GOPs at 62.5 and 125.0 mg kg−1 and OOPs at 80.0, 160, and 320 mg kg−1 did not have significant effects. The combination of 62.5 mg kg−1 GOPs + 160.0 mg kg−1 OOPs and the combination of 125.0 mg kg−1 GOPs + 320.0 mg kg−1 OOPs improved male sexual behavior, serum NO, testosterone, and cGMP contents and decreased PDE5 content. The combination of 62.5 mg kg−1 GOPs and 160.0 mg kg−1 OOPs had the best effects among four combined groups. These results suggested that GOPs in combination with OOPs had the synergistic effects of enhancing male sexual function, probably via elevating serum testosterone, NO, and corpus cavernosum cGMP level and decreasing the corpus cavernosum PDE5 level. GOPs and OOPs could be novel natural agents for improving male sexual function.

1985 ◽  
Vol 4 (1) ◽  
pp. 91-110 ◽  
Author(s):  
A. M. Hoberman ◽  
W. M. Weatherholtz ◽  
R. S. Durloo

The effects of a new experimental drug, KF-868, were investigated after administration to pregnant Sprague-Dawley rats at 0(vehicle), 0.1, 2.0, and 40.0 mg/kg per day during Days 7 through 17 of gestation by examination of term fetuses and naturally delivered offspring. Pregnant rats administered 0.1, 2.0, and 40.0 mg/kg per day gained significantly more weight during the dosage period than did the vehicle control group. Treatment-related physical signs, bloody crust on nose and stains on fur, were observed in the high dosage group. Fetal viability was significantly increased, and resorptions were significantly decreased for the mid and high dosage groups, when compared with the control group. Average fetal body weights for cesarean-delivered fetuses were less for the 40.0 mg/kg per day dosage groups than for the vehicle control group. Visceral and skeletal evaluations of fetuses revealed no difference between the control and test groups. Percent survival of pups was significantly less for the high dosage group than for the control group. Average rat body weights prior to mating for the high dosage group were generally less than for the control group. All physical and functional developmental values were comparable among the control and test groups. Evaluation of postweaning parameters of pups revealed no significant difference in sex maturation, behavior (open-field and water maze), and reproductive capacity. Average body weight gains during the 9-week growth period before mating were significantly less for the 40.0 mg/kg per day dosage group F1 generation female rats. Toxicity in fetuses and offspring was observed only at the highest dosage level. Dosage-dependent, significant increases in maternal body weight gain, as compared with control values, occurred for doses in the 3 KF-868-administered groups. These results indicate that 0.1 and 2.0 mg/kg per day dosages of KF-868 were not lethal and did not produce any adverse effects on the morphological or functional development of offspring. Toxicity was evident in offspring and fetuses of dams administered 40.0 mg/kg per day KF-868, 40,000 times as high as the daily therapeutic dose.


2016 ◽  
Vol 52 (2) ◽  
pp. 287-298 ◽  
Author(s):  
Bárbara Arroyo-Salgado ◽  
Jesús Olivero-Verbel ◽  
Angélica Guerrero-Castilla

ABSTRACT Contact with the pesticide dichlorodiphenyltrichloroethane (p,p′-DDT) can be the cause of various harmful effects in humans, wildlife, and the environment. This pesticide is known to be persistent, lipophilic, resistant to degradation, and bioaccumulive in the environment and to be slowly released into bloodstream. Growing evidence shows that exposure to DDT is linked to type 2 diabetes mellitus. Individuals exposed to elevated levels of DDT and its metabolite have an increased prevalence of diabetes and insulin resistance. To evaluate these possible relationships, experiments were performed on eight-week-old female mice, divided into three groups (n = 10 per group): Group 1 received a vehicle-control intraperitoneal (i.p.) injection of sesame oil; Groups 2 and 3 received an i.p. dose of 50 and 100 µg/g p,p′-DDT respectively, dissolved in sesame oil. All groups were treated once daily for four days. Real-time PCR analysis of several genes was undertaken. Additionally, biochemical parameters and histopathological changes were measured. NQO1, HMOX1, NR1I3 and NR3C1 were up-regulated in DDT-exposed animals compared to the vehicle control group, while only SREBP1 was down-regulated in the 100 µg/g group. MTTP and FABP5, not previously reported for DDT exposure, but involved in regulation of fatty acid fluxes, could also function as biomarkers cross-talking between these signaling pathways. These results suggest that beyond epidemiological data, there is increasing molecular evidence that DDT may mimic different processes involved in diabetes and insulin resistance pathways.


2019 ◽  
Vol 18 ◽  
pp. 153473541984637 ◽  
Author(s):  
Dongmei Chen ◽  
Yufei Yang ◽  
Peiying Yang

Quxie capsule (QX), a herbal remedy used in traditional Chinese medicine, is routinely used in advanced colorectal cancer treatment in Xiyuan Hospital in Beijing, China. However, the mechanism(s) underlying the effect of QX in colorectal cancer remain unclear, which hampers the optimal use of QX for the treatment of the disease. The transcription factor forkhead box O1 (Foxo1) plays important roles in regulation of cell cycle, apoptosis, and immune response in various cancers. In this study, we examined the antitumor efficacy of QX in a mouse model of colorectal cancer and further investigated the mechanism by which QX regulated Foxo1 protein-mediated pathways. QX administered via gavage daily for 2 weeks in mice carrying CT26 mouse colon tumors resulted in significantly lower mean tumor weight (0.93 ± 0.32 g) compared with that in vehicle control-treated mice (1.57 ± 0.57 g, P <.05). Foxo1 protein expression in tumors was also higher in the QX group than that in the vehicle control group. Furthermore, QX treatment upregulated apoptotic proteins such as Fas, Bim, and cleaved caspase-3 in tumor tissue compared with those in the vehicle control group. Intriguingly, the ratios of Th1/Th2 and Th17/Treg cells and levels of T-bet protein (the key regulator of Th1 and Th2 cells) were higher while the level of Foxp3 (the key regulator of Treg cells) was lower in QX-treated mice compared to vehicle control mice, revealing that Foxo1 upregulated T-bet and downregulated Foxp3 and induced a shift in immune balance. This shift could be critical in the antitumor efficacy of QX. Furthermore, knocking down Foxo1 in human colon cancer HCT116 cells partially blocked the effect of QX-elicited antiproliferative activity. Together, these results suggest that QX exerts antitumor activity in CT26 mouse colon cancer model partially mediated by Foxo1-induced apoptosis and antitumor immune response.


Author(s):  
Nicholas P. Clayton ◽  
Akash Jain ◽  
Stephanie A. Halasohoris ◽  
Lisa M. Pysz ◽  
Sanae Lembirik ◽  
...  

Bacillus anthracis and Yersinia pestis, causative pathogens for anthrax and plague, respectively, along with Burkholderia mallei and B. pseudomallei are potential bioterrorism threats. Tebipenem pivoxil hydrobromide (TBP HBr, formerly SPR994), is an orally available prodrug of tebipenem, a carbapenem with activity versus multidrug-resistant (MDR) gram-negative pathogens, including quinolone-resistant and extended-spectrum-β-lactamase-producing Enterobacterales. We evaluated the in vitro activity and in vivo efficacy of tebipenem against biothreat pathogens. Tebipenem was active in vitro against 30-strain diversity sets of B. anthracis, Y. pestis, B. mallei, and B. pseudomallei with minimum inhibitory concentration (MIC) values of 0.001 – 0.008 μg/ml for B. anthracis, ≤0.0005 – 0.03 μg/ml for Y. pestis, 0.25 – 1 μg/ml for B. mallei, and 1 – 4 μg/ml for B. pseudomallei. In a B. anthracis murine model, all control animals died within 52 h post challenge. The survival rates in the groups treated with tebipenem were 75% and 73% when dosed at 12 h and 24 h post challenge, respectively. The survival rates in the positive control groups treated with ciprofloxacin were 75% and when dosed 12 h and 25% when dosed 24 h post challenge, respectively. Survival rates were significantly (p=0.0009) greater in tebipenem groups treated at 12 h and 24 h post challenge and in the ciprofloxacin group 12 h post-challenge vs. the vehicle-control group. For Y. pestis, survival rates for all animals in the tebipenem and ciprofloxacin groups were significantly (p<0.0001) greater than the vehicle-control group. These results support further development of tebipenem for treating biothreat pathogens.


2017 ◽  
Vol 12 (1) ◽  
pp. 1934578X1701200
Author(s):  
Tomohiro Itoh ◽  
Yasuyoshi Miyake ◽  
Takayuki Yamaguchi ◽  
Shota Tsukaguchi ◽  
Rena Mitarai ◽  
...  

The anti-fatigue effect was investigated of the probiotic supplement, OM-X®, on forced swimming capacity in mice. Mice were administered either vehicle (distilled water; DW) or OM-X® (85 mg/kg body weight) by gavage for 4 weeks. Forced swimming tests were conducted weekly using the Ishihara-modified Matsumoto swimming pool. The endurance swimming time of the final forced swimming exercise in mice fed with OM-X® group showed an approximately 2-fold increase compared with the vehicle control group. Biomedical parameters, including blood lactate, blood superoxide dismutase (SOD) activity, serum triacylglycerol (TG), hepatic total lipids (TL), TG and phospholipid (PL) were significantly lower in mice fed with OM-X® than those in the vehicle control group. Furthermore, the mRNA expression levels of carbamoyl phosphate synthetase 1 (Cps1) and arginase 1 (Arg1), in the urea cycle, were increased by OM-X® feeding. Thus, our findings suggest promotion of lipid metabolism and up-regulation of the urea cycle, at least in part, for the anti-fatigue effect mediated by OM-X®.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4963-4963 ◽  
Author(s):  
Liqin Liu ◽  
Bee-Chun Sun ◽  
Jeanne Pistillo ◽  
Marc Payton ◽  
Ling Wang ◽  
...  

Abstract Abstract 4963 Phosphatidylinositol-3 kinase delta (PI3Kδ) is a class IA lipid kinase expressed primarily in leukocytes and is a key signaling molecule for immune receptors such as the B cell receptor (BCR). Dysregulated BCR-PI3Kδ signaling has been reported to play a role in B cell malignancy by mediating abnormal growth and survival. Recently we have identified that the potent and selective PI3Kδ inhibitor AMG 319 in combination with vincristine synergistically reduced cell viability in vitro and enhanced xenograft tumor regression in vivo when DLBCL cell line HT, which was relatively insensitive to AMG 319 in viability assays, was used as a model system. These findings suggest that inhibition of PI3Kδ with AMG 319 may enhance the effects of chemotherapeutic agents in B cell malignancy. To investigate the mechanism by which AMG 319 synergizes with vincristine in HT cells, we evaluated cell cycle and apoptosis after treatment with single agents or the combination. Vincristine alone at high concentration (4 nM) induced extensive G2/M arrest (51% versus 10% in vehicle control) at 24 hours while little or no G2/M arrest was detected at lower concentrations (0.8 and 0.16 nM). AMG 319 alone, at 0.33 μM, 3.3 μM and 10 μM did not induce G2/M arrest in HT cells. However, when AMG 319 was combined with a low concentration of vincristine at 0.8 nM, increased G2/M arrest (49%) was detected after 24 hours compared to each agent alone (21% in vincristine at 0.8 nM and 9% in AMG 319 at 10 μM) or vehicle control group (16%). This effect was AMG 319 concentration dependent (25%, 34% and 49% in vincristine at 0.8 nM combined with AMG 319 at 0.33, 3.3 and 10 μM, respectively). Interestingly, the enhanced G2/M cell cycle arrest with the drug combination was not sustained at 48 hours as cells underwent apoptosis as demonstrated by an increase in the SubG1 population and caspase-3 activity as well as a decrease in cell viability. In further support of these findings, a substantial increase in Annexin V (+) apoptotic cells (up to 68%) was observed in an AMG 319 concentration dependent manner at 48 and 72 hours in combination with vincristine as compared to that observed with the single agents (17% in vincristine at 0.8 nM; between 11%-23% in AMG 319 at 0.33, 3.3 and 10 μM) or vehicle control (around 10%). We then examined phosphorylation of Histone H3 at Ser10 and phosphorylation of cell cycle check point kinases Chk2 at Ser68 and Chk1 at Ser317, which are known to be associated with G2/M arrest. The phosphorylation of Histone H3 and Chk2 was increased between 3 to 18 fold in the drug combination group compared with either agent alone or the vehicle control group at 24 hours. In contrast, phosphorylation of Chk1 at Ser317 was unchanged. Lastly, modulation of pAkt (Ser473 and Ser308) was assessed and vincristine alone did not inhibit pAkt at all three concentrations (0.16 nM, 0.8 nM and 4 nM) up to 24 hours or change the maximum levels of pAkt observed. As expected, AMG 319 alone (in concentrations ranging from 3.3 nM to 3.3 μM) significantly inhibited pAkt (> 85% of inhibition in AMG 319 at 3.3 μM) at both 6 and 24 hour time points in a concentration-dependent fashion. The combination of vincristine with AMG 319 did not lead to further inhibition of pAkt. Taken together, these data suggest that the up-regulation of Chk2 (Ser68) is one of the underlying molecular events associated with the synergistic effects of AMG 319-vincristine combination on G2/M arrest, leading to cell growth inhibition and apoptotic death in HT cells. Therefore, inhibition of PI3Kδ with AMG 319 may enhance the effects of chemotherapeutic agents in B cell malignancy by inducing cell cycle arrest and apoptosis. Disclosures: Liu: Amgen: Employment. Sun:Amgen: Employment. Pistillo:Amgen: Employment. Payton:Amgen: Employment. Wang:Amgen: Employment. Archibeque:Amgen: Employment. Molineux:Amgen: Employment. Sinclair:Amgen: Employment.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Sachin Jain ◽  
Gajendra Pratap Choudhary ◽  
Dinesh Kumar Jain

Objectives. Pharmacological and antifertility activity evaluation ofJatropha gossypifoliain rats.Methods. The antifertility activity of the extracts ofJatropha gossypifoliain rats was evaluated using two experimental animal models. Estrogenic activity was evaluated in immature female rats using ethinyl estradiol as standard. Anti-implantation and early abortifacient activity was performed in female Wistar rats by determining the number of implantations and implantation resorptions.Results. In estrogenic activity evaluations, the ethanolic and aqueous extracts offered significant estrogen-like activity at 400 mg kg−1p.o. by increasing the uterine weight compared to vehicle control group. Ethanolic extract (400 mg kg−1, p.o.) treatment significantly decreased the number of implants and increased the number of resorptions compared to vehicle control group.Conclusion. The results of the present study provide the evidence of the anti-fertility activity ofJatropha gossypifoliaas claimed in the traditional use. The results are consistent with the literature reports related to the antifertility effect of flower extracts ofJatropha gossypifolia.


2016 ◽  
Vol 60 (10) ◽  
pp. 5906-5913 ◽  
Author(s):  
Kristina S. Wickham ◽  
Paul C. Baresel ◽  
Sean R. Marcsisin ◽  
Jason Sousa ◽  
Chau T. Vuong ◽  
...  

ABSTRACTIndividuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ. A single-dose administration of PQ was therefore assessed in our huRBC-SCID mouse model used to predict hemolytic toxicity with respect to G6PD deficiency. In this model, nonobese diabetic (NOD)/SCID mice are engrafted with human red blood cells (huRBC) from donors with the African or Mediterranean variant of G6PDd (A-G6PDd or Med-G6PDd, respectively) and demonstrate dose-dependent sensitivity to PQ. In mice engrafted with A-G6PD-deficient huRBC, single-dose PQ at 3.125, 6.25, or 12.5 mpk had no significant loss of huRBC compared to the vehicle control group. In contrast, in mice engrafted with Med-G6PDd huRBC, a single dose of PQ at 3.125, 6.25, or 12.5 mpk resulted in a significant, dose-dependent loss of huRBC compared to the value for the vehicle control group. Our data suggest that administration of a single low dose of 0.25 mpk of PQ could induce hemolytic anemia in Med-G6PDd individuals but that use of single-dose PQ at 0.25 mpk as a gametocytocidal drug to block transmission would be safe in areas where A-G6PDd predominates.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Sae-Kwang Ku ◽  
Young-Joon Lee ◽  
Sung-Dong Lee ◽  
Hyung-Rae Cho ◽  
Seung-Bae Moon ◽  
...  

We performed to evaluate the effect of POLYCAN (β-glucan) on cisplatin-(CDDP-)induced acute renal failure (ARF) in rats. POLYCAN was administered orally once a day for 32 days. Each of 8 rats per group was selected based on the body weight (BW) after acclimatization and they were sacrificed at 5 days after CDDP injection. There was significant (P<0.05) increase of BW after CDDP dosing in all POLYCAN groups than vehicle control and significant (P<0.01 or P<0.05) decrease of absolute and relative kidney weight were detected in all POLYCAN groups compared with vehicle control. In addition, serum BUN and creatinine level in all POLYCAN groups were significantly (P<0.01 or P<0.05) lower than vehicle control and the percentage of degenerative regions significantly (P<0.01) decreased in all POLYCAN groups. As the results of CDDP-induced ARF process, dramatic decrease of the BW, increase of the kidney weight, serum BUN, and creatinine level were detected in vehicle control group compared with sham control group. The changes by CDDP-induced ARF process in POLYCAN groups were significantly and dose-dependently improved compared with vehicle control group. Therefore, POLYCAN has enough potential to develop as a new agent of prevention or treatment for ARF.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
R. Estrada-Reyes ◽  
O. A. Ferreyra-Cruz ◽  
G. Jiménez-Rubio ◽  
O. T. Hernández-Hernández ◽  
L. Martínez-Mota

Chrysactinia mexicanaA. Gray (Asteraceae) andTurnera diffusaWilld (Turneraceae) are employed in traditional medicine as aphrodisiacs; however, there is no scientific evidence supporting the prosexual properties ofC. mexicana. The aim of this study was to determine whether an aqueous extract ofC. mexicana(Cm) stimulates rat male sexual behavior in the sexual exhaustion paradigm. Sexually exhausted (SExh) male rats were treated with Cm (80, 160, and 320 mg/kg), an aqueous extract ofT. diffusa(Td), or yohimbine. The sexual exhaustion state in the control group was characterized by a low percentage of males exhibiting mounts, intromissions, and ejaculations and no males demonstrating mating behavior after ejaculation. Cm (320 mg/kg), Td, or yohimbine significantly increased the proportion of SExh rats that ejaculated and resumed copulation after ejaculation. In males that exhibited reversal of sexual exhaustion, Cm (320 mg/kg) improved sexual performance by reducing the number of intromissions and shrinking ejaculation latency. The effects of treatments on sexual behavior were not related with alterations in general locomotion. In conclusion, the prosexual effects of Cm, as well as those of Td, are established at a central level, which supports the traditional use ofC. mexicanafor stimulating sexual activity.


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