Synthetic antimicrobial agents inhibit aflatoxin production.

Antimicrobial peptides (AMPs) are biologically active molecules that can eradicate bacteria by destroying the bacterial membrane structure, causing the bacteria to rupture. However, little is known about the extent and effect of AMPs on filamentous fungi. In this study, we synthesized small molecular polypeptides by an inexpensive heat conjugation approach and examined their effects on the growth of Aspergillus flavus and its secondary metabolism. The antimicrobial agents significantly inhibited aflatoxin production, conidiation, and sclerotia formation in A. flavus. Furthermore, we found that the expression of aflatoxin structural genes was significantly inhibited, and the intracellular reactive oxygen species (ROS) level was reduced. Additionally, the antimicrobial agents can change membrane permeability. Overall, our results demonstrated that antimicrobial agents, safe to mammalian cells, have an obvious impact on aflatoxin production, which indicated that antimicrobial agents may be adopted as a new generation of potential agents for controlling aflatoxin contamination.

Effects of Erlong Zuoci decoction on the age-related hearing loss in C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Erlong Zuoci decoction (ELZCD), a typical traditional Chinese medicine (TCM) prescription, has long been clinically used in treatment of deafness and tinnitus with the syndrome of "kidney yin deficiency". However, there are few studies to investigate its pharmacological mechanisms. Until now, there is not report about its effects on the age-related hearing loss (ARHL). AIM OF STUDY: The present study was conducted to observe the effects of ELZCD on the ARHL in C57BL/6J mice and explore the mechanisms. MATERIALS AND METHODS: ELZCD was fed to C57BL/6J mice from 3 months to 6 months in ELZCD group as a dose of 6g/kg/d. And the same volume of saline was fed to mice in ARHL group. 3-months-old C57BL/6J mice were used as control group. High performance liquid chromatography (HPLC) was used for the quality control of ELZCD. Auditory brainstem response (ABR) was used to assess the hearing function of mice. The morphologic changes were observed by hematoxylin eosin (HE) staining. Apoptosis was tested by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) method. Mitochondrial damage was detected by transmission electron microscopy (TEM). Quantitative RT-PCR (qRT-PCR) was used to observe the mRNA expression of p53 and Bak. Fluorescence immunohistochemical technique was used to test the protein expression of p53 and Bak. RESULTS: The hearing threshold of ARHL group was higher than that of control group (P<0.001) and ELZCD decreased the rise of hearing threshold levels of ARHL mice (P<0.001), which suggested ELZCD inhibited the hearing loss of ARHL mice. HE staining showed that ELZCD decreased the spiral ganglion (SG) cell damage and loss in ARHL. TUNEL test showed that the apoptotic SG cells increased in ARHL group compared to control group and decreased in ELZCD group compared to ARHL group. TEM observation showed that mitochondrial damage was obvious in SG cells of ARHL group and ELZCD inhibited the mitochondrial damage. The qRT-PCR results showed that the mRNA expression of p53 and Bak in ARHL group increased compared to that of control group (P<0.05), and ELZCD reduced the elevated mRNA expression levels of p53 and Bak (P<0.01, P<0.05). In addition, ELZCD inhibited the increased proteins expression (green fluorescence) of p53 and Bak. CONCLUSION: The results demonstrated that ELZCD prevented ARHL in C57BL/6J mice and p53/Bak-mediated mitochondrial apoptosis of SG cells might be involved in the mechanisms.

Ototoxicity of paclitaxel in rat cochlear organotypic cultures.

Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 µM. No obvious histopathologies were observed after 24h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 µM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 µM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea.

Monoammonium glycyrrhizinate inhibited the inflammation of LPS-induced acute lung injury in mice.

Monoammonium glycyrrhizinate (MAG) was the aglycone of glycyrrhizin derived from licorice. In this study, the anti-inflammatory effects of MAG on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and the possible mechanisms involved in this protection were investigated. Pretreatment with MAG prior to the administration of intratracheal LPS significantly induced a decrease in lung wet weight/dry weight ratio, in total leukocyte number and neutrophil percent in the BALF, and in myeloperoxidase (MPO) activity of lung in dose-dependent manners. At the same time, pretreatment with MAG also significantly improved the super oxide dismutase (SOD) activity and induced the malondialdehyde (MDA) content in the bronchoalveolar lavage fluid (BALF). Importantly, pretreatment with MAG prevented an increase in cyclic adenosine monophosphate-phosphodiesterase (cAMP-PDE) activity of lung in a dose-dependent manner. In addition, it can up-regulate the interleukin-10 (IL-10) level and down-regulate the tumor neurosis factor-α (TNF-α) level in the lung tissue of ALI mice. These results showed that anti-inflammatory effects of MAG against the LPS-induced ALI may be due to its ability of primary inhibition of cAMP-PDE activity, oxidative stress and its regulation of cytokine effects. Thus the results support that use of MAG is beneficial in the treatment of ALI and ARDS.

[Effects of Erxian Decoction and its separate prescriptions on the levels of luteinizing hormone and follicle-stimulating hormone in anterior pituitary cells from female rats].

OBJECTIVE: To investigate the effects of Erxian Decoction (EXD), a traditional Chinese compound herbal medicine and its separate prescriptions such as Wenshen Yijing Recipe (WSYJR, a recipe for warming kidney and replenishing essence), Ziyin Xiehuo Recipe (ZYXHR, a recipe for nourishing yin and dispersing fire) and Tiaoli Chongren Recipe (TLCRR, a recipe for regulating thoroughfare and conception vessels) and some extracts from EXD on the levels of LH and FSH in the primary cultured anterior pituitary cells from female rats. METHODS: EXD, its separate prescriptions and traditional Chinese herbal extracts from EXD were added directly to the incubators. The levels of LH and FSH were tested by radioimmunoassay. RESULTS: The levels of LH and FSH in the supernatant of anterior pituitary cells treated by EXD or its separate prescriptions including ZYXHR and TLCRR were increased significantly as compared with those in the blank control. There was a tendency for stimulating the secretions of LH and FSH in the WSYJR-treated group too. Dimethyl sulfoxide as the solvent of icariin and curculigoside could interfere with the results. CONCLUSION: EXD and its separate prescriptions such as ZYXHR and TLCRR can increase the levels of LH and FSH significantly.

[Effect of er xian decoction and its subdivisions on granulosa cells secretory function in rats].

OBJECTIVE: To investigate the effects of Er Xian Decoction (EXD) and its three subdivisions "warming Shen" ,"nourshing Yin" and "adjusting Chong and Ren" in regulating the level of estradiol (E2) on the primary cultured granulosa cells. METHODS: Effect of EXD and its three subdivisions, also part of the effective components of this formula, icariin and curculigoside, on level of E2 were carried out using primary cultural granulose cell as the experimental model. RESULT: EXD and its three subdivisions could stimulate the secretion of E2, especially the "warming Shen" group (P <0.05). All the composing of Chinese herbs of this formula could promote the level of E2 in different degree, and the Rhizoma Curculiginis, Radix Moromade Officinalis, and Herba Epimedii have the best effects (P <0. 01). CONCLUSION: The regulation of EXD on the hypothalamus-pituitary-gonad (HPG) axis may be related to promoting the secreting of E2 at the site of granulosa cell. The "warming Shen" subdivision has the better effect in promoting the secretion of E2.

[Effects on secretory function of rat gonad by Erxian decoction and its disassembled prescriptions].

OBJECTIVE: To explain functions, differences and coordination of three divided combinations of the "Erxian decoction", the famous traditional Chinese formula, on the effective sites of gonad gland at the cell level. METHOD: The effects of Erxian decoction and its main disassembled prescriptions, "Kidney Warming", "Yin Nourishing" and "Chong-ren Adjusting", on the level of testosterone (T) progesterone (P) estradiol (E2), respectively secreted by the primary culture Leydig cell, luteal cell and granulosa cell, were measured by radioimmunoassay. RESULT: (1) Erxian decoction could stimulate the T secretion while its three main disassembled prescriptions would seem no individual promoting effect on the secretion of T. (2) Erxian decoction and the "Kidney Warming" had the stimulating effect on P secretion, and the action of the whole formula being better than that of the "Kidney Warming". (3) Erxian decoction and its main disassembled prescriptions had the stimulating effect on E2 secretion, especially the whole formula. CONCLUSION: Erxian decoction can stimulate the secretion of T of the Leydig cell, P of luteal cell and E2 of granulosa cell. It can be seen that the effect of the whole formula is better than that of its main disassembled prescriptions.

[A model for quantitative cigarette smoking and response of airways to cigarette smoke in guinea pigs].

OBJECTIVE: To establish an animal model for quantitative cigarette smoking and to determine the acute response of airways to cigarette smoke in guinea pigs. METHODS: The device for inhaling quantitative cigarette smoking was made, which was double pass and single-direction with the minimum dead space. The changes of airway resistance(R(L))and dynamic lung compliance(Cdyn) in guinea pigs exposed to compound air consisting of 75% cigarette smoke and 25% oxygen were observed. Exudation of Evans blue in pulmonary vessels was also determined after consecutive inhalation of 60 ml smoke. RESULT: The R(L) increased from the baseline of (0.21+/-0.05) cmH(2)O x ml(-1) x s to (0.37+/-0.13) cmH(2)O x ml(-1) x s after 10 consecutive breaths of cigarette smoke exposure(P<0.01). The Cdyn decreased to (61+/-19)% of baseline at the ninth to eleventh breaths (P<0.01). The exudations of Evans blue significantly increased in all measured parts of the airways such as lower trachea, main bronchi, proximal intrapulmonary airways and distal intrapulmonary airways (P<0.01). CONCLUSION: The model established in this study is useful for measuring the acute responses of airways induced by cigarette smoke in guinea pigs. Acute inhalation of cigarette smoke decreases dynamic lung compliance, increases airway resistance and vascular permeability of pulmonary vessels in guinea pigs.