Ferulic acid (4-hydroxy-3-methoxycinnamic acid) (FA) is a ubiquitous health beneficial phenolic acid. Although FA has shown a diversity of biological activities including anti-inflammatory, antihypercholesterolemic and anticancer bioactivities, studies revealing its adverse effects are accumulating. Recently, 3D-cultures are shown to exhibit uniquely biological behaviors different from that of 2D cultures. To understand whether the cytotoxicity of FA against the T24 cell line (a bladder cancer cell line) in 2D-culture could consistently retain similar bioactivity if cultured in the 3D-systems, we conducted this experiment with 2 mM FA. Much higher cytotoxicity was found for 3D- than 2D-culture, showing (2D vs. 3D): apoptotic rates, 64% and 76%; cell killing rates,3.00×105 cells mmol⁻¹·h⁻¹and2.63×106cells mmol⁻¹·h⁻¹, attaining a 8.77-fold. FA upregulated the activities at 72 h (2D vs. 3D in folds that of control): SOD, 1.73-folds (P<0.05) versus 3.18 folds (P<0.001); and catalase, 2.58 versus 1.33-folds. Comparing to the control (without FA), Bcl-2 was prominently downregulated while Bax, caspase-3 and cleaved caspase-9 were more upregulated in 3D-cultures (P<0.05). Conclusively, different microenvironments could elicit different biological significance which in part can be ascribed to different mass transport rate.

The aqueous extract of Psidium guajava budding leaves (PE) bears an extremely high content of polyphenolic and isoflavonoids. Whether it could be used as an anti‐tumor chemopreventive in view of anti‐angiogenesis and anti‐migration, we performed the assay methods including the MTT assay to examine the cell viability; the ELISA assay to test the expressions of VEGF, IL‐6 and IL‐8; the western blot analysis to detect TIMP‐2; the gelatinolytic zymography to follow the expression of MMPs; the wound scratch assay to examine the migration capability; and the chicken chorioallantoic membrane assay to detect the suppressive angiogenesis. Results indicated that the IC50 of PE for DU145 cells was ~0.57 mg ml⁻¹. In addition, PE effectively inhibited the expressions of VEGF, IL‐6 and IL‐8 cytokines, and MMP‐2 and MMP‐9, and simultaneously activated TIMP‐2 and suppressed the cell migration and the angiogenesis. Conclusively, PE potentially possesses a strong anti‐DU145 effect. Thus, clinically it owns the potential to be used as an effective adjuvant anti‐cancer chemopreventive.

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 cytochromecwere 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.

Perilla frutescens (L.) Britt Labiatae (Pl), known as “Zi-So” and widely grown in China (red cultivar, Rpl) and Japan (green cultivar, Gpl), is frequently served on “Sa-Shi-Mi” dishes. Considering whether the perilla leaves substantially possess antimicrobial activity, we prepared the essential oils (EO: EOr and EOg), the pentane and ether [E: E(rp) and E(gp)] subfractions, the aqueous [Rpl(w) and Gpl(w)] and ethanolic extracts [pl(E), Rpl(E) and Gpl(E)] to compare their biological activities. Results indicated Gpl(E) and Rpl(E) contained huge amount (in mg/100 g) of polyphenoilcs (1472±1.0 vs. 1269.8±1.7), rutin (20.8±0.8 vs. 11.4±0.6), quercetin (29.8±0.9 vs. 13.6±0.6), and lutein (13.9±0.7 vs. 14.2±0.8). The total number of volatile constituents present in EOr and EOg were 27 in each but different phytochemicals. The top five major constituents (in %) in EOr were perilla aldehyde (54.35%), limonene (23.81%), trans-caryophyllene (7.2%), cis,trans-α-farnescene (7.02%), and linalool (2.40%); that in EOg were perilla aldehyde (65.26%), limonene (12.49%), cis,trans-α-farnescene (7.31%), trans- caryophyllene (5.91%), and linalool (2.75%); The top two constituents in E(rp) were perilla aldehyde (93.19%) and linalool (4.02%); that of E(gp) were perilla aldehyde (84.40%) and linalool (5.03%). EO and E showed moderate DPPH free radical scavenging-, ferrous ion chelating-, superoxide anion- and H₂O₂ -scavenging capabilities. At 1.0 mg/mL the Es always revealed to be superior to EOs against E. coli, S. aureus, V. parahemolyticus, and T. mentagrophytes. Amazingly, E was stronger than perilla aldehyde against S. typhimurium,. The cytotoxicity test indicated Gpl(E) was more toxic than Rpl(E) and the pl(E)s were more toxic than pl(w)s. Conversely, the pl(w)s showed stronger TNF-α suppressing activity than pl(E)s. The pentane subfractions were entirely ineffective. Conclusively, the Perilla EOs contain huge amount of polyphenoilcs, the Es exhibit the rather good antimicrobial and cytotoxic effects, while the pl(w)s possess rather promising anti-inflammatory effect, underlying the promising antimicrobial and antiinflammtory effects of perilla leaves.