Inhibitory Effect of Astaxanthin on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

This study investigates the inhibitory effect of astaxanthin (AST) on testosterone-induced benign prostatic hyperplasia (BPH) in rats. Except for the sham operation, BPH model rats were randomly assigned to five groups: the BPH model control rats, AST-treated BPH model rats (20 mg/kg, 40 mg/kg, and 80 mg/kg), and epristeride (EPR)-treated BPH model rats. After treatment, as compared with the BPH model control rats, the prostate and ventral prostate weights of the AST-treated rats decreased, while there was a marked decline in the 80 mg/kg AST-treated rats. The same effect was also observed in the prostate index and ventral prostate index. The proliferation characteristics of epithelia observed in the BPH model control group were gradually alleviated in the AST-treated rats. As compared with the BPH model control rats, lower epithelial thicknesses of prostates and fewer secretory granules in epithelia were observed in the AST-treated rats. The superoxide dismutase (SOD) activity of prostates increased in all the AST-treated rats with a significant increase in the 40 mg/kg and 80 mg/kg AST-treated rats. The testosterone (T) and dihydrotestosterone (DHT) levels of prostates in the AST-treated groups were lower than those in the BPH model control group, and a significant decline was found in the T level of prostates in the 40 g/kg and 80 mg/kg AST-treated rats and the DHT level of prostates in the 40 mg/kg AST-treated rats. These results indicate that AST might have an inhibitory effect on T-induced BPH in rats, possibly due to SOD activity regulation and T and DHT levels.

Eldecalcitol Plays a Role in Postmenopausal Osteoporosis through Mir-151a-3p/Socs5 Pathway

Objective: This study set out to explore the specific mechanism of Eldecalcitol in postmenopausal osteoporosis (PMOP) and its relationship with miR-151a-3p/SOCS5 pathway. Methods: Forty-five rats were randomly and equally divided into sham operation group (SOG), model control group (MCG) and Eldecalcitol group (EG). miR-151a-3p, SOCS5 and bone mineral density (BMD) levels in each group were detected. MC3T3-E1 cells were modeled and divided into control group (CG), model group (MG) and EG. miR-151a-3p-inhibitor and pcDNA3.1-SOCS were transfected into model cells. miR-151 A-3P, SOCS5, RANKL and OPG levels as well as cell activity of cells in each group were observed. Results: Eldecalcitol intervention in rats can reduce BMD reduction caused by PMOP, reduce the miR-151a-3p level and increase the SOCS5 level. Cell experiments found that Eldecalcitol intervention can improve cell activity, inhibit the miR-151a-3p level and promote the SOCS5 expression, all of which can improve bone resorption of model cells, increase cell activity, inhibit the RANKL level and promote the OPG level. Conclusion: Eldecalcitol plays a role in PMOP by inhibiting miR-151a-3p and promoting the SOCS5 level.

The Effect of Autophagy Induced by Mothers Against Decapentaplegic Homolog 3 (Smad3) Regulated by MicroRNA (miRNA)-23b on Renal Injury in Septic Rats

This study intends to investigate the mechanism by how microRNA (miRNA)-23b alleviates kidney damage in septic rats. Herein, septic rat model, control group and sham-operated model were set up to assess kidney tissue damage. Tissues were extracted from the rats and isolated into cells. Then cells were transfected with plasmids expressing miR-23b followed by analysis of the expression of miR-23b, Smad3, TLR4, HMGB1 and autophagy-related proteins (LC3, beclin-1) by western blot and RT-qPCR. The level of TNF-α, IL-6 and BUN and SCr were elevated in the model group and decreased after upregulation of miR-23b with increased LC3-II, Smad3 and Beclin-1 expression. miR-23b mimic group showed highest miR-23b expression followed by miR-23b NC group and miR-23b inhibitor group. The levels of TLR4, and HMGB1 and positive rate of NF-κBp65 in miR-23b mimic group were significantly lower than those in miR-23b inhibitor group (p < 0.05). Importantly, miR-23b directly targeted Smad3 and inhibited its expression. In conclusion, overexpressed miR-23b induces autophagy by promoting Smad3 expression, alleviates kidney damage in septic rats, and reduces inflammation and inactivates NF-κB signaling pathway.

The Antioxidant Effects of Whey Protein Peptide on Learning and Memory Improvement in Aging Mice Models

This study investigated the antioxidant effects of whey protein peptide on learning and memory in aging C57BL/6N mice. A total of 72 SPF male C57BL/6N mice were used. Twelve mice were randomly selected as the control group, and the other mice were intraperitoneally injected with D-galactose (100 mg/kg body weight for 6 weeks), during which, the mice in the control group were intraperitoneally injected with the same amount of normal saline. After 6 weeks, the blood was taken from the epicanthus and the serum MDA level was measured, according to which, the mice were randomly divided into the model control group, the whey protein group (1.5 g/kg body weight), and three Whey protein peptide (WHP) intervention groups (0.3 g/kg body weight, 1.5 g/kg body weight, 3.0 g/kg body weight). The water solution of the test sample was administered by oral gavage every day. The intervention period was 30 days, during which, the model control group, the whey protein group, and the whey protein peptide group continued receiving intraperitoneal injections of D-galactose, while the control group continued receiving intraperitoneal injections of normal saline. After the intervention, behavioral experiments were conducted in the following order: open field test, water maze test, and new object recognition test. After the behavioral experiment, the morphology of hippocampal formation was observed by HE staining and TUNEL labeling. Oxidative stress-related indexes in the serum, liver, and brain were detected. Expression levels of the cholinergic system-related enzymes and proinflammatory cytokines in brain tissue were detected. Western blot was used to detect the expression of synaptic plasticity-related proteins in the mouse brain. The results showed that WHP could significantly improve the accumulation of MDA and PC, increase the activities of SOD and GSH-Px, resist oxidative stress injury, and enhance the potential of endogenous antioxidant defense mechanisms. WHP can significantly improve the decline of aging-related spatial exploration, body movement, and spatial and non-spatial learning/memory ability. Its specific mechanism may be related to reducing the degeneration of hippocampal nerve cells, reducing the apoptosis of nerve cells, improving the activity of AChE, reducing the expression of inflammatory factors (TNF-α and IL-1β) in brain tissue, reducing oxidative stress injury, and improving the expression of p-CaMKⅡ and BDNF synaptic plasticity protein. These results indicate that WHP can improve aging-related oxidative stress, as well as learning and memory impairment.

Long-Term Administration of Anthraquinone Rhein on Induction of Constipation in Sprague-Dawley Rats via SCF/c-Kit Signaling Pathways

Background and Study Aims. It has been shown that abuse of laxatives is becoming a serious problem; therefore, a comprehensive understanding of its effect and possible mechanism on colon motility is essential to select effective treatments and avoid their abuse. Herein, we aimed to investigate the long-term stimulation of rhein on induction of constipation in rats and its underlying mechanisms. Materials and Methods. After establishing rat models of constipation, the rats were randomly divided into two equal subgroups and administered daily with normal saline (model control group) or 10 ml/kg PEG4,000 (PEG-treated group). Simultaneously, normal Sprague-Dawley (SD) rats were administered with normal saline (normal group). Physiological and fecal parameters were calculated, and intestinal transmission function was evaluated. After scarification, colonic tissues were freshly prepared for histological localization detected by immunohistochemical analysis and for the expression of stem cell factor (SCF) and c-kit proteins determined by western blot assay. Results. Following the initiation of rhein-induced rat constipation, body weight was lost slightly, the first time of black stool discharge was obviously longer, and the fecal moisture and number of fecal pellets decreased distinctly as compared with normal group. A decreased expression of SCF and c-kit was detected in model control group in comparison with normal group. Notably, compared with model control group, neither the alterations of fecal parameters and intestinal transmission function were effectively restored, nor the expression of SCF and c-kit was markedly elevated after administration of PEG4,000 for 30 d. Conclusion. Long-term stimulation of rhein can develop the constipation via SCF/c-kit signaling pathway, yet the symptoms of constipation and colon power cannot be alleviated or restored by PEG4,000. Collectively, these findings strongly suggest that long-term use of anthraquinone laxatives should be avoided for clinical treatment of constipation.

Immunomodulatory effect of the hydroalcoholic extract of Abrus precatorius L. leaves against cyclophosphamideinduced immunosuppression in mice

This study presents the immunomodulatory potential of Abrus precatorius Linn. (Indian wild licorice) leaves. A hydroalcoholic extract of A. precatorius leaves (EAPL) was prepared by maceration. Thirty male mice were divided into five groups as follows: control group, model control group (cyclophosphamide-treated), and three treatment groups (treated with EAPL at doses of 100, 200 and 300 mg/kg, per os, daily for 14 days). Parameters, including hematological, biochemical, organ indices, hemagglutination test (HA titer), delayed-type hypersensitivity (DTH), interleukin-2 (IL-2) level, splenocyte proliferation and liquid chromatography quadrupole time-of-flight mass spectrometry (LCQTOF- MS) analysis were evaluated. Histopathological examination was carried out for the spleen, kidney and liver. Cyclophosphamide (CPMD)-induced changes in white blood cells, lymphocytes and platelets were improved in the treatment groups. Total protein and albumin levels in the treatment groups were significantly higher. EAPL treatment significantly stimulated splenic T-lymphocytemediated proliferation. Neutrophil adhesion was insignificantly decreased in the model control group compared to the normal control group, which was slightly improved by EAPL treatment. EAPL treatment significantly improved the HA titer and cell-mediated immunity, which is an indication of antibody production. The IL-2 level was significantly higher in the treatment groups that received 200 and 300 mg/kg EAPL. LC-QTOF-MS analysis of EAPL showed the presence of flavonoids, lignans, iridoids and phenolic glycosides. These results suggest that A. precatorius leaves are a good candidate for a new immunomodulatory herbal formulation.

Effect of triamcinolone acetonide-loaded nanoparticles on diabetic retinopathy in rats

Triamcinolone acetonide acetate (TAA)-loaded nanostructured lipid carriers (NLC) were prepared to investigate their transdermal absorption in vitro and establish a diabetic retinopathy (DR) rat model. To evaluate the effect of triamcinolone acetonide-loaded nanoparticle capsules on improving the structure of the retina and pancreas, we measured blood glucose levels and investigated the pathological changes in the retina and pancreas. The effect of triamcinolone acetonide-loaded nanoparticle capsules on the morphology of the retina and pancreas of the rats with DR was determined and compared among the normal group, model control group, positive control group, and triamcinolone acetonide-loaded nanoparticle group. After treatment with triamcinolone acetonideloaded nanoparticle capsules for 2 months, the blood glucose and glycosylated hemoglobin levels were significantly lower (P < 0.01) and the pathological changes were less severe in the triamcinolone acetonide-loaded nanoparticle group than in the model control group. In addition, the arrangement of the photoreceptor cell layers in the retina was organized, intracellular and extracellular edema in each layer was reduced compared with that in the model control group, the capillary lumen was not occluded, and the peripheral cells were slightly edematous in the triamcinolone acetonide-loaded nanoparticle group. Triamcinolone acetonide-loaded nanoparticle capsules could effectively reduce the blood glucose and glycosylated hemoglobin levels and improve the structure of the retina and pancreas in the rats with DR.

Curative Effect and Mechanism of Guiren Runchang Granules on Morphine-Induced Slow Transit Constipation in Mice

Recent studies have identified the curative effects of traditional Chinese medicine for constipation. The mechanism of action of Guiren Runchang granules (GRGs) in the treatment of slow transit constipation (STC) was evaluated in this study. Here, we assessed the efficacy of GRG by comparing the differences in fecal characteristics, stool weight, and intestinal transit rate (ITR) among 6 groups (n = 12/group), which were administered three concentrations of GRG, mosapride, and saline. The influence of GRG on the SCF/c-kit pathway, AQP4, and serum motilin of mice was assessed through ELISA, western blot, and immunohistochemical analysis. The dry weight of mouse feces at 24 hr and ITR in the MD (medium-dose GRG; 9.44 g/kg/d) and HD (high-dose GRG; 18.88 g/kg/d) groups was higher than that in the MC (model control) group. The serum motilin of morphine-induced mice level was lower in the MC group than in the NC (normal control) group, and this condition was improved in the HD group. The HD group expressed significantly higher levels of SCF and c-kit protein but lower levels of AQP4 and simultaneously presented more SCF-positive and c-kit-positive cells. However, no differences in the serum SCF level were found among the six groups. Certain concentrations of GRG are effective in STC mice, the potential mechanism of which may be associated with repairing the SCF/c-kit pathway and reducing the expression of AQP4 in the colon. GRG improved the serum motilin level but had no influence on the serum SCF level.

A Lanosteryl Triterpene (RA-3) Exhibits Antihyperuricemic and Nephroprotective Effects in Rats

Considering the global health threat posed by kidney disease burden, a search for new nephroprotective drugs from our local flora could prove a powerful strategy to respond to this health threat. In this study we investigated the antihyperuricemic and nephroprotective potential of RA-3, a plant-derived lanosteryl triterpene. The antihyperuricemic and nephroprotective effect of RA-3 was investigated using the adenine and gentamicin induced hyperuricemic and nephrotoxicity rat model. Following the induction of hyperuricemia and nephrotoxicity, the experimental model rats (Sprague Dawley) were orally administered with RA-3 at 50 and 100 mg/kg body weight, respectively, daily for 14 days. Treatment of the experimental rats with RA-3, especially at 100 mg/kg, effectively lowered the serum renal dysfunction (blood urea nitrogen and creatinine) and hyperuricemic (uric acid and xanthine oxidase) biomarkers. These were accompanied by increased antioxidant status with decrease in malondialdehyde content. A much improved histomorphological structure of the kidney tissues was also observed in the triterpene treated groups when compared to the model control group. It is evident that RA-3 possesses the antihyperuricemic and nephroprotective properties, which could be vital for prevention and amelioration of kidney disease.

Constipation-relieving effect of L-arabinose

Purpose: To investigate the mitigating effect of L-arabinose on constipation in a mouse model of experimental constipation.Methods: Kunming mice were used as experimental animals to establish a constipation model. Intestinal propulsion, first defecation time, number of defecation pellets, and the weight of defecation pellets in 5 h were measured. L-Arabinose was given at 3 dose levels, viz, low dose (0.5 g/kg/day),medium dose (0.75 g/kg/day), and high dose (2.5 g/kg/day), and their effects on constipation were compared with that of the model control group.Results: Compared with the model control group, there were significant differences in ink propulsion (F= 22.67, p < 0.05); time taken for first black stool to appear (F = 19.51, p < 0.05), number of fecal pellets (F = 12.22, p < 0.05), and fecal weight (F = 5, p < 0.05) in the L-arabinose groups.Conclusion: L-Arabinose relieves constipation symptoms in an experimental mouse model of constipation. Therefore, L-arabinose may be useful in the management of patients with constipation, but further studies in humans are required to ascertain this. Keywords: L-Arabinose, Fecal pellets/grains, Constipation, Stool, Intestinal propulsion