AIM:To study the effect of Panax quinquefolium saponin (PQS) on cardiomyocyte apoptosis in-duced by thapsigargin ( TG) .METHODS:Primary cultured cardiomyocytes from neonatal SD rats were divided into con-trol group, TG group, PQS (40 mg/L, 80 mg/L and 160 mg/L) +TG group, si-PERK+TG group, and mock+TG group.The cells were treated with 1 μmol/L TG for 24 h to induce apoptosis.The PERK gene in the cardiomyocytes was knocked down by RNAi.The cell viability was detected by CCK-8 assay.Apoptosis was analyzed by flow cytometry.Wes-tern blotting was used to determine the expression of ERS molecules GRP78, CRT, ATF4 and CHOP, anti-apoptosis pro-tein Bcl-2 and pro-apoptosis protein Bax.RESULTS: Compared with control group, TG significantly and the apoptosis, reduced the cell viability (P<0.05), increased the phosphorylation of PERK and eIF2α, increased the expression of GRP78, CRT, ATF4, CHOP and pro-apoptosis protein Bax, and decreased the expression of anti-apoptosis protein Bcl-2 (P<0.05).Compared with TG group, PQS treatment (160 mg/L) significantly reduced the apoptosis and increased the cell viability (P<0.05).All the 3 different concentrations of PQS significantly increased the expression of anti-apoptosis protein Bcl-2 and reduced the expression of pro-apoptosis protein Bax (P<0.05) in a dose-dependent manner.PQS pre-treatment and knockdown of PERK both reduced the protein levels of GRP78, CRT, PERK, p-PERK, eIF2α, p-eIF2α, ATF4, CHOP and pro-apoptosis protein Bax, and increased the expression of anti-apoptosis protein Bcl-2 (P<0.05). CONCLUSION:PQS at concentration of 160 mg/L attenuated cardiomyocyte apoptosis induced by TG.PQS had the simi-lar effect as PERK knockdown on cardiomyocyte apoptosis.The mechanism may be associated with inhibiting PERK-eIF2α-ATF4-CHOP pathway of ERS-related apoptosis.

Objective To investigate the effects ofShipi-Gushen-Huayu Recipe on the expressions of collagen I, laminin(LN), transforming growth factor-β1(TGF-β1)andα-smooth muscle actin(α-SMA)in adriamycin-induced renal fibrosis in rats.Methods A total of male SD rats were randomly divided into four groups, with 10 rats in each group: a normal group, a model group, a treatment group and a fosinopril sodium group. Except the rats in the normal group, the rest rats were subjected to renal fibrosisvia tail intravenous injection of adriamycin(4 mg/kg). Two weeks after modeling, the rats in the rreatment group and in the fosinopril sodium group were intragastrically administrated daily withShipi-Gushen-Huayu Recipe extract(43 g/kg)and fosinopril solution(2 mg/kg), respectively,both in the normal group and model group with saline. After 30 days, 24-hours urine protein were determined, and the expressions of collagen I, LN, TGF-β1 andα-SMA in kidney tissue were detected with immunohistochemistry staining.Results The expressions of collagen I(24.64±0.67vs. 32.86±0.88), LN(18.71±0.72vs. 28.35±0.87), TGF-β1(14.71±0.68vs. 18.35±0.96)andα-SMA(17.64±0.74vs. 25.86±0.85)in the treatment group were significantly lower than those in the model group(allP<0.01). The expressions of collagen I, LN, TGF-β1 andα-SMA in the fosinopril sodium group were 27.33±0.73, 20.44±0.81, 15.44±0.85 and 19.33±0.77, respectively. There was no statistically significant difference between the expressions of collagen I, LN, TGF-β1 andα-SMA in the treatment group and in the fosinopril sodium group.ConclusionShipi-Gushen-Huayu Recipe can significantly down regulate the expressions of collagen I, LN, TGF-β1 andα-SMA in adriamycin-induced renal fibrosis in rats.

AIM:To investigate whether mitochondrial membrane potential (ΔΨm ) and the mitochondrial ap-optotic pathway are involved in the protective mechanism of Panax quinquefolium saponin ( PQS) against cardiomyocyte ap-optosis after ischemia/reperfusion ( I/R) injury in rat myocardium .METHODS: Ninety healthy male SD rats were ran-domly divided into sham group , I/R group, PQS (200 mg· kg -1 · d-1 ) +I/R group, cyclosporine A ( CsA) group, CsA (10 mg· kg-1 ) +I/R group and PQS +CsA +I/R group.The model of myocardial I/R injury in vivo was established by ligating the left anterior descending artery ( LAD) for 30 min followed by 120 min of reperfusion in the rats .The serum ac-tivity of lactate dehydrogenase ( LDH ) was measured by automatic chemistry analyzer .The myocardial infarct size was measured by Evans blue and 2,3,5-triphenyltetrazolium chloride (TTC) staining.Cardiomyocyte apoptosis was detected by in situ TDT-mediated dUTP nick end labeling (TUNEL).The protein levels of Bcl-2, Bax, cleaved caspase-3 and cytosol-ic cytochrome C were determined by Western blotting .ΔΨm was measured by laser scanning confocal microscopy and fluo-rescence microplate reader .RESULTS:Compared with I/R group, the serum content of LDH ,the infarction size in PQS+I/R group, CsA+I/R group and PQS +CsA+I/R group and the myocardial apoptotic index were decreased .Compared with I/R group, the fluorescence intensity of mitochondria after JC-1 staining was enhanced in PQS +I/R group, CsA+I/R group and PQS+CsA+I/R group, and the relative fluorescence units (RFU) ofΔΨm were improved in those 3 groups. In PQS+I/R group, CsA+I/R group and PQS+CsA+I/R group, the protein expression of Bcl-2 was increased, and that of Bax was decreased compared with I/R group.Moreover, in those 3 groups, the protein levels of cleaved-caspase-3 and cytosolic cytochrome C were decreased compared to I /R group, respectively.CONCLUSION:PQS attenuates myocardial injury and cardiomyocyte apoptosis during I /R, and the protective mechanisms of PQS were associated with the modulation ofΔΨm and the inhibition of mitochondrial apoptosis pathway .

OBJECTIVETo evaluate the clinical efficacy of syndrome differentiation-based treatment with traditional Chinese medicine (TCM) versus losartan therapy in addition to basic treatment for management of proteinuria in patients with chronic kidney disease.

METHODSThis multicenter, randomized, and case-controlled clinical trial was conducted among 81 consecutive patients meeting the inclusion criteria. The patients were randomized consecutively to receive TCM treatments according to the syndrome patterns in TCM (spleen and kidney Qi and Yin deficiency, and spleen and kidney Qi and Yang deficiency, n=60) or oral losartan therapy (50 mg/day, n=21) in addition to the basic treatments. All the patients were followed up for 24 weeks to observe the clinical effects.

RESULTSThe patients in TCM group showed a significantly higher overall response rate (93.33%) than those in losartan group (76.20%, P<0.05). The TCM score in the two groups were all decreased at week 24 as compared with baseline (P<0.01 or P<0.05). The TCM scores in both groups decreased significantly after the treatments as compared with the baseline scores (P<0.05). After a 8-week-long treatment, Scr, eGFR and Cys-C, U-Pro/24 h, and MA/Cr all decreased significantly in TCM group (P<0.05) but showed no significant changes in losartan group (P>0.05).

CONCLUSIONSyndrome differentiation-based TCM treatment in addition to basic treatments can produce satisfactory therapeutic effects on proteinuria in patients with chronic kidney disease by improving the clinical symptoms, reducing TCM symptom scores and proteinuria, and protecting the renal functions.

Adult ; Aged ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Losartan ; therapeutic use ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Phytotherapy ; Prospective Studies ; Proteinuria ; drug therapy ; etiology ; Renal Insufficiency, Chronic ; complications ; drug therapy

The effects of black rice anthocyanidins (BRACs) on retinal damage induced by photochemical stress are not well known. In the present study, Sprague-Dawley rats were fed AIN-93M for 1 week, after which 80 rats were randomly divided into two groups and treated with (n = 40) or without BRACs (n = 40) for 15 days, respectively. After treatment, both groups were exposed to fluorescent light (3,000 +/- 200 lux; 25degrees C), and the protective effect of dietary BRACs were evaluated afterwards. Our results showed that dietary BRACs effectively prevented retinal photochemical damage and inhibited the retinal cells apoptosis induced by fluorescent light (p < 0.05). Moreover, dietary BRACs inhibited expression of AP-1 (c-fos/c-jun subunits), up-regulated NF-kappaB (p65) expression and phosphorylation of IkappaB-alpha, and decreased Caspase-1 expression (p < 0.05). These results suggest that BRACs improve retinal damage produced by photochemical stress in rats via AP-1/NF-kappaB/Caspase-1 apoptotic mechanisms.
Animal Feed/analysis ; Animals ; Anthocyanins/administration & dosage/*pharmacology ; Antioxidants/administration & dosage/*physiology ; Blotting, Western ; Caspase 1/*genetics/metabolism ; Diet ; Dietary Supplements/analysis ; I-kappa B Proteins/genetics/metabolism ; NF-kappa B/*genetics/metabolism ; Neoplasm Proteins/genetics/metabolism ; Nucleocytoplasmic Transport Proteins/genetics/metabolism ; Oryza sativa/chemistry ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Proto-Oncogene Proteins c-jun/genetics/metabolism ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Retinal Diseases/etiology/*prevention & control ; Signal Transduction/*drug effects/radiation effects ; Transcription Factor AP-1/*genetics/metabolism