Detoxification and immunoprotection of Zn(II)-curcumin in juvenile Pacific white shrimp (Litopenaeus vannamei) feed with aflatoxin B1.

Aflatoxins, which was produced by Aspergillus flavus or Aspergillus parasiticus fungi during grain and feed processing or storage, could cause severe health problems and reduction of yield during shrimp cultures. To evaluate toxic effects of aflatoxin B1 (AFB1) in juvenile Pacific white shrimp (Litopenaeus vannamei) and potential protective effect of Zn(II)-curcumin (Zn-CM), four experimental diets (control, 500 µg/kg AFB1, 500 µg/kg AFB1+100 mg/kg Zn-CM, 500 µg/kg AFB1+200 mg/kg Zn-CM) were formulated in quadruplicate to feed the shrimp for 8 weeks. The results revealed that AFB1 could induce significant decrease in final body weight (FBW), weight gain (WG, %) and visible variations of the hepatopancreas structures in L.vannamei. Compared with AFB1 group, AFB1+100 mg/kg Zn-CM group significantly ameliorated the toxic effects of AFB1 on growth performance, while AFB1+100 mg/kg Zn-CM group had no effect on growth performance. Dietary AFB1+100 mg/kg Zn-CM enhanced phenoloxidase (PO) (P < 0.05) activity. Both dietary AFB1+100 mg/kg Zn-CM and AFB1+200 mg/kg Zn-CM reduced inducible nitric oxide synthase (iNOS) activity and glutathione (GSH) level, decreased the content of malondialdehyde (MDA) (P < 0.05) in hepatopancreas compared with AFB1 group. Transmission electron microscopy (TEM) analysis demonstrated that Zn-CM could relieve the microvilli transformation and mitochondria accumulation reduction caused by AFB1. Consequently, the results demonstrated that suitable Zn-CM could mitigate the AFB1-induced hepatotoxicity and immunotoxicity effects on L.vannamei.

Taurine zinc solid dispersions protect against cold-restraint stress-induced gastric ulceration by upregulating HSP70 and exerting an anxiolytic effect.

Pharmacological effects of solid dispersions (SDs) of a taurine zinc complex on gastric ulceration and anxiety were investigated. Pretreatment with taurine zinc (50, 100 or 200mg/kg) SDs dose-dependently protected rat gastric mucosa against cold-restraint stress (CRS)-induced gastric injury, and significantly attenuated increases in gastric mucosal H(+)K(+)-ATPase activity and lipid peroxidation and enhanced SOD activity. Taurine zinc also inhibited CRS-induced elevation of the serum stress hormones adrenocorticotropic hormone and corticosterone and upregulated HSP70 expression in the gastric mucosa. Moreover, taurine zinc (200mg/kg) SDs more potently protected the gastric mucosa from ulceration than the same dose of taurine, which may be attributed to a synergistic effect between taurine and zinc. Behavioral experiments in mice showed that taurine zinc SDs significantly increased the number of entries and time spent on the open arms in the elevated plus-maze test, time spent in the central area and total distance traveled in the open field test, and time spent and number of entries into the light compartment in the light/dark box test, indicative of reduced anxiety-like behaviors. This study demonstrates taurine zinc protected the gastric mucosa against CRS-induced gastric damage by decreasing oxidative stress, promoting endogenous HSP70 expression and attenuating psychological stress.

Zn(II)-curcumin protects against oxidative stress, deleterious changes in sperm parameters and histological alterations in a male mouse model of cyclophosphamide-induced reproductive damage.

The poor bioavailability and stability of curcumin limit its clinical application. A novel Zn(II)-curcumin complex was synthesized and its effects against cyclophosphamide (CP)-induced reproductive damage were compared with curcumin. Oral administration of Zn(II)-curcumin significantly prevented CP-induced elevation of malondialdehyde (MDA) level and reductions in superoxide dismutase (SOD) activity and glutathione (GSH) content in mouse testis. Zn(II)-curcumin significantly ameliorated CP-induced reductions in body and reproductive organs weights. Zn(II)-curcumin dose-dependently ameliorated CP-induced reproductive system impairments, by improving sperm parameters (sperm count, viability, motility) and reducing serum testosterone and histological alterations. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively alleviated CP-induced reproductive injury, leading to a reduced severity of testicular pathologic changes, lower MDA level, elevated SOD activity and GSH content, and increased sperm parameters and serum testosterone. These results suggest Zn(II)-curcumin more effectively protects against CP-induced reproductive damage than curcumin alone due to a synergistic reduction in oxidative stress.

Gastroprotective effect of taurine zinc solid dispersions against absolute ethanol-induced gastric lesions is mediated by enhancement of antioxidant activity and endogenous PGE2 production and attenuation of NO production.

Zinc plays a key role in maintaining gastric mucosal integrity, while alcohol dependency can lead to low zinc status. Complexes containing zinc have been reported to have better ability to protect gastric mucosa than the compounds alone. In this study, taurine zinc [Zn(NH3CH2CH2SO3)2] solid dispersions (SDs) were synthesized and investigated in an ethanol-induced ulcer model in rats. Gastric ulcer index; gastric mucosa malondialdehyde (MDA) level, glutathione (GSH) content, superoxide dismutase (SOD) activity and prostaglandin E2 (PGE2) production; and serum nitric oxide (NO) were assessed and histological analysis of the gastric mucosa tissue was performed. Taurine zinc (100, 200 mg/kg) SDs protected rat gastric mucosa from ethanol-induced injury. Moreover, the gastroprotective effect of taurine zinc SDs was accompanied by a decrease in serum NO and significant increase in gastric prostaglandin E2 (PGE2). When indomethacin, a non-selective COX inhibitor was administered before the last dose of taurine zinc, the gastroprotective effect of taurine zinc was weakened. Furthermore, taurine zinc (200 mg/kg) SDs protected against ulceration more significantly than the same dose of taurine alone, suggesting a synergistic effect between taurine and zinc. These results indicate taurine zinc protects the gastric mucosa against ethanol-induced damage by elevating antioxidants, decreasing lipid peroxidation and inhibiting the production of nitric oxide. The gastroprotective effect of taurine zinc was also partially mediated by endogenous PGE2 production.

Protective effects of seahorse extracts in a rat castration and testosterone-induced benign prostatic hyperplasia model and mouse oligospermatism model.

This study investigated the effects of seahorse (Hippocampus spp.) extracts in a rat model of benign prostatic hyperplasia (BPH) and mouse model of oligospermatism. Compared to the sham operated group, castration and testosterone induced BPH, indicated by increased penile erection latency; decreased penis nitric oxide synthase (NOS) activity; reduced serum acid phosphatase (ACP) activity; increased prostate index; and epithelial thickening, increased glandular perimeter, increased proliferating cell nuclear antigen (PCNA) index and upregulation of basic fibroblast growth factor (bFGF) in the prostate. Seahorse extracts significantly ameliorated the histopathological changes associated with BPH, reduced the latency of penile erection and increased penile NOS activity. Administration of seahorse extracts also reversed epididymal sperm viability and motility in mice treated with cyclophosphamide (CP). Seahorse extracts have potential as a candidate marine drug for treating BPH without inducing the side effects of erectile dysfunction (ED) or oligospermatism associated with the BPH drug finasteride.

Zn(II)-curcumin protects against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism.

Curcumin can chelate metal ions, forming metallocomplexes. We compared the effects of Zn(II)-curcumin with curcumin against hemorheological alterations, oxidative stress and liver injury in a rat model of acute alcoholism. Oral administration of Zn(II)-curcumin dose-dependently prevented the ethanol-induced elevation of serum malondialdehyde (MDA) content and reductions in glutathione level and superoxide dismutase (SOD) activity. Zn(II)-curcumin also inhibited ethanol-induced liver injury. Additionally, Zn(II)-curcumin dose-dependently inhibited hemorheological abnormalities, including the ethanol-induced elevation of whole blood viscosity, plasma viscosity, blood viscosity at corrected hematocrit (45%), erythrocyte aggregation index, erythrocyte rigidity index and hematocrit. Compared to curcumin at the same dose, Zn(II)-curcumin more effectively elevated SOD activity, ameliorated liver injury and improved hemorheological variables. These results suggest that Zn(II)-curcumin protected the rats from ethanol-induced liver injury and hemorheological abnormalities via the synergistic effect of curcumin and zinc.

Zinc(II)-curcumin accelerates the healing of acetic acid-induced chronic gastric ulcers in rats by decreasing oxidative stress and downregulation of matrix metalloproteinase-9.

Gastric ulcers form as a result of a multifaceted process which includes acid secretion, reactive oxygen species generation and extracellular matrix (ECM) degradation. The aim of this study was to investigate the possible mechanisms underlying the anti-ulcerogenic effects of the Zn(II)-curcumin complex, a curcumin derivative, on the healing of acetic acid-induced gastric ulcers in rats. The severely ulcerated gastric mucosa of control animals had a lower glutathione level (GSH) and superoxide dismutase activity (SOD), and increased malondialdehyde (MDA) content compared to sham operated rats (P<0.001). Zn(II)-curcumin solid dispersions (equivalent to 12, 24 and 48 mg/kg) dose-dependently reduced the gastric ulcer index, significantly increased SOD activity and GSH levels, and reduced the MDA content and matrix metalloproteinase-9 (MMP-9) mRNA expression in the gastric mucosa (P<0.05, compared to control animals). Zn(II)-curcumin exerted a greater anti-ulcerogenic effect than curcumin at the same dose (24 mg/kg), leading to a reduced severity of gastric ulcers, lower MDA content, and increased SOD activity and GSH levels (P<0.05). In conclusion, these results confirm that the Zn(II)-curcumin complex possesses an enhanced mucosal barrier defense activity compared to curcumin alone, due to its synergistic ability to decrease oxidative stress and attenuate MMP-9-mediated inflammation.

[Pharmacological researches of curcumin solid dispersions in treatment of cancer].

OBJECTIVE: To investigate the anticancer effect of curcumin Solid Dispersions (SDs). METHODS: Curcumin SDs were prepared by patent technology. The anticancer effect of curcumin SDs were investigated by vivo and vitro tests of SCG-7901, BEL-7402, S-180 and Ehrlich ascites tumor models. RESULTS: The results showed that Curcumin SDs had markedly anticancer effect and could improve the anticancer effect of cisplatin. CONCLUSION: Curcumin SDs could be developed into one kind of adjuvant drug for anticancer, as it has markedly anticancer effect, and could improve the anticancer effects of cisplatin.

[Studies on solubility enhancement of curcumin by Polyvinylpyrrolidione K30].

OBJECTIVE: To study solubility enhancement of curcumin by Polyvinylpyrrolidione K30 (PVP K30). METHODS: Solid dispersion systems (SDS) of curcumin in PVP K30 were prepared at various weight ratios by co-evaporation of curcumin and PVP K30 ethanol solution. The differential scanning calorimetry (DSC) and powder X-ray diffractometer method were used to describe the status of curcumin in carriers, the UV spectrometry method for determination of curcumin in mediums was established. RESULTS: The curcumin SDS was successfully prepared, the UV spectrometry method was accurate and reliable, and no interference occurred from carrier. The solubility rate in vitro of curcumin was significantly raised. Compared to curcumin, the solubility of curcumin in SDS increased at least 880 folds. CONCLUSION: PVP K30 improves the solubility of curcumin well.

[Effects of alligator Zhikegao on relieving cough dispelling phlegm and anti-inflammation].

OBJECTIVE: To research the effects of Alligator Zhikegao on relieving cough, dispelling phlegm and anti-inflammation. METHOD: The coughing tests in mice, the phenol red secreting tests in mice, ear edema tests in mice,and paw edema tests and subcutaneous cotton ball granuloma in rats were adopted for observing the related pharmacological effects of Alligator Zhikegao. RESULT: Alligator Zhikegao could obviously prolong the latent period and decrease the times of mouse coughing, and remarkably inhibit the mouse ear edema (P < 0.001), the rat paw edema and the hyperplasia of subcutaneous cotton ball granuloma in rats. Alligator Zhikegao 11.70 g x kg(-1) could significant improve the carbonic clearances of macrophages (P <0.05) and the hemolysin level in serum (P <0.01). CONCLUSION: Alligator Zhikegao has significant effects on relieving cough, dispelling phlegm, anti-inflammation and immunological regulation.

Determination of a new active steroid by high performance liquid chromatography with laser-induced fluorescence detection following the pre-column derivatization.

A sensitive analytical method for the determination of a new active steroid, butane acid-(5-androsten-17-one-3beta-ol)-diester (A1998), was developed by high performance liquid chromatography with laser-induced fluorescence detection following the pre-column derivatization with dansylhydrazine. The calibration curve for A1998 derivatization was found linear in the dynamic range from 0.025 to 5.0 microg/ml, with the precision less than 6% (CV) and the mean extraction efficiency greater than 92%. In 200 microl of plasma samples the limit of quantitation was as low as 0.025 microg/ml with a signal-to-noise ratio of 10. This assaying was further applied to the determination of the pharmacokinetic parameters of A1998 in rats with an intravenous injection of A1998. Values for clearance for elimination, volume of distribution at steady state and terminal half life in the above case were determined as 50.3+/-1.1 ml/min kg, 1329.0+/-111.0 ml/kg and 44.0+/-2.7 min, respectively.

Protective effects of 5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D -glucopyranosyloxy-flavone on experimental hepatic injury.

AIM: To investigate the pharmacological effects of rice flavone (5,4'-dihydroxy-3',5'-dimethoxy-7-O-beta-D-glucopyranosyloxy-flavone, RF) separated from panicle-differentiating to flowing rice on rat experimental hepatic injury. METHODS: Models of rat acute hepatic injury induced by carbon tetrachloride (CCl(4)) administration, rat hepatic fibrosis induced by thioacetamide, injury of primary cultured rat hepatocytes induced by CCl(4), respectively, were established. After treated with RF, content of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (Alb), hyaluronic acid (HA), the activity of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and hydroxyproline (Hyp) were measured and liver tissue was observed pathologically by hematoxylin-eosin (HE) staining. Effects of RF on pathological changes, function index, enzyme of scavenging free radicals and blood rheology were evaluated. RESULTS: In model of rat acute hepatic injury induced by CCl(4), RF can significantly decrease the contents of serum ALT, AST, increase the content of Alb, improve the dropsy and fat denaturalization of hepatocytes. In model of rat hepatic fibrosis induced by thioacetamide, RF can inhibit the increase of HA, Hyp and whole blood viscosity, and improve the activities of GSH-Px and SOD, and inauricular microcirculation. CONCLUSION: RF has apparent protective effects on hepatic injury by increasing activity of GSH-Px and SOD, scavenging free radicals produced by CCl(4), reducing blood viscosity, and improving microcirculation and blood supply.

[Protective effects of polysacchride of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan induced diabetic rats].

OBJECTIVE: To study the protective effects of polysaccharide of Spirulina platensis and Sargassum thunbeergii on vascular of alloxan (ALX) induced diabetic rats. METHOD: With the doses of polysaccharide of Spirulina platensis (PSP) and Sargassum thunbeergii (PST) compound (1:1) 12.261, 36.783, 110.349 mg x kg(-1) by i.g. administration to alloxan induced diabetic rats respectively for 6 weeks. Then the blood glucose and the TC, HDL-C, TG, NO, ET in serum were detected. The contraction and relaxation response to NE and ACh in aortic rings of the alloxan induced diabetic rats has been studied. RESULT: The results showed the compound of PSP and PST could decrease the blood glucose and the TC, TG, NO, ET in serum and increase HDL-C than in the alloxan induced diabetic rats. The contraction responses to NE in aortic rings of the alloxan induced diabetic rats were significantly elevated in the normal rats, and the responses to ACh were significantly lower. PSP and PST compound could significantly lower the responses to NE and significantly elevate the responses to ACh in aortic rings of the alloxan induced diabetic rats. CONCLUSION: PSP and PST compound could decrease blood glucose and could protect the vascular of alloxan induced diabetic rats.

[Anti-arrhythmic effect of starfish sterol].

AIM: To study the effect of modified starfish sterol [C03, succinic acid (5-epiandroene-17-one-3beta-ol) diester] on experimental arrhythmias. METHODS: Arrhythmias were induced by drugs (Aco, Oua, BaCl2 and adrenalin) i.v., ligating the left anterior descending coronary artery and electricity. RESULTS: C03 71.4 mg x kg(-1) (ig) was shown to increase the dose of Oua inducing VP, VT, VF and CA in guinea pigs (P < 0.01); C03 (26.8, 80.4 mg x kg(-1)) was found to increase the dose of Aco inducing VF and CA in rats (P < 0.01); C03 (8.9, 26.8, 80.4 mg x kg(-1)) increase the dose of barium chloride and delay the onset time of ventricular arrhythmias (P < 0.01); C03 (14.1, 42.3 mg x kg(-10) shorten time of recovering induced by adrenalin in rabbits (P < 0.01); C03 (80.4 mg x kg(-1)) was shown to reduce the number of ventricular arrhythmias induced by coronary artery ligation in rats (P < 0.05), C03 increase VFT induced by electricity in rabbits, VFT of C03 14.1 mg x kg(-1) increased from (5.1 +/- 2.5) V to (11.0 +/- 2.7) V (P < 0.01), 42.3 mg x kg(-1) increased from (6.1 +/- 1.7) V to (15 +/- 5) V (P < 0.01). CONCLUSION: Starfish sterol has anti-arrhythmic effect.