Hui Er Wang

Alpinia zerumbet potentially elevates high-density lipoprotein cholesterol level in hamsters

In folkloric plant medicines, Alpinia zerumbet (AZ) has been popularly recognized as an exellent hepatoprotector. To search for a good high-density lipoprotein cholesterol (HDL-C) elevating herbal preparation, we examined AZ for its antioxidant and hypolipidaemic bioactivities, especially its HDL-C elevating activity. AZ seeds contain 0.51% essential oils (SO), which are comprised of monoterpenoids, oxygenated monoterpenoids, sesquiterpenoids, oxygenated sesquiterpenoids, aldehydes, acid, and esters. Gas chromatography/mass spectrometry analysis indicated that most of the monoterpenes and sesquiterpenes were recoverable in pentane eluent, whilst the oxygenated monoterpenoids and sesquiterpenoids remained in ether eluent. The high contents of rutin, quercetin, and polyphenolics in ethanolic extract of AZ seeds exhibit moderate antilipoperoxidative but potent DPPH free radical scavenging bioactivities. Conclusively, both seed powder (SP) and SO are effective hypolipidaemics with amazingly potent HDL-C elevating capabilities. On the basis of hepatoprotectivity, SP is a more feasible hypolipidemic agent as well as a promising HDL-C elevating plant medicine.

Cytotoxicity of Ferulic Acid on T24 Cell Line Differentiated by Different Microenvironments

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−1 and 2.63 × 106 cells 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.

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.

Antiandrogenic therapy can cause coronary arterial disease

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

Valproic Acid Downregulates RBP4 and Elicits Hypervitaminosis A-Teratogenesis—A Kinetic Analysis on Retinol/Retinoic Acid Homeostatic System

Background Valproic acid (VPA) is an antiepileptic and anti-migraine prophylactic drug. VPA exhibits two severe side effects, namely acute liver toxicity and teratogenicity. These side effects are usually seen at the genetic and somatic levels. The cited action mechanisms involve inhibition of histone deacetylase, hypofolatenemia, hyperhomocysteinemia, and reactive oxidative stress. The proteomic information associated with VPA teratogenicity is still unavailable. We hypothesized that proteomic analysis might help us identify functional proteins that could be relevantly affected by VPA, and this phenomenon could be very sensitive in early embryonic stage, resulting in VPA teratogenicity. Methodology/Principal Findings Proteomic analysis on the chicken embryos at Hamburger and Hamilton (HH) stage 28 showed that there were significant downregulations of ovotransferrins, carbonic anhydrase-2, retinol binding protein-4 (RBP4), NADH cytochrome b5 reductase 2 (CYB5R2), apolipoprotein A1, and protein SET, together with upregulation of 60S ribosomal protein L22. Among these, RBP4 was the most significantly downregulated (−32%). Kinetic analysis suggested that this situation could trigger hypervitaminosis A (+39.3%), a condition that has been well known to induce teratogenesis.. Conclusions/Significance This is the first report showing that VPA dowregulates RBP4. Our finding not only has led to a possible mechanism of VPA teratogenesis, but also has initiated new preventive strategies for avoiding VPA teratogeneis.

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.

Antrodia cinnamomea exhibits a potent neuroprotective effect in the PC12 Cell-Aβ25-35 model - pharmacologically through adenosine receptors and mitochondrial pathway.

Antrodia cinnamomea has a diversity of therapeutic effects including anticancer properties. Its neuroprotective effect is rarely cited. We hypothesized that due to its high phenol, triterpenoid, and adenosine contents, it might exhibit a potent neuroprotective effect. The PC12 cell model was used to investigate its pharmaceutical effects. Congo red staining was used to identify the activation of Aβ25-35. Chemical analysis indicated that the ethanolic extract of Antrodia cinnamomea contained a huge amount (mg/g ethanolic extract of Antrodia cinnamomea) of polyphenolics (133 ± 7), flavonoids (114 ± 6), triterpenoids (175 ± 26), and adenosine (370 ± 17). When tested with Aβ25-35 (15 µM), the cell viability was suppressed in a dose-dependent fashion with an IC50 value of 10 µM. The biochemical parameters upregulated by Aβ25-35 (15 µM) involved TNF-α, ROS, MDA, NO, and the intracellular calcium ions. These adverse effects were effectively ameliorated by the ethanolic extract of Antrodia cinnamomea (1 µg/mL). The Western blot analysis revealed that Aβ25-35 downregulated BcL-2/Bax and upregulated cleaved caspases-9 and - 3 without affecting cleaved caspase-8. The G2/M arrest elicited by Aβ25-35 was ameliorated by the ethanolic extract of Antrodia cinnamomea. TUNEL assay confirmed the apoptosis, and the ethanolic extract of Antrodia cinnamomea downregulated adenosine A1 and adenosine A2A receptors. Taken together, Aβ25-35 tends to induce neurotoxicity on PC12 cells. The ethanolic extract of Antrodia cinnamomea is capable of suppressing its neurotoxicity by rescuing the mitochondrial apoptosis pathway and simultaneously by downregulating adenosine A1 and adenosine A2A receptors to retard neurodegeneration and memory dysfunction.

Hypolipidemic effects of different angiocarp parts of Alpinia zerumbet.

Context: In utilization of Alpinia zerumbet (Pers.) Burtt and Smith (Zingiberaceae) (AZ), usually the angiocarps are discarded without further use. Objective: We speculate whether the angiocarps could show hypolipidemic effect. Methods and methods: Several diets were prepared: Alpinia seed powder (ASP); Alpinia seed powder/husk (ASH): 40/60; and Alpinia seed essential oil (ASO): 0.01–0.10%. Sprague-Dawley rats divided into 11 groups were fed these diets for 8 weeks and tested for the hypolipidemic bioactivity. Results: The fecal neutral cholesterol excretion was increased, and the serum total triglyceride (TG) was significantly reduced from 153.7 mg/dL in the high-fat group (H) to 114.3–119.8 mg/dL by ASO; to 116.3–147.9 mg/dL by ASP; and to 116.2–145.3 mg/dL by ASH. Activity of superoxide dismutase (SOD) and glutathione peroxidase (GPX) were almost unaffected. The high-density lipoprotein (HDL) levels were mostly raised by ASO to 180.3–200.8 mg/dL. The low-density lipoprotein (LDL) levels were mostly reduced to 66.8–82.6 mg/dL by ASH. The level of arachidonic acid was mostly raised to 0.50–0.60% by ASO, compared with 0.37% of group H. More importantly, the significant reduction in hepatic TG and total cholesterol (TC) implicated a crucial liver protective effect. Discussion and conclusion: ASP and ASH consisted of high crude-fiber content, while ASO consisted of seed essential oil. Both the seed essential oil and the whole powder of AZ previously had been reported to possess potent hypolipidemic bioactivity. Conclusively, the hypolipidemic effect can be attributed to the combined effect of the essential oil and the crude fiber.

Schisandra chinensis peptidoglycan-assisted transmembrane transport of lignans uniquely altered the pharmacokinetic and pharmacodynamic mechanisms in human HepG2 cell model.

Schisandra chinensis (Turz Baill) (S. chinensis) (SC) fruit is a hepatoprotective herb containing many lignans and a large amount of polysaccharides. A novel polysaccharide (called SC-2) was isolated from SC of MW 841 kDa, which exhibited a protein-to-polysaccharide ratio of 0.4089, and showed a characteristic FTIR spectrum of a peptidoglycan. Powder X-ray diffraction revealed microcrystalline structures within SC-2. SC-2 contained 10 monosaccharides and 15 amino acids (essential amino acids of 78.12%w/w). In a HepG2 cell model, SC-2 was shown by MTT and TUNEL assay to be completely non-cytotoxic. A kinetic analysis and fluorescence-labeling technique revealed no intracellular disposition of SC-2. Combined treatment of lignans with SC-2 enhanced the intracellular transport of schisandrin B and deoxyschisandrin but decreased that of gomisin C, resulting in alteration of cell-killing bioactivity. The Second Law of Thermodynamics allows this type of unidirectional transport. Conclusively, SC-2 alters the transport and cell killing capability by a “Catcher-Pitcher Unidirectional Transport Mechanism”.

Active Volatile Constituents in Perilla frutescens Essential Oils and Improvement of Antimicrobial and Anti-Inflammatory Bioactivity by Fractionation

Abstract 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.