Shaozhen Hou

Impacts of cigarette smoking on immune responsiveness: Up and down or upside down?

Cigarette smoking is associated with numerous diseases and poses a serious challenge to the current healthcare system worldwide. Smoking impacts both innate and adaptive immunity and plays dual roles in regulating immunity by either exacerbation of pathogenic immune responses or attenuation of defensive immunity. Adaptive immune cells affected by smoking mainly include T helper cells (Th1/Th2/Th17), CD4+CD25+ regulatory T cells, CD8+ T cells, B cells and memory T/B lymphocytes while innate immune cells impacted by smoking are mostly DCs, macrophages and NK cells. Complex roles of cigarette smoke have resulted in numerous diseases, including cardiovascular, respiratory and autoimmune diseases, allergies, cancers and transplant rejection etc. Although previous reviews have described the effects of smoking on various diseases and regional immunity associated with specific diseases, a comprehensive and updated review is rarely seen to demonstrate impacts of smoking on general immunity and, especially on major components of immune cells. Here, we aim to systematically and objectively review the influence of smoking on major components of both innate and adaptive immune cells, and summarize cellular and molecular mechanisms underlying effects of cigarette smoking on the immune system. The molecular pathways impacted by cigarette smoking involve NFκB, MAP kinases and histone modification. Further investigations are warranted to understand the exact mechanisms responsible for smoking-mediated immunopathology and to answer lingering questions over why cigarette smoking is always harmful rather than beneficial even though it exerts dual effects on immune responses.

Role of the interaction between puerarin and the erythrocyte membrane in puerarin-induced hemolysis.

Adverse drug reactions (ADR), especially intravenous hemolysis, have largely limited the application of puerarin injections in clinics. This study investigated the underlying mechanisms of puerarin-induced hemolysis. Our results show that puerarin induced concentration-dependent and time-dependent hemolysis when human erythrocytes were incubated in saline solution with more than 2mM puerarin for over 2h. However, incubation in PBS or addition of 1mM of lidocaine to the saline solution completely abolished the hemolysis. Providing materials that could start ATP synthesis did not reverse the hemolysis, and puerarin did not affect Na(+)-K(+)-ATPase activity. In addition, puerarin (0.1-2mM) did not cause calcium influx or exhibited pro-oxidant activity in erythrocytes. Puerarin exhibited different influences on the membrane microviscosity of erythrocytes in saline and PBS. Moreover, 1mM lidocaine inhibited 8mM puerarin-induced reduction of membrane microviscosity in saline solution. SDS-PAGE analysis of membrane proteins revealed that 2mM puerarin treatment induced the appearance of several new protein bands but attenuated the expression of protein bands 2.1, 3, 4.1, 4.2 and 5. These results suggest that high concentrations of puerarin-induced hemolysis were associated with the changes of membrane lipids and of the composition of erythrocytes membrane proteins but not with ATP depletion, pro-oxidation and calcium influx. These changes could be related to the intercalation of amphiphilic puerarin at high concentration into the erythrocyte membrane in certain media, resulting in membrane disorganization and, eventually, cytolysis. Hence, in clinics, determining the optimal dose of puerarin is critical to avoid overdosing and ADR.

Sweet tea leaves extract improves leptin resistance in diet-induced obese rats

AIM OF THE STUDY Dietary obesity is usually characterized by leptin resistance and abnormal lipid metabolism. Lithocarpus polystachyus Rehd.(Sweet Tea) leaf is a kind of Chinese folkloric medicine, and it has been widely used for obesity, diabetes, and hypertension in South China. The present study is aimed at investigating the pharmacological mechanism of the anti-hyperleptinaemia effects of Sweet Tea leaves extract in high fat diet-induced obese rats. MATERIALS AND METHODS We induced high fat diet obesity for 14 weeks to test the corrective effects of three ST doses (75, 150 and 300 mg/kg per day) for 8 weeks. At the end of the experiment, body weight, fasting blood glucose and serum lipids, superoxide dismutase (SOD), malondialdehyde (MDA), fasting serum insulin and leptin, C-reactive protein, adiponectin and resistin levels were measured, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. mRNA gene expression of PPARγ (peroxisome proliferator-activated receptor γ) and C/EBPα(CCAAT/enhancer-binding protein α) in epididymal adipose tissue of DIO control and experimental groups were evaluated. RESULTS Sweet Tea leaves extract could significantly decrease the levels of serum lipids, attenuate body weight gain and lower circulating leptin and insulin levels, ameliorate the state of oxidative stress, raise serum adiponectin, reduce circulating CRP and resistin levels, and depress the expression of PPARγ and C/EBPα in epididymal adipose tissue of obese rats. CONCLUSION The present findings suggest that ST can effectively attenuate the leptin resistance at least through anti-hyperlipidemic activity and thus has the therapeutic potential in treating hyperlipidemia and hyperleptinaemia related to dietary obesity.

The hypoglycemic activity of Lithocarpus polystachyus Rehd. leaves in the experimental hyperglycemic rats

ETHNOPHARMACOLOGICAL RELEVANCE Leaves of Lithocarpus polystachyus Rehd. are used for the treatment of disorders such as diabetes, hypertension, and epilepsy in folk medicine of South China. The possible antidiabetic effects of the leaves were investigated in experimental type 2 and type 1 diabetic rats. MATERIALS AND METHODS Type 2 diabetic rats received orally three different extracts of Lithocarpus polystachyus Rehd. leaves for 4 weeks (aqueous extract [ST-1], ethanol extract [ST-2], flavonoid-rich fraction [ST-3]). At the end of the experiment biochemical parameters were tested and livers and pancreases were excised for histological study. After the comparison of the pharmacological test results of the three extracts, the one which showed the best bioactivity was further studied to confirm its antidiabetes effect on both type 2 and type 1 diabetic rats. RESULTS Compared to ST-1 and ST-2, ST-3 had better effects on regulation of blood glucose, glycosylated serum protein, cholesterol, triglyceride, malondialdehyde, superoxide dismutase and attenuation of liver injury in type 2 diabetic rats (p<0.01 or p<0.05). ST-3 administration for four weeks also significantly reduced the fasting serum insulin and C-peptide level and improved the insulin tolerance (p<0.05). In type 1 diabetic rats, ST-3 supplement for three weeks caused significant reduction in fasting blood glucose, total cholesterol, triglyceride, urea nitrogen, creatinine and liver mass, along with significantly inhibiting the decline of insulin level compared to diabetic control (p<0.05 or p<0.01). CONCLUSION The flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves (ST-3) had better beneficial effect than that of the ethanol or aqueous extract in experimental diabetic rats, which means that the bioactivity of the herbal leaves is probably due to the presence of flavonoids. The results also strongly suggest that the antidiabetic effect of ST-3 was possibly through multiple mechanisms of action including blood lipid and antioxidant mediation. The results indicated that the aqueous flavonoid-rich fraction of Lithocarpus polystachyus Rehd. leaves possessed significant protective activity in type 2 and type 1 diabetes.

The Extracts of Morinda officinalis and Its Hairy Roots Attenuate Dextran Sodium Sulfate-Induced Chronic Ulcerative Colitis in Mice by Regulating Inflammation and Lymphocyte Apoptosis

Morinda officinalis is beneficial for the treatment of inflammatory bowel disease (IBD). The hairy root with higher genetic and biochemical stability cultured from M. officinalis might have similar effects to treat IBD. In this study, the main chemical composition of the root extracts of M. officinalis (MORE) native plant and the hairy root extract of M. officinalis (MOHRE) was compared by quantitative HPLC. The difference of their therapeutic effects and potential mechanism was evaluated using 3% dextran sodium sulfate-induced chronic colitis in mice and T lymphocytes in vitro. The results found that MOHRE possesses many specific peaks unobserved in the chromatogram of native plant. The content of iridoids in the MORE (3.10%) and MOHRE (3.01%) is somewhat similar but quite different for their anthraquinones’s content (0.14 and 0.66%, respectively). Despite all this, treatment with both MORE and MOHRE significantly attenuated the symptoms of colitis, including diarrhea, body weight loss, colon shortening, histological damage, and decreased inflammatory cytokine levels. In addition, they dose-dependently increased the apoptosis of T lymphocyte in vivo and in vitro. And, the differences for treatment effects on ulcerative colitis (UC) between them both in this study were mostly insignificant. The results demonstrated that the effects of MORE and MOHRE for the treatment of UC are similar, although there are a few difference on their chemical composition, indicating the hairy root cultured from M. officinalis might be able to replace its native plant on treatment of UC. The successful derivation of a sustainable hairy root culture provides a model system to study the synthetic pathways for bioactive metabolites, which will make the use of bioreactors to largely produce traditional medicine become reality.

Effect of Dendrobium officinale on D-galactose-induced aging mice

ObjectiveTo examine the effect of Dendrobium officinale (DO) on D-galactose-induced aging mice.MethodsAging mice was induced by D-galactose at 0.125 g/kg for 10 weeks through subcutaneous injection except for the negative control group. After 10 days, according to complete random design, the aging modeling mice were randomized into 4 groups: aging control group (10 ML·kg-1·d-1) of distilled water), positive control group (vitamin B6 and ganodema lucidum tablets with a dose of 1 tablet/kg), DO-1 treatment group (DO juice with a dose of 1 g/kg), DO-2 treatment group (DO Polysaccharide with a dose of 0.32 g/kg), 14 mice in each group. All the animals were orally medicated daily for 9 weeks. Cognitive function assessment was performed using the maze test and step-down test. At the end of experiment, the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC) levels in the serum, the SOD, GSH-Px and nitric oxide (NO) levels in the cerebrum, the SOD and catalase (CAT) levels in the liver, the SOD and NO levels in the heart, and the SOD level in the kidney, were determined using commercial kits. The spleen, liver, heart, cerebrum and kidney were excised for histological study.ResultsCompared to aging control group, DO shortened the time of passing through the maze and prolong the step-down latency of aging mice (P <0.05 or P<0.01). DO markedly up-regulated serum levels of SOD, GSH-Px and T-AOC, and restored SOD levels in the heart, liver, kidney and cerebrum to normal status (P<0.05 or P<0.01). DO at the dose of 1 g/kg also signififi cantly improved the degree of spleen lesions (P<0.01).ConclusionsDO had marked anti-aging effect on D-galactose-induced model of aging. The underlying mechanism could be related to modulation on antioxidation system and immune system. The results indicated that DO could potentially be used as natural drugs or functional foods for preventing aging.

Dendrobium officinale Prevents Early Complications in Streptozotocin-Induced Diabetic Rats

Background. Dendrobium officinale (DO) Kimura et Migo is a precious Chinese herb that is considered beneficial for health due to its antioxidant and antidiabetes properties, and so on. In this research, we try to determine the preventive effect of DO on the early complications of STZ-induced diabetic rats. Methods. Type 1 diabetic rats were produced with a single intraperitoneal injection of STZ (50 mg/kg). DO (1 g/kg/day) was then orally administered for 5 weeks. Blood glucose, TC, TG, BUN, CREA, and GSH-PX levels were determined, and electroretinographic activity and hypoalgesia were investigated. Pathological sections of the eyes, hearts, aortas, kidneys, and livers were analyzed. Results. Treatment with DO significantly attenuated the serum levels of TC, TG, BUN, and CREA, markedly increased the amplitudes of ERG a- and b-waves and Ops, and reduced the hypoalgesia and histopathological changes of vital organs induced by hyperglycemia. The protective effect of DO in diabetic rats may be associated with its antioxidant activity, as evidenced by the marked increase in the serum level of glutathione peroxidase. However, DO had no significant effect on blood glucose levels and bodyweight of diabetic rats. Conclusions. DO supplementation is an effective treatment to prevent STZ-induced diabetic complications.

Protective roles and mechanisms of Dendrobium officinal polysaccharides on secondary liver injury in acute colitis

The purpose of this study was to investigate the protective roles and mechanisms of Dendrobium officinale polysaccharides (DOPS) on secondary liver injury in acute colitis. Firstly, the mice model of secondary liver injury in acute colitis was induced by 4% Dextran sodium sulfate (DSS). Inflammatory cell model was established by LPS-stimulated RAW264.7 cells. Then, the protective roles of DOPS were evaluated by both in vivo and in vitro experiment. The results showed that DOPS attenuated DSS-induced hepatic pathological damage, liver parameters, infiltration of macrophages, cytokines levels, MDA level and increased the antioxidant enzymes activities. In vitro, DOPS markedly inhibited inflammatory cytokines production and increased antioxidant enzymes activities. Finally, its molecular mechanisms were also observed. The results indicated that DOPS could down-regulated TNF-α signaling pathway and activated Nrf-2 signaling pathway in vivo and in vitro. These results suggested that DOPS may be an effective therapeutic reagent to attenuate secondary liver injury in acute colitis.

Evaluation of toxicity studies of flavonoid fraction of Lithocarpus polystachyus Rehd in rodents

ABSTRACT The aim of the study was to evaluate the safety of flavonoid fraction of Lithocarpus polystachyus Rehd (Sweet Tea‐F, ST‐F) in mice and rats through acute and sub‐chronic toxicity studies respectively. For acute toxicity study, a single dose of 5000 mg/kg of ST‐F was given orally to healthy KM mice. The mice were observed mortality and toxic symptoms for 24 h, then once a day up to 14 days. In the sub‐chronic toxicity study, ST‐F was administered orally at doses of 0, 70, 140, 560 mg/kg/day to rats for 26 weeks. Body weight and food intake were recorded weekly. Hematological, biochemical, coagulation and organ parameters were analyzed at the end of 26 weeks administration. Vital organs were evaluated by histopathology. In the acute toxicity study, ST‐F caused neither significant toxic symptoms, nor mortality in mice. In sub‐chronic toxicity study, daily oral administration of ST‐F at the dose of 70 mg/kg resulted in a significant increase (P < 0.05) in the relative body weight at the 10‐week, and the same situation brought at the dose of 140 mg/kg/day at the 22‐week. Hematological and biochemical showed significant changes (P < 0.01 or P < 0.05) in WBC, GLU, ALP, AST and serum electrolytes levels at the dose of 560 mg/kg/day. The amount of RBC decreased significantly (P < 0.05) while the content of PLT slightly increased (P < 0.05) at the dose of 140 mg/kg/day. In additional, no obvious histological changes were observed in vital organs of ST‐F treated animals compared to control group. The ST‐F may be exit slight side effects at the dose of 560 mg/kg/day in rats. Thus, the overall results show that the no‐observed adverse effect level (NOAEL) of ST‐F was considered to be 140 mg/kg for male SD rats. HIGHLIGHTSThe study shows that the flavonoid fraction of Lithocarpus polystachyus Rehd cause slight toxicity at 560 mg/kg/day in rats.In acute toxicity study, the oral LD50 value of Lithocarpus polystachyus Rehd is higher than 5000 mg/kg.The NOAEL level of ST‐F is considered to be 140 mg/kg for rats and which is 28 times higher than the average intake by human.

Influence of excessive exercise on immunity, metabolism, and gut microbial diversity in an overtraining mice model

The purpose of this study was to evaluate the negative influence of excessive exercise on immunity, substance and energy metabolism as well as gut microbiota in mice. Firstly, an overtraining model of Male Kunming mice was established by high‐intensity swimming exercise for 4 weeks. Then, a series of evaluation indicators, including the routine blood analysis, immune organ coefficient, digestive enzymes, and aquaporins expression levels of small intestine and colon tissue, histological examinations of liver, spleen, small intestine, and colon, were determined based on this model. Furthermore, 16S rRNA gene sequencing was also employed to measure the microbial composition in gut. The results found that immune parameters, substance and energy metabolism of all mice was altered and disturbed after high‐intensity swimming for 4 weeks, led to an atrophy of thymus and spleen as well as abnormal structural changes in liver when compared to non‐swimming mice. Besides, excessive swimming mice had lower microbial diversity compared to non‐swimming mice. However, there was no significant difference in gut microbial taxa between the two groups. The data indicated that excessive exercise exhibits negative impacts on immunity, substance and energy metabolism as well as gut microbial diversity.