Chiu Lan Hsieh

Brain Derived Metastatic Prostate Cancer DU-145 Cells Are Effectively Inhibited In Vitro by Guava (Psidium gujava L.) Leaf Extracts

Abstract: The aqueous extract of Psidium guajava L. (PE) inhibited the cancer cell DU-145 in a dose- and time-dependent manner. At 1.0 mg/mL, PE reduced the viability of PCa DU-145 (the androgen independent PCa cells) to 36.1 and 3.59%, respectively after 48 h and 72 h of incubations. The absolute cell viability suppressing capability (VSC)AC could reach 262.5 cells-mL-h/mg on exposure to PE for 72 h, corresponding to the safe ranges, i.e. the percent viability suppressing rates (PVSR) of 2.72 and 2.41 folds for DU-145 comparing to PZ-HPV-7 cells when treated with PE at 0.5 and 1.0 mg/mL respectively for 72 h. In addition, the colony forming capability of DU-145 cells was apparently lowered. The suppressing rates of which reached 8.09 and 5.96 colony/mg/day for D-145 and PZ-HPV-7 cells, respectively within the concentration range of PE at 0.1 ∼ 0.25 mg/mL. Cell cycle arrests at G0/G1 phase in both cells were observed by TUNEL assay and flow cytometric analysis, yet more prominently evident in DU-145. In addition, suppression of the matrix metalloproteinases MMP-2 and MMP-9, and the upregulation of active caspase-3 at 0.10 to 1.0 mg/mL in DU-145 were also effected in a dose-dependent manner by PE at 0.25 to 1.0 mg/mL, implicating a potent anti-metastasis power of PE. Conclusively, we ascribe the anticancer activity of PE to its extraordinarily high polyphenolic (165.61 ± 10.39 mg/g) and flavonoid (82.85 ± 0.22 mg/g) contents. Furthermore, PE might be useful for treatment of brain derived metastatic cancers such as DU-145, acting simultaneously as both a chemopreventive and a chemotherapeutic.

Quercetin and ferulic acid aggravate renal carcinoma in long-term diabetic victims

Many phytoantioxidants have therapeutic drawbacks due to their potent prooxidant bioactivity. It is hypothesized that phytoantioxidants (PAO) are beneficial only to the early-stage diabetes mellitus (DM) and will become ineffective once renopathy occurs. Gallic acid, rutin, EGCG, ferulic acid (FA), and quercetin were tried on the streptozotocin (STZ)-induced DM rat model for a 28 week experimental period. All of these PAO were shown to be ineffective for hypoglycemic action. The incidence of cataract (50%), injured glomerules, and renal cell carcinoma (RCC) was very common, among which the most severely affected involved the quercetin- and the FA-treated groups. The tumorigenicity of ferulic acid is still unclear. However, for quercetin, this can be attributted to (i) the prooxidant effect, (ii) the insulin-secretagogue bioactivity, and (iii) the competitive and noncompetitive inhibition on the O-methyltransferase to enhance the estradiol-induced tumorigenesis. Conclusively, quercetin and FA are able to aggravate, if not induce, nephrocarcinoma. It is time to reevaluate the tumorigenic detrimental effect of PAO, especially those exhibiting prooxidant bioactivity.

Ferulic acid is nephrodamaging while gallic acid is renal protective in long term treatment of chronic kidney disease

BACKGROUNDS & AIMS The long term therapeutic effect of ferulic acid (FA) and gallic acid (GA) in treatment of chronic kidney disease (CKD) has been lacking. METHODS Doxorubicin (DR, Adriamycin)-induced CKD rat model was established for this study. RESULTS DR significantly reduced levels of serum albumin, GOT, GPT, RBC, TNF-α, and urinary creatinine and elevated serum cholesterol, TG, BUN, creatinine, uric acid, WBC, platelet count, and IL-6. In DRCKD rats, FA and GA significantly increased kidney weight and glomerular volume. FA reduced glomerular filtration rate but GA did not. FA enhanced more collagen deposition than GA in renal cortex and glomeruli. Both FA and GA showed crucial hyperlipidemic activity. The inhibitory effects of FA and GA on MMP-2 were very comparable. GA suppressed MMP-2 more effectively than FA in DRCKD rats. Both FA and GA induced SOD elevation and MDA elimination. In DRCKD rats, Western blot analysis indicated that FA further up-regulated CD34, α-SMA, tissue pDGFR, p-PDGFR, and TGF-β; and down-regulated p-PI3K, and p-Akt. Since both PDGF-BB and TGF-β are considered to induce kidney prefibrosis stage, GA was proved to be more beneficial in this regard. CONCLUSIONS GA tends to protect the CKD while FA is not recommended for the long term CKD therapy.

Swimming Exercise Prevents Fibrogenesis in Chronic Kidney Disease by Inhibiting the Myofibroblast Transdifferentiation

Background The renal function of chronic kidney disease (CKD) patients may be improved by a number of rehabilitative mechanisms. Swimming exercise training was supposed to be beneficial to its recovery. Methodology/Principal Findings Doxorubicin-induced CKD (DRCKD) rat model was performed. Swimming training was programmed three days per week, 30 or 60 min per day for a total period of 11 weeks. Serum biochemical and pathological parameters were examined. In DRCKD, hyperlipidemia was observed. Active mesangial cell activation was evidenced by overexpression of PDGFR, P-PDGFR, MMP-2, MMP-9, α-SMA, and CD34 with a huge amount collagen deposition. Apparent myofibroblast transdifferentiation implicating fibrogenesis in the glomerular mesangium, glomerulonephritis and glomeruloscelorosis was observed with highly elevated proteinuria and urinary BUN excretion. The 60-min swimming exercise but not the 30 min equivalent rescued most of the symptoms. To quantify the effectiveness of exercise training, a physical parameter, i.e. “the strenuosity coefficient” or “the myokine releasing coefficient”, was estimated to be 7.154×10−3 pg/mL-J. Conclusions The 60-min swimming exercise may ameliorate DRCKD by inhibiting the transdifferentiation of myofibroblasts in the glomerular mesangium. Moreover, rehabilitative exercise training to rescue CKD is a personalized remedy. Benefits depend on the duration and strength of exercise, and more importantly, on the individual physiological condition.

Antiandrogenic therapy can cause coronary arterial disease

Abstract  Aim:  To study the change of lipid metabolism by antiandrogen therapy in patients with prostate cancer.

Anticancer Activity of Rhamnoallosan against DU-145 Cells Is Kinetically Complementary to Coexisting Polyphenolics in Psidium guajava Budding Leaves

Psidium guajava L. is a valuable farm fruit plant having many medicinal uses. Previously its budding leaves (PE) were shown to contain huge amounts of soluble polyphenolics (SP) including (in mg/g) gallic acid (348), catechin (102), epicatechin (60), rutin (100), quercetin (102), and rutin (100) and to exhibit potent anticancer activity. However, reconstitution of these polyphenolics recovered only 40% of the original bioactivity, and the soluble carbohydrate (SC) portion in PE was suspected to contribute the remaining. PE contained a novel rhamnoallosan, which had a carbohydrate/protein (w/w) ratio = 29.06%/10.27% (=2.83, average molecular mass of 5029 kDa), characteristically evidencing a peptidoglycan, consisting of a composition (mole % ratio) of rhamnose/allose/arabinose/tallose/xylose/fucose/glucose/mannose/galactose = 36.05:24.24:8.76:7.95:7.37:5.90:3.69:3.19:2.85 and of amino acid (in wt %) glycine/leucine/proline/alanine/methionine/isoleucine/valine/histidine/tyrosine/phenylalanine/cysteine/aspartic acid/lysine/glutamic acid = 37.12:12.68:10.05:8.97:5.99:4.89:4.83:4.25:4.05:2.78:1.86:1.10:0.73:0.70. Kinetic analysis showed comparable apparent cell-killing rate coefficients (k(app)) to be 4.03 x 10(3) and 2.92 x 10(3) cells mg(-1) h(-1), respectively, by SP and SC, evidencing the complementary anti-DU-145 bioactivity in nature.

The polyphenolics in the aqueous extract of Psidium guajava kinetically reveal an inhibition model on LDL glycation

Guava [Psidium guajava L. (Myrtaceae)] budding leaf extract (PE) has shown tremendous bioactivities. Previously, we found seven major compounds in PE, i.e., gallic acid, catechin, epicatechin, rutin, quercetin, naringenin, and kaempferol. PE showed a potentially active antiglycative effect in an LDL (low density lipoprotein) mimic biomodel, which can be attributed to its large content of polyphenolics. The glycation and antiglycative reactions showed characteristic distinct four-phase kinetic patterns. In the presence of PE, the kinetic coefficients were 0.000438, 0.000060, 0.000, and −0.0001354 ABS-mL/mg-min, respectively, for phases 1 to 4. Computer simulation evidenced the dose-dependent inhibition model. Conclusively, PE contains a large amount of polyphenolics, whose antiglycative bioactivity fits the inhibition model.

Exercise Ameliorates Renal Cell Apoptosis in Chronic Kidney Disease by Intervening in the Intrinsic and the Extrinsic Apoptotic Pathways in a Rat Model

We hypothesized that doxorubicin (DR) induced chronic kidney disease (CKD) could trigger the intrinsic and the extrinsic renal cell apoptotic pathways, while treadmill exercise could help prevent adverse effects. Male Sprague-Dawley rats were subjected to treadmill running exercise at a speed of 30 m/min, 30 or 60 min/day, 3 times per week, for a total period of 11 weeks. The physiological and biochemical parameters were seen substantially improved (DR-CKD control, 30 min, 60 min exercise): the ratio of kidney weight/body weight (0.89, 0.74, and 0.72); the WBC (1.35, 1.08, and 1.42 × 104 cells/μL); RBC (5.30, 6.38, and 6.26 × 106 cells/μL); the platelet count (15.1, 12.8, and 11.3 × 105/μL); serum cholesterol (659, 360, and 75 mg/dL); serum triglyceride (542, 263, and 211 mg/dL); BUN (37, 25, and 22 mg/dL). Bcl-2 and intramitochondrial cytochrome c were upregulated, while the levels of Bax, SOD, MDA, cleaved caspases 9, 3, 8, 12, and calpain were all downregulated in DRCKD groups with exercise. CHOP (GADD153) and GRP78 were totally unaffected. FAS (CD95) was only slightly suppressed in the 60 min exercise DRCKD group. Conclusively, exercise can ameliorate CKD through the regulation of the intrinsic and extrinsic apoptosis pathways. The 60 min exercise yields more beneficial effect than the 30 min counterpart.

Exercise rescued chronic kidney disease by attenuating cardiac hypertrophy through the cardiotrophin-1 → LIFR/gp 130 → JAK/STAT3 pathway

Background Chronic kidney disease (CKD) is usually associated with cardiac apoptosis and/or cardiac hypertrophy. We hypothesized that exercise can reduce the CKD-induced cardiac damage. Methods and results The doxorubicin-induced CKD (DRCKD) model was used in rats to compare two exercise models: 60-min running and 60-min swimming. Results indicated that in healthy normal groups, the signals cardiotrophin-1 (CT-1), interleukin 6 (IL-6), leukaemia inhibitory factor receptor (LIFR), and gp130 were upregulated and janus kinase (JAK) and signal transducer and activation of transcription (STAT) were downregulated by both exercises. In contrast, all signals were highly upregulated in CKD. After exercise training, all signals (CT-1, IL-6, LIFR, gp130, and STAT) were downregulated, with JAK being only slightly upregulated in the running group but not in the swimming group. The myocyte death pathway (CT-1/IL-6 → LIFR/gp130 → PI3K → Akt → Bad) was excluded due to no change found for Bad. Nitric oxide (NO; normal, 15.63 ± 0.86 µmol/l) was significantly suppressed in CKD rats (2.95 ± 0.32 µmol/l), and both running and swimming training highly upregulated the NO level to 30.33 ± 1.03 µmol/l and 27.82 ± 2.47 µmol/l in normal subjects and 24.0 ± 3.2 µmol/l and 22.69 ± 3.79 µmol/l in the DRCKD rats, respectively. The endothelial progenic cells CD34 were significantly suppressed in DRCKD rats, which were not rescued significantly by exercise. In contrast, the CD 34 cells were only slightly suppressed in the healthy subjects by exercise. Conclusion Both exercise regimens were beneficial by rescuing cardiac function in CKD victims. Its action mechanism was by way of inhibiting myocyte death and rescuing cardiac hypertrophy.

Anisotropic diffusion deviates chicken embryo chorioallantoic membrane assay (CAM) to reflect inherent therapeutic behaviors

Chorioallantoic membrane assay (CAM) has become a widely used tool for determination of anti-angiogenesis capability of many drugs including herbal extracts. Because varying results in same set of chicken embryos are often encountered, we developed the complex diffusion model that combined the Ficks second diffusion law, chemical-protein interaction (or binding) to explain the diffusion- or kinetic-limiting phenomena in egg white when performing CAM. In addition, we performed diffusion studies in egg white with Color Blue No. 1, Evans Blue, Color Red No. 40, and the aqueous extract of Psidium guajava budding leaves (PE) to support our model. Under same conditions, the diffusion coefficients of Blue No. 1, Evans Blue, Red No. 40, and PE were (2.0-2.8)x10(-9), (0.89-31)x10(-9), (2.8-12)x10(-9), and (7.0-21)x10(-9)m(2)s(-1), respectively, depending upon the distance diffused. Whilst at the interface of egg white and embryo (egg yolk), a site about 1cm apart from the aeration sac, the percent concentration reached only 10.5, 3.0, 3.6, and 2.2% of the original applied medicine, respectively. We conclude that CAM could only serve as a preliminary screening tool for angiogenesis, because the anisotropic diffusion in egg white affects greatly the effective dosages of medicines tested.