Renoprotective and hepatoprotective activity of Lepidium draba L. extracts on oxymetholone-induced oxidative stress in rat.

Misuse and abuse of anabolic androgenic steroids (AAS) such as oxymetholone (OM) cause side effects such as male infertility, cardiovascular disorders, musculoskeletal, and hepato-renal dysfunctions in athletes. The aim of this study was to evaluate the protective effects of Lepidium draba L. (L. draba) extract on OM-induced hepato-renal toxicity. Thirty adult male Wistar rats into six groups (n = 5) were randomly divided as follows: control (normal saline), OM (5 mg/kg/day), L. draba-treated (100, 200, and 400 mg/kg/d) plus 5 mg/kg/day OM, and L. draba (400 mg/kg/d) groups. Normal saline, OM and L. draba extract were orally administered for 30 days. On day 31 of the study, hepatic and renal biochemical parameters were measured. Serum cytokines (IL-1ß, IL-10, IL-6) tumor necrosis factor- α (TNF-α) and nitric oxide, levels alongside catalase, glutathione peroxidase, and superoxide dismutase activity were evaluated. Also, changes in liver and kidney histopathology were evaluated. Finally, the anti-oxidant properties of the extract were determined. The results of this study showed that in the groups treated with the L. draba extract, hepatic-renal biochemical parameters improved and also the level of nitric oxide and inflammatory cytokines decreased and the activity of anti-oxidant enzymes increased compared with the OM group. These findings revealed that L. draba, due to its high anti-oxidant properties and high content of polyphenols (especially flavonoids), can improve OM-induced hepato-renal oxidative damages. PRACTICAL APPLICATIONS: L. draba due to its remarkable anti-oxidant and anti-inflammatory properties can protects the kidney and liver injuries against oxymetholone. These features are attributed to the presence of phenolic and flavonoid components. This fidings would be helpful to desgin new therapeutic agents for treating and preventing liver/kidney injuries.

Andrographolide Induces Apoptosis in Gastric Cancer Cells through Reactivation of p53 and Inhibition of Mdm-2.

Andrographolide is a labdane diterpenoid isolated from Andrographis paniculata. The plant extract and andrographolide has long been used in traditional medicine practices mainly for gastrointestinal diseases and improving liver function. Andrographolide has shown various pharmacological properties including anti-inflammatory, antioxidant and anticancer activity. This study evaluated the effect of andrographolide on proliferation of human gastric carcinoma cells in relevance to p53 and Mdm-2 pathways. Andrographolide inhibited the proliferation of SGC7901 and AGS cells in a dose-dependent manner with estimated IC50 values 38 and 44 µM respectively. Effect of andrographolide on p53 activity was ascertained by using a p53 activator (RITA) which showed synergistic inhibition of cell proliferation. While andrographolide when used in combination with a p53 inhibitor (pifithrin-α) showed potent restriction over its response. Andrographolide caused decrease in mitochondrial membrane potential as an indicator of apoptotic activity. Andrographolide activated the expression of p53 protein and gene and downregulated the levels of Mdm-2 (negative regulator of p53). Andrographolide inhibited the colony formation abilities in SGC7901 in a p53-dependent manner followed by induction of mitochondrial intrinsic apoptosis through activation of caspases-9 and -3, cleavage of PARP, and inhibition of pro-apoptotic Bcl-2. Andrographolide induced p53 mediated apoptosis in gastric carcinoma cells which adds to a novel approach in anticancer therapies.

Nurse cell--derived small RNAs define paternal epigenetic inheritance in Arabidopsis.

The plant male germline undergoes DNA methylation reprogramming, which methylates genes de novo and thereby alters gene expression and regulates meiosis. Here, we reveal the molecular mechanism underlying this reprogramming. We demonstrate that genic methylation in the male germline, from meiocytes to sperm, is established by 24-nucleotide small interfering RNAs (siRNAs) transcribed from transposons with imperfect sequence homology. These siRNAs are synthesized by meiocyte nurse cells (tapetum) through activity of CLSY3, a chromatin remodeler absent in other anther cells. Tapetal siRNAs govern germline methylation throughout the genome, including the inherited methylation patterns in sperm. Tapetum-derived siRNAs also silence germline transposons, safeguarding genome integrity. Our results reveal that tapetal siRNAs are sufficient to reconstitute germline methylation patterns and drive functional methylation reprogramming throughout the male germline.

Protective effects of Acanthopanax senticosus - Ligustrum lucidum combination on bone marrow suppression induced by chemotherapy in mice.

This study investigated the combination effects of the Acanthopanax senticosus - Ligustrum lucidum (AS-LL) herb pair on bone marrow suppression caused by chemotherapy. A bone marrow suppression model was established by intraperitoneal injection (i.p.) of cyclophosphamide (CTX, 100 mg/kg). The changes in chemical composition between the AS-LL decocted together and single were analyzed, and their effects on the bone marrow nucleated cells, peripheral blood, thymus and spleen indices, in vitro hematopoietic cell culture, ELISA and cell cycle were detected. The results showed that the contents of the main active components, such as salidroside, isofraxidin and specnuezhenide in the sample of AS-LL decocted together, increased significantly compared to singles. Moreover, AS-LL decocted together exhibited a significantly better therapeutic effect on myelosuppression induced by CTX than AS and LL alone. AS-LL decocted together significantly increased the number of bone marrow nucleated cells and displayed a good regulatory effect on peripheral blood (p < 0.01), while significantly increased the thymus index (p < 0.01) and decreased the spleen index (p < 0.01). AS-LL significantly promoted the formation of cell colonies (p < 0.05), the proliferation and differentiation of hematopoietic progenitor cells, and played a positive regulatory role in hematopoietic factors. AS-LL also reduced the proportion of G0/G1 cells, increased the ratio of S and G2/M cells, and increased the cell proliferation index (PI). All these results implied that AS-LL decocted together might be a promising food additives and therapeutic agent for myelosuppression induced by chemotherapy.

Reduced body weight gain in ubiquilin-1 transgenic mice is associated with increased expression of energy-sensing proteins.

Ubiquilin-1 (Ubqln1), a ubiquitin-like protein, is implicated in a variety of pathophysiological processes, but its role in mediating body weight gain or metabolism has not been determined. Here, we demonstrate that global overexpression of Ubqln1 in a transgenic (Tg) mouse reduces the animal's body weight gain. The decreased body weight gain in Tg mice is associated with lower visceral fat content and higher metabolic rate. The Ubqln1 Tg mice exhibited reduced leptin and insulin levels as well as increased insulin sensitivity manifested by homeostatic model assessment of insulin resistance. Additionally, the reduced body weight in Tg mice was associated with the upregulation of two energy-sensing proteins, sirtuin1 (SIRT1) in the hypothalamus and AMP-activated protein kinase (AMPK) in the skeletal muscle. Consistent with the in vivo results, overexpression of Ubqln1 significantly increased SIRT1 and AMPK levels in the mouse embryonic fibroblast cell culture. Thus, our results not only establish the link between Ubqln1 and body weight regulation but also indicate that the metabolic function of Ubqln1 on body weight may be through regulating energy-sensing proteins.

XsFAD2 gene encodes the enzyme responsible for the high linoleic acid content in oil accumulated in Xanthoceras sorbifolia seeds.

BACKGROUND: Xanthoceras sorbifolia Bunge is a valuable oilseed tree that has linoleic acid-rich seed oil. Microsomal oleate desaturase (FAD2; EC 1.3.1.35) is responsible for the conversion of oleic acid to linoleic acid during fatty acid synthesis. In this study, XsFAD2 was cloned from developing embryos of X. sorbifolia. RESULTS: XsFAD2 contained three histidine boxes, a C-terminal endoplasmic reticulum retrieval motif, and five putative transmembrane domains representing the characteristics of membrane-bound fatty acid desaturase. XsFAD2 expression in yeast cells resulted in linoleic acid (18:2) and palmitolinoleic acid (16:2) production, confirming the biological activity of the enzyme encoded by XsFAD2. These fatty acids are not normally present in wild-type yeast. Phylogenetic analysis indicated that XsFAD2 is located in a subgroup of FAD2 enzymes specifically or highly expressed in developing seeds. The expression level of XsFAD2 in seeds was much higher than those in leaves and petals. Furthermore, XsFAD2 expression pattern correlated well with linoleic acid accumulated in seeds. CONCLUSION: Results suggested that XsFAD2 is responsible for the high linoleic acid content in X. sorbifolia seed oil. This study provides insight on the regulation mechanism of fatty acid synthesis in X. sorbifolia seeds and a valuable gene for improving the oil quality in oilseed trees.

[Effects of exogenous gamma-aminobutyric acid on antioxidant enzyme activity and reactive oxygen content in muskmelon seedlings under nutrient solution hypoxia stress].

The effects of exogenous gamma-aminobutyric acid (GABA) on antioxidant defense system and reactive oxygen species (ROS) in seedlings of two varieties with different resistance to hypoxia stress were studied under hypoxia stress in a nutrient solution culture system. The results showed that GABA treatments enhanced the activities of antioxidant enzyme including SOD (Fig. 1), POD (Fig. 2), CAT (Fig. 3), while the concentrations of H2O2 (Fig. 4), O(-.)2 (Fig. 5), MDA (Fig. 6) decreased under hypoxia stress. Among the treatments of three different GABA concentrations, the effect of 50 mmol/L GABA treatment was better than that of 25 mmol/L GABA and 100 mmol/L GABA treatments. The effect of treatment with GABA in "Dongfang xingguang" seedlings, which had stronger hypoxia-resistance to hypoxia stress, were better than that in "Xiyu No.1" seedlings which had lower hypoxia-resistance. It indicates that GABA treatment of exogenous spraying to leaves can increase the activities of antioxidant enzyme under the hypoxia stress and plays an important role in enhancing the resistance to hypoxia stress of muskmelon seedlings through keeping low ROS contents.